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Biomedical subjects

R W Price

Publications and source records attributed to R W Price.

At least 91 records · Page 5Linked to original sources
PubMed1986

Thrombotic cerebral vasculopathy associated with herpes zoster.

We describe the clinical, radiographic, and pathological findings in 3 patients with large-vessel cerebral vasculopathy following herpes zoster. Two of the patients were studied at postmortem examination, and a brain biopsy was performed in the third. Each of the 3 patients suffered thrombotic occlusions of large vessels without notable inflammatory or granulomatous changes following trigeminal or segmental herpes zoster infection. In the 2 autopsied patients, varicella-zoster virus (VZV) antigens were detected by immunoperoxidase staining within the media of the affected cerebral arteries. Little or no inflammation was associated with the foci of the VZV antigens. These studies provide evidence that the vasculopathy following herpes zoster may result from direct VZV infection of the artery and the in situ thrombosis can develop within the infected vessels in the absence of clear inflammatory vasculitis.

Adult↗
PubMed1986

Cerebral toxoplasmosis complicating the acquired immune deficiency syndrome: clinical and neuropathological findings in 27 patients.

We reviewed the clinical, neuroradiological, and serological findings in 27 patients with cerebral toxoplasmosis complicating the acquired immune deficiency syndrome, 19 of whom were also analyzed neuropathologically. The clinical manifestations of this disorder varied, ranging from headache and fever to coma. However, the characteristic presentation included focal neurological symptoms and signs, usually of subacute onset. In addition, two-thirds of the patients exhibited more generalized cerebral dysfunction with confusion and lethargy. The computed tomographic (CT) scan most commonly revealed ring contrast enhancement, which appeared to correlate best with the histological presence of vascular proliferation and inflammation surrounding the abscesses. However, in 5 patients the CT scan revealed either homogeneous enhancement or no enhancement, and in 3 patients the scans were negative. In general, CT scans underrepresented the number of lesions eventually documented pathologically. Double-dose contrast administration and preliminary experience with magnetic resonance imaging suggested that these techniques were superior to standard CT scanning in detecting Toxoplasma lesions. All patients were seropositive for IgG antibody against Toxoplasma gondii in blood, both before the onset of illness and at the time of presentation, although titers in some patients were as low as 1:8 and most patients did not exhibit rising titers. Prompt therapy resulted in rapid clinical improvement, documented by CT scan, associated with the development of an organizing tissue response in the host and elimination of free organisms. Response to treatment was sufficiently rapid in most patients to allow a trial of therapy as the favored approach to diagnosis.

Acquired Immunodeficiency Syndrome↗
PubMed1986

The AIDS dementia complex: I. Clinical features.

Of 70 autopsied patients with the acquired immune deficiency syndrome (AIDS), 46 suffered progressive dementia that was frequently accompanied by motor and behavioral dysfunction. Impaired memory and concentration with psychomotor slowing represented the most common early presentation of this disorder, but in nearly one half of the patients either motor or behavioral changes predominated. Early motor deficits commonly included ataxia, leg weakness, tremor, and loss of fine-motor coordination, while behavioral disturbances were manifested most commonly as apathy or withdrawal, but occasionally as a frank organic psychosis. The course of the disease was steadily progressive in most patients, and at times was punctuated by an abrupt acceleration. However, in 20% of patients a more protracted indolent course was observed. In the most advanced stage of this disease, patients exhibited a stereotyped picture of severe dementia, mutism, incontinence, paraplegia, and in some cases, myoclonus. The high incidence and unique clinical presentation of this AIDS dementia complex is consistent with the emerging concept that this complication is due to direct brain infection by the retrovirus that causes AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1986

The AIDS dementia complex: II. Neuropathology.

In order to define the histopathological substrate of the dementia that frequently complicates the acquired immune deficiency syndrome (AIDS), we analyzed the neuropathological findings in 70 autopsied adult AIDS patients, 46 of whom had suffered clinically overt dementia. Less than 10% of the brains were histologically normal. Abnormalities were found predominantly in the white matter and in subcortical structures, with relative sparing of the cortex. Their frequency and severity generally correlated well with the degree and duration of clinical dementia. Most commonly noted was diffuse pallor in the white matter, which in the pathologically milder cases was accompanied by scanty perivascular infiltrates of lymphocytes and brown-pigmented macrophages, and in the most advanced cases by clusters of foamy macrophages and multinucleated cells associated with multifocal rarefaction of the white matter. However, in nearly one third of the demented cases the histopathological findings were remarkably bland in relation to the severity of clinical dysfunction. In addition, similar mild changes were noted in over one half of the nondemented patients, consistent with subclinical involvement. Vacuolar myelopathy was found in 23 patients and was generally more common and severe in patients with advanced brain pathology. Evidence of cytomegalovirus (CMV) infection was noted in nearly one quarter of the brains and was associated with a relative abundance of microglial nodules, but correlated neither with the major subcortical neuropathology nor with the clinical dementia, indicating that CMV infection likely represented a second, superimposed process. This study establishes the AIDS dementia complex as a distinct clinical and pathological entity and, together with accumulating virological evidence, suggests that it is caused by direct LAV/HTLV-III brain infection.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Neuropathology of acquired immunodeficiency syndrome (AIDS): an autopsy review.

