Biomedical subjects
Publications and source records attributed to E G Fischer.
T-cell subpopulations were tested in multiple sclerosis (MS) patients before and after cyclophosphamide (n = 38) and corticotropin (n = 37) treatment and physiotherapy (n = 30). There were no specific changes of subset ratios immediately after immunosuppressive treatment. However, T-cell subpopulations showed great day-to-day variations in MS patients.
Beginning in 1984, we started a prospective study to evaluate the role of postoperative, pre-radiation chemotherapy in the treatment of infants and poor prognosis children with medulloblastoma. The study was designed to evaluate the role of pre-radiation chemotherapy in two specific patient populations: (a) children under the age of 2 years in which there was an attempt to delay definitive radiation and thus reduce the risk of toxicity to the developing nervous system; and (b) children over age 2 years with Stage T3 and T4 disease who were known to have a relatively poor prognosis with surgery and radiation. The five patients under age 2 years received cisplatinum (100 mg/m2) every 3 weeks and weekly vincristine (1.5 mg/m2) for a total of 9 weeks. Nitrogen mustard (6 mg/m2), procarbazine (100 mg/m2), and vincristine (1.5 mg/m2) (MOP) were given in 28 day cycles as long as there was no disease progression or until the child's second birthday, at which time the children were referred for radiation therapy. The 13 patients over 2 years of age received the 9 week course of cisplatinum and vincristine and then began radiation. Responses measured by computed tomography were obtained in 10 of 12 children with measurable disease at the start of chemotherapy. With a median follow-up of 22 months, 15 of 18 children were alive and free of disease. Except for mild ototoxicity in one child, the acute side effects have been well tolerated. In conclusion, it appears that some infants can have their radiation delayed until the age of 2 years. Although the follow-up time was short, all but three patients were free of disease, time exceeding the median time to failure with radiation alone. Pre-radiation chemotherapy might improve local control and survival in children with advanced stage medulloblastoma.
Occult lesions of the spine in children are a rare but recognizable cause of neurogenic dysfunction involving the lower extremities, and lower urinary and gastrointestinal tracts. We report the preoperative and postoperative urodynamic findings in 40 children with varying spinal abnormalities. Of these patients 28 were neonates or infants (average age 8.7 months) and 12 were older children (average age 11.7 years). Preoperative urodynamic testing revealed normal function in 18 of 28 children (64 per cent) in the younger age group in contrast to 1 of 12 (8 per cent) in the older age group. Of the 10 infants with abnormal studies postoperative urodynamic findings returned to normal in 6, while 2 others remained abnormal but were improved. In contrast, of 11 older children with abnormal preoperative evaluations 3 (27 per cent) reverted to normal postoperatively. The neurourological changes seen in these occult lesions are variable, may occur at any age, are progressive and are potentially reversible by surgical correction but this reversibility diminishes with age.
In the past few years it has become evident that neuropeptides may be direct mediators in the modulation of the immune response and the unspecific defense by the brain. Lymphocytes have been thought to have opioid receptors and to respond to opioids with an increase in blastogenesis, cytotoxicity and factor release. Lymphocytes are said to release various neuropeptides. Furthermore, there are some unexplained effects of morphine on the immune system and of the immune system on morphine withdrawal. The purpose of this paper is to review what has been previously published in this field. The well established modulation of phagocyte functions by opioids will only be scanned.
Autoantibodies against dopamine receptors in schizophrenic patients have been postulated. IgG was fractionated from sera of 15 schizophrenic patients (DSM III) in an acute episode. However, 3H-spiperone binding to dopamine receptors was not inhibited by this fraction.
Met-enkephalin has been found to have an effect on cell shape and motility of human polymorphonuclear leukocytes (PMNs). Specific binding of tritium-labeled Met-enkephalin to the cells could not be demonstrated. There was a rapid proteolytic degradation of the peptide in the medium, followed by uptake of the labeled tyrosine. The peptidase recognizes the N-terminal sequence of various endogenous opioid peptides. The protease inhibitors bestatin and bacitracin had but little effect on the degradation of Met-Enk.
A 35-year-old woman developed temporal lobe seizures. Isolated dilatation of the right temporal horn was demonstrated by computed tomography. She was asymptomatic for the next 10 months while on anticonvulsants before severe headaches, vomiting, and mental confusion prompted hospitalization. Both temporal horns were now dilated, there was marked periventricular edema, and cryptococci were cultured from the ventricular fluid. She succumbed after prolonged systemic and intrathecal antifungal therapy, having developed isolation and dilatation of both frontal horns and third and fourth ventricles. Cryptococcal or other fungal meningoencephalitis should be considered in the differential diagnosis of isolated dilatations of the ventricular chambers as noted in the present case.
The early events in the interaction of (125I)-Tyr27-beta-endorphin with human polymorphonuclear leucocytes were investigated. Using ultrastructural autoradiography we found that the labeled peptide specifically bound to the plasma membrane and was internalized within two minutes of incubation at 37 degrees C. Both processes could be inhibited by unlabeled beta-endorphin or by the opiate antagonist diprenorphine. This finding was confirmed by radioreceptorassays. With longer incubation times the specific association of the labeled beta-endorphin with the cells decreased. About 10% of the tracer was degraded within 10 min of incubation as shown by gel chromatography. The morphological changes induced by 125I-beta-endorphin in the granulocytes were investigated under the microscope. The labeled peptide had the same biological effect as unlabeled beta-endorphin.
