Assessment of the toxicity of man-made fibres. A final report of a workshop held in Paris, France 3-4 February 1994.
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Animals↗
Biomedical subjects
J M Davis
Publications and source records attributed to J M Davis.
War zone stress, personal resources, and PTSD in Persian Gulf War returnees.
Posttraumatic stress disorder (PTSD) can occur subsequent to war stress, but not all troops are negatively affected. A discriminant function model was used to study associations between personal and environmental resources and psychological outcomes subsequent to war zone stress. Among 775 Persian Gulf War exposed troops, 2 subsets were identified: 97 with PTSD diagnoses and 484 who had no psychological distress. A discriminant function, double cross-validated in random subsamples, classified 87% of troops, and demographic and stress severity variables did not alter results significantly. Personality hardiness commitment, avoidance coping, and perceived family cohesion emerged as consistent predictors of PTSD diagnosis. Findings suggest personal characteristics and environmental factors may alter vulnerability to negative war stress outcomes. Work is needed to identify mechanisms and causal pathways by which resource factors enhance or lower stress resistance.
Adaptation, Psychological↗
The acute immune response to exhaustive resistance exercise.
Ten young male adults (mean age 46.9 +/- 1.2 yrs) with 9.2 +/- 1.4 years of weight training experience and the ability to parallel squat at least 1.5 times their body mass were selected as subjects. The exercise session consisted of sets of 10 repetitions at 65% 1-RM of the parallel leg squat, with a cadence of one rep every 6 sec and 3 min rest between sets, to muscular failure. The average subject lifted a total of 9711 +/- 1576 kg during 98 +/- 14 reps for a total work output of 72.5 +/- 10.5 kJ before muscular failure occurred. Mean oxygen consumption during exercise was 1.58 +/- 0.06 l/min at 42.5 +/- 2.0% peak VO2. A strong leukocytosis, lymphocytosis, and lymphocytopenia, similar to what has been reported following high-intensity cardiorespiratory exercise, were measured following leg squat exercise. Con A-stimulated lymphocyte proliferation (unadjusted) rose 50% above preexercise levels (p = 0.07), but when these data were adjusted on a per T cell (CD3+) basis, no change from rest was observed. Natural killer cell cytotoxic activity (NKCA), when adjusted on a per NK cell (CD56+) basis, was decreased about 40% below preexercise levels for at least 2 h post-exercise. No significant increase in cortisol was seen after exercise, although norepinephrine and epinephrine increased moderately (465% and 133%, respectively), immediately following exercise. The data demonstrate that leg squat exercise to muscular failure results in a very similar immune response to that associated with intense endurance exercise, despite a lower mean oxygen consumption and only a moderate hormonal response.
Adult↗
Lymphocyte proliferative response to 2.5 hours of running.
The effect of 2.5 h of treadmill running at 75.6 +/- 0.9% VO2max on circulating leukocyte and lymphocyte subpopulations, epinephrine and cortisol concentrations, and the Con A-induced lymphocyte proliferative response was investigated in 22 experienced marathon runners (VO2max 57.9 +/- 1.1 ml.kg-1.min-1, age 38.7 +/- 1.5 yrs). Blood samples were taken 15 min before (07.15h) and immediately after exercise (10.00h), with three more samples taken during 6h of recovery (11.30, 13.00, 16.00h). Ten sedentary controls (34.7 +/- 1.0 ml.kg-1.min-1, 45.3 +/- 2.3 yrs) sat in the laboratory during testing and had their blood sampled at the same time points. Serum cortisol was elevated relative to controls for more than 3 h post-exercise, and correlated significantly with the 3-h post-exercise, and correlated neutrophil/lymphocyte ratio (r = 0.68, p < 0.001). The concanavalin A- (Con A) induced lymphocyte proliferative response was decreased relative to controls for more than 3 h post-exercise, and except for the immediate post-exercise time point, tended to parallel the decrease in T cell (CD3+) concentrations.
Adult↗
Central and peripheral factors in fatigue.
