M. Gary Hadfield

Endothelial fenestrations and other vascular alterations in primary melanoma of the central nervous system.

A primary malignant melanoma of the central nervous system is studied by light and electron microscopy. There were numerous endothelial fenestrae and basement membrane abnormalities in intrinsic tumor capillaries. It is felt that these vascular abnormalities may play a role in explaining why these tumors have an increased incidence of bleeding. No characteristic findings were encountered which would help distinguish this tumor from one of peripheral origin.

Progressive multifocal leukoencephalopathy with paramyxovirus-like structures, Hirano bodies and neurofibrillary tangles

SummaryWe have identified three structures that have not previously been reported in electron microscopic examinations of brain from patients with PML: 1. coiled nuclear bodies that may possibly represent tubular paramyxovirus nucleocapsids, 2. Hirano bodies and 3. Neurofibrillary tangles.The paramyxovirus-like material is interesting in view of reports of a transition between nuclear bodies and tubular paramyxovirus nucleocapsids and because of a possible interaction between syncytiogenic paramyxoviruses and Papova viruses in the pathogenesis of SSPE and PML. A study of the Hirano bodies in this case, taken in conjunction with the findings of others leads us to believe that these structures are formed from an overgrowth of neurofilaments. The presence of tangled masses of neurofilaments in the processes of neurons also seen in the present case is consistent with this hypothesis.

Ewing's Family of Tumors Involving Structures Related to the Central Nervous System: A Review

This review consolidates information gleaned from several case reports and larger series on Ewings sarcoma family of tumors (EFT) involving structures related to and found in the central nervous system (CNS). These tumors involve the skull, the spinal column, adjacent soft tissues, the meninges, and the brain. We have separated the cases by skull region and spinal column level, and we discuss the attendant differences in prognosis following treatment by neurosurgery, radiation, and chemotherapy. Light and electron microscopic features can be used to differentiate EFT from other small round blue cell tumors that involve the CNS (central primitive neuroectodermal tumor, lymphoma, etc.). Recent molecular and genetic findings in EFT provide new diagnostic methods. We conclude that EFT involving the CNS and adjacent structures is not so rare as previously stated and that the prognosis is more favorable, as a rule, than for the more common examples arising in the long bones and pelvis.

Acute hexachlorophene encephalopathy: Clinico-neuropathological correlation

SummaryThis is the first report of neuropathologic findings following oral ingestion of hexachlorophene in the human. The patient was a 7 year old boy who accidentally ingested 45 ml (approx.) of pHisoHex (hexachlorophene).Toxic reactions included nausea, vomiting, anorexia, diarrhea, decrease in visual acuity, blurred vision blindness, somnolence and disorientation. He developed cardiac arrhythmia, fever, isoelectric EEG and finally respiratory and cardiac arrest 61 h after admission.Autopsy findings showed interstitial myocarditis, pneumonitis and acute bronchiolitis. The brain was edematous. Light microscopy revealed mild diffuse vacuolization of white matter, occasional neuronal degeneration, most prominent on deepest layers of the visual cortex. Disintegration of myelin sheaths and necrosis of axon cylinders were present throughoutoptic pathways. Electron microscopy revealed large, empty extracellular and intramyelinic spaces formed by splitting and separation of the myelin lamellae. These changes are known to occur in experimental animals intoxicated with hexachlorophene, triethyltin, isonicotinic acid hydrazide and cuprizone. However, with respect to hexachlorophene, the localization of lesions to be optic pathways appears to be dependent upon an oral route of administration.

