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Biomedical subjects

J F Pasternak

Publications and source records attributed to J F Pasternak.

At least 37 records · Page 2Linked to original sources

Quantitative analysis of cerebral vessels in the newborn puppy: the structure of germinal matrix vessels may predispose to hemorrhage.

Intracerebral hemorrhage in premature infants commonly originates in the germinal matrix (GM). We performed a quantitative analysis of cerebral microvasculature from newborn puppies, a model for neonatal periventricular and intraventricular hemorrhage, at the light and electron microscopic level. GM vessels were compared with those of other brain regions in an effort to delineate pathogenetically significant structural features that might predispose to hemorrhage. Light microscopic examination revealed that GM vessel density (103.0 vessels/mm2) was similar to that in white matter (98.3 vessels/mm2), but lower than that of cortex (155.6 vessels/mm2) or caudate (259.9 vessels/mm2). Mean blood vessel diameter was slightly larger in GM (9.0 mu) than cortex (6.9 mu), caudate (7.9 mu), and white matter (8.9 mu). Ultrastructurally, GM vessels were thinner along greater portions of their circumferences than vessels from other brain regions, as shown by their smaller ratio of vessel wall area/vessel lumen area and their greater fraction of vessel wall with thickness less than 0.25 mu. In addition, a significantly larger fraction of GM capillary wall lacked direct contact with perivascular structures. We postulate that the larger size, thinner walls, and diminished support from surrounding neuropil, which characterize GM vessels, may render them more susceptible to both physical (e.g. hypertension) and metabolic (e.g. hypoxia) insults than vessels from other brain regions.

Animals↗

Autoregulation of cerebral blood flow in the newborn beagle puppy.

Regional cerebral blood flow (RCBF) was measured in 17 newborn beagle puppies under conditions of moderate hypotension, normotension, and moderate hypertension. RCBF demonstrated autoregulation over the blood pressure range 35-70 mm Hg. When arterial pressure exceeded 75 mm Hg, RCBF increased significantly for all grey matter structures, 2 of 4 white matter structures, and 2 of 3 germinal matrix structures. The magnitude of the hypertension-induced increase in RCBF was highest for thalamic and mesencephalic nuclei, intermediate in cerebral cortex and other subcortical nuclei, and lowest in white matter. The hypertension-induced increase in CBF was low (similar to white matter) in some areas of germinal matrix but higher (similar to midline cerebral cortex) to rostral germinal matrix. The differences in RCBF during hypertension between rostral germinal matrix and cerebral white matter may partially explain the vulnerability of the germinal matrix to hemorrhage.

Animals↗

Isolated ventricles following intraventricular hemorrhage.

Panventricular enlargement often follows intraventricular hemorrhage in the premature neonate. During a recent 12-month period, the authors identified five infants who required shunting because of symptomatic post-hemorrhagic hydrocephalus, which was progressive despite serial lumbar punctures and the use of indwelling subcutaneous ventricular reservoirs. In the first 6 months following placement of the initial shunt, four of the infants required an additional shunt for isolated ventricles. Two children had isolation of the lateral ventricles and required bilateral shunts. Two other children had isolation of the fourth ventricle from the lateral ventricular system and required posterior fossa shunts. All of the children were treated successfully using multiple shunts. In all cases, progressive dilation of the isolated ventricle was unaccompanied by the usual clinical signs of shunt malfunction. It appears that isolated ventricular systems are common following post-hemorrhagic hydrocephalus and these children must be followed closely with ultrasound and computerized tomography scanning.

Cerebral Hemorrhage↗

Regional variability of blood flow and glucose utilization within the subependymal germinal matrix.

Regional cerebral blood flow (RCBF) and local cerebral glucose utilization (LCGU) were studied in normal, awake newborn beagle puppies using quantitative autoradiography. A highly significant linear relationship between RCBF and LCGU was present for all brain structures. Special attention was directed to the subependymal germinal matrix (GM), the site of origin of periventricular hemorrhage in the premature human. A consistent variability in both RCBF and LCGU was found within GM. Both RCBF and LCGU were higher in rostral than posterior GM, and in peripheral than internal GM. The close coupling between RCBF and LCGU within GM suggests that GM blood flow is influenced by local energy needs. The quantitative relationship between RCBF and LCGU was similar within GM to that in cerebral white and gray matter, suggesting that the puppy GM predominantly utilizes glucose as fuel for energy production.

