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Biomedical subjects

F Issa

Publications and source records attributed to F Issa.

12 recordsLinked to original sources

A fully-automated environmental chamber for examination of long-term effects of intermittent hypoxia on medium-size animals.

We describe the design and construction of a fully-automated environmental chamber for the simultaneous exposure of up to four medium-size laboratory animals to long-term intermittent hypoxia. The air-sealed automated environmental chamber consists of a box equipped with a ventilation fan and three electrically-activated solenoid valves. Our system was used to expose four rabbits to 12 h of repetitive episodes of hypoxia (environmental O2 concentration 12-13%) lasting 45 min followed by breathing room air for 15 min. During environmental hypoxia, the mean arterial PaO2 and PaCO2 were 41 +/- 3.0 and 24 +/- 0.7 mmHg (mean +/- SEM), respectively. In this system, opening and closing of the solenoid valves is fully computerized to allow different settings of the duration and severity of hypoxia. The chamber is safe and fully automated and cost-effective for studying the effects of long-term intermittent hypoxemia in medium-size animals.

Animals↗

Clonidine does not potentiate the antipsychotic effects of neuroleptics in chronically ill patients.

Clonidine is a centrally acting antihypertensive and has been prescribed widely for more than 20 years. Because it decreases central norepinephrine activity, clonidine has been investigated as an antipsychotic. In most of the preliminary studies, clonidine was tested as the sole antipsychotic agent. We performed a double-blind, placebo-controlled, crossover study to compare a placebo plus a neuroleptic to clonidine plus a neuroleptic in a group of 16 chronically psychotic patients. Of these 16, 3 dropped out secondary to side effects of the clonidine and 1 withdrew from the study. The clonidine dosage varied from 0.2 to 0.6 mg per day. The concurrent neuroleptic (one of the following: haloperidol, thiothixene, thioridazine, mesoridazine, or fluphenazine) averaged 34 mg per day of haloperidol equivalents. Symptoms were monitored using the Psychiatric Symptoms Assessment Scale. The data provided evidence that a clonidine/neuroleptic combination was not more effective than a neuroleptic alone in this group of patients. These data suggest that the central antinorepinephrine activity of a neuroleptic is not potentiated further by clonidine.

Adjuvants, Pharmaceutic↗

MR and CT imaging in the Dyke-Davidoff-Masson syndrome. Report of three cases and contribution to pathogenesis and differential diagnosis.

Cerebral hemiatrophy or Dyke-Davidoff-Masson syndrome is a condition characterized by seizures, facial asymmetry, contralateral hemiplegia or hemiparesis, and mental retardation. These findings are due to cerebral injury that may occur early in life or in utero. The radiological features are unilateral loss of cerebral volume and associated compensatory bone alterations in the calvarium, like thickening, hyperpneumatization of the paranasal sinuses and mastoid cells and elevation of the petrous ridge. The authors describe three cases. Classical findings of the syndrome are present in variable degrees according to the extent of the brain injury. Pathogenesis is commented.

Adult↗

Monozygotic twins discordant for schizophrenia are discordant for N-CAM and L1 in CSF.

While schizophrenia has a genetic component, its pathogenesis is unknown. Abnormal concentrations of two cell recognition molecules (CRMs), neural-cell adhesion molecule (N-CAM) and L1 antigen have been described in the cerebrospinal fluid (CSF) of patients with schizophrenia. Studies of monozygotic twins discordant for schizophrenia may help separate genetic and environmental contributions to the disease. In the present study of monozygotic twins discordant for schizophrenia, the affected twins had increased N-CAM and decreased L1 antigen in their CSF. Non-affected twins were not different from normals. Although processes related to genetic instability cannot be entirely ruled out, these results suggest that these abnormalities are not a part of the genetic predisposition to become schizophrenic. Thus the changes in N-CAM and L1 antigen may reflect either the events which precipitated the onset of schizophrenia, or events which are associated with the experience of having the disease.

Analysis of Variance↗

Transforming growth factors beta 1 and beta 2 in the cerebrospinal fluid of chronic schizophrenic patients.

