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M D Bell

Publications and source records attributed to M D Bell.

At least 55 records · Page 3Linked to original sources

Recombinant human adenovirus with rat MIP-2 gene insertion causes prolonged PMN recruitment to the murine brain.

Single injections of recombinant cytokines/chemokines into tissue have provided insights into their possible roles during the inflammatory response. Adenoviral technology may allow us to mimic the in vivo situation more closely, with protein generated in a continuous but transient fashion. Replication-deficient human type 5 adenovirus containing a rat macrophage inflammatory protein-2 (MIP-2) gene insertion and cytomegalovirus promoter was injected into the mouse brain to investigate the inflammatory response to continuous overproduction of MIP-2. Adenovirus with a LacZ gene insertion expressing beta-galactosidase was used as a control. At doses of 10(4) to 10(7) plaque-forming units, a minimal inflammatory response was detected to the LacZ virus, with leukocyte recruitment that was restricted to the injection site. A dose of 10(7) plaque-forming units of both the LacZ and the MIP-2 vector produced extensive transgene product expression that persisted for at least 7 days. Astrocytes, recognized by their morphology, were the predominant cell type expressing MIP-2 and beta-galactosidase. A dose of 10(7) plaque-forming units of MIP-2 vector caused dramatic polymorphonuclear leukocyte (PMN) recruitment to the brain parenchyma after 2 days. PMN recruitment was still observed after 4 and 7 days, but had become more localized to the injection site and was associated with numerous foam-like macrophages. At both 2 and 7 days the blood-brain barrier was breached in the region of leukocyte recruitment. Despite the extent of leukocyte recruitment there were no overt signs of neuronal degeneration or demyelination. Our findings demonstrate that continuous production of MIP-2 in the CNS results in persistent PMN recruitment to the brain parenchyma with no evidence of tachyphylaxis. The lack of PMN recruitment to the brain parenchyma following CNS injury may be a result of deficient production of PMN chemoattractants.

Adenoviruses, Human↗

Adhesion molecule expression on murine cerebral endothelium following the injection of a proinflammagen or during acute neuronal degeneration.

The acute inflammatory response in the murine CNS is different from that observed in other tissues. Few polymorphonuclear leukocytes are recruited to the brain parenchyma and there is a delay in the recruitment of monocytes. Leukocyte recruitment to sites of inflammation is dependent on adhesion molecules expressed on the endothelium. The atypical kinetics of leukocyte recruitment to the CNS may be the result of deficient or delayed adhesion molecule expression on the cerebral endothelium. Using immunohistochemistry, the present study demonstrates that following the intracranial injection of a proinflammagen, lipopolysaccharide, or following acute neuronal degeneration elicited with kainic acid, the adhesion molecules ICAM-1 and VCAM were readily upregulated on cerebral endothelium in a time course comparable with that demonstrated on non-CNS endothelium. Both molecules were expressed on vessels, irrespective of their size, at 24 h after kainic acid or 6 h after lipopolysaccharide injection but leukocyte recruitment was negligible. The expression of ICAM-1 was demonstrated not only on endothelium but also on microglia especially in response to nerve terminal degeneration. PECAM was constitutively expressed at high levels on cerebral endothelium and did not change during brain injury. However, PECAM was induced on astrocytes after lipopolysaccharide injection or during acute neuronal degeneration, the latter providing a particularly strong stimulus. This study indicates that the expression of these adhesion molecules on CNS endothelium is neither deficient or delayed and that they are unlikely to be limiting factors in leukocyte recruitment to the CNS.

Animals↗

Inflammation in the nervous system.

Earlier studies on inflammation in the CNS have largely focused on conditions with an immune component. Recent evidence has emerged, however, that the innate, acute inflammatory response in the CNS parenchyma is quite unlike that in other tissues. The meninges and ventricular compartments show more typical responses, as does the parenchyma of the brain in immature animals. It is becoming apparent that the cells of the mononuclear phagocyte lineage dominate inflammatory responses in the CNS parenchyma.

Animals↗

Psychiatric symptoms and work performance among persons with severe mental illness.

The study examined the relationship between psychiatric symptoms and work performance for 61 subjects with a DSM-III-R diagnosis of schizophrenia or schizoaffective disorder who participated in a work rehabilitation program. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) to predict performance on the Work Personality Profile at three and 13 weeks of the program. Twenty-seven percent of the variance in work performance measures could be explained by symptom components measured by the PANSS, including the cognitive, negative, and hostility components, but the positive component did not predict work performance. Ratings of symptoms done concurrently with ratings of work performance were more powerful predictors than ratings of symptoms done at three and 13 weeks before ratings of work performance.

Adult↗

Social skills at work. Deficits and predictors of improvement in schizophrenia.

