Biomedical subjects
F C Dohan
Publications and source records attributed to F C Dohan.
Choroid plexus histoplasmoma: clinical, pathologic, and imaging findings.
Histoplasmosis of the choroid plexus has not previously been described. We report its occurrence, as well as its clinical, pathologic, and imaging characteristics in one case. Clinically, our patient's choroid plexus lesion produced encephalopathy and third nerve palsy. On imaging it appeared as a hemorrhage or calcification. Cerebrospinal fluid studies were consistent with a chronic meningeal process uncomplicated by hemorrhage. Stereotactic biopsy of the choroid plexus was required to establish the diagnosis of cerebral histoplasmosis. Pathologic examination also revealed prominent abnormal calcification, which permitted the lesion of masquerade as a hemorrhage on computed tomographic and magnetic resonance images.
Opioid and tachykinin neuropeptides in prolactin-secreting human pituitary adenomas.
Two opioid neuropeptides, methionine enkephalin (ME) and beta-endorphin (BE), and one tachykinin neuropeptide, substance P (SP), were quantified in 10 prolactin (PRL)-secreting human pituitary adenomas and in 10 control human pituitaries. Immunohistochemical techniques provided appropriate staining for PRL. Reversed-phase high performance liquid chromatography (RP-HPLC) was used to purify these three neuropeptides before their analysis, radioimmunoassay (RIA) was used for the quantification of SP-like immunoreactivity (SP-LI), and liquid secondary-ion mass spectrometry (LSIMS) was used for the qualitative and quantitative analysis of ME and a tryptic peptide of BE. This study shows that, for 90% of the cases studied here (excluding one hypothyroidism case), the tachykinin A neuropeptide SP-LI level is decreased, the POMC peptide BE level is not altered, and the proenkephalin A neuropeptide ME level is increased in these PRL-secreting tumors.
Reports by patients and their families of memory change after left anterior temporal lobectomy: relationship to degree of hippocampal sclerosis.
Memory decline represents the primary neuropsychological morbidity of anterior temporal lobectomy. Recent investigations using laboratory tests of memory have reported an association between the neuropathological status of the resected left mesial temporal region and memory outcome, with adverse memory outcome associated with a lack of significant left hippocampal pathology. The purpose of this investigation was to examine the relationship between the reports by the patients and their families of observed postoperative changes in day-to-day memory function and the degree of hippocampal sclerosis in resected left mesial temporal lobes. Twenty patients and a close family member (parent or spouse) of each of the patients completed standardized questionnaires assessing pre- to postoperative changes in verbal and spatial memory; these were related to the neuropathological findings. The results indicated that patients without left hippocampal sclerosis reported significantly worse memory outcome than those with hippocampal sclerosis. The ratings provided by the relatives of the patients yielded a comparable effect, and objective memory tests supported the reports by the patients and their families. The neuropsychological findings associated with left hippocampal pathology are of clinical significance and should be considered in surgical evaluation and in the counseling process.
Cardiac arrest following vertebrobasilar stroke.
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Declarative memory following anterior temporal lobectomy in humans.
This study hypothesized that verbal memory decline following anterior temporal lobectomy (ATL) is associated with a lack of significant neuropathology in resected left, but not right, hippocampus and is limited to measures of episodic memory only. Tests of immediate (digit span), semantic (visual naming), and episodic memory as measured by the California Verbal Learning Test (CVLT) were administered before and 6 months after resection of the anterior left (n = 36) or right (n = 26) temporal lobe. There were no effects of hippocampal pathology on measures of immediate or semantic memory for either ATL group or for episodic memory for the right ATL group. Left ATL patients who demonstrated no/mild hippocampal sclerosis exhibited significantly greater postoperative decline in episodic memory compared with those with moderate/marked hippocampal sclerosis on multiple CVLT indices (recall measures, learning characteristics, and contrast measures).
Diffuse axonal injury: windows for therapeutic intervention allowed by its pathobiology.
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The reduction of postlaminectomy peridural fibrosis in rabbits by a carbohydrate polymer.