The causes of fatigue during muscular exercise include factors that reside in the brain (central mechanisms) as well as the muscles themselves (peripheral mechanisms). Central fatigue is largely unexplored, but there is increasing evidence that increased brain serotonin (5-HT) can lead to central (mental) fatigue, thereby causing a deterioration in sport and exercise performance. Although there are also strong theoretical grounds for a beneficial role of nutrition in delaying central fatigue, the data are much more tenuous. Dietary supplementation with branched-chain amino acids (BCAA) in low doses produces small and probably inconsequential effects on peripheral markers of brain 5-HT synthesis (plasma free tryptophan/BCAA), whereas larger doses are likely to be unpalatable, reduce the absorption of water in the gut, and may increase potentially toxic ammonia concentrations in the plasma. Alternatively, carbohydrate supplementation results in large reductions in plasma free tryptophan/BCAA and exercise time to fatigue is significantly longer, but it is difficult to distinguish between the effects of carbohydrate feedings on central fatigue mechanisms and the well-established beneficial effects of carbohydrate supplements on the contracting muscle. These data support the exciting possibility that relationships exist among nutrition, brain neurochemistry and sport performance. However, while the evidence is intriguing and makes good intuitive sense, our knowledge in this area is rudimentary at best.
Brain↗
Large-volume leukapheresis using regional citrate anticoagulation to collect peripheral blood progenitor cells.
The use of peripheral blood progenitor cells (PBPC) for hematopoietic rescue after high-dose chemotherapy is limited by the number of leukaphereses required to collect an adequate number of hematopoietic progenitors. To optimize the collection of PBPC, we evaluated a single large-volume leukapheresis protocol with citrate anticoagulation. A group of 23 patients received cyclophosphamide (4 g/m2) and GM-CSF (5 micrograms/kg/day for 15 days) as PBPC mobilization, with a single outpatient 6 h leukapheresis performed on the COBE Spectra 15 days later. Citrate (0.190 mmol/ml) was infused at 1.2 ml/L of blood/minute with a whole blood to citrate ratio between 17:1 and 25:1. Calcium chloride (50 mM) was administered at a citrate to calcium molar ratio between 10:1 and 5:1 to prevent hypocalcemia. A median 36.6 L (range 24.4-46.4) blood was processed using 338 mM citrate (269-473) and 50 mM calcium (25-75). A median 5 x 10(6) CD34+ cells/kg (< 0.3-24) and 6.2 x 10(5) CFU-GM/kg (< 0.001-29) were collected, representing 5.6 and 5.9 more PBPC, respectively, than were in circulation at the initiation of leukapheresis. We conclude that a 6 h large-volume leukapheresis following cyclophosphamide and GM-CSF mobilization is safe, can recruit hematopoietic progenitors into the circulatory compartment, and allows the collection of high numbers of PBPC in a single procedure.
Adolescent↗
Case report: congenital adrenal hyperplasia and malignant Leydig cell tumor.
Leydig cell tumors are very rarely seen testicular tumors and can be difficult to distinguish from testicular tumors of the adrenogenital syndrome. Testicular tumors of the adrenogenital syndrome are confined to patients with congenital adrenal hyperplasia. The authors report a case of a patient with malignant Leydig cell tumor and a history of congenital adrenal hyperplasia (adrenogenital syndrome). To the authors' knowledge, this has not been reported previously.
Adrenal Hyperplasia, Congenital↗
A missense mutation in rpoD results in an A-signalling defect in Myxococcus xanthus.
The Myxococcus xanthus asg genes (asgA, asgB, and asgC) are necessary for production of extracellular A-signal, which is thought to function as a cell-density signal. Previous analyses of the asgA and asgB genes suggest that they perform regulatory functions. In this work, we localized asgC to a region that contains genes homologous to rpsU, dnaG, and rpoD of the Escherichia coli macromolecular synthesis (MMS) operon. Surprisingly, asgC767 was found to be a mutant allele of rpoD, the gene encoding the major sigma factor of M. xanthus. The mutation in asgC767 results in a glutamate to lysine substitution at amino acid 598, which lies within conserved region 3.1 of the major sigma factors. Previous studies have shown that the asg mutants share a number of growth and developmental phenotypes. We found that A-signal restores developmental expression of an A-signal-dependent gene (omega 4521) in the asgC767 (rpoDEK598) mutant background in a manner similar to that seen in the asgA and asgB mutants. Because the asg mutants have very similar phenotypes and the asg genes encode proteins that appear to have regulatory functions, we hypothesize that the asg gene products function together in a regulatory pathway that is required for extracellular A-signal production.
Amino Acid Sequence↗
The sizes, shapes, and mineralogy of asbestos structures that induce lung tumors or mesothelioma in AF/HAN rats following inhalation.