A case of a previously healthy 7-year-old girl with a left frontoparietal tumor identified as an Acanthamoeba-induced granuloma is reported, and the literature on Acanthamoeba meningoencephalitis is reviewed. Unlike most reported cases, the Acanthamoeba central nervous system infection presented in this girl as a discrete tumor without meningeal involvement or diffuse encephalitis. A favorable outcome was obtained following total excision of the mass and treatment with ketoconazole.
The authors report a study of the cerebral vasculature of premature rabbits pertaining to the germinal matrix (GM). A pigmented silicone material (Microfil) was injected into the carotid artery of anesthetized rabbits. Methyl methacrylate vascular casts of a similar group of premature rabbits were examined by scanning electron microscopy. The GM is supplied by arteries from both the basal and convexity surfaces of the brain. Vessels could be identified as arteries or veins by their typical patterns of branching and by the characteristic impressions made on the methyl methacrylate casts by endothelial nuclei. Specific evidence of structural weaknesses in the vasculature, which could be a site of predilection for GM bleeding, was not observed. The similarities in basal ganglia vasculature between premature rabbits and humans justifies using the rabbit model to study vascular aspects of the GM and intraventricular hemorrhage.
Living human polymorphonuclear leucocytes were incubated with various opiate agonists and antagonists in radioreceptor assays. Binding of the opiate antagonists 3H-naloxone and 3H-diprenorphine and of the benzomorphan 3H-ethylketocyclazocine was found at 4 degrees C and at 37 degrees C, 3H-naloxone binding was stereospecific. Binding of the opiate agonist 3H-dihydromorphine was present at 37 degrees C but not at 4 degrees C and had a different time course as compared to the antagonists. At both temperatures no specific binding of the proteolytic stable analogue 3H-D-Ala-D-Leu-enkephalin was found. Autoradiography showed an unspecific accumulation of 3H-naloxone inside the cells and a specific localization of grains at the cell membrane.
The effects of beta-endorphin(beta-End), an endogenous opioid, were tested in vitro on shape changes in polymorphonuclear leukocytes (PMNs). Cell shape changes indicate alterations of the functional status of the cells. Within 2 min, beta-End but not the opioid alkaloid levorphanol or the antagonist, diprenorphine, induced a cell spreading. Subsequently, beta-End and levorphanol (10(-8) M), but not the dextrorotatory isomer, stimulated an elongation of the cells. Both effects of beta-End could be antagonized by diprenorphine in an equimolar concentration. Thus, the effects were stereo-specific and antagonizable. In this test system, the morphological changes evoked by beta-End were equal to the effects of FMLP, a chemotactic substance, used as a reference. Our findings indicate that endogenous opioids might play a role in modulating the initial phase of the PMNs' offensive behaviour, presumably cell adherence and motility.
Between 1972 and 1981, 37 children with craniopharyngioma were cared for at Children's Hospital, Boston. In this paper, the results of treatment with radiation therapy after conservative operations are compared with those following an initial attempt to excise the tumor. Radiation therapy was equally, if not more, effective than attempted excision in controlling subsequent tumor growth. Although this was not a controlled study, the complications of each approach are indicated, and it is inferred that conservative operations combined with radiation therapy offer less risk for psychosocial impairment than does attempted tumor excision when patients are considered as a group. The ultimate effect that either approach might have on quality of life remains to be defined, and therapy must still be individualized to the particular clinical problem.
A 61-year-old woman with Down syndrome presented with progressive deterioration of gait over 9 months. Cranial CT without and with intravenous administration of contrast material demonstrated a posterior fossa cyst. The cyst did not communicate with the fourth ventricle or subarachnoid spaces as proven by CT following a metrizamide ventriculogram. Surgical fenestration of the cyst into the fourth ventricle was done. In addition, a moderate atlantoaxial subluxation with 2 mm movement from extension to flexion was present, which was thought not to be clinically significant, but which might require a spinal fusion at a future time. Ependymal cells were found as a result of a biopsy of the cyst wall.
The investigation of psychoneuroimmunological pathways represents a growing field of research. This paper reviews the current state of knowledge about a direct correlation of endogenous opioids and immunologically competent cells.
Two patients are described with congenital hemihypertrophy and vascular abnormalities of the brain on the side of the hypertrophy and in the posterior fossa. The abnormalities observed included giant aneurysm, capillary hemangioma, and arteriovenous malformation. Vascular anomalies in the affected limbs are common in congenital hemihypertrophy, and neurological abnormalities and hypertrophy of the brain have been reported. The presence of vascular abnormalities of the brain in this condition may provide an opportunity to further the understanding of the development of cerebrovascular malformations.
The authors present neurological findings and data from psychophysiological tests administered during the follow-up period of 35 patients with craniopharyngioma. Group I patients who were treated by irradiation alone or by radiotherapy and conservative surgical procedures (including biopsy, cyst aspiration, and shunting), showed significantly less frontal lobe and visual perceptual dysfunction than Group II patients, in whom radical tumor resection was attempted by a subfrontal exposure. Frontal lobe dysfunction was demonstrated in sorting tests by perseverative responses, inflexibility of behavior, and lack of inhibitory control, while intelligence quotients remained relatively unaffected. Immediate memory defects and decreased manual dexterity were present, to different degrees, in both treatment groups. On the basis of these preliminary data and a maximum follow-up period of 10 years, the authors conclude that primary irradiation of a craniopharyngioma appears associated with a lower morbidity rate and may avoid the frontal lobe disorders seen in the patients with extensive tumor resection.
Four infants underwent craniectomy for craniosynostosis and subsequently developed an expanding cranial defect with herniation of brain. All four had an unrepaired laceration of the dura. The pathophysiology of this entity and of the growing fracture of childhood are discussed, and a unified interpretation of the consequences of unrepaired dural defects is proposed.