Animals↗

A model for human medulloblastoma. Growth, morphology, and chromosomal analysis in vitro and in athymic mice.

A model was developed for the in vitro and in vivo study of the continuous cell line, TE-671, derived from a human medulloblastoma. TE-671 grew in vitro as sheets of uniform triangular- to spindle-shaped cells with round to oval nuclei and sparse cytoplasm. The in vitro population doubling time was 31.48 hours (h). Mean colony forming efficiency in an agarose medium was 9.0 +/- 3.0%. TE-671 grew subcutaneously in athymic mice as lobulated masses composed of sheets of small uniform cells with round hyperchromatic nuclei and scanty cytoplasm. Perivascular pseudorosettes were commonly seen in early in vivo passage. The in vivo doubling time of subcutaneous tumors was 3.17 +/- 1.02 days, with a latency to 500 mm3 of 20.66 +/- 1.48 days. The cell cycle time (Tc) was 24 h, S phase was 14 h, G1 phase was seven h, and G2 phase was three h. Intracerebral tumors grew as discrete masses composed of diffuse sheets of small anaplastic cells with frequent mitoses and perivascular pseudorosettes. Both in vitro and in vivo chromosome studies revealed modal chromosome counts in the near tetraploid range with the same marker chromosomes as described in the original report of this cell line. The in vitro and in vivo growth of TE-671 provides the best available experimental model for the analysis of the biological properties and chemosensitivity of human medulloblastoma.

Animals↗

Regional cerebral blood flow in the beagle puppy model of neonatal intraventricular hemorrhage: studies during systemic hypertension.

The newborn beagle puppy serves as an animal model for intraventricular hemorrhage (IVH) of the premature infant. Since increased systemic blood pressure has been implicated in the genesis of IVH in both babies and puppies, we studied regional cerebral blood flow in control and hypertensive puppies. Hypertension significantly increased blood flow to all structures. The largest increases occurred in gray matter, especially deep cerebral and brainstem nuclei. Blood flow also increased to deep hemispheric white matter, but the magnitude of the increase was smaller. Hypertension also increased blood flow to the subependymal germinal matrix (GM). The magnitude of the increase to most of the GM was small and similar to deep hemispheric white matter. The increase to the most rostral GM was higher and equal to the mean increase seen in gray matter. This rostral-caudal gradient of hypertension-induced hyperperfusion may explain the tendency for IVH to occur in rostral GM in premature babies. However, the failure to find a disproportionate increase in blood flow to GM during hypertension implies that additional factors besides hypertension-induced GM hyperperfusion may be involved in the pathogenesis of IVH.

Animals↗

Spatial distribution of proliferating cells in avian sarcoma virus-induced gliomas.

We studied the regional distribution of proliferating tumor cells in five avian sarcoma virus-induced gliomas. The labeling index and spatial distribution of [3H]thymidine (dThd)-labeled tumor cells were determined in serial sections of each tumor with a computer-assisted digitizing system. The density of [3H]dThd-labeled cells showed marked regional variation in each tumor, and the ratio of the density of [3H]dThd-labeled cells in tumor periphery to tumor center varied from 0.86 to 1.38. The labeling index generally, but not always, reflected [3H]dThd-labeled cell density. This study indicates that proliferating pools of glioma tumor cells exhibit regional variability in concentration and that the highest numbers of proliferating cells may be predominantly located in central regions of tumor and not in tumor periphery as assumed previously. In all tumors, large numbers of proliferating cells were present in all parts of the tumor.

Animals↗

A computerized system for continuous physiologic data collection and analysis: initial report on mean arterial blood pressure in very low-birth-weight infants.

