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Biomedical subjects

T S Berger

Publications and source records attributed to T S Berger.

14 recordsLinked to original sources
PubMed1995

Nonsteroidal human progesterone receptor modulators from the marine alga Cymopolia barbata.

The co-transfection assay is a novel functional assay using cells transiently transfected with plasmids encoding intracellular receptors and corresponding reporter genes. Using this assay, natural product extracts were tested to identify compounds that modulate intracellular receptor activity, measured as changes in reporter gene activity. A crude extract of the marine alga Cymopolia barbata was found to inhibit progesterone-stimulated reporter gene expression in cells transfected with the human progesterone receptor (hPR) and an appropriate reporter construct. Purification of the active constituents of the extract, guided by the co-transfection assay, yielded two diastereomers of cyclocymopol monomethyl ether, possessing opposing pharmacological activities with the hPR. The antagonist (3R)-cyclocymopol monomethyl ether (LG100127) blocked 1 nM progesterone-stimulated reporter gene expression with an IC50 value of 549 +/- 55 nM in the co-transfection assay. The agonist (3S)-cyclocymopol monomethyl ether (LG100128) had efficacy similar to that of progesterone and an EC50 value of 35 +/- 2 nM. Stimulation by progesterone of the hPR in the human breast cancer cell line T-47D results in enhanced expression of alkaline phosphatase; LG100127 blocked alkaline phosphatase expression stimulated either by progesterone or by LG100128, and LG100128 mimicked progesterone in this assay. Both diastereomers displaced [3H]progesterone from baculovirus-expressed hPR. LG100127 and LG100128 each interacted with the human androgen receptor but did not interact with the human glucocorticoid receptor, estrogen receptor, vitamin D receptor, or retinoid receptors. In summary, these in vitro studies describe the first nonsteroidal pharmacophores for the hPR and demonstrate the use of the co-transfection assay in their discovery.

Animals↗
PubMed1994

Acquired Chiari malformations: incidence, diagnosis, and management.

The acquired descent of the cerebellar tonsils radiographically indistinguishable from Chiari I malformations has been previously reported. The relationship between lumbar shunting procedures for hydrocephalus and symptomatic Chiari malformations has been established. We report the cases of 10 children with lumboperitoneal shunts in whom previous radiographic studies had confirmed a normal hindbrain configuration. Seven of the 10 patients acquired tonsillar descent into the foramen magnum, detected by magnetic resonance imaging, whereas the others remained normal. Four of seven patients were symptomatic; two underwent the removal of the lumboperitoneal shunt and conversion to a ventriculoperitoneal shunt, and two underwent posterior fossa decompression. Further magnetic resonance imaging revealed that one of the two patients who underwent conversion shows ascent of the cerebellar tonsils. All four patients became asymptomatic less than 6 months after treatment. In this article, we discuss seven cases of acquired Chiari malformations and the complete reversal of an acquired Chiari malformation after surgical treatment, as documented by magnetic resonance imaging. Cases of asymptomatic acquired Chiari malformations are reported, including those resulting from shunting for intracranial hypertension without hydrocephalus. We conclude that a craniospinal pressure gradient creates a potential for cerebellar tonsil descent and recommend that ventriculoperitoneal shunting be performed in children with communicating hydrocephalus to avoid this potential complication. We also recommend annual surveillance of the cervicomedullary junction in children with lumboperitoneal shunting. Finally, if symptomatic tonsillar descent occurs from lumbar shunting, a trial conversion to ventriculoperitoneal shunting may eliminate the need for posterior fossa decompression.

Adolescent↗
PubMed1994

The role of hemispherectomy in the treatment of holohemispheric hemimegaloencephaly.