Spinal peridural fibrosis following total laminectomy in New Zealand White rabbits was significantly decreased by the intraoperative application of GT1587, a semi-synthetic carbohydrate polymer. The application of a similar polymer, GT1043, or phosphate-buffered saline (PBS) was not as effective. Laminectomies were performed at L-2 and L-4 in 25 rabbits. Absorbable gelatin sponge soaked with GT1043, GT1587, or PBS was applied in a blinded fashion to the operative sites, with untreated (sham) laminectomy sites serving as controls. Animals were sacrificed after 2 or 4 weeks. The extent of peridural fibrosis was evaluated by gross microdissection and histological analysis. Dense scar formation and dural adhesions were evident at both time intervals in the sham- and PBS-treated laminectomy sites. The sites treated with GT1587 showed significantly decreased peridural scar formation and dural adhesions, whereas GT1043 treatment caused modest reduction of scar formation at only the 2-week examination. The healing of skin and lumbosacral fascia was not affected by treatment of the laminectomy site with GT1587. These results suggest that GT1587 may prove beneficial in preventing postlaminectomy dural adhesions and peridural fibrosis in humans.
Pathological status of the mesial temporal lobe predicts memory outcome from left anterior temporal lobectomy.
This investigation tested the hypothesis that the degree of impairment to memory function caused by an anterior temporal lobectomy (ATL) is inversely related to the pathological status of the resected hippocampus. Specifically, the greatest risk to postoperative memory function should be to patients with no or minimal hippocampal sclerosis, i.e., those with a functional hippocampus. Forty patients who underwent a partial resection of the left (n = 21) or right (n = 19) anterior temporal lobe were administered tests of immediate and delayed verbal and figural memory, both preoperatively and 6 months postoperatively. The degree of postoperative impairment in memory function was then investigated as a function of the degree of hippocampal sclerosis, as determined by a standardized procedure. For a left ATL, an absence or mild degree of hippocampal sclerosis was associated with significantly greater postoperative impairment of both verbal and figural memory, compared with patients with moderate or marked sclerosis. No statistically significant relationship was noted for patients who underwent a right ATL, but the findings were in the same direction for five of six memory measures. It may be possible to predict and avoid surgically induced impairment of memory function among patients who undergo left ATL through the use of preoperative hippocampal volumetric magnetic resonance imaging. Better clinical tests of right hippocampal function are needed to predict the outcome for patients who undergo a right ATL.
Immunocytochemical evidence of lymphocytic derivation of neoplastic cells in malignant angioendotheliomatosis.
Neoplastic angioendotheliomatosis is a rare disorder usually characterized by primarily cutaneous or neurological symptoms. Approximately 40 cases of malignant angioendotheliomatosis with primary central nervous system (CNS) symptoms have been reported. Some investigators have postulated a hematopoietic origin for this neoplasm. Most of the literature, however, has perpetuated the idea that the often bizarre symptoms seen with this entity result from neoplastic endothelial cell proliferation within the small vessels of affected organs, including the brain and spinal cord. This report describes the immunohistochemical examination and confirmation of the cell of origin of this neoplasm based on five previously unpublished cases of malignant angioendotheliomatosis with primarily CNS symptoms. It includes the first documentation of a T-cell lymphoma presenting as malignant angioendotheliomatosis. All cases include autopsy findings, and in four cases the diagnosis was made postmortem. One case was proven by stereotactic biopsy, but the patient succumbed as a result of severe intracranial bleeding that occurred at the time of biopsy. Tissues were studied with avidin-biotin peroxidase immunohistochemical techniques using a panel of monoclonal antibodies directed against the leukocyte common antigen, LN-1, LN-2, and anti-Factor VIII, and also using Ulex europaeus agglutinin 1. Based on the results obtained, the authors conclude that the proliferative cells seen within the vessel lumina are of lymphocytic origin and agree that the condition should more properly be designated intravascular lymphomatosis. The therapeutic implications of this conclusion point to the possible administration of chemotherapy and radiotherapy in an effort to achieve remissions in an otherwise relentlessly progressive neurological disorder.
Hyperthermia for the treatment of brain tumors.
Brain malignancy, either primary or metastatic, in general is associated with a very poor outcome in spite of the best therapy modern medicine has to offer. The multimodality approach appears to offer the best chance of achieving our goal of improved survival (quality and quantity) and ultimately cure. Hyperthermia, though its application to brain cancer remains experimental, has proven itself in its ability to improve cancer therapy results. There are many methods available to apply hyperthermia to the brain and its application, thus far, has been quite safe. Continued research in this exciting field is warranted.
