Retention fluids of chronic sinusitis induce neutrophil adherence to microvascular endothelial cells.

The adherence of circulating leukocytes to the vascular endothelium is a critical step in the emigration of leukocytes through blood vessel walls to inflammatory lesions. The influence of nasal secretions on the adherence of neutrophils to the vascular endothelium was investigated using monolayers of human mucosal microvascular endothelial cells derived from the inferior turbinate. Preincubation of vascular endothelial cells with retention fluids from the maxillary sinus of the patients with chronic sinusitis showed increased neutrophil adherence. Recombinant IL-1 beta was also tested and found to induce adherence of neutrophils to human mucosal microvascular endothelial cells. However, no adhesive effect was observed with the nasal secretions of nasal allergy. An enzyme-linked immunosorbent assay detected considerable amounts of IL-1 beta in the chronic sinusitis retention fluids, while the amounts of IL-1 alpha and TNF-alpha were very low. The increased adhesion of the neutrophils by the retention fluids of chronic sinusitis was also neutralized by the incubation with anti-IL-1 beta antibody in a dose dependent manner. These findings suggest that IL-1 beta in the paranasal secretion of chronic sinusitis induces the adherence of neutrophils to vascular endothelium and subsequent infiltration of neutrophils in the paranasal sinuses, thus contributing to the persistence of chronic sinusitis.


Expression of epithelial membrane antigen and secretory component in carcinomas of the laryngeal ventricle, epiglottis and vocal cord.

Expression of epithelial membrane antigen (EMA) and secretory component (SC) in 11 laryngeal carcinomas from the laryngeal ventricle was studied immunohistochemically and the results were compared with findings in carcinomas originating from the epiglottis and vocal cord. EMA was almost constantly present in laryngeal carcinomas of each type, while the expression of SC was observed in 7 of 11 (64%) ventricle carcinomas, 9 of 34 (26%) carcinomas from the epiglottis and 2 of 11 (18%) carcinomas from the vocal cord. In 4 ventricle carcinomas, immunostaining for SC was intense. It would appear that some carcinomas in the laryngeal ventricle originate from cells of the secretory glandular acini or the epithelium.


Serum concentration fluctuation and bioavailability comparison between indomethacin sustained-release and conventional capsules during steady state.

The comparison between indomethacin conventional capsule (CC) po 25 mg q 8 h or 25 mg tid and indomethacin sustained-release capsule (SRC) po 25 mg bid in human by crossover design showed that both maximal serum concentration (Cmax) and fluctuation index (FI%) of SRC were significantly lower than those of CC during steady state (P < 0.01). No practical differences were observed between the 2 preparations in the trough serum concentration (Cmin) and area under serum concentration-time profiles (AUC0-tau) (P > 0.05). The time period reaching maximal serum concentration (Tmax) of SRC was much more delayed than that of CC (P < 0.01). It suggested that SRC possesses a better controlled release property and could avoid a higher serum peak concentration of CC.


Effects of ohmefentanyl on CA1 field potentials in rat hippocampus slices.

The effects of ohmefentanyl (OMF), a new opiate agonist with high affinity and high specificity for mu receptors, was examined on CA1 field potentials in the transverse hippocampal slices. OMF showed two effects upon the evoked population spikes (PS) recorded in stratum pyramidale: 1) a concentration-dependent increase in the amplitude of PS, which was largely reversed by naloxone, and 2) production of a naloxone-reversible additional PS at high stimulus intensities. No significant change was seen in field excitatory postsynaptic potential (EPSP) recorded simultaneously in stratum radiatum. The EC50 for OMF and morphine were 6.6 and 3700 nmol.L-1, respectively. Thus OMF was 560 times more potent than morphine. The mechanism of augmentation by OMF of PS could be attributed to disinhibition as judged from the paired-pulse paradigm.


Effects of l-stepholidine on synaptosomal Ca(2+)-ATPase and subcellular calmodulin in rat striatum.

Our results showed that l-stepholidine (l-SPD) inhibited basal Ca(2+)-ATPase activity in rat striatal synaptosomes with an IC50 of 31.5 mumol.L-1, suggesting its interaction with Ca2+ transport. l-SPD inhibited also calmodulin (CaM)-activated basal Ca(2+)-ATPase in a concentration-dependent manner. A complete reversal of CaM activation of Ca(2+)-ATPase was observed with l-SPD 10 mumol.L-1. The activity of synaptosomal Ca(2+)-ATPase and membrane-bound CaM level were decreased in haloperidol (1 mg.kg-1.d-1, ip) and l-SPD (5, 10, and 30 mg.kg-1.d-1, ip) treated rats for 7 and 14 d, respectively. But the activity of Ca(2+)-ATPase and membrane CaM level were increased after treatment with the same of doses haloperidol and l-SPD for 21 d. During the treatments with haloperidol and l-SPD cytosolic and nuclear CaM levels were not altered. These results suggest that l-SPD may modulate the release and synthesis of dopamine (DA) and the negative feedback regulation of presynaptic DA receptors by altering Ca2+ and CaM regulating processes in the central dopaminergic nervous system.


Vascular permeability increased by histamine aerosol, capsaicin, and electric stimulation of vagus nerves in guinea pigs.

The present study was to clarify the tissue differences in vascular permeability enhanced by 0.1% histamine aerosol, capsaicin (50 micrograms.kg-1, iv), and electric stimulation of vagus nerves (ESV, 12 V, 5 ms, 16 Hz, for 90 s) in different parts of airways, heart, esophagus, ileum, kidney, and liver of guinea pigs using Evans blue (30 mg.kg-1, iv) as a tracer. All the treatments significantly increased the dye extravasation in trachea, main bronchi, proximal and distal intrapulmonary airways (by 64-722%), as well as in the heart (by 89-126%), most remarkable for capsaicin on trachea and main bronchi. Capsaicin also markedly increased the dye content in esophagus. These results demonstrate that neurogenic inflammation induced by capsaicin and ESV primarily increases vascular permeability in the respiratory tract and heart.


Effect of dizocilpine maleate on cerebral anoxia and ischemic damage in rodents.

The Protective effects of dizocilpine maleate (DM) against anoxia in mice and ischemic damage in rats of 4-vessel occlusion (4-VO) were studied. DM 0.5 or 1.0 mg.kg-1 ip significantly prolonged the survival time of mice in closed containers. DM 0.5 and 1.0 mg.kg-1 ip 30 min prior to 4-VO obviously accelerated the electroencephalographic recovery, reduced the neuronal loss in the hippocampus, and increased the survival rate after 72-h reperfusion. These effects followed a dose-dependent manner. Our results indicate that selective non-competitive N-methyl-D-aspartate receptor blocker DM protects against anoxic and ischemic cerebral damage.


Effect of intracerebral injection of pirenzepine on electroencephalography and convulsions in conscious rabbits.

Intracerebroventricular (icv) injection of pirenzepine (Pir) 2 mg.kg-1 caused EEG spike discharges, which first appeared in amygdala or hippocampus and then in midbrain reticular formation and cortex. After that rabbits developed clonic convulsions. Injection (300 micrograms) into amygdala or hippocampus also produced EEG spike discharges Hemicholinium 3 (HC-3) 50-150 micrograms.kg-1 icv inhibited the EEG spike and seizure discharges in varying degrees produced by Pir. It is suggested that Pir has a central stimulatory action which is related to cholinergic mechanism.


Circadian effects of scopolamine on memory, exploratory behavior, and muscarinic receptors in mouse brain.

Mice were maintained at light-dark cycle with lights on from 05:00-19:00 for 10 d in laboratory. The study was performed at 07:00-09:00, 15:00-17:00, and 21:00-23:00 in June and July. Scopolamine (Scop, 0.1 and 0.4 mg.kg-1, ip) was injected 15 min prior to training or the first exploratory test. The amnesic effects of Scop showed hyperresponses at 07:00-09:00 and 15:00-17:00, and hyporesponses at 21:00-23:00 using step-through and step-down tasks. The circadian effects of Scop on exploratory behavior were consistent with the findings above mentioned. The numbers of [3H]quinuclidinyl benzilate ([3H]QNB) binding sites in the temporal cortex and hippocampus were more at 08:00 and 16:00 than those at 22:00. However, muscarinic receptor levels in the striatum were lower at 08:00 than those at 22:00. These results indicated that the effects of Scop on memory, behavior in a novel environment, and muscarinic receptors in brain regions showed circadian changes in mice.


Global depletion of myocardial norepinephrine and ATP after left coronary artery occlusion in rats.

After ligation of the left coronary artery in rats, myocardial norepinephrine (NE) and ATP depletions in both infarcted (IZ) and non-infarcted zone (NIZ) were studied. In IZ, the depletions of NE and ATP were biphasic and the depleting rate constants were found to be K1 = 0.71 h-1 and K2 = 0.015 h-1 for NE, and K1' = 0.52 h-1 and K2' = 0.016 h-1 for ATP. In NIZ, the depletion of NE was monophasic, slowly progressive, and quite durable with rate constant K3 = 0.018 h-1. The depletion of ATP was transient. Propranolol (Pro) and verapamil (Ver) were beneficial but only partly effective against NE and ATP depletions.


Electrophysiological effects of cimetidine on rabbit myocardium.

Effects of cimetidine (Cim) were studied electrophysiologically on fast action potential (AP) in rabbit papillary muscle and slow AP in pacemaker cell of rabbit sinoatrial node (SAN) as well as on atrioventricular (A-V) conduction in anesthetized rabbit. Cim (0.01, 0.1, 1, and 2 mmol.L-1) induced prolongations of AP duration (APD) and effective refractory period (ERP), slowing down of the maximal rate of rise of phase 0 (Vmax) and of the slope of phase 4 depolarization (SP4), and a decrease of AP amplitude (APA) in concentration-dependent manners. Cim (100 mg.kg-1 iv) prolonged the A-V conduction. The results suggest that Cim, like quinidine, shows a membrane stabilizing effect, which may be the electrophysiological basis of the anti-arrhythmic effect of Cim.


Effects of m-nisoldipine on transmembrane currents of guinea pig papillary muscles.

Effects of m-Nis on the transmembrane currents were studied using single sucrose gap voltage clamp technique. The amplitude of slow inward current (I(si)) was 10.6 +/- 4.1 microA. Maximal inward current was induced at a membrane potential range between -20 to -25 mV. The amplitude of I(si) were significantly decreased by m-Nis (0.2 mumol.L-1) with a reduction of 47.3%. The transient inward current (I(ti)) induced by ouabain was also greatly depressed or prevented by m-Nis, resulting in the inhibition of DAD.


[Evaluation of the tissue-to-blood partition coefficient R for physiological pharmacokinetic models].