While the impact of social learning programs upon social deficits in schizophrenia has been widely studied, less is understood about which patients have the poorest social skills, and among those which patients have deficits most refractory to rehabilitation. To explore these questions, this study compared the symptom levels and performance on neuropsychological testing of 91 subjects with impaired and unimpaired social skills enrolled in a vocational rehabilitation program. After 10 weeks of rehabilitation and a supportive group treatment, social skills among a subsample of 41 subjects with initially impaired social skills were reassessed. Results indicate that subjects with initially impaired social skills had significantly higher levels of negative symptoms. However, multiple regression analysis revealed that cognitive impairments at intake, rather than level of negative symptoms, predicted improvement among subjects with initially impoverished social skills (R2 = .35). Results suggest that level of cognitive impairment is associated with the persistence of social skills deficits in schizophrenia.

Cognition Disorders↗

Cognitive deficits in schizophrenia. Prediction of symptom change for participators in work rehabilitation.

While recent studies have found that most patients with schizophrenia who participate in work rehabilitation experience symptom improvement, there appears to be a subgroup of patients whose symptoms remain stable or even worsen. The present study explores the hypothesis that cognitive impairment is one factor which reduces the clinical effectiveness of rehabilitation and accounts for a lack of improvement in some patients. To explore this question, performance on two neuropsychological tests was used to predict improvement on six symptom dimensions for 59 subjects who completed 5 months of work in a rehabilitation program. Discriminant function analyses indicated that quadratic combinations of standardized scores on the Wisconsin Card Sorting Test and thought disorder scores from the Gorham Proverbs Test could correctly classify 83% of subjects as improved or unimproved on a total symptom measure, and between 84% and 100% of subjects as improved or unimproved on various symptom dimensions, with greater levels of cognitive impairments at intake predicting no symptom improvement. Implications for the potential role of cognitive remediation in rehabilitation are discussed.

Adult↗

Upregulation of the macrophage scavenger receptor in response to different forms of injury in the CNS.

The monoclonal antibody 2F8 was used to localize the macrophage scavenger receptor by immunohistochemistry. In control adult mice, macrophage scavenger receptor expression in the brain was restricted to stromal and epiplexus macrophages of the choroid plexus, meningeal macrophages and to perivascular sites. Microglia did not express the receptor. In the developing mouse brain, macrophage scavenger receptor expression was high on meningeal macrophages and detectable on immature microglia in the supraventricular corpus callosum, cingulum, cavum septum and the periaqueductal area. In the aged mouse brain, the pattern of macrophage scavenger receptor expression was no different from that in the young adult brain. Macrophage scavenger receptor expression on resident microglia and recruited macrophages was detected 24 h after an intrahippocampal injection of either lipopolysaccharide or kainic acid. Macrophage scavenger receptor expression was also detected in microglia 3 days after optic nerve crush both in the nerve segment distal to the crush site and in the superior colliculus. These studies indicate a potential role for the macrophage scavenger receptor in the CNS in the clearance of debris during acute neuronal degeneration.

Animals↗

Concurrent validity of the cognitive component of schizophrenia: relationship of PANSS scores to neuropsychological assessments.

Cognitive symptoms of schizophrenia may represent a separate component of the disorder that is distinct from positive or negative syndromes. In a previous study, we reported a factor analysis of the Positive and Negative Syndrome Scale (PANSS) that revealed five components, one of which we labeled the Cognitive component. In the present study, we explored the validity of the PANSS Cognitive component by examining correlations between neuropsychological measures and the five factor-analytically derived PANSS scores for 147 subjects with diagnoses of schizophrenia or schizoaffective disorder. Higher scores on the PANSS Cognitive component were significantly correlated with poorer performance on all neuropsychological tests, including the Wisconsin Card Sorting Test (WCST), the Digit Symbol Substitution Task, the Slosson Intelligence Test, and the Gorham Proverbs Test. Multiple regression revealed that these test scores explained 37% of the variance in the Cognitive component score. Neuropsychological tests have very limited associations with the other PANSS components. These results suggest that the Cognitive component of the PANSS is a valid measure of cognitive deficits in schizophrenia, and they support the hypothesis that Cognitive impairment is a distinctive feature of schizophrenia independent of positive and negative syndromes.

Adult↗

Five-component model of schizophrenia: assessing the factorial invariance of the positive and negative syndrome scale.

A five-component model of schizophrenia has been presented by Kay and Sevy based upon an analysis of the Positive and Negative Syndrome Scale. Kay and Sevy found factorial validity for negative and positive syndromes, and they identified excitement, depressive, and cognitive components as well. They suggested that subtypes and syndromes can be mapped along dimensions presented in their model. The present study compares the five-component solution for a new sample of 146 subjects to a reanalysis of the Kay and Sevy data. Despite divergent demographic characteristics, the two samples produce similar dimensions. Correlations of component loadings and subject scores as well as confirmatory factor analysis are presented. Discussion focuses on points of agreement and important differences in the symptoms assigned to each component. How the dimensions relate to rationally derived models of positive and negative syndromes is reviewed, and implications for subtyping and other methods of examining the heterogeneity of schizophrenia are considered.

Adult↗

Vascular anomaly of the bundle of His associated with sudden death in a young man.

