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Biomedical subjects

H R Brashear

Publications and source records attributed to H R Brashear.

35 records · Page 2Linked to original sources

Anticerebellar antibodies in neurologically normal patients with ovarian neoplasms.

Several groups of investigators have confirmed the occurrence of antibodies to Purkinje and other cerebellar neuronal populations in the serum and spinal fluid of patients with paraneoplastic cerebellar degeneration. Although this antibody response suggests that paraneoplastic cerebellar degeneration may have an autoimmune basis, it is not known what role anticerebellar antibodies play in the pathogenesis of this disorder or whether the presence of antibodies invariably results in cerebellar injury. We identified 3 patients with ovarian malignancies in whom high titers of circulating anticerebellar antibodies were present without clinical evidence of cerebellar disease. We followed these patients clinically and serologically until their deaths from their neoplasms. All 3 patients remained neurologically normal. In 2 of the patients, anticerebellar antibodies persisted at high titer. CSF obtained from 1 of these patients postmortem did not contain detectable levels of anticerebellar antibody, but histopathologic examination of her cerebellum revealed patchy loss of Purkinje cells. In the 3rd patient, antibody titers fell with removal of the primary tumor and chemotherapy but did not rise with tumor recurrence. Indirect immunofluorescence did not reveal anticerebellar antibodies in the serum or CSF of other patients with neoplasms, patients with other cerebellar disease, or normal controls. The present study demonstrates that patients with ovarian malignancies may occasionally develop antibodies that react with cerebellar neuronal antigens and can maintain this antibody response for protracted periods of time without clinically evident cerebellar injury. Tumor recurrence may not be accompanied by rise in titers of anticerebellar antibodies.

Aged↗

Immunoperoxidase labelling of rat brain sections with sera from patients with paraneoplastic cerebellar degeneration and systemic neoplasia.

Sera from patients with systemic cancer found by immunofluorescence staining to have antibodies to human cerebellar cell populations were reacted with vibratome sections of rat cerebellum and examined by peroxidase-antiperoxidase (PAP) methods. Seven patients with clinically or pathologically confirmed paraneoplastic cerebellar degeneration and two neurologically normal patients with high titers of anticerebellar antibodies were studied. Sera from all antibody-positive patients, but not from controls, produced intense staining of brain sections. Sera from patients with ovarian adenocarcinoma reacted predominantly with Purkinje cells and neurons within brainstem nuclei. Sera from patients with oat cell carcinoma and one patient with ductal carcinoma of the breast produced nuclear and cytoplasmic staining of neurons throughout the central nervous system. Serum from a patient with Hodgkin's disease labeled the peripheries of Purkinje cells and Golgi II cells. Serum from a patient with mixed mesodermal sarcoma of the ovary labeled Purkinje cells, basket cells, and scattered astrocytes. Staining of extraneural tissues was not observed. This study confirms the presence of antineural antibodies in patients with systemic neoplasia with and without paraneoplastic cerebellar degeneration and suggests that the antigens recognized by this antibody response may vary with the associated neoplasm.

Adenocarcinoma↗

The distribution of neuritic plaques and acetylcholinesterase staining in the amygdala in Alzheimer's disease.

The relationship between neuritic plaque formation in Alzheimer's disease and cholinergic innervation of brain regions is unclear. Many neuritic plaques are found in the amygdala, which also receives dense cholinergic innervation from the ventral forebrain, predominantly to the basolateral complex. To determine whether the regional distribution of neuritic plaques is related to the pattern of cholinergic innervation, we studied serial sections through the amygdala of four patients with Alzheimer's disease and four neurologically normal patients. We compared acetylcholinesterase reactivity, neuritic plaques stained with thioflavine S, and cytoarchitectural features in adjacent sections. Neuritic plaque counts were high in most amygdaloid nuclei but were significantly lower in the most acetylcholinesterase-positive region, the lateral portion of the basal nucleus of the amygdala. Acetylcholinesterase reactivity was reduced in the Alzheimer's cases, but the basal nucleus was easily recognized by the characteristic large neurons. The morphology of neuritic plaques also differed in the various regions. These results show that neuritic plaques occur to varying degrees in all nuclei of the amygdala, but are significantly less frequent in the region that receives the most prominent innervation from the cholinergic ventral forebrain.

Acetylcholinesterase↗

Stability of posterior fracture-dislocations of the hip. Quantitative assessment using computed tomography.

The treatment of a posterior fracture-dislocation of the hip is strongly influenced by the surgeon's assessment of stability of the hip after the dislocation has been reduced. Stability is inversely related to the size of the posterior acetabular fragment. Computed tomography was used to measure the size of the fracture fragment in nine cadavera of adults. Progressive increments of bone were removed from the posterior part of the acetabular wall in sixteen hips. After each osteotomy, the hip was tested for stability and was measured by computed tomography until it became unstable. All hips from which less than 20 per cent of the posterior part of the acetabular wall was removed were stable, while those from which more than 40 per cent was removed were unstable.