The tissue-to-blood partition coefficient R, fraction of drug unbound in blood fB and intrinsic clearance of elimination organ/tissue Cl'L are important parameters used in physiological pharmacokinetic models. Simple equations to evaluate R by AUC were derived in this paper for single bolus iv, the tissue-to-blood partition coefficient of nonelimination organ/tissue was exactly the ratio of AUC between tissue and blood, those equations were examined by the experimental data of rats following iv ethoxybenzamide 20 mg.kg-1, and compared with other methods. Equations to evaluate fBCl'L and other parameters were also given for linear elimination model.


[Muscarinic receptor subtypes in respiratory center and their functions].

Radioreceptor binding assays using [3H]quinuclidinyl benzilate and [3H]pirenzepine were performed on the pons and medulla oblongata (MeOb) of rat brain. The M1 cholinergic receptor (M1-R) was found to account for approximately 30-40% of the total muscarinic receptors (M-R) in the pons and MeOb, and the M2 accounted for about 60-70%. The receptor binding capacities of scopolamine and atropine were compared with those of pirenzepine (Pir) and AF-DX 116 on the 2 parts of the brain. The affinity values (pKi) suggest that the selectivity of scopolamine for M1-R is greater than for M2-R, and that of atropine for M2 is greater than for M1. In conscious rabbits, the respiratory frequency (FR), tidal volume (TV), and minute ventilation volume (MVV) were determined. Arterial blood samples were taken intermittently and analyzed for pO2, pCO2, and pH. When pilocarpine (a M1-R subtype selective agonist) was given, excitatory effects on respiration were seen through FR, TV, MVV, and the pO2, pCO2, and pH. When 6 beta-acetoxy nortropane (6 beta-AN, a novel M2-R subtype selective agonist) was given, the effects were inhibitory. These results were reversed after administration of Pir, scopolamine, AF-DX 116, and atropine. Thus, it shows that Pir and scopolamine inhibit respiration by blocking the M1-R subtype of the respiratory center, while the excitatory effects of AF-DX 116 and atropine are brought about by blocking the M2-R subtype of the respiratory center.


[Effect of mexiletine on energy metabolism of ischemic brain in mice].

After 30 s ischemia induced by decapitation, the contents of ATP and phosphocreatine (PC) in mouse brain reduced, while that of lactic acid (LA) increased. When mexiletine (3.1-50 mg.kg-1) was injected ip 30 min before decapitation, the brain ATP and PC reduction, and LA accumulation were both alleviated in a dose-dependent manner. These findings suggested that mexiletine was effective in ameliorating the energy exhaustion in the ischemic brain.


[Effects of 3 henbane drugs on acute forebrain ischemia and reperfusion injury in rats].

After 30-min ischemia and 60-min reperfusions in rats by ligating bilateral vertebral and common carotid arteries, the brain calcium contents were increased from 171 +/- 6 micrograms in control group to 192 +/- 10 micrograms with abnormal EEG activities and ischemic injury in the brain tissues. Anisodamine 6.67 mg.kg-1, scopolamine 0.67 mg.kg-1 or atropine 0.67 mg.kg-1 injected ip decreased the elevated calcium contents of the rat brain to the level of control, reduced the ischemic injury of brain tissue, and promoted the recovery of EEG activities. The findings showed that the 3 henbane drugs might prevent the brain tissues from ischemic damage through reducing intracellular Ca2+ accumulation resulted from ischemia and reperfusion event.


[Inhibitory effects of neferine and tetrandrine on portal vein and papillary muscle in rats].

To determine the vascular selectivity, the inhibitory effects of verapamil (Ver), neferine (Nef), and tetrandrine (Tet) on the spontaneous contractile force of portal vein and contractile force of the paced papillary muscle of left ventricle were studied in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The vascular selectivity was expressed by the IC50 ratio (IC50 for papillary muscle/IC50 for portal vein). The results showed that the vascular selectivity values of Ver, Nef, and Tet were 1.15, 0.32, and 0.20, respectively in WKY and 0.80, 0.24, and 0.10, respectively in SHR. It is concluded that Nef and Tet, in contrast with Ver which is devoid of selectivity for either tissue, are more liable to inhibit the myocardium than the vascular smooth muscle. In addition, the IC50 value of Tet for inhibition of the portal vein in SHR was nearly 10-fold higher than that in WKY (237 and 27 mumol.L-1, respectively). This indicates that the response of portal vein to Tet is decreased in SHR.


[Role of catecholamines in action of nicotine on slow action potentials in guinea pig papillary muscles].

The action potential duration (APD) of histamine-induced slow action potentials (SAP) and force of contraction (FC) were potentiated by nicotine (0.6-1.0 mmol.L-1) on guinea pig papillary muscles in a concentration-dependent manner. In the presence of atropine, nicotine concentration dependently suppressed the action potential amplitude (APA), APD, the maximal upstroke velocity (Vmax), and FC in catecholamine-depleted (reserpine 2.5 mg.kg-1 ip, 15 h prior to the experiment) muscles. Nicotine (0.6 mmol.L-1) itself induced SAP and enhanced FC. These 2 effects were antagonized by verapamil. A linear relationship existed between APA of nicotine-induced SAP and 1g [Ca2+]0 with a slope of 23.2 mV for a 10-fold change in [Ca2+]0. These results suggested that the effects of nicotine on enhancing Isi were mediated by the release of catecholamines in myocardium.


[Effects of propafenone, quinidine, and their combination on ventricular fibrillation threshold in dogs].

The effects of propafenone (Pro), a new Ic anti-arrhythmic agent (AAA), quinidine (Qui), and their combination on ventricular fibrillation threshold (VFT) and other electrophysiological properties were evaluated in 20 dogs. VFT was determined by a train of pulses, 4 ms in duration, delivered at 10 ms intervals. The results showed that in normal anesthetized, open-chest dogs: (1) Pro decreased VFT by 21.4%; (2) Qui increased VFT by 75.5%; (3) the Pro-induced decreased VFT was abolished by simultaneous administration of Qui; and (4) the above effects of the two drugs used separately or in combination on VFT were not related to their effects on ventricular effective refractory period and atrioventricular conduction time.


[Effects of ketotifen on human neutrophil respiratory burst and intracellular free calcium].

The stimulatory effect of FMLP 5 nmol.L-1, OAG 25 nmol.L-1 and calcimycin 10 nmol.L-1 on luminol-dependent chemiluminescence (CL) was observed in human neutrophils (Neu). The rest level of Neu intracellular free calcium ([Ca]i) measured by Ca(2+)-sensitive probe Quin 2/AM was calculated to be 200 +/- s 19 nmol.L-1. By the addition of FMLP 0.1 nmol.L-1 or calcimycin 0.5 nmol.L-1, the peak [Ca]i increased to 769 +/- 104 nmol.L-1 and 953 +/- 53 nmol.L-1, respectively. Ketotifen (50-300 mumol.L-1) inhibited Neu CL in a dose-dependent manner with activator FMLP. Inhibition was also seen when Neu CL was activated by calcimycin and OAG, respectively. However, ketotifen did not inhibit Neu [Ca]i increment activated by FMLP and calcimycin.


[Therapeutic effects of epimeric glycyrrhizic acids on hepatic injury in rats].

The effects of the epimeric glycyrrhizic acids (GA), 18 alpha-form and 18 beta-form, on D-galactosamine (Gal)-induced acute liver injury and fulminating hepatic failure (FHF) in rats were studied. In rats of acute liver injury, extensive liver parenchymal cell damage was observed by the elevation of alanine aminotransferase (ALT) activity and confirmed by significant histopathological changes 24 and 48 h after ip Gal 450 mg.kg-1. Moreover, marked elevation in the liver putrescine levels occurred along with that of serum ALT. The spermidine and spermine levels did not alter significantly. GA 18 alpha-form 300 mg.kg-1 ip suppressed the elevation of serum ALT and liver putrescine levels, and improved all the histopathologic features. On the other hand, GA 18 beta-form 300 mg.kg-1, which exhibited inhibitory effects 24 h after ip Gal, showed no action 48 h after ip Gal. The ALT levels in the serum from GA 18 alpha-form, 18 beta-form, vs control groups after 24 h were 70 +/- 24 (P < 0.01) and 78 +/- 42 (P < 0.01) vs 155 +/- 57, and after 48 h were 74 +/- 25 (P < 0.01) and 258 +/- 99 (P > 0.05) vs 293 +/- 110. The putrescine contents (nmol.g-1) in the liver from GA 18 alpha-form, 18 beta-form, vs control after 24 h were 34 +/- 9 (P < 0.01) and 51 +/- 12 (P < 0.01) vs 139 +/- 29, and after 48 h were 16 +/- 3 (P < 0.01) and 150 +/- 11 (P > 0.05) vs 156 +/- 23.(ABSTRACT TRUNCATED AT 250 WORDS)


[Pharmacokinetics of gentamicin after intratracheal administration in tracheotomy patients].

Seventeen tracheotomy patients were given gentamicin (Gen) into trachea at the dosage of 2 and 4 mg.kg-1. Gen concentration in serum was determined by fluorescence polarization immunoassay. Pharmacokinetic parameters were calculated by micro-computer pharmacokinetic program (MCPKP). T1/2Ka, Tp, and Cmax were 0.6 +/- 0.3 h, 1.7 +/- 0.7 h, and 4.6 +/- 1.8 micrograms.ml-1, respectively in 4 mg.kg-1 group and 0.3 +/- 0.3 h, 0.9 +/- 0.5 h, and 0.4 +/- 0.2 microgram.ml-1, respectively in 2 mg.kg-1 group (P < 0.05). T1/2Kel was 30 +/- 11 h in patients of serum creatine (Cr) > 2 mg% and 6 +/- 5 h in patients of Cr < 2 mg% (P < 0.01). No significant difference could be found between Cmax of different renal function patients (P > 0.05).


[Absorption of ceftizoxime from peritoneal dialysate and its pharmacokinetics in chronic kidney failure patients].

The pharmacokinetics of ceftizoxime (Cef) and its diffusivity across the peritoneal membrane were studied in 10 chronic kidney failure patients undergoing continuous ambulatory peritoneal dialysis. Cef was determined by HPLC. The results showed that the disposition of Cef could be described with a 2-compartment open model after 1 g intravenous infusion. VD = 20 +/- 5 L, AUC = 1237 +/- 327 micrograms.ml-1.h. T1/2 beta = 16.9 +/- 4.5 h, which was much longer than that of patients with normal renal function. Therefore, the regulation of dose regimen was necessary when treating patients with renal failure. Cef was partly eliminated by peritoneal dialysis with the ClD of 2.9 +/- 1.0 ml.min-1. The bidirectional exchange of Cef was seen between blood and dialysate. It is more suitable to describe the diffusive characteristics of Cef from dialysate (or blood) into blood (or dialysate) with a zero order constant rate model. The absorption percentage of Cef after 0.5 g instilled with peritoneal dialysate was 90.4 +/- 7.0%.