In the brains and spinal cords of 153 adult patients dying with acquired immunodeficiency syndrome (AIDS) at New York and Memorial Hospitals a subacute encephalitis with multinucleated cells was present in 28% of all patients. This encephalitis was characterized by multinucleated cells primarily located in the white matter and associated with myelin pallor and sparse infiltrates of rod cells, macrophages, gemistocytic astrocytes and lymphocytes. The incidence per 12 month period ranged from 0 to 43% and significantly increased between 1983-84 (14%) and 1984-85 (43%). Recent virologic and pathologic studies suggest that this encephalitis may be caused by direct LAV/HTLV-III infection of the central nervous system (CNS). Cytomegalovirus encephalomyelitis and toxoplasmosis were the most common opportunistic infections (26% and 10%, respectively). Progressive multifocal leukoencephalopathy, herpes simplex ventriculitis, varicella-zoster leukoencephalitis and fungal infections were infrequent (less than 3% each). A nonspecific encephalitis with microglial nodules and with mild white matter changes occurred in 17%, vacuolar myelopathy in 29% and CNS lymphoma in 6%. Less than 20% of patients had either normal brains or terminal metabolic encephalopathies. This survey shows that neuropathologic complications of AIDS are frequent. Infections are the most common complication and are caused by probable LAV/HTLV-III infection, or by opportunistic organisms.

Acquired Immunodeficiency Syndrome↗
PubMed1986

AIDS encephalopathy.

It is now recognized that AIDS is frequently complicated by a progressive encephalopathy characterized by dementia and motor dysfunction. This article reviews the early and late clinical features of this disorder and examines current evidence that it is due to direct brain infection by the retrovirus that causes AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Neurobiology of human herpesvirus infections.

Critical to the adaptation of herpes simplex virus type 1 (HSV-1) to its human host is a complex interaction with the peripheral nervous system. The "life cycle" of the virus depends not only on axoplasmic transport which carries virus to and from the infected ganglia, but also on variable expression of the virus within ganglionic neurons. During latency, limited viral gene expression allows the virus to persist undetected by immune defenses, while intermittent reactivation, perhaps triggered by metabolic perturbation of these neurons, leads to production of new virus with subsequent transmission. In parasitizing its host, the virus exploits a number of the specialized properties of neurons and supporting cells. A second important type of HSV-1 infection involves the central nervous system (CNS). Herpes encephalitis, an uncommon yet severe disease, represents an aberrant interaction of the virus and host that is at present poorly understood. This review examines current understanding of HSV-1 infections of both the peripheral and CNS from a neurobiological perspective.

Herpesviridae↗
PubMed1985

Vacuolar myelopathy pathologically resembling subacute combined degeneration in patients with the acquired immunodeficiency syndrome.

Twenty of 89 consecutive patients with the acquired immunodeficiency syndrome (AIDS) in whom autopsies were performed over a 3 1/2-year period had a vacuolar myelopathy that was most severe in the lateral and posterior columns of the thoracic cord. Light and electron microscopy showed that vacuoles were surrounded by a thin myelin sheath and appeared to arise from swelling within myelin sheaths. Signs and symptoms referable to the spinal-cord lesions, including paraparesis, often accompanied by spasticity or ataxia (or both), were present in all five patients with marked pathological changes, in five of seven patients with moderate changes, and in two of eight patients with mild changes. Fourteen patients were demented. The clinical presentation was sufficiently distinctive to provide a guide for antemortem diagnosis. Possible causes of the vacuolar changes include uncharacterized viral infection or a metabolic derangement related to selective nutritional deficiency.

Acquired Immunodeficiency Syndrome↗
PubMed1985

HTLV-III infection in brains of children and adults with AIDS encephalopathy.

Unexplained debilitating dementia or encephalopathy occurs frequently in adults and children with the acquired immune deficiency syndrome (AIDS). Brains from 15 individuals with AIDS and encephalopathy were examined by Southern analysis and in situ hybridization for the presence of human T-cell leukemia (lymphotropic) virus type III (HTLV-III), the virus believed to be the causative agent of AIDS. HTLV-III DNA was detected in the brains of five patients, and viral-specific RNA was detected in four of these. In view of these findings and the recent demonstration of morphologic and genetic relatedness between HTLV-III and visna virus, a lentivirus that causes a chronic degenerative neurologic disease in sheep, HTLV-III should be evaluated further as a possible cause of AIDS encephalopathy.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Alteration of tyrosine hydroxylase activity in PC12 cells infected with herpes simplex virus type 1.

