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Biomedical subjects

L R Ment

Publications and source records attributed to L R Ment.

At least 73 records · Page 4Linked to original sources

Beagle puppy model of intraventricular hemorrhage. Effect of superoxide dismutase on cerebral blood flow and prostaglandins.

Intraventricular hemorrhage (IVH) represents a major problem for preterm neonates and is thought to occur secondary to alterations in cerebral blood flow (CBF) to damaged germinal matrix tissues. Many investigators believe that both local CBF and changes in capillary morphology and permeability may be partially controlled by prostaglandins. To evaluate this hypothesis, the authors have studied the effects of superoxide dismutase (SOD), a known free-radical scavenger, on newborn beagle pups that were randomly assigned by computer to four groups consisting of either SOD- or saline-pretreated animals that underwent either insult by hemorrhagic hypotension/volume reexpansion or no insult. Prostaglandin levels were determined prior to and 60 minutes following the administration of the solutions, and carbon-14 iodoantipyrine autoradiography was performed for determination of CBF. It was demonstrated that, although SOD significantly decreased the incidence of IVH in this model (p less than 0.05), it caused no alterations in baseline CBF or prostaglandin levels. In addition, SOD did not prevent either the systemic blood pressure changes or the alterations in CBF found in response to a hemorrhagic hypotensive insult. The authors propose that neonatal IVH results from a combination of factors, one of which is prostaglandin-mediated alterations in CBF to a damaged capillary matrix.

Animals↗

Beagle puppy model of perinatal cerebral infarction. Acute changes in cerebral blood flow and metabolism during hemorrhagic hypotension.

Asphyxia, with its attendant hypotension, is by far the most common cause of neonatal cerebral infarction and frequently results in lesions of the parieto-occipital white matter. This study examines the effects of hypotension on regional cerebral blood flow (CBF), local cerebral glucose utilization (LCGU), and serum prostaglandin levels in newborn beagle pups. The animals (24 to 96 hours old) were anesthetized, tracheotomized, and paralyzed. Pups were randomly divided into two groups: one was subjected to hemorrhagic hypotension and the other received no insult. Hypotension was induced by slow venous hemorrhage to maintain a mean arterial blood pressure of 20 to 30 mm Hg. Autoradiographic determinations of LCGU using carbon-14 (14C)-2-deoxyglucose were performed 45 minutes after randomization to groups. Autoradiographic determinations of CBF were performed using 14C-iodoantipyrine on a second group of pups 15 minutes after randomization. Prostaglandins were measured immediately before and 15 minutes after insult or control manipulation. There were no significant differences in the values for thromboxane B2 or 6-keto-prostaglandin F1 alpha, the stable breakdown products of thromboxane A2, and prostacyclin. Prostaglandin E2 levels significantly increased in response to hemorrhagic hypotensive insult. In addition, although regional CBF was maintained in cortical and central gray matter structures during hypotension, CBF to the periventricular temporal and parietal white matter zones significantly decreased, and LCGU was increased in these same regions during hypotensive insult. The uncoupling of CBF and metabolism in these periventricular white matter regions may be responsible for the neuropathological sequelae of perinatal asphyxia.

Animals↗

Intraventricular hemorrhage in a term neonate secondary to a third ventricular AVM. Case report.

An initially healthy infant born of an uncomplicated full-term gestation was brought for evaluation of the acute onset of vomiting, irritability, lethargy, and opisthotonus at 14 days of age. Computerized tomography demonstrated an intraventricular hemorrhage. Arteriography defined an angioma on the roof of the third ventricle which was successfully removed via the transcallosal interfornicial approach on the 34th day of life. Other than an easily controlled seizure disorder, the postoperative course was uneventful. At 8 months of age the child is developing normally. Arteriovenous malformations should be considered in the differential diagnosis of intraventricular hemorrhage in full-term neonates without predisposing trauma or bleeding diathesis. High-speed digital subtraction arteriography may be used to screen for this diagnosis. The transcallosal interfornicial exposure offers a satisfactory approach for excising third ventricular angiomas in young infants.

Cerebral Hemorrhage↗

Beagle puppy model of perinatal cerebral infarction. Acute changes in regional cerebral prostaglandins during hemorrhagic hypotension.