[Influence of dexamethasone and epinephrine on glycogen content and cytosol glucocorticoid receptors in hyperthyroid rat liver].

The influence of hyperthyroidism on the action of drugs affecting rat liver glycogen content and its mechanism were investigated. The thyroid-induced hyperthyroidism of rat served as the model. In normal rats, dexamethasone (5 mg.kg-1, ip) increased the content of liver glycogen and decreased the Bmax of glucocorticoid receptors (GCR) in liver cytosol. These effects were minimized or even disappeared in hyperthyroid rat models. On the other hand, in normal rats, epinephrine (0.20 mg.kg-1, ip) decreased the content of liver glycogen. This effect was potentiated in hyperthyroid rat models. Epinephrine did not affect the Bmax of GCR in liver cytosol of normal and hyperthyroid rats. These results suggested that hyperthyroidism may be one of the causes effecting the individual differences of drug action, and that the influence of hyperthyroidism on the glycogen-increasing action of dexamethasone correlated well with the changes in glucocorticoid receptor. The mechanism of the influence of hyperthyroidism on the glycogen-decreasing action of epinephrine is to be further explored.


Utilization and patterns of care in comprehensive psychiatric care organizations. A review of studies and some methodological considerations.

This article reviews and analyzes studies on the utilization of care and patterns of care in psychiatric care organizations with a defined catchment area responsibility. Eight studies fulfilled the inclusion criteria. The main results of the studies were reviewed with regard to distribution of utilization, typical patterns of care, sociodemographic characteristics, clinical characteristics and, when appropriate, organizational characteristics related to utilization. The results show that a small proportion of patients use a large proportion of resources. Sociodemographic factors such as living alone or having no occupation in some of the studies predicted a higher utilization. Only one study reported sex differences, men being more common among heavy users. In most of the studies a psychosis diagnosis predicted a higher utilization. A history of prior contacts with psychiatric care predicted a higher utilization in 2 studies. It is concluded that future studies should make efforts to develop standardized models of classification of patterns of care to enhance possibilities of comparisons. Cost, as a common unit for summarizing and comparing resource utilization, has not been used, but is viewed as a highly relevant measure. Furthermore, measures of utilization should be separated from evaluations of outcome or quality of care. However, the latter is a neglected area that should also be promoted in studies of utilization of psychiatric care to create knowledge of the relationship of utilization to outcome.


Predicting symptoms of depression from reports of early parenting: a one-year prospective study in a community sample.

The purpose of this study was to determine whether (reported) parental over involvement and lack of affection identify initially healthy subjects at risk for depression. One thousand subjects from the province of Utrecht, the Netherlands were randomly selected by using telephone addresses and asked to participate in a one-year prospective study on psychological risk factors of depression. From the 108 subjects that finally participated on both occasions, the reports of parental upbringing (Parental Bonding Instrument) of initially non-depressed subjects with a Zung Self-rating Depression Scale score below 49 points were used to predict new cases of depression one year later. Initially non-depressed subjects who reported maternal over involvement in the upper quartile of the distribution had an 8.5-fold increased risk (95% confidence interval 0.9 to 80.6) of becoming depressed one year later. Although initial reports of low paternal affection were positively associated with initial symptoms of depression, this characteristic failed to show predictive value. Parental upbringing deficiencies have frequently been shown in cross-sectional inpatient studies in which retrospective retrieval from memory because of depressive state characteristics may have caused negative colouring. Our results would suggest that maternal over involvement reported in the absence of a depressed mood still proves to be an important psychological risk factor in the aetiology of depression.


Factor study of the Geriatric Depression Scale.

A sample of 234 people between the ages of 60 and 95 was studied using the Brink-Yesavage Geriatric Depression Scale (GDS). The GDS has good concurrent validity with the Hamilton Rating Scale for Depression with the Melancholia Scale (r = 0.77), which confirms the clinical utility of this scale. A factor analysis of principal components with an oblimin rotation was performed. The results obtained imply that structural validation cannot be made in relation to Beck's cognitive model of depression. It can be concluded that the elimination of the somatic items does not add any theoretical correspondence with the model, as the factors tend to group the various items into one dimension.


Clusters in a cohort of untreated schizophrenia: prognostic importance, atypical cases and the familial versus sporadic distinction.

In search of features of prognostic importance, a cohort of patients admitted to a mental hospital in 1925 was investigated by means of multivariate clustering techniques. Using K-means cluster analysis or Q-factor analysis, a group containing cases with unfavourable prognosis was isolated. Other groups derived were prognostically heterogeneous. One group of patients, in early phases similar to good prognosis schizoaffective psychoses, could be distinguished and characterized by non-symptom items. There was initial periodicity and onset was acute. They were, on average, younger than the other subjects and there was no personality deviation or emotional disturbance before onset of disease. A family history of mental illness was rare. Two of the factors were positively and negatively characterized by items covering familial history of mental illness, thus seemingly confirming the familial vs sporadic distinction in the subclassification of schizophrenia. Though the clinical pictures were distinctively different at the time when the ratings underlying the analysis were made, approximately the same proportion of cases in the two groups had independently been diagnosed as paranoid schizophrenia--also taking the course of illness into account. It could furthermore be shown that the population at risk--siblings and children of subjects--as well as the observed number of years at risk in these groups were significantly smaller in the sporadic group than in the familial group. This was a combined effect of a lower fertility in subjects and parents in the sporadic group and a higher rate of drop out due to mortality and other reasons among siblings of these subjects. The same tendency was indicated when subjects with and without family history irrespective of factor belongingness were compared. It cannot be concluded that the familial vs sporadic distinction is without relevance in the research on schizophrenia, but its essence may easily be obscured, if the population at risk is not taken into account.


Folate, vitamin B12 and cognitive impairment in patients with Alzheimer's disease.

This study examines the relationship between folate, vitamin B12 and severity of cognitive impairment in patients with Alzheimer's disease (AD) as compared with other disorders associated with cognitive impairment. The patients were 97 consecutive referrals to an AD clinic. Forty patients had either possible or probable AD, 31 had other dementias (OD) and 26 had mild cognitive impairment (cognitively impaired, not demented; CIND). Patients had blood drawn for serum, red cell folate and B12, as well as other biochemical indicators of nutrition, within 24 h of the Mini-Mental State Examination (MMSE). In the AD group, only B12 was significantly correlated with MMSE. Using regression analysis, B12 contributed significantly to variance in MMSE. There was no correlation between MMSE and serum, red cell folate or B12 in the OD or CIND group and no significant correlation between MMSE and other nutritional indices in any group. These findings suggest the possibility of a specific relationship between B12 levels and severity of cognitive impairment in patients with AD.


Multidimensional ordering of psychopathology. A factor-analytic study using the Comprehensive Psychopathological Rating Scale.

The aim of the study was to search for a multidimensional order in the psychopathology of the functional mental disorders in general. A heterogeneous group of 192 patients was investigated by means of a semistructured interview based on the Comprehensive Psychopathological Rating Scale. Principal component factor analysis revealed 5 clinically meaningful dimensions interpretable as representing dysregulation of emotion and motivation, perceptual and behavioural disintegration and dysregulation of autonomic functions.


Psychiatric service use: a cohort study of first attenders.

A retrospective cohort study was undertaken of all 1047 first-ever psychiatric service attenders to Christchurch general psychiatric services in 1981. All episodes of care were examined to the end of 1989. Only 24% of contacts were as an inpatient. Long-term contacts and frequent presenters formed only 15% of the sample. Nearly all cases not immediately discharged remained within the adult general service. Demographic and clinical variables and patterns of resource use are discussed.


Depressive symptoms and depression among elderly people in Athens.

A total of 251 elderly residents of 2 boroughs of greater Athens were examined by a psychiatrist. For the assessment of depressive symptoms, the Center for Epidemiological Studies Depression (CES-D) Scale was used. Cognitive functioning was also evaluated. The prevalence of affective disorders of any type was estimated by a clinical examination with a semistructured psychiatric interview (PEF) supplemented by DSM-III criteria. A total of 27.1% of the elderly respondents reported a significant number of dysphoric or depressive symptoms and were identified as depressed cases. Respondents who had lower socioeconomic status, were widowed, were experiencing stressful life events or were living alone exhibited a significant degree of depressive psychopathology. An association between depressed mood and cognitive impairment was also found. A total of 9.5% of the sample was diagnosed as suffering from any type of affective disorder (1.6% major depression, 0.6% bipolar, 5.5% dysthymic disorder and 2.0% adjustment disorder with depressed mood). Affective disorders constitute nearly half of the total number of psychiatric diagnoses (20.3% at the sample). It is interesting that, of the 27.1% of the sample with depressed mood (> or = 16 score on CES-D Scale), only 9.5% of the sample were diagnosed as suffering from clinical types of depression.


Saccade programming during short duration fixations: an examination of copy typing, letter detection, and reading.

Three experiments examined saccade programming during short duration fixations between 50 ms and 150 ms. In experiment 1, subjects copy typed text, in experiment 2, subjects read and executed a letter detection task, and in experiment 3, subjects read for comprehension only. Fixation duration had no effect on the size of the departing saccade in the copy typing task; however, saccades leaving short duration fixations were larger than saccades leaving all other fixation durations in the letter detection task and smaller than saccades leaving long fixation durations in the standard reading task. Within Morrison's (1984) model, these results imply, first, that consecutive shifts of attention during a fixation can take different directions and, second, that successive shifts of attention during a fixation support different purposes. Within Fischer's (1986, in press) model, the results imply that the engagement/disengagement of attention and saccade programming do not constitute independent events.


Diagnostic classification by experts and novices.

The present study examines differences between experts and novices in classifying symptoms and the effect of the nature of the task on classifying. The study involved three groups of subjects, two expert groups (n = 12, n = 10) and one novice group (n = 12). Thinking-aloud protocols were collected for two classification tasks: sorting of behavioural symptoms into predefined categories and intuitive clustering of behavioural symptoms. In a third task, experts and novices were asked to make typicality ratings of behavioural symptoms. The protocols were analyzed with respect to seven cognitive operations: (a) asking or giving information, (b) associating, (c) abstracting or labelling, (d) explaining, (e) neutral matching, (f) identifying, and (g) differentiating. Results showed an effect of experience and an effect of the task on the relative frequencies of these operations. No differences were found in typicality rating of experts versus novices. These contradictory findings are discussed in relation to Kolodner's model about the evolution of expertise.


Spatial attention and expectancy for colour, category and location: further evidence against the spotlight model.