During infection with herpes simplex virus type 1 (HSV-1) the activity of tyrosine hydroxylase (TH) in PC12 pheochromocytoma cells was initially depressed reaching a nadir at 6 hours post-inoculation, but recovered rapidly with a return to baseline activity by 8 to 9 hours post-inoculation. Subsequently, TH activity again fell with a second more variable rise in activity occurring at 24 hours post-inoculation. Studies with metabolic inhibitors and 2 temperature-sensitive viral mutants indicated that these alterations of TH activity were dissociated from morphological cytopathology and likely required expression of "late" viral gene products. Immunotitration using anti-TH antibody suggested that early depression of TH activity resulted principally from loss of enzyme protein rather than simple enzyme inactivation, and that reconstitution of activity at 9 hours was related to augmented enzyme synthesis. These observations illustrate the complexity of perturbed cellular metabolism during HSV-1 infection and suggest involvement of two unexpected processes: alteration of a specialized cell function as a result of viral genes expressed late in the replicative cycle, and augmented synthesis of a cell-coded gene product during the course of infection.

Cells, Cultured↗
PubMed1984

Diagnostic imaging of herpes simplex virus encephalitis using a radiolabeled antiviral drug: autoradiographic assessment in an animal model.

To develop a new approach to the diagnosis of herpes simplex encephalitis, we used a radiolabeled antiviral drug, 2'-fluoro-5-methyl-1-beta-D-arabinosyluracil labeled with carbon 14 ([14C]FMAU), as a probe for selectively imaging brain infection in a rat model by quantitative autoradiography. A high correlation was found between focal infection, as defined by immunoperoxidase viral antigen staining, and increased regional [14C]FMAU uptake in brain sections. Two potential sources of false-positive imaging were defined: high concentrations of drug in the choroid plexus because of its higher permeability compared with brain, and drug sequestration by proliferating uninfected cell populations. Our results support the soundness of the proposed strategy of using a labeled antiviral drug that is selectively phosphorylated by herpes simplex virus type 1 thymidine kinase in conjunction with scanning methods for human diagnosis, and also define some of the factors that must be taken into account when planning clinical application.

Animals↗
PubMed1984

Early inhibition of acetylcholinesterase and choline acetyltransferase activity in herpes simplex virus type 1 infection of PC12 cells.

Early in the course of productive Herpes simplex virus type 1 (HSV-1) infection of PC12 cells, activities of both acetylcholinesterase (AChE) and choline acetyltransferase (CAT) fell. Studies using metabolic inhibitors and a temperature-sensitive mutant of the virus suggested that the decline in activities of both enzymes was associated with events occurring early in the replicative cycle related to expression of the immediate-early (alpha) group of viral polypeptides. HSV-1 gene products thus may alter specialized cell functions well before the production of viral progeny and initiation of cell lysis. The early clinical manifestations of nervous system viral infection may reflect focal metabolic disturbance rather than, or in addition to, simple cell death.

Acetylcholinesterase↗
PubMed1984

Enhanced regional uptake of 2-deoxy-D-[14C]glucose in focal herpes simplex type 1 encephalitis: autoradiographic study in the rat.

We used the 2-deoxy-D-[14C]glucose (14C-DG) quantitative autoradiographic method to assess regional glucose metabolism in rats with focal herpes simplex virus type 1 (HSV-1) encephalitis. High 14C-DG uptake was detected in infected brain structures of both immunocompetent and immunosuppressed animals, likely as a result of increased glucose utilization by infected glia and neurons. Inflammatory infiltrates did not show augmented 14C-DG tissue uptake, and indeed regional isotope uptake declined in the later stages of infection as viral replication waned and necrosis developed. 14C-DG uptake was also depressed in uninfected brain regions that received afferents from the infected visual pathway.

Animals↗
PubMed1983

Progressive multifocal leukoencephalopathy: a burnt-out case.

A patient with Hodgkin's disease developed progressive multifocal leukoencephalopathy (PML), documented by brain biopsy to be associated with JC virus infection. His disease progressed over several months, resulting in severe neurological deficit, but then stabilized with little or no further clinical progression during the remaining year of his life. Histopathological evaluation of the brain at autopsy supported the clinical impression that brain infection was arrested. Whereas the brain biopsy exhibited the histological features of active PML including giant bizarre astrocytes, at postmortem examination brain lesions appeared inactive, with regression of astrocytic changes and elimination of oligodendroglial inclusions. Similarly, JC virus antigen, present in the brain biopsy, was not detected in the autopsied brain. This case provides further evidence that PML is not invariably fatal and that clinical and cytological remission can occur.

Adult↗