The role of hemispherectomy in treating holohemispheric hemimegaloencephaly, a unilateral brain malformation, is still not well defined. The authors describe the cases of five infants presenting with intractable seizures, progressive neurological deficits, and severe developmental delay. Electroencephalography (EEG) showed generalized polyspikes from the megaloencephalic hemisphere and progressive slowing on the opposite side in all children; contralateral seizure spikes occurred in three children. Three of the five children underwent hemispherectomy for intractable seizures before 2 years of age, after which the seizures subsided completely in two children and improved remarkably in the third. Preoperative Wada testing proved useful in evaluating pharmacologically the effect of hemispherectomy on contralateral polyspikes. Postoperative EEG revealed the absence of polyspikes in the operated hemisphere and decreased slowing on the contralateral side. Psychomotor development in the surgically treated infants exceeded that of the children not undergoing hemispherectomy. Of the two children treated medically, one died at 4 years of age in status epilepticus and the other (now 5 years old) has frequent seizures and severe developmental delay. Based on these results, hemispherectomy appears to be a useful procedure for controlling seizures and improving psychomotor development in children with hemimegaloencephaly involving the entire hemisphere. Surgery in infancy can prevent or minimize seizure foci and encephalopathic changes that may develop in the contralateral hemisphere. Staging the procedure and exercising meticulous hemostasis make surgery relatively safe in infants who otherwise may have significant blood loss associated with increased blood flow to the megaloencephalic hemisphere.

Anticonvulsants↗
PubMed1993

Sigmoid sinus thrombosis after closed head injury in children.

In the literature, clinical descriptions of sigmoid sinus thrombosis occurring after closed head injury in children are rare. One to 5 days after trauma to the back of the head, five children (aged 1 to 7 yr) presented with gait ataxia, vomiting, and headache. Trauma was mild in four children. Computed tomography of all the children, performed within 5 days after the injury, showed focal hyperdensity in the region of the left sigmoid sinus. Four children had extra-axial hyperdense collections along the left transverse sinus, and three had skull fractures adjacent to the left sigmoid sinus. Magnetic resonance imaging (MRI) of all the children, performed 2 to 6 days after injury, showed left sigmoid-sinus thrombosis and decreased flow or thrombosis within the lateral third of the left transverse sinus. All the children had MRI scans 4 to 6 weeks after their diagnosis and were followed up for 1 to 12 months. In four children whose symptoms subsided completely within 2 to 10 weeks, MRI showed recanalization of the sigmoid sinus within 4 to 6 weeks after injury. In one child whose symptoms resolved after 6 months, sigmoid-sinus thrombosis persisted with the formation of collateral flow. We conclude that traumatic sigmoid-sinus thrombosis should be suspected when a child has persistent or delayed gait ataxia and vomiting after injury to the back of the head. Computed tomography characteristically demonstrated focal hyperdensity within the sigmoid sinus that we term the dense sigmoid-sinus sign. Because the sinus recanalized and the symptoms subsided in most children within 6 weeks, we conclude that prophylactic medical or surgical intervention is not indicated.

Child↗
PubMed1992

Interaction of glucocorticoid analogues with the human glucocorticoid receptor.

Transient co-transfection of receptor cDNA and suitable reporter genes was used to study human glucocorticoid receptor (hGR) function in a neutral mammalian cell background. A variety of natural and synthetic steroids were analyzed for their ability to activate gene expression through the hGR and to bind to extracts of cells expressing the hGR cDNA. There was very good correlation between these two in vitro parameters for these compounds. Furthermore, correlation of these data with reported in vivo anti-inflammatory potencies was surprisingly close, with two exceptions. The in vitro data suggest an explanation for the discrepant compounds, consistent with published data on their metabolic fate in vivo. The co-transfection assay has utility as a quantitative predictor of in vivo glucocorticoid pharmacology.

Animals↗
PubMed1991

Color Doppler US imaging during pediatric neurosurgical and neuroradiologic procedures.