A study of spatial attention is reported in which different colours and categories of object tended to appear at different locations. Subjects made speeded orientation judgements to alphanumeric characters that could appear either above or below the centre of a display. In the Colour Condition subjects were informed that red characters tended to appear at one location (p = 0.8), while green characters tended to appear at the other. In the Category Condition letters tended to appear at one location, and digits at the other. Before each trial subjects were cued to expect either a red or a green character (Colour Condition); or a letter or a digit (Category Condition). It was found that spatial selectivity varied according to the colour, or category of object presented. The latter finding replicated an earlier report (Lambert 1987). Spatial selectivity was appropriate for the character presented, even when it was in the uncued colour (or category). It is concluded that subjects are able to form and make use of complex attentional expectancies concerning combinations of colour with location, and category with location. Theoretical implications of these results are discussed.


Enhancement of the Simon effect by response precuing.

When stimuli are presented to the left or right of fixation, and stimulus location is irrelevant, responses are faster if the stimulus location coincides with the location of the assigned response. This phenomenon is called the Simon effect. The present study examined the influence on the Simon effect of attentional precues that signaled the likely stimulus location and intentional precues that signaled the likely response. Experiment 1 was a close procedural replication of an experiment by Verfaellie, Bowers, and Heilman (1988); consistent with their findings, the Simon effect was enhanced by the intentional precue and unaffected by the attentional precue. Experiments 2 and 3 demonstrated the importance of the intentional precue with simpler procedures that involved only intentional and attentional precues, respectively. Finally, the intentional precuing enhancement of the Simon effect was obtained when two stimuli were assigned to each response, regardless of whether the hands were uncrossed (experiment 4) or crossed (experiment 5). Overall, the results indicate that response precuing enhances the Simon effect and favor response-selection accounts over those that attribute the effect to stimulus identification.


Biochemical parameters associated with low bone density in healthy men and women.

A causal role in age-related bone loss has been attributed to alterations in vitamin D status, the bone mineral regulating hormones, and/or renal function. We assessed biochemical parameters of bone metabolism and renal function in healthy subsets of young and old men (n = 191) and women (n = 120) and evaluated the relationships between these parameters and bone mineral density (BMD) in the radius, spine, and femur. There were no significant associations between BMD at any site and serum 25-OHD, 1,25-(OH)2D, PTH, or creatinine clearance in either young men or in young or old women, after controlling for age. In old men, however, lower radius BMD was significantly related to higher PTH and higher 1,25-(OH)2D and marginally related to lower 25-OHD values. In young men, there were unexpected but significant associations between lower femoral neck BMD and higher serum osteocalcin and urinary calcium/creatinine excretion after age adjustment. In old women, lower spine and radius BMD was also significantly correlated with higher serum osteocalcin. In this healthy, vitamin D-replete population, there were significant cross-sectional declines in BMD in the femur in young and old men and at all sites in old women. Elevated remodeling may be an important feature that contributes to reduced femoral BMD in young men and reduced spine and radius BMD in old women. However, compromised renal function or levels of 1,25-(OH)2D or elevated PTH appear to be neither necessary nor relevant as determinants of osteopenia in the spine or femur in these normal, healthy men and women.


Transcriptional activation of c-fos and c-jun protooncogenes by serum growth factors in osteoblast-like MC3T3-E1 cells.

The present study was undertaken to clarify the relationship between c-fos and c-jun protooncogene expression and the differentiation and/or proliferation of osteoblasts, using osteoblast-like MC3T3-E1 (E1) cells. c-fos mRNA was barely detectable, whereas c-jun mRNA was constitutively expressed in E1 cells after serum deprivation for 24-72 h. When serum was added, a rapid and transient induction of c-fos and c-jun mRNAs was observed. The c-fos and c-jun mRNAs reached peak levels at 30 minutes, with a rapid disappearance of c-fos mRNA within 3 h and a much slower decrease in c-jun mRNA. The addition of serum together with cycloheximide, an inhibitor of protein synthesis, resulted in the superinduction of both c-fos and c-jun mRNAs. Among various growth factors, PDGF, EGF, and bFGF mimicked the serum effect, whereas IGF-I and TGF-beta failed to induce c-fos and c-jun mRNA. The effects of PDGF, EGF, and bFGF were completely abolished by pretreatment with actinomycin D, an inhibitor of RNA synthesis, suggesting a transcriptional mechanism. Nuclear runoff experiments showed that the transcription rate of c-fos and c-jun protooncogenes was increased by serum and growth factors. The effects of PDGF, EGF, and bFGF were inhibited by H-7 or staurosporine, inhibitors of protein kinase C (PKC), but not by HA1004 with a much weaker inhibitory activity, suggesting the involvement of PKC for the activation of the protooncogenes.(ABSTRACT TRUNCATED AT 250 WORDS)


Mechanical properties of trabecular bone within and adjacent to osseous metastases.

Despite radiographic and histologic evidence of trabecular bone density changes within and adjacent to osseous metastases, there currently exist no data to demonstrate whether these changes are important in predicting the risk of fracture. To determine if these density changes result in significant reductions in mechanical properties, trabecular bone specimens were prepared from lower thoracic and lumbar vertebrae from two cadavers with radiographic, gross, and histologic evidence of lytic and/or blastic osseous metastases. Each specimen was classified as normal, lytic, or blastic based on appearance in fine-grain radiographs of 8-9 mm thick coronal plane sections. Specimens were tested to failure in uniaxial compression, and tissue and apparent densities were measured. Mean tissue densities were within normal ranges. The mean apparent density for all specimens combined was within the normal range for human vertebrae, and the mean apparent density for radiographically normal (0.131 g/ml) and lytic (0.111 g/ml) specimens was less than the mean apparent density of blastic (0.182 g/ml) specimens (p < 0.02). The moduli of lytic and blastic specimens were less than for normal specimens (p < 0.025). The strength of lytic specimens was less than normal (p = 0.057), but the strength of blastic specimens was not (p > 0.1). Apparent density explained significant fractions of the variations in both modulus (p < 0.001) and strength (p < 0.001). The data suggest that blastic changes associated with osseous metastases to trabecular bone disrupt the normal dependence of trabecular mechanical properties on apparent density, but lytic changes do not.(ABSTRACT TRUNCATED AT 250 WORDS)


Osteogenesis associated with bone gla protein gene expression in diffusion chambers by bone marrow cells with demineralized bone matrix.

Diffusion chambers with rat bone marrow cells and demineralized bone matrix (DBM) were implanted subcutaneously to syngeneic 8-week-old rats and were harvested every week 3-7 weeks after implantation, and histochemical examination, determination of alkaline phosphatase activity, total calcium and phosphorus, the bone-specific vitamin K-dependent gla-containing protein (BGP) content, and detection of BGP mRNA relative to mineralization were performed. Alkaline phosphatase in diffusion chamber implants reached the highest activity at 4 weeks and then decreased. Calcium and phosphorus deposits occurred at 4 weeks after implantation and were followed by marked increases until 7 weeks, which was comparable to the accumulation of BGP. The BGP gene within the diffusion chambers began to be expressed at 5 weeks, and its expression increased markedly at 7 weeks after implantation. At 4-5 weeks after implantation, new bone adjacent to the membrane filters and cartilage toward the center of the diffusion chamber were observed histochemically. Light microscopic and immunohistologic examinations of chambers with marrow cells and DBM revealed production of mineralized matrices, typical of bone characterized by the appearance of BGP and mineralized nodules. In contrast, bone marrow cells alone did not show extensive bone formation and yielded very low values for these biochemical parameters. The present experiments demonstrate the potential of bone marrow cells and DBM to produce not only cartilage formation but also membranous bone formation associated with increasing expression of BGP mRNA during the later stages of bone formation, as well as a marked accumulation of BGP.


Racial differences in pre- and postmenopausal bone homeostasis: association with bone density.

The disparity in fracture incidence and bone mass in women of European (white) and African (black) ancestry is of unknown etiology. To determine if racial differences in bone mass reflected racial differences in the mechanisms of bone turnover underlying bone mineral loss, we measured serum osteocalcin, serum alkaline phosphatase, fasting urinary calcium and hydroxyproline excretion, 24 h urinary excretion of calcium and sodium, and dietary intakes of calcium and vitamin D in 263 healthy pre-, peri-, and postmenopausal white and black women. In addition, radial and spinal bone density were measured cross-sectionally for comparison with biochemical measures of bone turnover. The biochemical parameters thought to reflect bone resorption (fasting urinary calcium and hydroxyproline excretions) were lower in black than in white women throughout the age and menopausal stages studied. The parameters thought to reflect bone formation (alkaline phosphatase and osteocalcin), were similar in the two racial groups among the premenopausal women, but osteocalcin was significantly lower among the peri- and postmenopausal blacks. Cross sectionally measured radial bone density increased with age in premenopausal black women, but it did not change with age in the white premenopausal subjects, a statistically significant difference. In peri- and postmenopausal women radial density declined significantly with years after menopause in both racial groups, but the rate of decline was significantly slower in the black women. Lumbar bone density in premenopausal white and black women did not change with age. After menopause lumbar bone density declined significantly and similarly in both racial groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Prostaglandin E2 alleviates cyclosporin A-induced bone loss in the rat.

Cyclosporine A (CsA) administered to the male and female rat produces high-turnover osteopenia. Prostaglandins have both bone-resorbing and bone-forming properties, but administration of prostaglandin E2 (PGE2) to the rat in vivo produces a net increase in cancellous bone. To investigate the effects of PGE2 on CsA-induced alteration in bone mass, 43 male Sprague-Dawley rats (9 weeks old) were administered 15 mg/kg of CsA by oral gavage and/or 6 mg/kg of PGE2 by subcutaneous injection daily for 21 days according to the following protocol: group A was an age-matched control; group B received CsA only; group C received PGE2 only; and group D received CsA and PGE2. Serum was assayed on days 0, 7, 14, and 21 for bone gla protein (BGP), PTH, and 1,25-dihydroxyvitamin D [1,25-(OH)2D]. A computerized image analysis system was used for bone histomorphometry of the proximal tibial metaphysis after double tetracycline labeling. Compared to control animals (group A), treatment with CsA alone (group B) and PGE2 alone (group C) significantly elevated BGP levels. Combination therapy (group D) resulted in BGP levels that were significantly higher on days 7 and 14 than with either agent alone. 1,25-(OH)2D was significantly elevated in the CsA group only (group B). Therapy with CsA alone (group B) resulted in a significant osteopenia. The concurrent administration of PGE2 with CsA (group D) alleviated the altered bone mass induced by CsA alone by adding a significant amount of additional bone. This report confirms and extends the current knowledge of the different effects of CsA and PGE2 on bone mineral metabolism and demonstrates that PGE2 can alleviate the deleterious effects of CsA on bone.


beta-Glycerophosphate-induced mineralization of osteoid does not alter expression of extracellular matrix components in fetal rat calvarial cell cultures.