Transforming growth factor beta s (TGF beta s) are potent immunosuppressive molecules released in the brain after injury. We hypothesized that TGF beta levels in cerebrospinal fluid (CSF) of schizophrenic patients would be altered because TGF beta can influence neural cell adhesion molecule (N-CAM) expression in vitro. The levels of TGF beta 1 and beta 2 in CSF of patients with schizophrenia and normal controls measured by ELISA showed no differences. There was evidence that the stability of TGF beta in CSF may be altered in schizophrenia. For a limited sample, TGF beta 1 and N-CAM concentrations were significantly correlated in normal patients (r = 0.98) but not in schizophrenics. The results do not support an active neurodegeneration or anti-inflammatory response in the central nervous system, which is reflected in the CSF of chronic schizophrenics.

Adult↗

A multidimensional approach to analysis of cerebrospinal fluid biogenic amines in schizophrenia: I. Comparisons with healthy control subjects and neuroleptic-treated/unmedicated pairs analyses.

Recent hypotheses and findings indicate that measurements of interactions between cerebrospinal fluid (CSF) biogenic amine systems, rather than measurement of CSF biogenic amine metabolites, better correlate with clinically important findings in schizophrenia. To test hypotheses, we used a recent technological advance in high performance liquid chromatography with electrochemical detection and combined it with multivariate statistical analyses to study biogenic amine concentrations in CSF in schizophrenia. This approach enabled the study of the interactions of several metabolites of each of the three major neurotransmitter pathways (dopaminergic, noradrenergic, and serotonergic) to test existing hypotheses regarding the neurobiochemical basis of schizophrenia. Twenty biogenic amines, their metabolites, and other compounds from 24 medication-free schizophrenic patients and 12 normal control subjects were simultaneously measured using a recently developed technique of gradient high performance liquid chromatography coupled with a 16-channel electrochemical array detector. After covariation for storage time, results of a stepwise discriminant function analysis comparing the control and patient groups identified tryptophan, tryptophol, and epinephrine as discriminating variables. Hotelling's paired T2 test from a subgroup of schizophrenic patients studied while they were and were not receiving neuroleptic treatment did not yield any significant differences between subgroups. A discussion of the findings and a comparison with previous studies of CSF biogenic amines in schizophrenia are presented.

Adult↗

A multidimensional approach to analysis of cerebrospinal fluid biogenic amines in schizophrenia: II. Correlations with psychopathology.

As part of a multidimensional study of cerebrospinal fluid biogenic amine metabolites in schizophrenia, the relationship between neurochemical measures and psychopathology assessed using the Psychiatric Symptom Assessment Scale (PSAS) was analyzed. In a group of 20 unmedicated patients, 3,4-dihydroxyphenylacetic acid (DOPAC) was a predictor of symptom severity in a stepwise multiple regression model. Values of 3-hydroxykynurenine and metanephrine in the unmedicated state predicted clinical response in a stepwise multiple regression model, as measured by improvement in PSAS mean item score following 6 weeks on a standard dose of neuroleptic. In a subgroup of 14 patients in whom both off- and on-medication concentrations of cerebrospinal fluid biogenic amines and metabolites were measured, change in 3-hydroxykynurenine predicted clinical outcome in a multiple regression model. These findings point toward the need to examine the role of the kynurenine pathway of tryptophan metabolism in the pathophysiology of schizophrenia.

Adult↗

Effects of water loading in schizophrenic patients with polydipsia-hyponatremia: an MRI pilot study.

We conducted an MRI pilot study of three schizophrenic patients with the syndrome of polydipsia-hyponatremia. Paired MRI scans were obtained at baseline and in the water-loaded state to study the acute effects of water loading and accompanying changes in serum sodium and osmolality on brain structures. We report the pilot data on the observed individual MRI changes of reduced volume of the lateral ventricles in all three patients, and the third ventricles in two patients, in the water-loaded state. These changes were not statistically significant possibly because of small sample size.