Perinatal cerebral infarction is a not uncommon finding in newborn babies surviving intensive care. Asphyxia, with its attendant hypotension, is the most common cause of this problem and may result in neuropathological changes in the periventricular white matter. Previous studies have demonstrated uncoupling of cerebral blood flow and metabolism in the periventricular white matter regions of newborn beagle pups exposed to hemorrhagic hypotension. This work examines the effects of hypotension on serum and regional cerebral prostaglandin levels in the newborn beagle pup. The animals were anesthetized, tracheostomized, and paralyzed. Pups were randomly assigned to two groups: one was subjected to hemorrhagic hypotension and the other received no insult. Hypotension was induced by slow venous hemorrhage calculated to maintain a mean arterial blood pressure at 20 to 30 mm Hg. Serum prostaglandin determinations were made immediately before and 15 minutes after random assignment to hypotension or control groups. In addition, regional cerebral prostaglandin determinations were performed 15 minutes after randomization. Analysis of the serum prostaglandin data revealed that there were no significant differences in the values for thromboxane B2 or 6-keto-prostaglandin (PG) F1 alpha, which are the stable breakdown products of thromboxane A2 and prostacyclin, respectively. Prostaglandin E2 levels increased in response to hemorrhagic hypotension insult. Regional cerebral prostaglandin determinations demonstrated decreases in thromboxane B2 and 6-keto-PGF1 alpha in both gray and white matter. Although gray matter PGE2 was increased in pups exposed to hemorrhagic hypotension, this increase was not found in the periventricular white matter of injured pups. This regional difference in PGE2 synthesis in response to insult may explain the periventricular white matter neuropathological changes attributed to it.

Animals↗

Outcome of fetal ventriculomegaly.

Ventriculomegaly was diagnosed in 50 fetuses in the perinatal ultrasound unit of Yale-New Haven Medical Center. The outcomes were elective abortion, 13 (26%); antepartum death, 0 (0%); intrapartum death, 7 (14%); neonatal death within 24 h, 11 (22%); neonatal death after 24 h and within 28 days, 3 (6%); death after 28 days, 2 (4%); survival, 14 (28%). 70% of the deaths were associated with severe congenital anomalies or intrapartum cephalocentesis. Of the 14 survivors, 6 (43%) had Bayley mental or Stanford-Binet scores of over 80, 2 (14%) had scores from 65 to 80, and 6 (43%) had scores of less than 65. The differences in outcome between this antenatal population and previously described neonatal populations with ventriculomegaly may result from the high rate (84%) of abnormalities in association with ventriculomegaly in this study and selection biases in neonatal studies.

Abnormalities, Multiple↗

Delayed hemorrhagic infarction. A cause of late neonatal germinal matrix and intraventricular hemorrhage.

Although a single perinatal or postnatal event may be directly correlated to intraventricular hemorrhage (IVH) in some infants, in other infants IVH may be related to a series of insults. Asphyxia, hypotension, and a pressure-passive low cerebral blood flow (CBF) may lead to an infarction. Subsequent events known to cause sudden rises in the CBF may then produce a hemorrhage into damaged tissues. We report two cases of this proposed model for delayed hemorrhage into infarcted tissues, or late IVH. Both neonates were severely asphyxiated, and both experienced profound hypotension and a low CBF on the first postnatal day. Late IVH was found in both neonates; at 2 to 3 months of age, one neonate was found to have computed tomographic evidence for diffuse encephalomalacia, and the other neonate was noted to have an occipital porencephalic cyst.

Cerebral Hemorrhage↗

Communicating hydrocephalus secondary to superior vena caval obstruction. Occurrence after Mustard's operation for transposition of the great arteries.

Communicating hydrocephalus was observed on computed tomographic (CT) scans in two infants who had previously undergone Mustard's operation for transposition of the great arteries. Obstruction of the superior limb of the intracardiac baffle developed in these children, resulting in venous obstruction to the head and upper extremities that resulted in cranial enlargement. Radiologic clues included a bulging superior vena cava and a prominent azygous system on chest roentgenogram, split cranial sutures on skull films, and enlarged subarachnoid spaces and dilated ventricles on CT scans. Two-dimensional echocardiography showed the obstructed baffle, as well as signs of redirected blood flow. Angiography and measurement of venous pressures confirmed the obstruction, and surgical correction was successful. Follow-up CT scans showed resolution of the hydrocephalus. Increased venous pressure, leading to decreased CSF absorption and increased intraventricular and subarachnoid CSF accumulation in an infant with an expandable cranium, is a possible explanation for the development of cranial enlargement and hydrocephalus under these circumstances.