A 24-year-old black man suddenly collapsed while playing basketball. He died despite prompt cardiopulmonary resuscitation. The only abnormality found at autopsy was a vascular anomaly confined to the atrioventricular bundle of His within the cardiac conduction system. This arborizing collection of abnormal and increased number of blood vessels lacked both elastic fibers and smooth muscle, both of which were replaced by collagen. The number of vessels in the decedent's bundle of His was quantitatively compared with 117 normal controls by using a point-counting method. The percentage of points landing on vessels per total points counted (% VP/TP) in this man was 31% compared with 5.6 +/- 2.7% SD in the controls. No vascular malformations were seen elsewhere. This lesion has not been previously reported in the medical literature. This case confirmed the occasional usefulness of sampling the cardiac conduction system in sudden death with no obvious autopsy findings.

Adult↗

Progressive multifocal leukoencephalopathy in 47 HIV-seropositive patients: neuroimaging with clinical and pathologic correlation.

The authors investigated the spectrum of radiologic findings in a large series (n = 47) of patients seropositive to human immunodeficiency virus (HIV) 1 and with pathologically proved progressive multifocal leukoencephalopathy, to determine the characteristic imaging pattern of the disease. Thirty-six computed tomographic (CT) scans and 29 magnetic resonance (MR) imaging studies obtained in the 47 patients were retrospectively reviewed and correlated with pathologic and clinical findings. Contrast agents were used in 32 CT procedures and 13 MR imaging studies. Lesions typically were hypoattenuating on CT scans and were characterized by areas of increased signal intensity without mass effect on dual-echo MR images. Lesions most often involved periventricular and subcortical white matter in parietooccipital or frontal lobes. Fifteen patients had posterior fossa lesions, and disease was limited to the posterior fossa in two. Lesions were also in the corpus callosum (seven patients), thalamus (eight patients), and basal ganglia (seven patients). In comparison with CT, MR imaging demonstrated greater sensitivity for the extent and number of lesions.

Adolescent↗

Esophageal-atrial fistula resulting in systemic "meat and vegetable" emboli.

An 85-year-old demented woman died in the state hospital and her death was investigated by our office, based on allegations of neglect. At autopsy, a feeding catheter was found passed through an esophageal-atrial fistula into the left atrium. Fragments of striated muscle and plant wall (cellulose) embolized to the systemic organs including heart, kidney, and brain. Her dilated esophagus suggests a premortem esophageal motility disorder that contributed to the formation of the fistula. This is the first reported case of an esophageal-atrial fistula in the medical literature.

Aged↗

Sudden death due to intravascular hemolysis after bladder irrigation with distilled water.

A 45-year-old white man was hospitalized with gross hematuria, one month after cystoscopy and biopsy for the same complaint. The biopsy revealed cystitis glandularis. One day after admission, he developed seizures and died within hours. Autopsy, laboratory tests, and further questioning of the hospital staff showed that he died of acute hyponatremia and massive intravascular hemolysis after irrigating the bladder with sterile water. Two deep bladder ulcers with exposed veins served as the portals of entry. Until now, this fatal complication had been described only during transurethral surgery. Both a careful autopsy and hospital investigation is necessary to differentiate in-hospital natural death from iatrogenic fatality.

Death, Sudden↗

Fatal virus-associated hemophagocytic syndrome in a young adult producing nontraumatic splenic rupture.

A 24-year-old man with no previous medical history was admitted to a local hospital with pancytopenia after a recent "viral illness." During his hospitalization, he developed sudden abdominal distension and hypotension. Surgical exploration of his abdomen revealed a ruptured spleen. The spleen was removed, but the patient did not survive the operation. We investigated this unexpected and unexplained hospital death for any traumatic or iatrogenic injury. The cause of death after review of the clinical history, autopsy, and microscopic sections was virus-associated hemophagocytic syndrome (VAHS). VAHS consists of a generalized histiocytic proliferation and marked hemophagocytosis associated with a systemic viral infection. Clinically it presents as pancytopenia and organomegaly. This recently described entity is often confused with malignant histiocytosis. This is the first case report of VAHS producing nontraumatic splenic rupture, thus adding to the differential diagnosis of spontaneous splenic rupture and sudden natural death.

Adult↗

Positional asphyxiation in adults. A series of 30 cases from the Dade and Broward County Florida Medical Examiner Offices from 1982 to 1990.

Over a 9-year period, 30 cases of positional (or postural) asphyxia were identified in the Dade and Broward County (Florida) Medical Examiner Offices. The victims had an average age of 50.6 years with no significant sex or racial differences as compared with the general medical examiner population. Chronic alcoholism or acute alcohol intoxication was a significant risk factor in 75% of cases and these had an average postmortem ethanol concentration of 0.24 g%. Signs of mechanical asphyxiation (petechiae and/or combined lung weights greater than 900 g) were present in 93% of cases. Victims were commonly (43%) found in a restrictive position producing hyperflexion of the head and neck. Two deaths involved restraint vests ("poseys") in elderly, demented, wheel-chair-confined victims. Scene photographs of the undisturbed decedent are extremely helpful in confirming a suspicion of postional asphyxia.

Adolescent↗