Caffeine and the olfactory bulb

Caffeine, a popular CNS stimulant, is the most widely used neuroactive drug. Present in coffee, tea, chocolate, and soft drinks as well as over-the-counter and prescription medications, it influences millions of users. This agent has achieved recent notoriety because its dependency consequences and addictive potential have been re-examined and emphasized. Caffeines central actions are thought to be mediated through adenosine (A) receptors and monoamine neurotransmitters. The present article suggests that the olfactory bulb (OB) may be an important site in the brain that is responsible for caffeines central actions in several species. This conclusion is based on the extraordinarily robust and selective effects of caffeine on norepinephrine (NE), dopamine (DA), and particularly serotonin (5HT) utilization in the OB of mice. We believe that these phonomena should be given appropriate consideration as a basis for caffeines central actions, even in primates. Concurrently, we review a rich rodent literature concerned with A, 5HT, NE, and DA receptors in the OB and related structures along with other monoamine parameters. We also review a more limited literature concerned with the primate OB. Finally, we cite the literature that treats the dependency and addictive effects of caffeine in humans, and relate the findings to possible olfactory mechanisms.

Anterior Horn Changes of Motor Neuron Disease Associated with Demyelinating Radiculopathy

Morphologic study of the spinal cord of a patient with generalized motor deficits revealed changes in the anterior horns characterized by the selective loss of large motor neurons, gliosis and the abnormal accumulation of 10 nm filaments which appeared as argyrophilic spheroids in the perikarya and axons of motor neurons. The ventral roots were predominantly affected and showed a variable loss of axons. The remaining axons displayed prominent onion-bulb formations, frequent axonal sprouting and occasionally evidence of active demyelination. The coexistence of a demyelinating motor radiculopathy and anterior horn changes simulating those of amyotrophic lateral sclerosis (ALS) may contribute to our understanding of the unresolved question of whether the neuronal perikaryon or its axon is the primary target in the pathogenesis of ALS. These observations also indicate that a rigid separation of pathogenetic mechanisms into neuronopathy, axonopathy and myelinopathy may not be always possible.

Granulomatous angiitis of the nervous system: a case report of long-term survival.

In 1977, a 61-year-old man developed an occipital hemorrhage, and a biopsy specimen revealed granulomatous angiitis of the nervous system. No concurrent infection or systemic vasculitis was present. After initial treatment with steroids and cyclophosphamide, the patient did well on chronic steroids alone for 4 years. He then independently stopped taking the steroids and suffered a second hemorrhage. Steroids were reinstated, and he did well for 3 more years before he experienced a third hemorrhage. Intravenous steroids were given acutely and tapered to a chronic maintenance dose. Although granulomatous angiitis of the nervous system usually causes death within weeks to months of the appearance of symptoms, the patient is still alive more than 12 years since the tissue-proven diagnosis. This unusually long survival is attributed to the continued use of steroids, even when the patient is asymptomatic.

Simultaneous HPLC Analysis of Catecholamines and Indoleamines in Mouse Brain Tissue Following Acetate Extraction and Treatment with Ascorbate Oxidase

Abstract A refined HPLC Method for the determination of monoamine levels in six brain regions is presented. Analyses are made for the olfactory tubercles, prefrontal cortex, septum, striatum, amygdala and hypothalamus of adult male ICR mice. This system permits the simultaneous analysis of norepinephrine, dopamine, serotonin and their major metabolites during a single run of approximately twenty-five minutes without prior clean-up of samples.

HPLC Determination of Monoamines in Rat Brain after Enzymatic Treatment with Ascorbate Oxidase and Sulfatase

Abstract The simultaneous analysis of norepinephrine, dopamine and serotonin along with their respective metabolites, MHPG, DOPAC and 5HIAA is accomplished in rat brain by using a recently developed HPLC technique. Sulfated MHPG is decongegated with sulfatase for detection purposes and endogenous ascorbate is diminished with ascorbate oxidase to reduce the front.

Is silicon a human carcinogen

Abstract This work reviews the literature concerned with the carcinogenesis of silicon in humans. Many of the studies deal with large cohorts of industrial workers. We sort these according to the type of silicon exposure and its consequences. An association of silica dust and fibers with lung and stomach cancers is widely reported and still other types of cancer are linked to silicon exposure. The risk is far greater if silicosis is present. On the other hand, still other studies show no association between silicon and cancer in humans, especially when confounding variables such as smoking and concomitant exposure to other carcinogens are taken into consideration. Though the literature is controversial, the weight of evidence nevertheless strongly supports an important role for silicon in the production of cancer in humans.