Echocardiography↗

Perinatal cerebral infarction.

The diagnosis of perinatal cerebral infarction, although frequently suggested clinically, has been made most commonly at postmortem examination; few infants surviving stroke are reported in the literature. We evaluated 18 infants with perinatal cerebral infarction in a recent twelve-month interval. Seven were preterm neonates, 6 of whom had experienced neonatal intraventricular hemorrhage. Three full-term infants were thought to have experienced cerebral infarction in utero and had evidence of well-defined strokes on computed tomographic scans performed shortly after birth. Eight infants developed stroke at term. The most common cause of cerebral infarction in our series was perinatal asphyxia. Fourteen of the infants were seen with neonatal seizures. Fourteen of the 18 have died or are faring poorly at 4 to 12 months of age (corrected).

Asphyxia Neonatorum↗

Beagle puppy model of intraventricular hemorrhage: ethamsylate studies.

Intraventricular hemorrhage (IVH) remains a major problem of preterm neonates, and ethamsylate, an inhibitor of specific prostaglandin-synthetic enzymes has been demonstrated to prevent IVH in these patients. We have examined the effects of ethamsylate on newborn beagle pups who were, by randomized computerized design, assigned to four cells consisting of (a) either ethamsylate or saline pretreatment and (b) either insulted or not insulted with hemorrhagic hypovolemia/volume re-expansion. Prostaglandin levels were obtained prior to and thirty minutes following administration of the solutions and 14C iodoantipyrine autoradiography was performed for cerebral blood flow (CBF) determinations. Ethamsylate produced a significant decrease in the incidence of IVH in this model (p less than 0.05). Following drug administration, ethamsylate-pretreated pups had significant declines in thromboxane B2 and 6-keto PGF1 alpha levels, the major breakdown products of thromboxane A2 and prostacyclin. Although ethamsylate significantly lowered baseline CBF in all brain regions examined in insulted and non-insulted pups (p less than 0.05), in the drug-treated group it did not prevent the changes seen in CBF to the germinal matrix region which were detected in the saline-pretreated pups. Nor did it significantly blunt the blood pressure changes in response to the hemorrhagic hypovolemia/volume re-expansion insult found in the latter group of animals. In addition, only ethamsylate pretreated pups had marked hypotensive responses to the reperfusion phase of the insult. Although the diminution of baseline CBF may contribute to the prevention of neonatal IVH which this drug has been demonstrated to exhibit, ethamsylate may also act as a capillary stabilizing agent.

Animals↗

Intraventricular hemorrhage in the preterm neonate: timing and cerebral blood flow changes.

Serial cranial ultrasound studies, 133xenon inhalation cerebral blood flow determinations, and risk factor analyses were performed in 31 preterm neonates. Contrast echocardiographic studies were additionally performed in 16 of these 31 infants. Sixty-one percent were found to have germinal matrix or intraventricular hemorrhage. Seventy-four percent of all hemorrhages were detected by the thirtieth postnatal hour. The patients were divided into three groups: early GMH/IVH by the sixth postnatal hour (eight infants) interval GMH/IVH from 6 hours through 5 days (10), and no GMH/IVH (12). Cerebral blood flow values at 6 postnatal hours were significantly lower for the early GMH/IVH group than for the no GMH/IVH group (P less than 0.01). Progression of GMH/IVH was observed only in those infants with early hemorrhage, and these infants had a significantly higher incidence of neonatal mortality. Ventriculomegaly as determined by ultrasound studies was noted equally in infants with and without GMH/IVH (50%) and was not found to correlate with low cerebral blood flow. The patients with early hemorrhage were distinguishable by their need for more vigorous resuscitation at the time of birth and significantly higher ventilator settings during the first 36 postnatal hours, during which time they also had higher values of PCO2. An equal incidence of patent ductus arteriosus was found across all of the groups. We propose that early GMH/IVH may be related to perinatal events and that the significant decrease in cerebral blood flow found in infants with early GMH/IVH is secondary to the presence of the hemorrhage itself. Progression of early GMH/IVH and new interval GMH/IVH may be related to later neonatal events known to alter cerebral blood flow.

Blood Flow Velocity↗

Evidence for late developmental deficit in very low birth weight infants surviving intraventricular hemorrhage.