When fetal rat calvarial cells are cultured in medium containing vitamin C, osteoid nodules develop after approximately 15 days of culture. Upon addition of an organic phosphate (beta-glycerophosphate, beta GP), these nodules mineralize. We have now used this system to explore the suggestion made by others that a negative feedback may exist between matrix mineralization on the one hand and the synthesis of alkaline phosphatase and bone matrix collagen on the other by analyzing the synthesis of these proteins and the levels of their mRNAs in mineralizing and nonmineralizing cultures. Our results indicate that in the osteoid nodule-bone nodule system, matrix mineralization did not affect the mRNA levels for osteopontin, type I collagen, bone sialoprotein, or osteocalcin. Synthesis of total protein and collagen and the osteocalcin content of culture media were also not different in the mineralizing and nonmineralizing cultures. However, alkaline phosphatase mRNA was increased in early mineralizing cultures and alkaline phosphatase activity in the cell layer was also increased in mineralizing cultures. Thus, the hypothesis that a direct negative feedback exists between mineralization and matrix protein synthesis is not supported by our experiments.


Lateral spine densitometry is a more sensitive indicator of glucocorticoid-induced bone loss.

Osteoporosis is a common complication of glucocorticoid therapy. Bone density measurement is now commonly used in assessing which steroid-treated patients require specific interventions to reduce fracture risk. The recently developed techniques for the measurement of bone mineral density (BMD) of the vertebral body alone, by dual-energy x-ray absorptiometry (DXA) in the lateral projection, may be particularly useful in this context since steroid-induced bone loss is most marked in trabecular-rich regions like the vertebral body. This possibility has been assessed in the present study by the measurement of BMD in the lateral and anterioposterior (AP) projections in 28 women receiving chronic glucocorticoid treatment. The two BMD measurements were significantly related (r = 0.62, p < 0.001). When expressed in relation to age-appropriate normal values, lateral BMDs were lower than AP BMDs both in percentage terms (70.8 +/- 4.4 versus 90.3 +/- 2.6%, p < 0.001) and in terms of Z scores (-1.42 +/- 0.22 versus -0.91 +/- 0.24, p = 0.027). AP BMD Z scores classified 12 patients as osteopenic, whereas a further 7 were so categorized by lateral BMD Z score. It is concluded that lateral DXA scanning is a more sensitive indicator of glucocorticoid-induced osteopenia than conventional BMD measurement in the AP projection.


Excessive L-thyroxine therapy decreases femoral bone mineral densities in the male rat: effect of hypogonadism and calcitonin.

Excess thyroid hormone decreases bone mineral density (BMD), a potential problem in managing patients with differentiated thyroid carcinoma and nontoxic goiter who require lifelong TSH-suppressive doses of thyroid hormone. We studied the effect of thyroid hormone excess on vertebral and femoral BMD and the role of hypogonadism in modulating this effect in a rat model. The potential role of calcitonin (CT) in preventing thyroid hormone-associated bone loss was also investigated. A total of 40 male Sprague-Dawley rats were divided into four groups. Groups 1 and 2 were orchidectomized (ORX); groups 3 and 4 were sham operated (SO). Groups 1 and 3 received 20 micrograms intraperitoneal L-thyroxine (L-T4) per 100 g body weight daily for 3 weeks; groups 2 and 4 received vehicle IP. Another 40 rats were divided into four groups. Groups 1 and 2 received L-T4, and groups 1 and 3 received CT, 2.5 U per 100 g body weight, subcutaneously (SC) daily for 3 weeks. BMD of the L4 and 5 and the right femur were measured by dual-energy x-ray absorptiometry at baseline and at the end of the study. Orchidectomy decreased femoral (P < 0.05) but not lumbar BMD. The administration of excess L-T4 decreased femoral (cortical) BMD in both SO (P < 0.05) and ORX rats (P < 0.05) without affecting lumbar (trabecular) BMD. CT increased lumbar BMD in both vehicle (P < 0.001) and L-T4-treated rats (P < 0.001). However, CT did not affect femoral BMD in vehicle-treated rats and did not prevent the L-T4-induced femoral bone loss.(ABSTRACT TRUNCATED AT 250 WORDS)


Subdural effusions: determination of contrast medium influx from CSF to the fluid accumulation by computed tomography as an aid to the indications for management.

In 46 patients with subdural effusions CSF dynamics and especially the influx of contrast medium from CSF to the subdural fluid accumulation was investigated by serial computed tomography (CT). In 16 cases the subdural effusion was of traumatic and in 30 cases of non-traumatic origin. The results allowed a subdivision of the patients into three groups. Group 1: patients without contrast medium influx into the subdural fluid accumulation; group 2: patients with delayed influx; group 3: patients with immediate influx. In group 1 patients the subdural effusion acted as a space-occupying process with absolute indication for surgical treatment. Also in group 2 patients the further course showed that a surgical indication was given, because the fluid accumulation did not resolve under conservative management but increased in size, and/or the neurological deficit worsened. In all group 3 patients the subdural effusions decreased and finally disappeared conservatively. Group 1 patients with effusions on traumatic origin generally had more severe injuries than the patients of the other groups. The investigations caused no serious complications. This diagnostic method proved to be a reliable means for early differentiation between the possibility of conservative management or the indication for operative treatment in cases with subdural effusions of different origin.


Craniocervical junction malformation treated by transoral approach. A survey of 25 cases with emphasis on postoperative instability and outcome.

An experience with 25 consecutive cases of craniocervical junction (CCJ) malformations operated upon via the transoral route is reported. Twenty-two patients also underwent posterior occipito-cervical stabilization with alloplastic material and in only one patient was transoral odontoidectomy and fusion with bone autograph performed. Indication for the transoral route consisted of an irreducible ventral compression of the cervicobulbar junction by the abnormal bone complex. Two patients died during the early postoperative period and the remaining 23 survivors were followed for an average of 3.5 years: 17 of these showed marked improvement and 5 a stabilization of the neurological disturbances. A further patient, who refused posterior stabilization, eventually died because of progressive cranial settling. Long-term results have shown this approach to be decisive in the surgical management of well-selected CCJ anomalies.


Microsurgical anatomy and operative technique for extreme lateral lumbar disc herniations.

The anatomy of the lateral aspect of the lumbar spine and our lateral microsurgical technique for extreme lateral lumbar disc herniations (ELLDH) is described. This study was based on the microdissection of 4 cadavers, on the morphometric evaluation of these as well as 6 dried cadaver spines and 8 lumbar CT scans, and on the use of this technique on over 200 cases. Level dependent changes in the posterior arch cause a shift of the disc space distally relative to the facet joint, an increasing amount of bone to overlie the intervertebral foramen, and a decreasing amount of working space within the exposure in the caudal direction. Therefore, more bone removal from the lateral aspect of the pars interarticularis and supero-lateral aspect of the facet joint is required in the lower lumbar spine. When the exposed ligamentum flavum is resected, the dorsal root ganglion is seen and access to the herniation and disc space is achieved. Level dependent changes in the pedicles and transverse processes lead to an alteration in the course and relationships of the nerves, thereby influencing the pathophysiology of and surgical technique for the ELLDH. The operative target is the lateral aspect of the pars interarticularis and not the intertransverse space as has been previously described. Our techniques allows for the early identification of the nerve with minimal risks of injury to it, to the adjacent vessels and to the structural integrity of the facet joint and pars interarticularis.


A primate model for acute and late cerebral vasospasm: angiographic findings.

A subarachnoid haemorrhage (SAH) in the squirrel monkey was produced by injection of blood via a permanently implanted catheter connected to the cisterna magna and a cannula stereotactically inserted into the interpeduncular cistern. Repeated angiographic examinations of the vertebro-basilar and right internal carotid arteries revealed a biphasic vasospasm with a maximal acute spasm at ten minutes and maximal late spasm at six days after blood injection. The present study has shown that a reproducible biphasic vasospasm can be produced in the squirrel monkey and evaluated by repeated angiographic examinations. The model is suitable in the study of basic mechanisms underlying vasospasm in a primate and, due to the size of the animal, autoradiographic evaluation of the cerebral blood flow and metabolism can be performed at an acceptable cost.


Effect of lesioning of medullary catecholamine neurons or the median eminence on the development of cerebral vasospasm in the squirrel monkey.

Injections of blood into the interpeduncular fossa and cisterna magna in the squirrel monkey produce an angiographically demonstrable, biphasic cerebral vasospasm with a maximal acute spasm at ten minutes and a maximal late spasm at six days after the subarachnoid haemorrhage (SAH). Selective lesioning of the A2 nucleus in the medulla oblongata or the median eminence in the hypothalamus prior to the SAH prevents the development of both the acute and late cerebral vasospasm. The present data indicate that the A2 nucleus and the median eminence participate in the development of vasospasm in the squirrel monkey.


A new model for non-invasive, reproducible fixation of a stereotaxic frame using an orthodontic resin plate. Technical note.

The authors describe a new method for reproducible, non-invasive fixation of a stereotaxic localizing frame. A localizing system similar to that of Brown-Roberts-Wells for MR can be fixed at the base of the facial skeleton to the upper dental arch by an orthodontic resin plate. Results of trials with CT scan, advantages and disadvantages are discussed. The new fixture could be employed in open surgery and in fractionated radiotherapy.


Changes in CSF pressures during experimental acute arterial subdural bleeding in pig.

The effects of acute arterial subdural bleeding on cerebrospinal fluid (CSF) pressure and 12 other vital parameters were studied in spontaneously breathing pigs (group 1, n = 9) and in mechanically ventilated pigs (group 2, n = 18) to analyze quantitatively the bleeding course and the lethal mechanism. Spontaneously breathing animals all succumbed after a mean bleeding volume of 45.6 +/- 8.9 ml, corresponding to about 50 per cent of the intracranial volume, and a mean bleeding duration of 11.0 +/- 2.6 min. Rapid rise in CSF pressures, marked transtentorial pressure gradients, and progressive reductions of cerebral perfusion pressure leading to a permanently iso-electric EEG, apnoea and to a terminal rise in arterial pressure (Cushing response), was the rule in these animals. The mechanically ventilated animals had smaller bleeding volumes (34.3 +/- 8.1 ml), but longer bleeding durations (13.8 +/- 5.8 min). In this group 7 animals survived. They had no pressure gradients, and only moderate changes in arterial pressure and EEG. The 11 animals that succumbed had marked transtentorial pressure gradients, but smaller increments in arterial pressure than the spontaneously breathing animals. At autopsy, subdurally located blood was found throughout the intracranial and spinal subdural compartments and along the spinal nerve roots in both groups. The results of this study suggest that survival after acute subdural haematoma is influenced by the presence of transtentorial pressure gradients and by the spinal sac acting as a space for expansion. The beneficial effect of artificial ventilation is discussed.