Acetabulum↗

Cholinergic and GABAergic afferents to the olfactory bulb in the rat with special emphasis on the projection neurons in the nucleus of the horizontal limb of the diagonal band.

We have examined the location of cholinergic and GABAergic neurons that project to the rat main olfactory bulb by combining choline acetyltransferase (ChAT) and glutamic acid decarboxylase (GAD) immunohistochemistry with retrograde fluorescent tracing. Since many of the projection neurons are located in subcortical basal forebrain structures, where the delineation of individual regions is difficult, particular care was taken to localize projection neurons with respect to such landmarks as the ventral pallidum (identified on the basis of GAD immunoreactivity), the diagonal band, and medial forebrain bundle. In addition, sections with fluorescent tracers or immunofluorescence were counterstained for Nissl substance in order to correlate tracer or immunopositive neurons with the cytoarchitecture of the basal forebrain. The majority of the cholinergic bulbopetal neurons are located in the medial half of the nucleus of the horizontal limb of the diagonal band (HDB), whereas only a few are located in its lateral half. A substantial number of cholinergic bulbopetal cells are also found in the sublenticular substantia innominata. A small number of cholinergic bulbopetal neurons, finally, are located in the ventrolateral portion of the nucleus of the vertical limb of the diagonal band. At the level of the crossing of the anterior commissure, approximately 17% of the bulbopetal neurons in the HDB are ChAT-positive. The noncholinergic bulbopetal cells are located mainly in the lateral half of the HDB. GAD-containing bulbopetal neurons are primarily located in the caudal part of the HDB, especially in its lateral part. About 30% of the bulbopetal projection neurons in the HDB are GAD-positive. A few GAD-positive bulbopetal cells, furthermore, are located in the ventral pallidum, anterior amygdaloid area, deep olfactory cortex, nucleus of the lateral olfactory tract, lateral hypothalamic area, and tuberomamillary nucleus. The topography of bulbopetal neurons was compared to other projection neurons in the HDB. After multiple injections of fluorescent tracer in the neocortex, retrogradely labeled neurons were concentrated in the most medial part of the HDB, while neurons projecting to the olfactory and entorhinal cortices were located in the ventral part of the HDB. These results show that the cells of the HDB can be divided into subpopulations based upon projection target as well as transmitter content. Furthermore, these subpopulations correspond, at least to a considerable extent, to areas that can be defined on cyto- and fibroarchitectural grounds.

Animals↗

Distribution of GABAergic and cholinergic neurons in the rat diagonal band.

GABAergic neurons are coextensive with cholinergic neurons in the medial septum-diagonal band complex. Serial sectioning, sequential staining and double immunofluorescence techniques employing antibodies to glutamate decarboxylase and choline acetyltransferase revealed the distribution of these transmitter-specific neurons in the rat. Morphologically, the two types of neurons appear similar, in that they are predominantly large multipolar cells, but they are characterized by different, overlapping distributions in the diagonal band. Glutamate decarboxylase-positive cells are scattered throughout the nucleus of the vertical limb of the diagonal band, while choline acetyltransferase-positive neurons are more numerous medially and are distributed in groups corresponding to the dorsal and ventral aspects of the nucleus. In the rostral parts of the nucleus of the horizontal limb of the diagonal band, the choline acetyltransferase-positive cells tend to be located medially, whereas caudally they spread dorsal to the nucleus to become continuous with other large cholinergic neurons in the ventral pallidum and sublenticular substantia innominata. The large majority of glutamate decarboxylase-positive neurons remain in a more ventral and lateral position within the nucleus of the horizontal limb and are particularly numerous just lateral to the diagonal band fibers as they join the medial forebrain bundle. Cholinergic neurons were estimated to be about two times more numerous than GABAergic neurons. Approximately 1% of the choline acetyltransferase-positive neurons were also glutamate decarboxylase-positive in double immunofluorescence studies, but not in sequentially stained or serial sections.

Acetylcholine↗

Encephalomyeloneuritis simulating Guillain-Barré syndrome.

A patient with encephalomyeloneuritis (EMN) had clinical and laboratory features consistent with severe acute inflammatory polyneuropathy (Guillain-Barré syndrome). CNS involvement was suggested clinically only by transient downbeat nystagmus and by contraction of tensor fascia lata on plantar stimulation. Postmortem examination revealed pathologic changes typical of EMN without systemic neoplasm. Clinical manifestations of the profound central pathology were largely obscured by severe radiculoneuropathy. Pathologic verification of clinically diagnosed inflammatory polyneuropathy is unusual, and CNS disease, therefore, may be more frequent than appreciated, especially in clinical "variants."

Adult↗

Sacral abnormalities--computed tomography versus conventional radiography.

