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Biomedical subjects

S Hyman

Publications and source records attributed to S Hyman.

51 records · Page 3Linked to original sources

Ultrastructural morphology of the olfactory pathway for cerebrospinal fluid drainage in the rabbit.

Previous physiological studies indicate that the olfactory region serves as a major pathway for cerebrospinal fluid (CSF) drainage into the lymphatic system. The present study was undertaken to determine the ultrastructural characteristics of this egress route. New Zealand White rabbits received a single bolus injection of the tracer ferritin (MW 400,000) into both lateral ventricles in such a manner as not to raise the intraventricular pressure above the normal level. The animals were sacrificed via intracardiac perfusion of fixative between less than 12 minutes and 4 hours following injection. The cribriform region was removed en bloc, decalcified, sectioned coronally, and prepared for light and electron microscopic examination. The arachnoid, dura, and periosteum surrounding the fila olfactoria passing through the cribriform plate merge together and form the perineurium, which consists of multiple layers of loosely overlapping cells with widely separated junctions and few vesicles. The perineurium surrounding the olfactory filaments at the superficial submucosal level is only one cell thick. The subarachnoid space freely communicates with the perineural space surrounding each filament. No morphological barrier between the perineural space and the loose submucosal connective tissue was identified. Whether or not the perineurium was multi- or single-layered, ferritin was noted in abundance between the loosely overlapping perineural cells and in the submucosal connective tissue. The distribution of ferritin at 12 minutes was similar to that at 4 hours; however, the quantity of ferritin was increased at 4 hours. These results indicate that no significant barrier to CSF drainage is present at the rabbit cribriform region and that CSF reaches the submucosal region rapidly via open pathways.

Animals↗

Intraorbital cerebrospinal fluid outflow and the posterior uveal compartment of the hamster eye.

An ultrastructural and tracer study was undertaken to determine normal outflow pathways of cerebrospinal fluid (CSF) at the terminal subarachnoid space (SAS) of the optic nerve. In the morphological studies, the optic nerve dura and arachnoid were found to be continuous with the sclera of the eye beyond the optic nerve SAS. The pia mater is continuous with the inner sclera and the lamina fusca of the eye. Montages and serial sections demonstrated that the distal SAS is divided into numerous tortuous channels to form an "arachnoidal trabecular meshwork". Spaces of this meshwork continue into "microcanals" which bypass the outer arachnoid barrier layers of the optic nerve meninges to reach the sclera and posterior intraorbital connective tissue. Ferritin infused into the cisterna magna entered the optic nerve SAS within 1 min and reached arachnoidal trabecular meshwork channels and the microcanals within 8 min. It then passed into intraorbital connective tissue spaces at the posterior pole of the eye. Ferritin appeared to be blocked by the lamina fusca and a newly discovered "posterior compact zone" which together prevented its entrance into the choroidal interstitium. These observations suggest that a "subarachnoidal-scleral-orbital outflow pathway" provides a route for CSF drainage from the optic nerve SAS to intraorbital connective tissue. The previously described "posterior uveal compartment" in the hamster eye (Kelly et al. 1983) appears to be relatively isolated from this subarachnoidal-scleral-orbital CSF outflow.

Animals↗

Observations in studies of quantitative kinetics of tritium labelled hematoporphyrin derivatives (HpDI and HpDII) in the normal and neoplastic rat brain model.

Increasing interest has developed in the use of the photodynamic agent, Hematoporphyrin derivative (HpD) for photoradiation therapy (PRT) as adjunctive therapy of malignant glial tumors of the brain. HpD, injected systemically, is preferentially taken up and retained by neoplastic tissue. Early studies of such uptake have largely relied on gross fluorescence as evidence of tissue uptake. In this study HpD was labelled with a tritiated radioisotope (3H) in order to quantify tissue uptake in visceral and in normal and neoplastic brain tissues in a rat brain model. 3H-HpD was injected intravenously at a 10 mg/kg dose into 30 Sprague-Dawley rats (Group A) without tumors in order to clarify method. Separately, 3H-HpD of like dosage was injected into 20 Fischer-344 rats (Group B), 5 control and 15 with a 9L gliosarcoma implanted in the left anterior cerebral cortex. Post injection sacrifice occurred at 6, 24 and 48 hours. From the Sprague-Dawley group multiple somatic and cerebral specimens were assayed. Differential areas within the brain showed no significant difference in uptake. The tumor area, peritumoral margin, and distant uninvolved areas of the Fischer-344 9L rats were likewise assayed. Definite uptake of normal visceral and cerebral tissue occurred with a markedly higher uptake differential in tumor areas. Such differential was relatively consistent from trial to trial, but multiple separate values obtained in the respective study groups were often unreliabe in their reproducibility and at variance with previously reported tissue level studies. These findings implied an instability of 3H-HpD, subsequently confirmed chromatographically as contamination probably due to time related degradation and exchange. Therefore, 3H-HpD appears to inherently carry such a risk for contamination. The compound Photofrin II (HpDII) represents a chromatographic fraction of HpD (HpDI), currently considered its most photodynamically active and purest component. Tritiated Photofrin II was used for quantification. An assay was performed with 5 Fischer-344 9L brain tumor rats (Group C), sacrificed at 24 hours. Photofrin II provided results more reliably reproducible. Contamination, degradation, and exchange of 3H-Photofrin II did not appear to occur. Neoplastic brain levels of the Photofrin II isotope were higher than in the HpD studies, and highly fluorescent. Normal brain values were consistently minimal and without fluorescence. The differential tumor/brain ratio in Photofrin II was consequently much higher. The isolated active substrate of HpDI and HpDII (Photofrin II) appears to be the compound DiHematoporphyrin Ether (DHE).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Effect of heparin reversal following endarterectomy in an atherosclerotic animal model.