A system for continuous measurement and analysis of mean arterial blood pressure (MABP) by microcomputer is presented. The system allows prolonged recording and maintenance of fine detail by sequential evaluation and storage of up to 3,600 data points per hour. Fifteen preterm appropriate-for-gestational-age (AGA) infants weighing less than or equal to 1,500 g (very low birth weight) who were free of pulmonary and neurologic disease were monitored continuously from birth to 5 days of age. MABP was recorded via an umbilical arterial catheter with a pressure transducer and module interfaced with the microcomputer. Software was developed to analyze this stored data rapidly. MABP was found to correlate significantly with gestational age from 3 to 15 hours of age (P less than .05). Significant correlation was rare after 20 hours of age. MABP increased as a function of postnatal age in 11 infants. This increase was greater (0.31 to 0.54 mm Hg/h) for the least mature infants (27 to 29 weeks of gestation). The increase for the most mature infants (31 to 32 weeks of gestation) was low (0 to 0.24 mm Hg/h), and in three infants a small negative slope was seen. The steep rise in MABP during the first 40 hours of life in the least mature infants may be due to the perfusion requirements of extrauterine life. These pressures may be at or near the threshold for rupture of immature vascular beds such as are found in the subependymal germinal matrix and thus predispose to intraventricular hemorrhage.

Blood Pressure Determination↗

Regional measurements of blood flow in experimental RG-2 rat gliomas.

Regional measurements of blood flow (F) were performed in transplanted intracerebral RG-2 rat gliomas using [14C]iodoantipyrine, Kety-Schmidt blood flow equations, and quantitative autoradiography. Twenty-nine intracranial tumors in ten rats were analyzed by location; 18 intraparenchymal, seven meningeal, two third-ventricular, and two fourth-ventricular tumors were studied. For all tumors, averaged mean F was 91 +/- 33 (S.D.) ml/hg/min. In all but one tumor, mean F was intermediate between normal cortex and corpus callosum values. There was moderate regional variation: averaged mean F was lower in tumor center (78 +/- 47 ml/hg/min) than in tumor periphery (93 +/- 30 ml/hg/min). Within individual tumors, F showed moderate variation which correlated to some extent with histological features; a regional F of less than 10 ml/hg/min was observed in only one tumor within an area of necrosis. F in regions of brain immediately surrounding the tumor was higher than in tumor periphery. Blood flow to RG-2 tumors seems unlikely to limit drug delivery any more than to normal brain, and the consistent levels from tumor to tumor and within individual tumors make the RG-2 model an excellent one with which to study drug delivery in experimental brain tumors.

Animals↗

Regional measurements of blood-to-tissue transport in experimental RG-2 rat gliomas.

Regional measurements of blood-to-tissue transport were performed in transplanted RG-2 rat gliomas using [alpha- 14C]aminoisobutyric acid (AIB), quantitative autoradiography, and equations to express a unidirectional transfer constant. Thirty-eight intracranial tumors in ten rats were analyzed according to location; 23 intraparenchymal tumors, eight meningeal tumors, six fourth-ventricular tumors, and one third-ventricular tumor were studied. Except for the small third-ventricular tumor, the transfer constant (K) for AIB was similar in all groups and ranged from 0.031 to 0.038 ml/g/min. Within individual tumors, regional variation of K was also small, although some local variation could be correlated with histological features. The K for AIB decreased in brain around tumor and, at a distance of 300 microns from tumor edge, had returned to values similar to those of normal cortex (0.002 ml/g/min). An average extraction fraction (E) of 0.09 was calculated for AIB in the RG-2 tumors. The low E suggests that delivery of water-soluble chemotherapeutic drugs to RG-2 tumors should be limited more by capillary permeability or surface area than by blood flow. RG-2 is an ideal experimental tumor with which to test drug delivery and the methods that attempt to increase drug delivery in brain tumors.

Aminoisobutyric Acids↗

An infant with chronic, relapsing polyneuropathy responsive to steroids.

A seven-week-old infant presented with an acute flaccid paraparesis. Her subsequent course was punctuated by numerous exacerbations, in association with minor intercurrent illness and remissions produced by corticosteroid treatment. Postmortem examination revealed a chronic inflammatory polyradiculopathy. She represents the youngest patient yet described with a chronic, relapsing, steroid-responsive polyneuropathy.