Seventeen examples of different pathologic conditions, including malignant and benign tumors, and inflammatory, traumatic, and congenital lesions involving the sacrum, are presented. The value of computed tomography is compared with that of conventional methods with respect to diagnostic evaluation and clinical management of these patients. Computed tomography proved to be more accurate in delineating the extent of bony lesions, diagnosing adjacent soft tissue involvement, evaluating the progress of a lesion, and defining the approach for biopsy of a sacral lesion or determining the feasibility of surgery.

Adolescent↗

Pure word deafness after bilateral primary auditory cortex infarcts.

In pure word deafness, comprehension and repetition of speech are impaired, but reading, writing, and spontaneous speech are preserved. Pure word deafness is distinguished from generalized auditory agnosia by the preserved ability to recognize environmental sounds. We examined a patient with pure word deafness associated with bilateral infarctions of the primary auditory cortex, who could use auditory affective intonation to enhance comprehension. The primary auditory cortex seems to be essential for comprehending speech, but comprehension of nonverbal sounds and affective prosody may be mediated by other cerebral structures such as the auditory association cortex.

Agnosia↗

Antibodies to cerebellar Purkinje cells in patients with paraneoplastic cerebellar degeneration and ovarian carcinoma.

Sera from 2 patients with ovarian carcinoma and paraneoplastic cerebellar degeneration confirmed postmortem were reacted with frozen sections of human cerebellum and stained using indirect immunofluorescence methods. Both sera produced bright cytoplasmic staining of Purkinje cells and of neurons within deep cerebellar nuclei. Titration of these sera to end point revealed staining at final dilutions of 1:640 and 1:2,560, respectively. Neither of these sera reacted with sections of human cerebrum, basal ganglia, spinal cord, peripheral nerve, lung, liver, kidney, or ovary. Staining of Purkinje cells was not obtained with sera from 34 normal, healthy controls, 5 patients with oat cell carcinoma of the lung, 6 patients with inflammatory central nervous system disorders, or 12 of 14 neurologically normal patients with ovarian carcinoma. Sera from 2 neurologically normal patients with ovarian carcinoma, however, produced staining of Purkinje cells and deep nuclei similar to that obtained with sera from patients with paraneoplastic cerebellar degeneration. The present study documents the presence of antibodies to Purkinje cells in patients with ovarian carcinoma and cerebellar degeneration and demonstrates that development of these antibodies may antedate the onset of clinically evident cerebellar degeneration.

Antibodies↗

Pseudodiphtheria: prominent pharyngeal membrane associated with fatal paraquat ingestion.

Three patients presented with prominent pharyngeal membranes suggestive of tonsillar-pharyngeal diphtheria, but later found to be caused by oral ingestion of the herbicide paraquat. In all cases appropriate therapy was delayed because of failure to include paraquat in the differential diagnosis: Paraquat ingestion should be considered in all patients with prominent tongue and pharyngeal membranes.

Adult↗

Computed tomography of acetabular fractures.

Computed tomography (CT) is helpful in delineating the extent and configuration of fractures of the acetabulum. These injuries are frequently complex, and the precise pathological anatomy is not easily demonstrated by conventional radiographs. In some cases CT will reveal a fracture which may not be seen on the radiograph. In addition, the extent of soft-tissue damage and joint involvement is precisely demonstrated with CT. Five cases are presented to illustrate the value of CT in acetabular fractures.

Acetabulum↗

Tuberculosis of the wrist: a report of ten cases.

Ten patients with tuberculosis of the wrist are reported. In three, the disease was limited to the tenosynovium and these patients were treated by synovectomy. Seven patients had disease involving the carpal bones. In six of these an arthrodesis of the wrist was done, and solid fusion was attained in four. In all of the patients the wrist disease became inactive under treatment with isoniazid and para-aminosalicyclic acid.

Adult↗

The effects of cosmic particle radiation on pocket mice aboard Apollo XVII: appendix III. evaluation of viscera and other tissues.

Histopathological findings in the lungs, livers, bone marrows, small intestines, gonads, kidneys, and other tissues of the four pocket mice (Perognathus longimembris) that survived the Apollo XVII flight were evaluated in the light of their immediate environment and as targest of HZE cosmic ray particles. Results of this study failed to disclose changes that could be ascribed to the HZE particle radiation. Decreased numbers of erythropoietic cells in the bone marrow of the flight mice were probably related to the increased oxygen pressure. The small intestine showed no changes. Ovaries and tests appeared normal. Two of the three surviving male flight mice displayed early stages of spermatogenesis, just as ground-based controls did at the same season. Abnormalities were also not found in the thyroid, parathyroids, adrenals, or kidneys. The status of the juxtaglomerular apparatus could not be evaluated. The lungs exhibited nonspecific slight rections. A variety of incidental lesions were noted in the livers of both the flight mice and their controls. The heart muscle showed nothing that could be regarded as pathological. Sections of skeletal muscle examined were free from significant change.

Adrenal Cortex↗