Telescopic suction tube for microsurgery.

An adjustable telescopic suction tube has been developed for microsurgery. Owing to this innovation, the surgeon can easily set the suction tube to a suitable length by gently pulling the end of the telescopic tube out or in.


Subcortical topography and proportions of the pyramidal tract.

The pyramidal tract (PT) was dissected in 30 normal human hemispheres according to the method of Klingler. The various dimensions as well as the cerebral landmarks were studied. The pyramidal tract is built up like a fan in the white matter by a thin layer of fibers of 2.8-3.5 mm in thickness. The fibers converge toward the internal capsule to a solid fiber tract with a lateral and apdiameter of 7.8 +/- 1.6 mm and 17.5 +/- 2.1 mm, respectively. This configuration of the PT presents different possibilities of damage during surgery. The evaluation of the three-dimensional course of the PT is possible by using three cerebral landmarks, the precentral gyrus, the entrance into the internal capsule and the posterior limb of the internal capsule. Their topography is described. Additionally the pyramidal tract can be defined medially by the sulcus cinguli and the roof of the lateral ventricle and laterally by the superior sulcus circularis Insulae. The possible displacement of the PT by space occupying lesions and the intra-operative orientation is discussed.


The termination of the vein of "Labbé" and its microsurgical significance.

Information about the termination of the inferior anastomotic vein of Labbé is of crucial importance in the subtemporal neurosurgical approach and its modifications. An intradural course has been observed in all cases. The vein of Labbé reaches in 3/4th the anterior third of the transverse sinus, in 73% of all cases tracing a so-called tentorial sinus. By dissecting the vein of Labbé out of its dural bed and shifting its fixation point, microsurgical access is facilitated considerably.


Anterior lateral ventricular subependymal giant cell astrocytomas. Microsurgical aspects of two cases.

The surgical management of two cases of lateral ventricular subependymal giant cell astrocytoma, arising in the head of the Caudate nucleus, and causing hydrocephalus due to obstruction of the foramen of Monro is described. One lesion, in a patient with tuberous sclerosis, was resected using a transcallosal approach and the other, in a patient with no stigmata of tuberous sclerosis, using a frontal, trans-cortical transcystoventricular approach. The microsurgical aspects of excision and pathological anatomy of both tumours were very similar. Following tumour excision and pellucidotomy both patients had partial resolution of their hydrocephalus with complete resolution of their preoperative symptoms. The merits of transcallosal and transcortical approaches to these lesions are discussed.


Endo-suprasellar teratoma with teeth formation. Case report.

A highly ossified teratoma was diagnosed and surgically treated in a 2-year old girl. More than 150 teeth were macroscopically identified during the operation. Pathological study established the diagnosis of mature teratoma with teeth formation. Only six analogous cases have been reported previously and only two patients survived the operation.


Intracranial dermoid cysts with nasal dermal sinuses.

Dermal sinuses penetrating the dura are important in that they may be complicated by C.N.S. infection, and this complication can be prevented by early surgery. Although well recognised over the occiput and lumbar spine, nasal dermal sinuses extending intracranially are much rarer and have received little attention in the neurosurgical literature. Two unique cases are presented, together with a literature review, discussing the anatomy, radiology, and management of the condition.


Lesions of the sensorimotor region: somatosensory evoked potentials and ultrasound guided surgery.

In 10 patients with lesions of the sensorimotor cortex cortical SEP were registered to identify the postcentral gyrus, and intra-operative ultrasound sonography served to locate the lesion. The combination of both techniques helped to find the optimal approach to the lesion. Postoperative results were considered favourable, as only one patient suffered transient postoperative deterioration, six were unchanged and in three patients the pre-operative motor deficits were improved. The combination of intra-operative ultrasound and neurophysiological identification of the sensorimotor cortex is concluded as being useful in surgery within this region.


The basal interhemispheric approach for acute anterior communicating aneurysms.

We reviewed the surgical outcome in 85 patients with ruptured anterior communicating artery (ACoA) aneurysms, who were operated on within 72 hours of onset via a basal interhemispheric (BIH) approach (Group 1, N = 48), or an anterior interhemispheric (AIH) approach (Group 2, N = 37). The age, sex ratio and pre-operative grade (Gr) were similar for both groups. The outcome at the time of discharge was as follows for group 1: excellent or good 88%; fair, 6%; vegetative state, 2% and death 4%. For group 2, it was: excellent or good 78%; fair, 16%; vegetative state, 3%; and death, 3%. A significant correlation between admission grade and outcome was found in both groups. The outcome in group 1 was better than in group 2 for patients with a Glasgow Outcome Scale (GOS) better than fair (p < 0.07). No patient in group 1 had postoperative anosmia, but nine patients in group 2 became anosmic. The total number of complications was also significantly less in group 1. Our overall mortality rate was 4%. In conclusion, the BIH approach was more beneficial for treating acute ACoA aneurysm.


Acute head injuries in the elderly. An analysis of 136 consecutive patients.

136 patients older than 70 years, admitted to our neurosurgical ward directly after head trauma, were analysed. 40% of them were admitted with low GCS, below 9 points, and showed a mortality of 85%. 45 patients had intracranial mass lesions--the commonest was subdural haematoma, with a low incidence of epidural haematomas. In patients admitted with GCS above 12, mortality was 20%, mainly due to pneumonia. Satisfactory results were achieved in 30% of trauma victims. From patients with intracranial space occupying lesions and GCS below 9 points on admission practically all died, despite aggressive surgical treatment and intensive care. Thus, especially in departments with limited resources, therapy can be limited, or even no therapy may be introduced in this group. Surgical treatment can be limited only to patients who are conscious on admission. In patients with non-surgical lesions, low GCS--below 9 points--leads to mortality of 80%, and in this group we propose aggressive intensive care for 24 hours and the limitation of further "maximal" therapy only to those, who significantly improve within this period of time. If the patient has a non-surgical lesion and is conscious after trauma, aggressive treatment of extracranial complication is the most important, because brain injury can usually be well tolerated by these patients. If pneumonia or heart complications do not occur this group of old patients often have a good prognosis.


Aqueous two-phase systems for biomolecule separation.

Over the past thirty years, aqueous polymer two-phase technology has evolved, both experimentally and theoretically, into a separation science with many useful applications in biomolecule purification and bioconversion. This paper summarizes the developments in the applications of aqueous two-phase systems to biotechnology. The main topics to be considered are the phase diagram and its characteristics, fundamentals of biomolecule partition, large-scale and multi-stage aqueous two-phase biomolecule purification, and extractive bioconversions. The first topic involves a discussion of the thermodynamics of aqueous polymer two-phase formation and how it is influenced by such factors as polymer molecular weight and concentration, temperature, and salt type and concentration. Next, the theoretical and experimental aspects of biomolecule partition in aqueous two-phase systems will be discussed in light of the factors which influence biomolecule partition: polymer concentration and molecular weight; temperature; salt type and concentration; the addition of charged, hydrophobic and affinity derivatives. Having reviewed the fundamentals of phase diagram formation and biomolecule partition, the next two topics are applications of aqueous two-phase technology. The first set of applications involve the large-scale extraction of proteins using one to three equilibrium stages and multi-stage purifications using countercurrent distribution, liquid-liquid partition chromatography and continuous countercurrent chromatography. The second application, and very promising area for future aqueous two-phase technology, is the extractive bioconversion which permits the simultaneous production and purification of a biomolecule.


Diamine oxidase activity and related substrates in rat liver after chronic ethanol feeding.

Chronic ethanol feeding as 12% or 36% of total calories caused a dose-dependent diminution of diamine oxidase activity in rat liver. Hepatic cadaverine and histamine levels were unmodified by ethanol, whereas putrescine increased, partially in relation to the decrease in diamine oxidase activity. Such results may be of interest in view of an aggravation of ethanol-induced hepatic damage when exogenous diamines and polyamines reach the liver in potentially toxic amounts.


The clearance rate of plasma kallikrein by the liver increases during the acute-phase response to inflammation.

The effect of the acute-phase response on the clearance rate of plasma kallikrein by the exsanguinated liver was studied in three groups of rats: a control group and two other groups that received either turpentine or an endogenous pyrogen preparation. The plasma kallikrein clearance rates were significantly higher in both inflamed groups.


Hepatoprotective effects of lobenzarit disodium on acetaminophen-induced liver damage in mice.

We have studied the effects of the immunomodulator drug lobenzarit in the model of acute hepatotoxicity induced by a high oral dose (600 mg/kg) of acetaminophen in mice. Lobenzarit at doses of 25, 50 and 100 mg/kg i.p. decreased significantly the activity of alanine aminotransferase in serum, which was increased by acetaminophen alone, and increased the concentration of reduced glutathione in mice liver, which is depleted by acetaminophen. Lobenzarit also reduced liver damage induced by acetaminophen in mice, which was observed by electron microscopy. The hepatoprotective effects of lobenzarit were dose-dependent and they were produced when lobenzarit was administered 30 min before acetaminophen or 2 and 4 h after it. It is concluded that lobenzarit exerts some effects which resemble those of an antidote of acetaminophen such as N-acetylcysteine.


The role of 5-hydroperoxyeicosatetraenoic acid in neutrophil activation.

5-Hydroperoxyeicosatetraenoic acid (5HPETE) has been recently reported to play an important role in regulating and modulating neutrophil function. In order to clarify the mechanism of neutrophil activation by 5HPETE, we have measured the cytosolic free calcium, which is thought to be necessary for neutrophil activation using fura-2-loaded human neutrophils. Low concentration of 5HPETE, which is thought to be produced during cell activation, had minimal effect on cytosolic free calcium by itself but dose-dependently augmented FMLP-stimulated increase in cytosolic free calcium in the presence or absence of extracellular calcium without converting to LTB4. 5HPETE had no effect on 3H-FMLP binding to human neutrophils. The present data suggested that 5HPETE would augment FMLP-stimulated increase in cytosolic free calcium by enhancing the influx of extracellular calcium and/or the release of calcium from intracellular pool, which resulted in augmentation of neutrophil activation by primary agonist such as FMLP.


Hypoxia/reoxygenation stimulates endothelial cells to promote interleukin-1 and interleukin-6 production. Effects of free radical scavengers.