Child, Preschool↗

Regional cerebral blood flow in the newborn beagle pup: the germinal matrix is a "low-flow" structure.

The newborn beagle pup serves as a model for neonatal intraventricular hemorrhage (IVH). Fluctuations in germinal matrix blood flow are left to play a major role in the pathogenesis of IVH. We studied regional cerebral blood flow in awake newborn beagle pups utilizing [14C]-iodoantipyrine as a blood flow indicator and quantitative autoradiography. The equilibrium [tissue]:[blood] partition coefficient for iodoantipyrine was 1.13 +/- .06 for grey matter. Blood flow was calculated for cerebral cortex (frontal = 59 +/- 9 ml/100 g/min), 14 subcortical nuclear structures (e.g., caudate = 45 +/- 6 ml/100 g/min), 3 white matter structure (centrum semiovale = 7 +/- 1 ml/100 g/min), and germinal matrix (7 +/- 1 ml/100 g/min) (mean +/- S.E.). We conclude that under normal physiologic conditions the germinal matrix receives relatively low blood flow. This information can be used for comparison with germinal matrix blood flow during adverse experimental conditions.

Animals↗

Computed tomography of virally induced canine brain tumors: a preliminary report.

Seven neonatal dogs were inoculated intracerebrally with Avian Sarcoma Virus (ASV) and studied by computed tomography (CT) for intracranial tumors. The tumor yield was five anaplastic astrocytomas and two sarcomas, with an average latency of 57 days. Computed tomography accurately detected all tumors over 5 mm in diameter and predicted the size of the tumors within 3 mm. The intensity of contrast enhancement was directly related to the dose of Conray-60. The area of enhancement on the CT scan correlated precisely with tumor permeability as determined histologically with horseradish peroxidase (HRP). Edema seen in CT scans correlated well with edema present in histological sections. Peritumoral edema was impermeable to both Conray-60 and HRP. The ASV-induced canine brain tumor model appears well suited for future CT studies.

Animals↗

Porencephaly from periventricular intracerebral hemorrhage in a premature infant.

In two thirds of the premature infants who survived large periventricular intracerebral hemorrhage, a porencephalic cyst developed at the site of parenchymal hemorrhage. The porencephaly seems to develop as a result of local parenchymal destruction by the hemorrhage itself. These cysts can occur in the absence of posthemorrhagic hydrocephalus or increased intracranial pressure. Three of four infants who were observed for at least five months had lateralized motor deficit that corresponded to the cyst.

Brain↗

Failure of daily lumbar punctures to prevent the development of hydrocephalus following intraventricular hemorrhage.

A prospective study of 48 infants with periventricular-intraventricular hemorrhage was carried out to evaluate the role of daily lumbar punctures, instituted from the time of diagnosis of the hemorrhage, in prevention of posthemorrhagic hydrocephalus and improvement in immediate outcome. The data lead to the following conclusions: (1) minor hemorrhage (Grade I) is associated with minimal risk of death or hydrocephalus; (2) moderate hemorrhage (Grade II) is associated with low risk of death and intermediate risk of hydrocephalus, and serial lumbar punctures do not reduce these risks; and (3) severe hemorrhage (Grade III) is associated with high risks of death or hydrocephalus or both, and serial lumbar punctures also do not reduce these risks.

Brain↗

Steroid-responsive encephalomyelitis in childhood.

The syndrome of parainfectious encephalomyelitis evolves from an antecedent infection. Several etiologic agents have been associated with this complication, although the pathogenesis in each instance may prove to be more uniform. Considerable evidence suggests that the syndrome is mediated immunologically. The seven cases reported here were clinically similar, although the infectious etiologies were diverse. Leptospirosis antedated the neurologic syndrome in two cases, and a "viral" illness preceded the other five cases. The evolution of the syndrome was slowly progressive in each case, and six patients had prominent involvement of rhombencephalic structures. The progressive course was reversed rapidly with eventual full recovery in each instance after initiation of corticosteroid therapy. Our experience with these cases coupled with a review of the literature suggests that corticosteroid therapy should be considered in the subacute or chronic cases of parainfectious encephalomyelitis.

Adrenal Cortex Hormones↗