Genetics and idiopathic schizophrenia.
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Genetic hypothesis of idiopathic schizophrenia: its exorphin connection.
This brief overview proposes a testable oligogenic model of the inheritance of susceptibility to idiopathic schizophrenia: "abnormal" genes at each of a few complementary loci. The model is based on my assumptions as to the likely genetic abnormalities at possibly four or five interacting loci that would permit exorphins, the opioid peptides from some food proteins, especially glutens and possibly caseins, to go from gut to brain and cause symptoms of schizophrenia. Exorphins may reach the brain cerebrospinal fluid (CSF) in harmful amounts because of their genetically increased, receptor-mediated transcellular passage across the gut epithelial barrier plus decreased catabolism by genetically defective enzymes. A schizophrenia-specific, genetically enhanced affinity for exorphins by opioid receptors influencing dopaminergic and other neurons would permit sustained dysfunction at low CSF exorphin concentrations. Tests of each postulated genetic abnormality are suggested. This model is supported by a variety of evidence, including a significant effect of gluten or its absence on relapsed schizophrenic patients, the high correlation of changes in first admission rates for schizophrenia with changes in grain consumption rates, and the rarity of cases of schizophrenia where grains and milk are rare.
Malignant nerve sheath tumor of the facial nerve: case report and discussion.
The third reported case of a malignant nerve sheath tumor of the facial nerve is presented. The clinical course and pathological findings are described and serve as the basis for a discussion concerning malignant nerve sheath tumors arising in the cranial nerves.
Mycobacterium tuberculosis meningitis: a report of twelve cases and a literature review.
Twelve recent cases of Mycobacterium tuberculosis meningitis were presented, and the literature was reviewed. There are no particularly new or unique therapies or approaches to the management of this most serious disease. The major obstacle to successful diagnosis and treatment of tuberculous meningitis continues to be a lack of clinical suspicion of its presence. As illustrated in the cases presented, it has been our experience that patients already moribund or nonresponsive do not respond, regardless of the intervention undertaken. The most sensitive and economical method of detecting M. tuberculosis in the CSF may be LPA. However, this has not yet been widely validated or accepted. Larger volumes of CSF should be sent to the laboratory for testing and centifuged to about 5x concentrations before both acid-fast bacilli staining and culture are attempted. If tuberculous meningitis is suspected, three-drug therapy can be started immediately without jeopardizing subsequent culture confirmation of the presence of the TB bacillus. In addition, these patients must be followed closely to detect hydrocephalus at the earliest possible moment. When patients fail to respond to appropriate antituberculosis and pressure-reducing therapy, hydrocephalus should be actively sought by either CT or radioisotope cisternography. Although the decision to proceed to ventricular drainage or shunting must be individually made in adult patients with infection-related hydrocephalus, we agree with others that surgical intervention should be considered early and should be performed if the level of consciousness deteriorates, intracranial pressure increases, or ventricular enlargement or enhancing basal exudates are identified on CT.
Presentation of central nervous system sarcoidosis as intracranial tumors.
Five cases of sarcoid presenting as an intracranial tumor are reported. In one instance, the lesion presented as a tumor in the cerebellopontine angle, a site not previously reported for the initial presentation of sarcoid isolated to the central nervous system. The role of computerized tomography, surgery, and steroid therapy is discussed. In the absence of pulmonary involvement, serum angiotensin-converting enzyme levels do not appear to be helpful in predicting steroid response.
Is schizophrenia rare if grain is rare?
If, as hypothesized, neuroactive peptides from grain glutens are the major agents evoking schizophrenia in those with the genotype(s), it should be rare if grain is rare. To test this, we analyzed the results of our clinical examinations (e.g., kuru) and observations of anthropologists on peoples consuming little or no grain. Only two overtly insane chronic schizophrenics were found among over 65,000 examined or closely observed adults in remote regions of Papua New Guinea (PNG, 1950-1967) and Malaita , Solomon Islands (1980-1981), and on Yap , Micronesia (1947-1948). In preneuroleptic Europe over 130 would have been expected. When these peoples became partially westernized and consumed wheat, barley beer, and rice, the prevalence reached European levels. Our findings agree with previous epidemiologic and experimental results indicating that grain glutens are harmful to schizophrenics.
Where is schizophrenia rare?
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