Muhammad Husain

The brain stem reticular formation in schizophrenia.

Post-mortem brain tissue was obtained from four patients with schizophrenia and five controls to study cell groups in the brain stem reticular formation. Cholinergic neurons in the pedunculopontine nucleus (PPN) and lateral dorsal tegmental nucleus (LDT) were labeled using nicotinamide adenosine dinucleotide phosphate (NADPH)-diaphorase histochemistry, while catecholaminergic neurons of the locus ceruleus (LC) were labeled immunocytochemically using an antibody to tyrosine hydroxylase. In schizophrenic patients, there were increased numbers of neurons in the PPN labeled by NADPH-diaphorase and reduced cell size in the LC. These results implicate the reticular formation as a possible pathophysiological site for at least some patients with schizophrenia. This also suggests that some of the deficits observed may be based on faulty neurodevelopment.

Prognostic factors in patients with surgically resected stages I and II non-small cell lung cancer

BACKGROUND About one-third to one-half of patients with early stages of non-small cell lung cancer (NSCLC) succumb to their disease. In this study, we attempted to identify prognostic factors that predict outcome in patients with stages I and II NSCLC. METHODS A retrospective evaluation of 454 patients with surgically resected stages I and II NSCLC was performed to determine the impact of various clinical, laboratory, and pathological factors on patient outcome such as overall survival (OS) and event-free survival (EFS). RESULTS Patients older than 65 years had shorter EFS and OS than younger patients (p = 0.002). Patients with preoperative hemoglobin less than or equal to 10 g% had shorter EFS and OS compared to patients with a hemoglobin greater than 10 g% (p = 0.001). Expectedly, OS and EFS were shorter in patients with stage II as compared to stage I patients (p < 0.001). In a multivariate analysis, age, hemoglobin level, and stage remain significant predictors for EFS and OS. CONCLUSIONS Older age, anemia, and higher stage are important prognostic factors in patients with surgically resected stage I and II NSCLC.

An in vitro 1H nuclear magnetic resonance study of the temporoparietal cortex of Alzheimer brains

The concentrations of selected metabolites in the posterior temporoparietal cortex of 13 Alzheimers diseased (AD) and four nondemented postmortem brains (of individuals between the ages of 63 and 95) were determined using high-resolution 1H nuclear magnetic resonance (NMR) spectroscopy. The estimates for glutamate and inositol for AD brains did not show any statistically significant difference (P>0.05) from those for the nondemented brains. The putative neuronal marker N-acetyl aspartate (NAA), creatine, and GABA were decreased in AD brains compared with the nondemented brains. The estimates for creatine, glutamate, and GABA showed significant linear correlations with those of NAA. Creatine, glutamate, GABA, and NAA appeared to be negatively correlated with the neurofibrillary tangles. Our results support a neuronal loss in the posterior temporoparietal cortices of AD brains.

Microbubble Potentiated Ultrasound as a Method of Stroke Therapy in a Pig Model: Preliminary Findings

PURPOSE Low-frequency ultrasound (LFUS) with intraarterial or intravenous microbubbles can recanalize thrombosed dialysis grafts and arteries. A similar method for declotting intracranial arteries in an animal model has been developed. MATERIALS AND METHODS Swine underwent selective cerebral angiography, and 1 mL of 2-6 hour old clot was placed in one ascending pharyngeal artery and rete mirabile. This occluded the primary brain blood supply from the rete mirabile in the base of the skull. Human albumin octafluoropropane microbubbles were injected through the same catheter in 0.5-1.0-mL doses for a total of 4.5 mL in 21 minutes. Transcutaneous pulsed-wave 1-MHz ultrasound was administered through a temporal approach using 2.2 W/cm(2). Repeated angiography was performed through 24 minutes. Saline controls underwent an identical process on the opposite side. Declotting was graded on a scale of 0-4, and flow used the 0-3 thrombolysis in myocardial infarction (TIMI) scale. Success was defined as declotting of grade >/= 3 (>70% clearing) with flow of >/= 2. RESULTS Seven pigs received 14 declotting sequences. Average clot age was 217 minutes. Average declotting score was 3.1, and flow was 2.1 for microbubbles and 1.4 and 0.1 for saline controls, P =.016 in each. Success occurred with microbubbles in six of seven attempts and in controls in zero of seven attempts, P =.031. CONCLUSIONS LFUS with microbubble augmentation rapidly lyses intracranial clot and restores flow at ultrasound ranges similar to those required in humans. Further development of this possible acute stroke therapy is justified.