Experience with color Doppler imaging (CDI) during 16 pediatric intraoperative and one percutaneous neuro-radiologic procedures was reviewed to assess whether CDI increased the success rate or decreased the procedure time, thus contributing substantially to procedure performance. Intraoperative CDI was used to rapidly identify abnormal vessels or displacement of normal vessels and correlated with preoperative studies. In six cases (four vascular malformations, one mycotic aneurysm, and one hamartoma), surgical resection was altered on the basis of flow information obtained. In one case of percutaneous embolization of a Galenic malformation, CDI provided information contributing to the cessation of the procedure. In six cases (debulking of three gliomas, resection of one vascular malformation, and two biopsies of nonneoplastic conditions), information was added but did not alter the surgical approach. In the remaining four cases (three cerebrospinal fluid drainage procedures, one posterior fossa decompression), no additional information was obtained. Consultation among the ultrasound staff, neuroradiologists, and neurosurgeons before the operative procedure maximized the usefulness of CDI, thus aiding in the success of surgery.

Adolescent↗
PubMed1990

Surgical management of epilepsy associated with cerebral arteriovenous malformations.

Between 1982 and 1986, 27 patients with seizure disorders due to cerebral arteriovenous malformation (AVM) were surgically treated by the authors. These patients had no history or clinical manifestation of intracranial hemorrhage. All were treated with anticonvulsant agents by their neurologists but became disabled due to inadequate control of seizures by medication, side effects of the anticonvulsant drugs, or the effects on their professional lives of even infrequent seizures. The age of the patients ranged from 13 to 61 years. There were 13 males and 14 females. The AVM's were smaller than 2 cm in four patients, between 2 and 4 cm in five, and larger than 4 cm in 18. The most frequent location of the AVM's was in the temporal lobe, followed by the frontal, parietal, and occipital lobes. All patients had preoperative electroencephalography (EEG) and intraoperative electrocorticography. Intraoperative recording of the amygdala and the hippocampus by depth electrodes was performed if the AVM's were located in the temporal lobe. Superficial or posterior temporal lobe AVM's often have remote seizure foci that involve the amygdala and hippocampus. All patients underwent craniotomy and total excision of their AVM's. Surgery was carried out under local anesthesia to allow localization by electrical stimulation if the AVM involved the speech area or the sensorimotor cortex. Based on the EEG findings, excision of the epileptogenic lesion in addition to the AVM was performed in 18 patients. In seven patients with AVM's located in the temporal lobe, remote seizure foci were identified and excised. The remote epileptic activity was particularly prominent in AVM's in the temporal lobe and usually involved mesial temporal structures. Microscopic study of excised seizure foci showed gliosis in 26 cases, hemosiderin deposits in 10, and focal hemorrhage in four. There were no operative deaths. Two patients developed a hemiparesis and three suffered temporary dysphasia after surgery. Two patients had visual field deficits. The results of postoperative seizure control during the average follow-up period of 3 years 11 months were excellent in 21 patients, good in three, fair in two, and poor in one. The latter patient, whose epileptic lesion was not completely excised because of its location in the motor cortex, had poor seizure control postoperatively. Another patient required a second operation to remove a remote seizure focus. In this series, proposed mechanisms of seizure associated with cerebral AVM include focal cerebral ischemia secondary to arteriovenous shunting, gliosis of the surrounding brain, and a secondary epileptogenesis in the temporal lobe.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1989

Management of cerebral cavernous angiomas in children presenting with seizures.

Until recently intracranial cavernous angiomas were thought to be rare vascular malformations that usually presented in adulthood as an intracerebral hemorrhage, an expanding mass lesion, or with the new onset of seizures. Prior to the advent of computed tomography (CT), and more recently magnetic resonance imaging (MRI), their diagnosis in childhood was extremely rare. However, the CT and MRI features of cavernous angioma are quite distinctive and allow early diagnosis and treatment. Advances in surgical techniques permit successful removal of these potentially devastating lesions and amelioration of the associated seizure disorder. Seven children with cerebral cavernous angiomas have been treated at the Children's Hospital Medical Center since 1980. Six children presented with seizures and one with an intracerebral hemorrhage. All had characteristic findings on CT and/or MRI and underwent surgical excision of symptomatic lesions. Intraoperative sonography, electrocorticography, and cortical mapping were used when indicated and were found to be helpful in the surgical management of these patients. Our experience suggests that symptomatic cerebral cavernous angiomas in children are not as rare as previously thought and that surgical treatment using modern neurosurgical techniques is both safe and appropriate and can be helpful in the management of associated seizures.