Vascular endothelium produces and/or interferes with various cytokines. Previous studies have demonstrated interactions of these inflammatory and immunological mediators with oxygen-derived free radicals. The present work examines the relationship between hypoxia/reoxygenation (H/R) and cytokine production by cultured endothelial cells. Human umbilical vein endothelial cell (HUVEC) monolayers were incubated for 24 h in normoxia or submitted to 5 h hypoxia/19 h reoxygenation. Then, interleukin-1 (IL-1) alpha and beta, and interleukin-6 (IL-6), were measured in culture supernatants by specific enzyme immunoassays and bioassays, respectively. Under these conditions, the spontaneous production of IL-1 and IL-6, detected in normoxic HUVEC, greatly increased after H/R treatment. The observed enhancement was cycloheximide-sensitive and, consequently, reflected a de novo protein synthesis. Superoxide dismutase and glutathione peroxidase prevented H/R-induced IL-1 and IL-6 increase. These results constitute the first demonstration that H/R stimulates HUVEC to promote IL-1 and IL-6 production and strongly suggest a role for oxygen-derived free radicals in the cytokine synthesis.


Macrophage tumoricidal mechanisms are selectively altered by prenatal chlordane exposure.

Macrophages (m phi) derived from mice treated in utero with chlordane show a significant delay of tumoricidal induction activity. In this study, m phi from chlordane-treated animals required a 48 h in vitro period of induction with interferon-gamma and lipopolysaccharide (IFN/LPS) before they could kill P815 targets. Similarly, m phi from chlordane-treated animals also failed to produce an immediate H2O2 burst upon perturbation. Conversely, their stimulated control m phi counterparts were tumoricidal by 2 h and exhibited a respiratory burst without any delay. Moreover, levels of the second messenger, inositol triphosphate (IP3), were significantly delayed in chlordane-treated animals following interaction with IFN/LPS. When nitrate/nitrite production was analyzed as an alternate mechanism for killing tumors, stimulated m phi from both normal and chlordane-treated animals responded equally. The data show that chlordane differentially introduces defects in m phi biochemical mechanisms associated with tumor killing.


A synthetic peptide metalloproteinase inhibitor, but not TIMP, prevents the breakdown of proteoglycan within articular cartilage in vitro.

IL1-stimulated pig articular cartilage fragments were cultured in the and absence of various metalloproteinase inhibitors. Tissue inhibitor of metalloproteinases (TIMP) was unable to stop the release of proteoglycan from the cartilage. Incubation of cartilage with a potent synthetic metalloproteinase inhibitor inhibited the release of proteoglycan in a dose-dependent fashion. The results suggest that low-M(r) metalloproteinase inhibitors may have therapeutic potential in limiting connective tissue breakdown in conditions such as rheumatoid arthritis.


The effect of hyaluronan on interleukin-1 alpha-induced prostaglandin E2 production in human osteoarthritic synovial cells.

An in vitro study on the effects of hyaluronan (HA) on interleukin-1 alpha-induced prostaglandin E2 (PGE2) production in human osteoarthritic synovial cells indicated that PGE2 induction was suppressed by HA in a dose- and molecular weight-dependent manner.


Protein kinase C inhibits stimulation of adenylate cyclase by the histamine H2 receptor in rat parietal cells.

The action of protein kinase C on the stimulation of adenylate cyclase activity by the histamine H2 receptor was investigated in rat parietal cells. Protein kinase C was activated by preincubating cells with 12-O-tetradecanoylphorbol 13-acetate (TPA), and adenylate cyclase activity was measured in sonicated extracts. TPA (100 nM) inhibited adenylate cyclase activity stimulated by histamine (100 nM-500 microM). This effect was related to the concentration of TPA. TPA (100 nM) enhanced the stimulation of adenylate cyclase activity by forskolin (100 microM) but had no effect on the stimulation by NaF (10 mM). In conclusion, protein kinase C inhibits stimulation of adenylate cyclase by the histamine H2 receptor. This action could be mediated by changes in the number of affinity of histamine H2 receptors or in the coupling of the receptor to the stimulatory guanine nucleotide regulatory subunit Gs.


The effect of WEB 2086 on PAF-induced eosinophil chemotaxis and LTC4 production from eosinophils.

We investigated the effect of WEB 2086, a selective platelet-activating factor (PAF) receptor antagonist, on PAF-induced eosinophil chemotaxis and LTC4 production. WEB 2086 inhibited PAF-induced eosinophil chemotaxis in normals and asthmatics. To further determine if WEB 2086 is a selective PAF receptor antagonist, we examined the effect of WEB 2086 against formyl-methionyl-leucyl-phenylalanine (fMLP)-induced or eosinophil chemotactic factor of anaphylaxis (ECF-A)-induced eosinophil chemotaxis. WEB 2086 did not have a significant inhibition against fMLP or ECF-A-induced eosinophil chemotaxis. These results suggest that WEB 2086 is a selective and potent inhibitor of PAF-induced eosinophil chemotaxis and LTC4 production from eosinophils, due to its antagonism of PAF-receptors.


Effects of capsaicin on cutaneous vasodilator responses in humans.

The neurovascular responses to noxious electrically evoked axon reflex (EAR) stimulation and iontophoretic application of endothelium-dependent [acetylcholine (ACh)] and independent [sodium nitrite (NaNO2)] vasodilator substances were examined in human forearm skin using laser Doppler flowmetry, before and after repeated topical applications of the neurotoxin capsaicin (chronic capsaicin pre-treatment). Following 3 or 4 days of capsaicin pre-treatment the normal vasodilator response to acute application of capsaicin was significantly reduced as was the EAR response. There were, however, no significant changes in the vasodilator responses to either ACh or NaNO2, suggesting that the neurogenic axon reflex is in series with the endothelial and microvascular smooth muscle mechanisms of vasodilatation. Recovery of normal EAR occurred within 2-4 weeks of cessation of capsaicin pre-treatment.


Characterization and pharmacological modulation of soluble phospholipase A2 generated during glycogen-induced rat peritonitis.

Soluble phospholipase A2 (PLA2) activity was assessed in rat peritoneal lavage fluid after an intraperitoneal injection of 6% glycogen. Enzyme activity immediately increased 5-fold above basal by 4 h. Activity decreased by only 30% at 18 h and remained at this elevated level through 72 h. The initial rise in PLA2 activity was coincident with protein extravasation but not with polymorphonuclear leukocyte infiltration, suggesting that the early PLA2 activity could be, in part, blood-derived. Mononuclear cell influx occurred later (4 h), peaked by 6-8 h but remained elevated through 72 h possibly contributing to the persistence of PLA2 activity through 20-72 h. The exudate PLA2 measured at 4-6 h (early) and 20-24 h (late), after glycogen administration, were biochemically compared. They were found to be neutral pH active, Ca(2+)-dependent and were similarly inhibited by the inhibitors, p-bromophenacylbromide, ellagic acid, gossypol and luffariellolide. Oral administration of dexamethasone to rats inhibited the appearance of PLA2 activity in the peritoneal lavage fluid as well as cellular influx and protein extravasation. Indomethacin had no effect on these parameters. These studies demonstrate that PLA2 is an integral component of glycogen-induced peritonitis and can be pharmacologically manipulated.


A low molecular weight component derived from the milk of hyperimmunised cows suppresses inflammation by inhibiting neutrophil emigration.

An earlier study demonstrated that hyperimmunisation of dairy cows with a polyvalent bacterial vaccine stimulated the secretion of a small molecular weight anti-inflammatory moiety in the milk. This hyperimmune milk factor (HIMF) has been further investigated in the present experiments. HIMF was found to suppress the cellular phase of the response to carrageenin and also the neutrophil-dependent reverse passive Arthus reaction. These results, together with the observation that the administration of HIMF led to an increase in the number of circulating neutrophils, suggested that the agent might inhibit inflammation by interfering with the ability of neutrophils to emigrate from the vasculature. In vivo studies carried out to evaluate this possibility demonstrated that HIMF suppressed neutrophil emigration by up to 75%. In vitro experiments established that the ability of neutrophils to respond to chemotactic stimuli or adhere to endothelial cells was not affected by HIMF. It is possible, therefore, that the agent modulates inflammation by down-regulating the synthesis of inducible pro-inflammatory cytokines or adhesion molecules. Attempts are presently being made to isolate the active moiety to allow the activity of the agent at the molecular level to be studied in more detail.


Oral, anti-inflammatory activity of a potent, selective, protein kinase C inhibitor.

The protein kinase C family of enzymes is thought to be important in mediating signal transduction. Ro 31-8830 is a novel, potent inhibitor of protein kinase C, derived from the non-selective protein kinase inhibitor staurosporine. In this paper we demonstrate the selectivity of Ro 31-8830 for protein kinase C over other protein kinases and its ability to inhibit protein kinase-C-mediated events in platelets and lymphocytes. In addition, we describe a novel system for the in vivo evaluation of inhibitors of protein kinase C, and we demonstrate the oral anti-inflammatory activity of Ro 31-8830. This finding has implications for the treatment of inflammatory disorders in the clinic.


Antiarthritic profile of BF-389--a novel anti-inflammatory agent with low ulcerogenic liability.

BF-389, dihydro-4-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-methyl-2H-1,2- oxazin-3(4H)-one, is a potent, orally active, antiarthritic and analgesic agent with low ulcerogenic potential. A comparison of the activity profiles of BF-389 and naproxen showed similarities in: (1) suppression of developing and chronic adjuvant arthritis (AA); (2) maximal inhibitory response, as shown by the E(max) values in the developing and established AA models; (3) inhibition of bone degenerative changes associated with chronic adjuvant arthritis; and (4) analgesic activity in the acetic acid and phenylquinone writhing assays. Though BF-389 has been shown to be a potent inhibitor of cyclooxygenase, IC50 = 0.84 +/- 0.25 microM against the production of PGE2 in vitro, there is a great difference from most cyclooxygenase inhibitors; it also inhibits the 5-lipoxygenase enzyme. For BF-389, the IC50 for in vitro LTB4 formation was found to be 3.65 +/- 1.19 microM. The ulcerogenic potential of BF-389 was compared to that of naproxen using a five-day in vivo ulcerogenic rat assay. The UD50 for naproxen was found to be approximately 30 mg/kg/day, p.o. Based upon efficacy in the DEV AA and EST AA models, UD50/ED50 values for naproxen were estimated to be 0.7 and 1.9, respectively. For BF-389 the UD50 was shown to be 520 (389-695) mg/kg/day, p.o., and the corresponding UD50/ED50 values were calculated to be 84 and 28, respectively, thus demonstrating the wide margin of safety between efficacy and ulcerogenicity in rats.


Suppression of pulmonary granulomatous inflammation by immunomodulating agents.

We demonstrated previously that macrophages and macrophage-derived cytokines including lymphocyte-activating factors (LAFs) play a critical role in lung granuloma formation in mice and that granulomas sizes correlated with LAF activity in the lesions. In the present study, we examined the effects of D-penicillamine (D-Pc), 2-acetylthiomethyl-3-(4-methyl-benzoyl)propionic acid (KE-298) and dexamethasone (Dex) on dextran bead-induced lung granulomas in mice. KE-298 is a newly synthesized compound containing sulfur (S) similar to D-Pc. Large granulomas developed, which reached peak intensity within 3 days and declined in size thereafter. Aqueous lung extracts of the mice contained high levels of LAF that were correlated with granuloma sizes. The lesions and local LAF activity were inhibited by administration of these agents. The most potent inhibitor was Dex. The suppressive effect of KE-298 was similar to that of D-Pc. These results suggest that suppression of granulomas may be attributed to inhibition of LAF activity/synthesis by these agents.