Data from inhalation studies in which AF/HAN rats were exposed to nine different types of asbestos dusts (in 13 separate experiments) are employed in a statistical analysis to determine if a measure of asbestos exposure (expressed as concentrations of structures with defined sizes, shapes and mineralogy) can be identified that satisfactorily predicts the observed lung tumor or mesothelioma incidence in the experiments. Due to limitations in the characterization of asbestos structures in the original studies, new exposure measures were developed from samples of the original dusts that were re-generated and analyzed by transmission electron microscopy using a direct transfer technique. This analysis provided detailed information on the mineralogy (i.e., chrysotile, amosite, crocidolite or tremolite), type (i.e., fiber, bundle, cluster, or matrix), size (length and width) and complexity (i.e., number of identifiable components of a cluster or matrix) of each individual structure. No univariate measure of exposure was found to provide an adequate description of the lung tumor responses observed among the inhalation studies, although the measure most highly correlated with tumor incidence is the concentration of structures > or = 20 microns in length. Multivariate measures of exposure were identified that do adequately describe the lung tumor responses. Structures contributing to lung tumor risk appear to be long (> or = 5 microns) thin (0.4 microns) fibers and bundles, with a possible contribution by long and very thick (> or = 5 microns) complex clusters and matrices. Potency appears to increase with increasing length, with structures longer than 40 microns being about 500 times more potent than structures between 5 and 40 microns in length. Structures < 5 microns in length do not appear to make any contribution to lung tumor risk. This analysis did not find a difference in the potency of chrysotile and amphibole toward the induction of lung tumors. However, mineralogy appears to be important in the induction of mesothelioma with chrysotile being less potent than amphibole.
Administration, Inhalation↗
Cerebrospinal fluid levels of phenylacetic acid in mental illness: behavioral associations and response to neuroleptic treatment.
Cerebrospinal fluid levels of phenylacetic acid (CSF PAA) were obtained from normal controls and from drug-free psychiatric inpatients (schizophrenia, major depression, mania, and schizoaffective disorder). Post-treatment CSF PAA levels were obtained from 16 patients after 4 weeks of neuroleptic treatment. Phenylacetic acid levels were higher in women and were significantly correlated with age. There were no differences in CSF PAA levels between the various diagnostic groups and no difference between the paranoid and the nonparanoid subtypes of schizophrenia. CSF PAA was significantly correlated with several measures of psychopathology, especially the Brief Psychiatric Rating Scale hostility/suspiciousness factor. Neuroleptic treatment did not result in significant PAA changes. These findings are discussed in light of the amphetamine-like role ascribed to phenylethylamine, the precursor of PAA.
Adult↗
Carbohydrates, branched-chain amino acids, and endurance: the central fatigue hypothesis.
The mechanisms of central fatigue are largely unexplored, but the central fatigue hypothesis suggests that increased brain serotonin (5-HT) can cause a deterioration in sport and exercise performance. There is now convincing evidence that exercise-induced increases in the plasma free tryptophan (f-TRP)/branched-chain amino acids (BCCA) ratio are associated with increased brain 5-HT and the onset of fatigue during prolonged exercise. Furthermore, when drugs are administered to alter brain 5-HT, they have the predicted effects on exercise performance. The influence of nutritional manipulations of f-TRP/BCCA on performance is less well established. The effects of BCCA supplementation on exercise performance are mixed, and the published studies often suffer from methodological flaws. Alternatively, dramatic reductions in f-TRP/BCCA and enhanced performance accompany carbohydrate feedings during prolonged exercise. However, it is difficult to distinguish between the effects of carbohydrate feedings on mechanisms that reside in the brain versus the muscles themselves.
Amino Acids, Branched-Chain↗
Neutrophil lipoxygenase activation and leukosequestration in postischemic myocutaneous flaps: role of LTB4.
Reperfusion of ischemic tissues leads to eicosanoid- and polymorphonuclear leukocyte (PMN)-dependent injury. The present experiments were undertaken to examine the effect of myocutaneous flap ischemia-reperfusion on neutrophil 5-lipoxygenase activity and to define the role of leukotriene B4 (LTB4) in postischemic PMN infiltration into such composite tissue grafts. Anesthetized Yorkshire pigs underwent 6 h of rectus abdominis myocutaneous flap ischemia or sham ischemia, and LTB4 generation was measured in calcium ionophore-stimulated neutrophils isolated from the circulation. At 30 min of reperfusion, neutrophil generation of LTB4 increased from a baseline value of 31.0 +/- 6.8 to 98.5 +/- 5.1 ng/5 x 10(6) PMN (P < 0.01) and was significantly greater than those neutrophils isolated from animals subjected to sham ischemia and reperfusion (54.3 +/- 4.1 ng/5 x 10(6) PMN; P < 0.01). Pretreatment of animals with the LTB4-receptor antagonist, SC-41930 (n = 5), significantly attenuated reperfusion-associated 5-lipoxygenase activation (60.3 +/- 11.6 ng LTB4/5 x 10(6) PMN; P < 0.01), suggesting the presence of a positive feedback mechanism for eicosanoid biosynthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Combined effects of nitric oxide and hyperoxia on surfactant function and pulmonary inflammation.
