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Biomedical subjects

J C Goodman

Publications and source records attributed to J C Goodman.

At least 37 records · Page 2Linked to original sources
PubMed1998

The role of semantic context and memory in the acquisition of novel nouns.

Three studies assessed the ability of 2-year-olds to use semantic context to infer the meanings of novel nouns and to retain those meanings a day later. In the first experiment, 24 2-year-olds heard novel nouns in sentences that contained semantically constraining verbs (e.g., "Mommy feeds the ferret"). They chose from a set of four novel object pictures to indicate the referent. Children learned a majority of the novel words. However, they occasionally failed to choose the correct object even when they understood the verb. Experiment 2 examined whether this was due to an inability to identify some of the pictures of novel objects. Experiment 3 tested 24 2-year-olds' memory for the newly learned nouns following a 24 hr delay and found significant retention. Results are discussed in terms of learning mechanisms that facilitate vocabulary acquisition in young children.

Age Factors↗
PubMed1998

Homonymous hemianopsia due to a dural cavernous hemangioma.

The clinical and radiographic features of extra-axial cavernous hemangiomas are described, and a case of homonymous visual field loss due to a dural-based occipital cavernous hemangioma is reported. A patient presented with a homonymous hemianopsia due to an enhancing tentorial mass lesion. The preoperative clinical and magnetic resonance imaging features were suggestive of meningioma. The patient underwent gross total resection of the lesion and the final pathologic examination was consistent with cavernous hemangioma. There was complete resolution of the visual field defect after surgery. Extra-axial cavernous hemangiomas differ from intra-axial cavernous hemangiomas in their clinical and radiographic features. The former lesions may mimic meningioma and should be considered in the differential diagnosis of a dural-based mass. Early recognition of the lesion is important because surgical removal of cavernous hemangiomas may be associated with a higher morbidity and mortality rate than meningiomas.

Dura Mater↗
PubMed1997

Reduction in thermal hyperalgesia by intrathecal administration of glycine and related compounds.

We have previously shown in animal models that enhanced segmental glycine release is produced by neuroaugmentation techniques commonly used to control pain in humans. Our current hypothesis is that glycine administered intrathecally reduces the pain response evoked by the hotplate analgesia meter method. Neuropathic rats created by unilateral partial ligation of the sciatic nerve were treated with intrathecal infusion of glycine, strychnine, MK-801, or 5-7 DKA at 0.1 mumol for 2 hours at a rate of 10 microliters/min. Time required for limb withdrawal at 42 degrees C was significantly increased after glycine administration but not altered by strychnine, a specific glycine receptor antagonist. Administration of the NMDA receptor antagonist, MK-801, blocked the influence of glycine, with a less obvious antagonistic response from 5.7 DKA. Our results provide evidence that glycine and related compounds significantly modify thermal hyperalgesia, and may operate primarily through the NMDA receptor complex.

Analgesia, Epidural↗
PubMed1997

Neurotoxicity of intracerebral injection of a replication-defective adenoviral vector in a semipermissive species (cotton rat).

The neurotoxicity of an adenoviral vector (Adv.RSVtk) carrying the gene for herpes simplex virus thymidine kinase (HSVtk) was tested in the cotton rat, a semipermissive host. Adv.RSVtk was injected intracerebrally in cotton rats at a dose of 5.0 x 10(6) or 7.5 x 10(7) p.f.u. No signs of illness were observed. Histological inspection at 12 and 28 days after injection showed inflammation of the ependyma and choroid plexus and at the injection site. No demyelination, viral inclusions, cerebral edema, necrosis, cavities or vascular necrosis were seen in the brains. There was no significant difference between animals injected with 5.0 x 10(6) or 7.5 x 10(7) p.f.u., nor was there a difference between animals analyzed at 12 or 28 days after vector injection. This inflammation was similar in animals that had been preimmunized with wild-type virus and in animals that had been treated with ganciclovir. No histopathology, was observed in the lungs of the animals and no replication-competent virus was detected. These experiments indicate that Adv.RSVtk has limited neurotoxicity which would not prohibit its use in a limited phase I clinical trial in humans that have malignant tumors of the central nervous system.

Animals↗
PubMed1997

Hyperglycemia increases brain injury caused by secondary ischemia after cortical impact injury in rats.

OBJECTIVE: To examine the effects of glucose infusion on the histologic brain damage caused by controlled cortical impact injury alone and by cortical impact injury complicated by secondary ischemia. DESIGN: Prospective, randomized study. SETTING: University laboratory. SUBJECTS: Male Long-Evans rats. INTERVENTIONS: Three experimental conditions were studied: a) 2.5-mm deformation impact (velocity 4 m/sec) injury followed by 40 mins of bilateral carotid occlusion; b) sham impact injury followed by 40 mins of bilateral carotid occlusion; and c) 2.5-mm deformation impact (velocity 4 m/sec) injury followed by sham carotid occlusion. For each experimental condition, animals were randomized to receive either glucose solution or saline solution before the induced injury and the sham impact injury. Contusion volume and neuron density in the CA1 and CA3 regions of the hippocampus were measured 2 wks after the injury. MEASUREMENTS AND MAIN RESULTS: Parenteral administration of 2.2 g/kg glucose solution increased the blood glucose concentration from 6.7 +/- 3.3 to 17.9 +/- 10.6 mmol/L before the impact injury, and to 12.3 +/- 5.6 mmol/L before carotid occlusion. Hyperglycemia had the greatest effect on the consequences of the impact injury complicated by secondary ischemia, increasing contusion volume from 1 to 30.6 mm3 in the animals that received saline or glucose solution, respectively (p = .005), and reducing the density of normal appearing neurons in the CA1 area of the hippocampus from 201 to 144 cells/mm2 in the animals that received saline solution and glucose solution, respectively (p = .038). The impact injury alone and bilateral carotid occlusion alone caused minimal neuronal loss in the hippocampus and minimal contusion or infarction at the impact site. Individually, these mild injuries were not adversely affected by infusion of glucose solution. CONCLUSION: Hyperglycemia increases brain damage when traumatic brain injury is complicated by secondary ischemia.