Adult↗

Supraventricular arrhythmias and the relation to thyroid dysfunction in a group of Syrian patients.

A group of 104 patients with supraventricular arrhythmias were classified according to the etiology. Twelve patients had serum levels of thyroid hormones considerably above and one patient had levels below the limits of normal reference range for our population. Only two of the hyperthyroid patients had many of the signs and symptoms of thyrotoxicosis, while the other 10 patients presented with only the arrhythmias. Three patients had some cardiac lesion together with the hyperthyroidism. Lastly, the main arrhythmia in those hyperthyroid patients was auricular fibrillation, (58%).

Atrial Fibrillation↗

Studies of oxygenation during sleep in patients with interstitial lung disease.

The pattern of change in arterial oxyhemoglobin saturation (SaO2%) during sleep was characterized in 13 patients with interstitial lung disease (ILD), 12 of whom had restrictive ventilatory impairment. Four patients snored during sleep. During the studies, 9 patients had unequivocal rapid eye movement (REM) sleep episodes. The total duration of each patient's REM episodes averaged 49 min (range, 26 to 93 min), which was 22 +/- 7% (1SD) of the total sleep duration. Seven of these 9 patients were nonsnorers but had definite falls in SaO2% during REM sleep (mean fall in SaO2%, 8 +/- 3%), and in 6 of them the falls in SaO2% were transient, with a mean duration of 28 +/- 12 s and a total duration of 6.4 +/- 3.9 min or 16 +/- 12% of the total REM sleep duration. The other nonsnorer showed sustained desaturation (SaO2, 80 to 85%) for his entire REM sleep period of 26 min. In the nonsnoring patients, the falls in SaO2% during REM sleep (8 +/- 3%) were usually greater than those occurring during awake exercise (6 +/- 7%). Two snorers had unexpected sleep apnea syndrome (minimal SaO2% during NREM sleep, 83 and 77%, respectively; minimal SaO2% during REM sleep, 58 and 67%, respectively). The other snorers had greater than 10% falls in SaO2% during NREM sleep. The breathing frequency in NREM sleep in patients with ILD (mean, 23 +/- 5 breaths/min) was persistently above the normal range (mean, 15 +/- 0.4 breaths/min). The possibility of sleep hypoxemia should be considered in the management of patients with ILD.

Adult↗

Elevated concentration of N-CAM VASE isoforms in schizophrenia.

Neural cell adhesion molecule (N-CAM) is a cell recognition molecule, four major isoforms (180, 140, 120, and 105-115 kDa) of which are present in brain. N-CAM has several roles in cellular organization and CNS development. Previously we have found an elevation in CSF N-CAM 120 kDa in the CSF of patients with schizophrenia, bipolar disorder, and depression. We now report an increase in the variable alternative spliced exon (VASE), a 10 amino acid sequence inserted into the fourth N-CAM domain, in the CSF of patients with schizophrenia, but not in bipolar disorder or depression. VASE-immunoreactive (VASE-ir) bands were measured in CSF from patients with schizophrenia (n = 14), bipolar disorder I (n = 7), bipolar disorder II (n = 9), unipolar depression (n = 17) and matched controls (n = 37) by Western immunoblotting. Three VASE-ir bands were distinguished in lumbar CSF corresponding to heavy (165 kDa), medium (155 kDa) and low (140 kDa) MW. A logarithmic transformation was applied to the VASE protein units and analyzed with a MANOVA. There was a 51% and 45% increase in VASE heavy (p = 0.0008) and medium (p = 0.04) MW protein, respectively, in patients with schizophrenia as compared with normal controls. Current neuroleptic treatment in patients with schizophrenia had no effect on CSF VASE concentrations. VASE concentration correlated significantly with behavioral ratings in patients with schizophrenia but not affective disorders. Thus, VASE immunoreactivity is increased in schizophrenia but not in affective disorders. These results provide further evidence of an abnormality of N-CAM protein in chronic schizophrenia and suggest differences between schizophrenia and affective disorders in regulation of N-CAM.

Alternative Splicing↗