NO and its derivative ONOO- are potent free radicals that can cause cell damage, especially in the presence of O2. To determine the potential pulmonary toxicities of nitric oxide (NO) and peroxynitrite (ONOO-) in vitro, Survanta (2.5 mg/ml) was exposed to ONOO- (0.3-8 mM) in the presence of two different buffering systems (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid and phosphate buffer) and minimum surface tension (MST) was determined with an oscillating bubble surfactometer. Significant increases in MST were seen only with exposure to 8 mM ONOO-, indicating that in vitro, high concentrations of ONOO- can inhibit natural surfactant function. The in vivo effects of NO and hyperoxia were then studied in four groups of newborn piglets ventilated for 48 h with 21% O2, 100% O2, 21% O2 and 100 ppm NO, or with 90% O2 and 100 ppm NO. Five animals served as an untreated control group. Bronchoalveolar lavage fluid (BAL) obtained at 48 h was subjected to centrifugation and the surfactant pellet was reconstituted to 5 mg phospholipid/ml. Significant increases in MST were seen in surfactant from piglets ventilated with NO and 90% O2, compared with either untreated controls or piglets ventilated with 21% O2 for 48 h (P < 0.05, analysis of variance). Significant increases in neutrophil chemotactic activity (NCA) of BAL were also found in the NO and O2 group (P < 0.05), with significant positive interaction between NO and O2 found (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Indomethacin does not alter natural killer cell response to 2.5 h of running.
The effect of 2.5 h of treadmill running at 75.6 +/- 0.9% maximal O2 uptake (VO2max) on natural killer (NK) cell cytotoxic activity (NKCA) was investigated in 22 experienced marathon runners (VO2max 57.9 +/- 1.1 ml.kg-1.min-1, age 38.7 +/- 1.5 yr). Blood samples were taken before (0715) and immediately after exercise (1000), with three more samples taken during 6 h of recovery (1130, 1300, and 1600). Ten sedentary controls (VO2max 34.7 +/- 1.0 ml.kg-1.min-1, age 45.3 +/- 2.3 yr) sat in the laboratory during testing and had their blood sampled at the same time points. The pattern of change in NKCA over time was significantly different between groups [F(4,27) = 6.53; P = 0.001], with the runner's NKCA dropping 51-61% below preexercise levels throughout 6 h of recovery. Preincubation of blood mononuclear cells in vitro with indomethacin had no effect on the difference in pattern of change in NKCA between groups [F(4,17) = 8.59; P = 0.001] and did not attenuate the postexercise reduction in the runners. When NKCA was adjusted on a per-NK cell basis, group differences and the postexercise decline in NKCA were eliminated [F(4,80) = 0.65; P = 0.63]. Serum cortisol and plasma epinephrine in the runners were elevated relative to control subjects during recovery from exercise, but no significant correlation with changes in NK cells or NKCA was found. These data indicate that NKCA is decreased significantly during recovery from 2.5 h of running due to a numerical redistribution of NK cells.
Adult↗
Elevation of CSF somatostatin concentrations in mania.
OBJECTIVE: The aim of this study was to compare levels of CSF somatostatin (somatotropin release-inhibiting factor) in drug-free patients with different major psychiatric disorders. METHOD: CSF somatostatin concentrations were measured in 66 drug-free inpatients with Research Diagnostic Criteria diagnoses of schizophrenia, major depressive disorder, manic disorder, or schizoaffective disorder. RESULTS: In comparison with both the patients with schizophrenia and the patients with schizoaffective disorder, the manic patients had markedly elevated CSF somatostatin concentrations. The depressed patients had significantly higher levels than the schizophrenic patients. CONCLUSIONS: Mania is associated with relatively higher CSF somatostatin concentrations.