A focal atherosclerotic plaque was induced in the aortas of New Zealand White female rabbits by a balloon injury and an atherogenic diet. Under general anesthesia and systemic heparinization, endarterectomy was performed using the operating microscope. Animals were sacrificed at 5, 10, 20, and 60 min following the endarterectomy and operated aortic segments were perfused and examined using scanning electron microscopy. Each segment was compared to a similar segment of endarterectomized aorta from a normal, nonatherosclerotic rabbit. Thrombus formation including aggregated platelets, red cells, and fibrin was found to be more pronounced in the atherosclerotic segments. Ten more atherosclerotic rabbits underwent identical procedures except that heparin was reversed using protamine sulfate 5 min following the endarterectomy. When these specimens were compared to a similar atherosclerotic group without heparin reversal, it was evident that a tremendous thrombogenic process had taken place in the "reversed" segments. This study suggests that atherosclerosis may alter thrombogenesis following an operative vascular procedure and that early reversal of heparin following an endarterectomy should be viewed with caution.

Animals↗

Cerebrospinal fluid drainage as influenced by ventricular pressure in the rabbit.

Artificial cerebrospinal fluid (CSF) containing radioisotope iodinated (125I) serum albumin (RISA) and either blue dextran or indigo carmine was given to white New Zealand rabbits over 4 hours. In one group it was given by ventriculocisternal perfusion, in one by ventricular infusion, and in one by cisterna magna infusion. Blood was sampled continuously from the superior sagittal sinus (SSS) or intermittently from the systemic arterial circulation. Removal of CSF from the cisterna magna during the ventriculocisternal perfusion kept the intracranial pressure (ICP) at 0 to 5 torr, whereas ventricular or cisterna magna infusion raised the ICP to 20 to 30 torr and 15 to 20 torr, respectively. In the two groups with raised ICP, an increased concentration of RISA was present in the optic nerves, olfactory bulbs, episcleral tissue, and deep cervical lymph nodes; but this was not found in the group with normal ICP. In all three groups, the concentration of RISA in the SSS blood was the same as in the systemic arterial blood. The concentration gradient of RISA across the cerebral cortex was similar in both the ventriculocisternal perfusion and the ventricular infusion groups. With cisterna magna infusion, the concentration of RISA was the same on the cortical surface and less in the ventricles compared with the ventricular infusion. It is concluded that, with elevated ICP, CSF drained via pathways that are less evident under normal pressure. Drainage of CSF was similar irrespective of whether the infusion site was the ventricles or cisterna magna. It did not appear that acute dilatation of the ventricles during ventricular infusion compromised the subarachnoid space over the surface of the hemisphere, as the concentration of RISA on the convexities and in the SSS blood did not significantly differ between the groups. Transcortical bulk transfer of CSF was not evident with raised ICP.

Animals↗

Lipid cell tumor of the ovary.

A 32-year-old nulligravida, with a history of abdominal hysterectomy for multiple leiomyomas of the uterus, was seen initially with signs of masculinization. Normal values for 17-ketosteroids, 17-hydroxycorticosteroids, and plasma cortisol eliminated the adrenal as the source of the excess androgen as well as Cushing syndrome. Increased plasma testosterone and androstenedione levels in the peripheral blood as well as in the right ovarian vein sampling implicated the right ovary, which revealed a lipid cell tumor (0.5 to 1.3 cm in maximum dimension).

Adrenal Rest Tumor↗

Peroneal spastic flat foot. Its treatment by osteotomy of the os calcis.

A series of patients treated by osteotomy of the os calcis for the relief of peroneal spastic flat foot is reviewed. The late results have been evaluated, and the literature reviewed. It is suggested that this is an effective method of treatment which has advantages over tarsal fusions.

Adolescent↗

Blood-brain barrier: penetration of morphine, codeine, heroin, and methadone after carotid injection.

Labeled morphine, codeine, heroin, or methadone was injected as a bolus into the common carotid artery of the rat, and the rat was decapitated 15 seconds later. The brain uptake of the drug was calculated by measurement of the brain content of the drug as a percentage of a labeled, highly diffusible reference substance simultaneously injected. The uptake of morphine was below measurability; the uptake of codeine was 24 percent; heroin, 68 percent; and methadone, 42 percent. Brain uptakes of morphine and codeine were also studied after intravenous injection and correlated well with uptakes after carotid injection; the uptake of codeine being nearly complete by 30 seconds. These studies indicate that brain uptake of certain of these drugs is very rapid and that uptake of heroin injected intravenously is probably limited by the regional flow of blood in the brain. The possible relation of this rapid penetration of the blood-brain barrier by heroin to its strongly addictive properties is discussed.

Animals↗