88 very low birth weight preterm infants who had been evaluated with neonatal computed tomography scanning and/or echoencephalography were subsequently brought to follow-up. Serial neurodevelopmental testing at 6, 12, and 18 months corrected age demonstrated that even the lesser grades of germinal matrix and intraventricular hemorrhage may be associated with a relatively less favorable neurodevelopmental outcome.

Cerebral Hemorrhage↗

Posthemorrhagic hydrocephalus. Low incidence in very low birth weight neonates with intraventricular hemorrhage.

In addition to seizures and long-term neurodevelopmental handicaps, infants with intraventricular hemorrhage (IVH) are at risk for posthemorrhagic hydrocephalus (PHH), and the incidence of this problem in preterm infants with known IVH has been reported to vary from 25% to 74%. Over a 46-month period, 438 neonates of 1250-gm birth weight or less were admitted to this Newborn Special Care Unit, and 269 survived the first 36 postnatal hours. Of these, 265 patients underwent computerized tomography and/or cranial ultrasound scanning for evaluation of germinal matrix and/or intraventricular hemorrhage (GMH/IVH): 133 infants were found to have experienced GMH/IVH, and 27 of these died within the 1st postnatal week. Of the 95 survivors with GMH/IVH, 43 were known to have GMH only; the other 52 experienced IVH and were therefore at risk for PHH. Patients with GMH/IVH underwent repeat investigations for the development of ventriculomegaly and possible PHH. Only five patients with IVH developed PHH, defined as ventriculomegaly, elevated intracranial pressure, and increasing occipitofrontal head circumference. Serial cranial ultrasound studies of 95 other consecutively admitted patients in this birth-weight range revealed an equal incidence (45%) of low intracranial pressure ventriculomegaly in both the hemorrhage and non-hemorrhage groups, but none of them required shunting for hydrocephalus. One infant with congenital aqueductal stenosis was also identified.

Cerebral Hemorrhage↗

Beagle puppy model of intraventricular hemorrhage. Effect of indomethacin on local cerebral glucose utilization.

The newborn beagle puppy has been demonstrated to provide a good model for neonatal intraventricular hemorrhage (IVH). A study was designed to determine if indomethacin can prevent IVH, and if indomethacin would produce changes in local cerebral glucose utilization (LCGU). By computerized random design, newborn beagle puppies were pretreated with either indomethacin (a known inhibitor of prostaglandin synthetase) or saline, and then assigned either to receive a hemorrhagic hypotension/volume reexpansion insult or to receive no insult. Pretreatment with indomethacin produced a marked drop in the incidence of IVH as well as significant alterations in the blood pressure responses to the hemorrhagic hypotension/volume reexpansion insult. Carbon-14 autoradiography was used to determine LCGU: no alterations were demonstrated in cerebral metabolism in uninjured pups pretreated with indomethacin compared to saline-pretreated animals. In addition, although the hemorrhagic hypotension/volume reexpansion insult produced marked alterations in LCGU in both groups of traumatized pups, indomethacin prevented the changes in LCGU in the germinal matrix and white matter that were found in the saline-pretreated animals.

Animals↗

Perinatal management of meningomyelocele.

During a 24-month period, nine neonates with a meningomyelocele were delivered. Of these, four meningomyeloceles were detected antenatally with ultrasound during the third trimester. Sonographic diagnosis was based upon a discontinuity in the fetal spine and the presence of a protruding sac. Obstetric management included serial sonography until fetal pulmonic maturity was established, and subsequent low transverse cesarean section. A method of atraumatic abdominal delivery is described. Neonatal management consisted of early closure of the spinal defect and appropriate shunting of hydrocephalus. A team approach to the perinatal management of meningomyelocele is recommended for optimal outcome.

Cesarean Section↗

The ramp injection of radiotracers for blood flow measurement by emission tomography.

A prototype instrument based on the coincidence detection of annihilation radiation was built to control the arterial concentration of a radionuclide as a uniformly increasing ramp function over a preset injection interval (ranging from 1.6 min to 13.6 h). The device was designed to accommodate radionuclides of different physical and biological half-life, and the physiological characteristics of the system being studied. A kinetic model based on the Kety-Schmidt integral was developed to permit the determination of cerebral blood flow (CBF). Both the kinetic model and the ramp injector were tested in cats studied with the PETT III positron emission tomograph and 4-(18F)-fluoroantipyrine as the CBF tracer. The ratio lambda/f of the brain-to-blood partition coefficient (lambda) and blood flow (f) were determined simultaneously by serial measurements with positron emission tomography.

Animals↗