Adult↗
Platelet serotonin-2A receptors: a potential biological marker for suicidal behavior.
OBJECTIVE: Abnormalities in the serotonergic system have been implicated in suicidal behavior. Higher numbers of serotonin-2 (5-HT2) receptors have been reported in the post-mortem brain of suicide victims. In order to further examine the role of 5-HT2A receptors in suicidal behavior, the authors studied 5-HT2A receptors in platelets of suicidal and nonsuicidal patients as well as normal comparison subjects. METHOD: 5-HT2A receptor levels were determined by using [125I]LSD as a radioligand in platelets obtained from hospitalized psychiatric patients (N = 131) and nonhospitalized normal comparison subjects (N = 40) during a drug-free baseline period. Patients were diagnosed according to DSM-III-R criteria, and suicidal behavior was identified by using the Hamilton Depression Rating Scale. RESULTS: The mean maximum number of binding sites (Bmax) of platelet 5-HT2A receptors for all suicidal patients was significantly higher than for nonsuicidal patients or normal comparison subjects. This significant difference remained when subgroups of suicidal patients with depression, schizophrenia, schizoaffective disorder, or bipolar illness were compared to the other two subject groups. The higher number of platelet 5-HT2A receptors in suicidal patients was independent of diagnosis. While there was no significant difference in Bmax between patients with serious suicidal ideation and those who made suicidal attempts, both groups had significantly higher Bmax than normal comparison subjects. CONCLUSIONS: The observed higher number of platelet 5-HT2A receptors in suicidal patients is independent of diagnosis and appears to be associated with both the brain and the platelets of suicidal patients. These results thus suggest the potential usefulness of platelet 5-HT2A receptors as a biological marker for identifying suicide-prone patients.
Adult↗
Predicting the "revolving door" phenomenon among patients with schizophrenic, schizoaffective, and affective disorders.
OBJECTIVE: A subpopulation of chronically mentally ill patients, sometimes referred to as "revolving door" patients, are frequently readmitted to psychiatric units. This study examined the relationships among demographic features, diagnostic characteristics, and frequency of hospitalization of patients from four state hospitals. METHOD: Two semistructured, standardized instruments, the Schedule for Affective Disorders and Schizophrenia and a life events history, were administered to 135 inpatients who met the Research Diagnostic Criteria for schizophrenia (N = 56), schizoaffective disorder (N = 33), unipolar major depressive disorder (N = 23), and bipolar disorder (N = 23). Criminal history was assessed by arrest records. The main outcome measure was the number of hospitalizations. RESULTS: Chi-square and trend test analyses indicated that substance abuse and noncompliance with medication regimens were significantly associated with higher frequencies of hospitalization. A multiple regression model, which included alcohol/drug problems, medication noncompliance, and six sociodemographic and diagnostic variables (age, gender, race, marital status, years of education, and diagnosis) accounted for a significant proportion of the ability to predict frequency of hospitalization. Half of this predictability was due to the relationship of substance abuse and medication noncompliance with number of hospitalizations. CONCLUSIONS: Alcohol/drug problems and noncompliance with medication were the most important factors related to frequency of hospitalization. Preventing these behaviors through patient education may reduce rehospitalization rates.
Adult↗
State psychiatric hospital patients with past arrests for violent crimes.
OBJECTIVE: This study examined associations between four types of major psychopathology--schizophrenia, schizoaffective disorder, and bipolar and unipolar affective disorders--and history of violent crime. The effects of demographic variables, substance abuse, psychosis, and paranoia on history of violent crime were also determined. METHODS: Diagnostic assessments using the Schedule for Affective Disorders and Schizophrenia and Research Diagnostic Criteria identified 172 state hospital inpatients with the four diagnoses of interest, as well as those with co-existing substance use disorders. Based on arrest records, patients were categorized according to the most violent crime for which they had been arrested. RESULTS: Patients with schizoaffective disorder were significantly more likely than those in the other diagnostic groups to have been arrested for a violent crime. Similar results were found for psychotic patients compared with nonpsychotic patients, patients who had paranoid schizophrenia compared with patients who had schizophrenia without paranoid features, and patients who had co-existing substance abuse compared with those with no history of substance abuse. Patients from racial minority groups and male patients were also more likely than white patients and female patients to have been arrested for a violent crime. CONCLUSIONS: Demographic features, a diagnosis of schizoaffective disorder, psychosis, paranoid symptoms, and substance abuse may all be associated with violent behavior.
Adolescent↗