Adolescent↗
PubMed1988

Traumatic intracranial aneurysms in childhood: two cases and a review of the literature.

Traumatic intracranial aneurysms in childhood are rare. To date, 67 well-documented cases in children have been reported. We present 2 additional cases and review the literature. Traumatic aneurysms can best be categorized based on mechanism of injury and location. Aneurysms secondary to penetrating trauma occur most commonly in teenage boys suffering gunshot wounds. Aneurysms secondary to nonpenetrating trauma occur at the skull base or in the periphery, with motor vehicle accidents and falls as the most common modes of injury. Skull base traumatic aneurysms most commonly involve the petrous, cavernous, or supraclinoid carotid artery and also show a predominance in teenage boys. Peripheral traumatic aneurysms can further be divided into distal anterior cerebral artery aneurysms secondary to trauma against the falcine edge and distal cortical artery aneurysms associated with an overlying skull fracture. Peripheral traumatic aneurysms tend to occur in younger patients with a less marked male predominance. Two-thirds of the patients suffered symptomatic aneurysmal hemorrhage, with an associated mortality rate of 31%. The clinical presentation, diagnosis, and treatment of traumatic intracranial aneurysms are discussed.

Adolescent↗
PubMed1985

Radiation-associated gliomas: a report of four cases and analysis of postradiation tumors of the central nervous system.

Four cases of radiation-associated gliomas are described. All patients were white men, irradiated in childhood for craniopharyngioma, anaplastic ependymoma, retinoblastoma of the orbit, and Burkitt's lymphoma, respectively. The dose ranged from 1800 to 5900 rads, and the latency period was 5 to 25 years. All primary and secondary tumors were verified histologically, and no evidence of persistence of the primary tumors was found. All secondary tumors arose in the fields of irradiation. Ninety-six cases of radiation-induced tumors of the central nervous system have been reported in the literature to date. Twenty-four were gliomas and occurred mainly in young men.

Adolescent↗
PubMed1982

Bilateral epidural hematomas.

Sixty-four cases of bilateral epidural hematomas were reviewed. The factors of patient age, direction of injuring forces, location of hematomas, presence of associated skull fracture, and time interval between injury and onset of signs and symptoms were analyzed. The results of this analysis show that bilateral epidural hematomas may develop slowly indicate that they occur with traumatic forces predominantly oriented in the anteroposterior direction, have fewer overlying fractures associated with them than unilateral epidural hematomas, and commonly contain venous blood. the differences between unilateral and bilateral epidural hematomas in direction of injuring forces, frequency of overlying skull fracture, and type of hemorrhage suggests that varying mechanisms may be responsible for production of these hematomas. Serial angiograms and CT scans have shown delayed accumulation of blood in bilateral epidural hematomas. This finding challenges the theory that epidural hematomas develop within minutes following injury.

Brain Injuries↗
PubMed1975

Salmonella meningitis.

Three cases of salmonella meningitis in infants were successfully treated with a combination of intraventricular and systemic antibiotics after standard treatment had failed. The intraventricular antibiotics were administered through a subcutaneously implanted ventriculostomy reservoir. The ventricular fluid cultures were positive in all cases. The organisms in the ventricle may periodically reinoculate the subarachnoid space and add to the difficulty in curing salmonella meningitis. Details of the prolonged treatment (29-59 days) and the antibiotic levels obtained are presented. No local reservoir complications were encountered. All three patients were developing normally 10 to 18 months following treatment including two who required a shunt procedure for nonabsorptive hydrocephalus.

Ampicillin↗