Structural and functional changes of blood-brain barrier and indication of prion amyloid filaments in experimental amyotrophic leucospongiosis.

The reproduction of amyotrophic leukospongiosis (AL) agent in the central nervous system (CNS) of guinea pigs was accompanied by local disturbance of blood-brain barrier (BBB), which manifested in passing of horseradish peroxidase through the endothelium of some of capillaries (10-14%). The disturbance of BBB function coincided with dystrophic changes in a number of pericapillary astrocyte foot processes and in pericytes. In the walls of altered vessels we observed congophilic (amyloid) deposits, which formed immunocomplexes with monoclonal antibodies to the AL agent protein PrP 27-30 kD. By electron microscopic the deposits consisted of masses of filaments with diameter of 5-10 nm located between the basement membrane and endothelium of the vessels.


Combining insulin and oral agents in diabetes: indications and controversies.

Patients with noninsulin-dependent diabetes demonstrate peripheral insulin resistance that is aggravated by increased hepatic glucose production and results in elevated serum insulin and serum glucose levels. These levels can be affected by intensive diabetic management, including diet, exercise, lifestyle modifications and insulin or sulfonylurea therapy. Sulfonylureas stimulate endogenous insulin production, increase peripheral sensitivity to insulin and suppress hepatic glucose production. In spite of its added expense, increased potential for side effects and questionable efficacy, combination therapy with insulin and a sulfonylurea is often considered in noninsulin-dependent diabetics with difficult-to-control disease.


Mercury toxicity. Agency for Toxic Substance and Disease Registry.

Because mercury has several forms and because it produces subtle effects at chronic low-level exposures, mercury toxicity can be a difficult diagnosis to establish. Elemental mercury vapor accounts for most occupational and many accidental exposures. The main source of organic methyl mercury exposure in the general population is fish consumption. Children are at increased risk of exposure to elemental mercury vapor in the home because it tends to settle to the floor. The chemical and physical forms of mercury determine its absorption, metabolism, distribution and excretion pathways. The central nervous system and kidneys are key targets of mercury toxicity. Chelation therapy has been used successfully in treating patients who have ingested mercury salts or inhaled elemental mercury. There is no antidote for patients poisoned with organic mercury.


Evaluation of fetal arrhythmias.

Fetal arrhythmias occur in approximately 1 to 3 percent of all pregnancies. Successful management depends on early identification and evaluation. Arrhythmias are classified as irregular, bradycardiac or tachycardiac. With proper monitoring, fetuses with irregular arrhythmias can usually be delivered by family physicians. For fetuses with bradyarrhythmias or tachyarrhythmias, referral to a high-risk specialists for ongoing fetal surveillance and delivery is necessary.


Clinical and imaging evaluation of the solitary pulmonary nodule.

Management of a solitary pulmonary nodule remains a common clinical problem. The main goal of management is to choose a diagnostic and therapeutic scheme that is appropriately matched to the patient's clinical risk of malignancy. Clinical risk can be estimated from consideration of data on the overall prevalence of malignancy in solitary pulmonary nodules in various populations, the size of the pulmonary nodule, the patient's age and the patient's history of smoking. Nodules that have not grown for at least two years and those that are calcified are usually benign and require no further work-up. Suspicious nodules require further evaluation. The approach for patients at low clinical risk for malignancy may be clinical and radiographic observation, while that for patients at moderate to high risk for malignancy may be needle biopsy or thoracotomy. Whenever possible, the patient should be encouraged to participate in the decision-making process concerning the management of this clinical problem.


Comparative testing of an FTIR remote optical sensor with area samplers in a controlled ventilation chamber.

A portable Fourier transform infrared remote optical sensing spectrometer was deployed and tested in a constant ventilation test chamber by using a tracer gas source. Continuous beam path measurements were collected and compared to air samples obtained from a computer-controlled, multiple-point sampling array connected to a flame ionization detector. Measurements were gathered at two different room ventilation rates and at two different dispersion conditions. A homogeneous dispersion condition had a uniform tracer concentration over the beam path and an inhomogeneous dispersion condition had a nonuniform tracer concentration distribution over the length of the beam path. Overall, the beam measurements and the point sample readings showed good agreement regardless of the room ventilation rate. Comparative data obtained from the inhomogeneous dispersion conditions did have higher variability, probably as a result of the different spatial and temporal resolution of the two sampling techniques. The tests demonstrate that a remote sensing system can be applied to an indoor room scale setting, but the dispersion of contaminant in the beam path is an important factor to consider when interpreting the beam data.


An investigation of dust generation by free falling powders.

To identify the dust generation processes, aluminum oxide powder was dropped as a free falling slug in a test chamber. The effect of the slug's mass, diameter, and drop height upon the aerosol concentration and size distribution was measured with an aerodynamic particle sizer. To differentiate between aerosol generated during the free fall and at the end of the fall, the slug was dropped either onto a flat surface or into a container of water that suppressed dust generation associated with the impact at the end of the fall. Aerosol generation occurred during the slug's free fall as well as at the end of the fall. The falling solid induced an airflow that followed the falling solid to the end of the fall. This induced airflow contained the aerosol generated during the free fall. At the end of the free fall, the induced airflow, combined with air jets created on impact, dispersed the aerosol throughout the test chamber. Additional measurements were made by using "neutral buoyancy" helium-filled bubbles to visualize the airflow in the test chamber. The airflow and ensuing turbulence were sufficient to keep large, inspirable particles suspended throughout the test chamber for periods greater than 10 min. During experimental work, the effect of drop height, mass, and slug diameter upon aerosol generation by a single slug of powder was studied. The results indicated that the manner in which a powder is handled may be as important as material dustiness as measured by a dustiness tester. Aerosol generation can be reduced by minimizing the contact between the falling powder and the air.


An assessment of critical anthropometric dimensions for predicting the fit of a half-mask respirator.

The purpose of this study was to determine if facial dimensions for a group of subjects were predictive of the fit factors measured while one brand of half-mask respirator was worn. Fit factors and 12 facial dimensions measured on 30 female and 38 male subjects were analyzed by correlation coefficients; weighted, multiple linear regression; and discriminant analysis. Data were analyzed for all subjects, gender subgroups, a race subgroup (whites only), and race/gender subgroups. Significant correlation coefficients with the log-transformed fit factors were found for four dimensions; four dimensions had significant coefficients in four or more multiple linear regression models. Only two dimensions had significant coefficients in four or more discriminant analysis models. Menton-subnasale (lower face) length was the only dimension included in all three of these groups. Gender-specific regression models had very high coefficient of determination values (R2 > 0.85). Discriminant analysis of the data for all subjects and race/gender subgroups found very good predictive scores for statistical software-generated models and menton-subnasale length alone; these scores were significantly better than those for the model with the respirator test panel dimensions (face length and lip width). These analyses found that facial dimensions were good predictors of respirator fit for those subjects wearing one brand of half-mask respirator. Lower face length was consistently indicated as being correlated or associated with fit. These results would indicate that dimensions other than those currently used may be more appropriate to define a half-mask respirator test panel.


Hydrocarbon exposures at petroleum bulk terminals and agencies.

Occupational exposures to the 55 hydrocarbon components of gasoline and petroleum products were measured at the bulk terminals and agencies of six Ontario petroleum companies during the summer of 1986. A total of 82 long-term (full-shift) and 111 short-term personal samples were taken over 3 months. The data, expressed as concentrations in milligrams per cubic meter, were highly variable and appeared to fit the lognormal distribution well. Full-shift exposures of bulk terminal drivers, agency drivers, and plantmen to total hydrocarbons (THC), computed as an n-hexane equivalent, and other hydrocarbon components for which exposure limits exist can be expected to exceed their respective 1986-1987 threshold limit value-time-weighted average (TLV-TWA) no greater than 1% of the time on the basis of the lognormal model. The short-term THC exposures of agency truck drivers can be expected to exceed the 1986-1987 TLV-short-term exposure limits about 7% of the time while top-loading and more than 17% while off-loading. For benzene, the short-term exceedance percentages are 1% and 4% for top- and off-loading operations, respectively. For long-term benzene exposures, up to 69% of the assessments can be expected to exceed the 1990-1991 proposed TLV-TWA of 0.3 mg/m3 (0.1 ppm). The full-shift hydrocarbon exposures of agency drivers were significantly higher than those for bulk terminal drivers. At the bulk terminals, the short-term hydrocarbon exposures during top-loading were significantly higher than during bottom-loading.


Evaluation of eight bioaerosol samplers challenged with aerosols of free bacteria.

The need to quantify airborne microorganisms in the commercial microbiology industry (biotechnology) and during evaluations of indoor air quality, infectious disease outbreaks, and agriculture health investigations has shown there is a major technological void in bioaerosol sampling techniques to measure and identify viable and nonviable aerosols. As commercialization of microbiology increases and diversifies, it is increasingly necessary to assess occupational exposure to bioaerosols. Meaningful exposure estimates, by using area or environmental samplers, can only be ensured by the generation of data that are both precise and accurate. The Andersen six-stage viable (microbial) particle sizing sampler (6-STG) and the Ace Glass all-glass impinger-30 (AGI-30) have been suggested as the samplers of choice for the collection of viable microorganisms by the International Aerobiology Symposium and the American Conference of Governmental Industrial Hygienists. Some researchers consider these samplers inconvenient for evaluating industrial bioprocesses and indoor or outdoor environments. Alternative samplers for the collection of bioaerosols are available; however, limited information has been reported on their collection efficiencies. A study of the relative sampling efficiencies of eight bioaerosol samplers has been completed. Eight samplers were individually challenged with a bioaerosol, created with a Collison nebulizer, of either Bacillus subtilis or Escherichia coli. The samplers were evaluated under controlled conditions in a horizontal bioaerosol chamber. During each experimental run, simultaneous samples were collected with a reference AGI-30 to verify the concentration of microorganisms in the chamber from run to run and day to day.(ABSTRACT TRUNCATED AT 250 WORDS)


Growth changes and orthodontic treatment in a patient with condylolysis.

A patient with acquired bilateral degeneration of the mandibular condyles was treated orthodontically. The flattening of condyles and the shortening of the ramus began at adolescence. The facial profile changed to a convex type, with a marked mandibular retrognathia and severe Class II malocclusion. The cause seems to be due to a condylolysis of the mandible.