A role for telomeric and centromeric instability in the progression of chromosome aberrations in meningioma patients

The primary chromosome aberration in meningiomas is monosomy or deletion of chromosome 22. Common secondary aberrations include losses or deletions of chromosomes 1p, 14q, and 10q and unstable chromosome aberrations including rings, dicentrics, and telomeric associations. Despite the analysis of several hundred tumors by cytogenetic and molecular techniques, the mechanisms involved in the progression of chromosome aberrations in meningioma remain poorly understood.

Decreased mesopontine choline acetyltransferase levels in schizophrenia. Correlations with cognitive functions.

The objective was to replicate a reported decrease of choline acetyltransferase (ChAT) in the mesopontine tegmentum of deceased schizophrenics and to see if such a decrease is related to their cognitive status as measured during life. Rigorous antemortem psychiatric evaluations were performed on our large population of schizophrenic patients. Mesopontine tissue was collected promptly following death from eight of these patients, from an additional five schizophrenics without systematic premortem psychiatric evaluation, and from control subjects. ChAT content of this brain tissue was determined using Western immunoblot analysis. There were 13 schizophrenic patients and 8 control subjects. The mean age of subjects in the two groups was similar (64 +/- 9 yr vs 63 +/- 10 yr). Even in the face of reduced post mortem intervals in the patients with schizophrenia, mesopontine tegmental ChAT concentrations were depressed by 70% in schizophrenic patients (1.28 +/- 1.74 vs 4.39 +/- 3.20 ng ChAT/micrograms tissue protein, P < 0.01), and correlated with orientation and reasoning (rs = 0.90 and 0.98, respectively) in those subjects assessed antemortem. Mesopontine ChAT concentrations are depressed in schizophrenia and correlate significantly with measures of cognitive performance in patients with this disorder.

Chromosome aberrations in four ependymomas

Cytogenetic analysis of short-term cultures from three untreated and one recurrent ependymoma revealed clonal aberrations in three of the four tumors. A posterior fossa ependymoma from a 3-year-old male patient showed trisomy 11 as the sole clonal chromosome aberration. A recurrent spinal ependymoma from a 35-year-old male showed hypertriploid clones with abnormalities involving chromosomes 1p11,7q21, and 10p13. A 62-year-old male patient with a cerebellar ependymoma showed a hypodiploid stem-cell line with clonal structural aberrations of both the long and short arms of chromosome 1, an interstitial deletion of 2q, trisomy 7, and monosomy for chromosomes 11, 13, and 16. A 3-year-old female patient with posterior fossa ependymoma showed a normal 46,XX karyotype. Chromosome 1 aberrations appear to be the most consistent finding in this small series of tumors, with the net loss or rearrangement of chromosome 1 pter-->p22 material from two of the four tumors. These findings, in addition to a previously published case [1], suggest a possible role for genes on the short arm of chromosome 1 in the cytogenetic evaluation of ependymomas.

Multiple intraparenchymal brain plasmacytomas with spontaneous intratumoral hemorrhage

The case of a patient with two intraparenchymal brain plasmacytomas without cranial or dural attachment and with intratumoral hemorrhage is presented. Computed tomographic (CT) findings are described. Autopsy revealed two discrete intraparenchymal plasmacytomas with intratumoral hemorrhage, one cerebral and one cerebellar. There have been few case reports of brain plasmacytoma without cranial or dural attachment, and this case of multiple such intracranial, intraparenchymal plasmacytomas with hemorrhage is certainly unique. Intratumoral hemorrhage with intracranial plasmacytoma is extraordinarily rare. The literature of intracranial involvement with myeloma and plasmacytoma and the CT appearance of intracranial plasmacytoma are surveyed.

Neonatal Subependymal Giant Cell Astrocytoma

Subependymal giant cell astrocytoma (SEGCA) is a benign, slow-growing glial tumor that manifests with signs and symptoms of obstructive hydrocephalus most often in adolescent patients with tuberous sclerosis complex (TSC). Neonatal highly aggressive SEGCA is very rare. We report a 5-month-old child with TSC presenting with a cystic mass lesion in the left frontal lobe as well as multiple other periventricular masses. After initial conservative treatment, the child was readmitted with intractable seizures, a massive increase in the size of the left frontal lobe tumor and obstructive hydrocephalus. Despite surgical interventions, the child succumbed to the intracranial lesions. In this report, we discuss the challenges of managing SEGCA and the importance of further studies, including genetic studies, that may lead to a better understanding of its pathophysiology.

Congenital Aneurysmal Hemorrhage and Astrocytoma in an Infant

The authors present the unusual case of an infant who presented at 4 weeks of age with a spontaneous intracerebral hemorrhage due to rupture of a congenital left middle cerebral artery aneurysm. He recovered only to present at 4 months of age with a right frontoparietal desmoplastic cerebral astrocytoma of infancy. The association of brain tumor and aneurysm is discussed, as are the cytogenetic findings associated with this rare form of benign astrocytoma.