Animals↗
PubMed1997

Increased CSF glutamate following injection of ALS immunoglobulins.

To reconcile the autoimmune and excitotoxic hypotheses regarding the etiology of amyotrophic lateral sclerosis (ALS), we injected rats intraperitoneally with ALS immunoglobulins and monitored CSF glutamate, aspartate, glutamine, and glutathione. CSF glutamate was significantly increased at 24 and 72 hours compared with both basal levels and disease control injected rats. CSF aspartate was increased at 72 hours. Glutamine and glutathione were unchanged. These data suggest that ALS immunoglobulins may enhance CSF glutamate and aspartate levels and contribute to motoneuron injury.

Amyotrophic Lateral Sclerosis↗
PubMed1996

Growth retardation and cysteine deficiency in gamma-glutamyl transpeptidase-deficient mice.

gamma-Glutamyl transpeptidase (GGT) is an ectoenzyme that catalyzes the first step in the cleavage of glutathione (GSH) and plays an essential role in the metabolism of GSH and GSH conjugates of carcinogens, toxins, and eicosanoids. To learn more about the role of GGT in metabolism in vivo, we used embryonic stem cell technology to generate GGT-deficient (GGTm1/GGTm1) mice. GGT-deficient mice appear normal at birth but grow slowly and by 6 weeks are about half the weight of wild-type mice. They are sexually immature, develop cataracts, and have coats with a gray cast. Most die between 10 and 18 weeks. Plasma and urine GSH levels in the GGTm1/GGTm1 mice are elevated 6-fold and 2500-fold, respectively, compared with wild-type mice. Tissue GSH levels are markedly reduced in eye, liver, and pancreas. Plasma cyst(e)ine levels in GGTm1/GGTm1 mice are reduced to approximately 20% of wild-type mice. Oral administration of N-acetylcysteine to GGTm1/GGTm1 mice results in normal growth rates and partially restores the normal agouti coat color. These findings demonstrate the importance of GGT and the gamma-glutamyl cycle in cysteine and GSH homeostasis.

Animals↗
PubMed1996

Adenoviral-mediated thymidine kinase gene transfer into the primate brain followed by systemic ganciclovir: pathologic, radiologic, and molecular studies.

Transduction of experimental gliomas with the herpes simplex virus thymidine kinase gene (HSV-tk) using a replication-defective adenoviral vector (ADV/RSV-tk) confers sensitivity to ganciclovir (GCV) leading to tumor destruction and prolonged host survival in rodents. To determine treatment tolerance prior to clinical trials, we conducted toxicity studies in 6 adult baboons (Papio sp.). The animals received intracerebral injections of either a high dose of ADV/RSV-tk [1.5 x 10(9) plaque-forming units (pfu)] with or without GCV, or a low dose of ADV/RSV-tk (7.5 x 10(7) pfu) with GCV. The low dose corresponded to the anticipated therapeutic dose; the high dose was expected to be toxic. Magnetic resonance imaging (MRI) of the brain was obtained before treatment and at 3 and 6 weeks after treatment. Animals receiving the high-dose vector and GCV either died or became moribund and required euthanasia during the first 8 days of treatment. Necropsies revealed cavities of coagulative necrosis at the injection sites. Animals receiving only the high-dose vector were clinically normal; however, lesions were detected with MRI at the injection sites corresponding to cystic cavities at necropsy. Animals receiving the low-dose vector and GCV were clinically normal, exhibited small MRI abnormalities, and, although no gross lesions were present at necropsy, microscopic foci of necrosis were present. The vector sequence was detected by polymerase chain reaction (PCR) at the injection sites and in non-adjacent central nervous system tissue in all animals. Recombinant DNA sequence was detected outside of the nervous system in some animals, and persisted up to 6 weeks. The viral vector injections stimulated the production of neutralizing antibodies in the animals. No shedding of the vector was found in urine, feces, or serum 7 days after intracerebral injection. This study suggests that further investigations including clinical toxicity trials of this form of brain tumor therapy are warranted.

Adenoviruses, Human↗
PubMed1996

Lactic acid and amino acid fluctuations measured using microdialysis reflect physiological derangements in head injury.

We examined the extracellular neurochemical milieu in 34 head injured patients using microdialysis while simultaneously monitoring intracranial pressure, cerebral perfusion pressure, and jugular venous oxygen saturation. Derangements of anaerobic metabolism reflected by increased lactate and lactate/pyruvate ratios, and release of amino acids were seen at the same time as physiological deterioration in the majority of instances. Clinical microdialysis may provide insights into the neurochemistry of head injury, and such information may lead to new methods of monitoring and treating head injured patients.

Adult↗
PubMed1996

Reduction in the mechanonociceptive response by intrathecal administration of glycine and related compounds.

We have previously reported that enhanced glycine release is produced by epidural spinal cord stimulation, a clinical method for treating neuropathic pain. Our current hypothesis is that glycine administered intrathecally reduces neuropathic pain as measured by the Randall-Selitto method. Neuropathic rats created by unilateral partial ligation of the sciatic nerve were treated with intrathecal infusion of glycine, strychnine, MK-801, or 5,7-DKA at 0.1 mumol, or artificial CSF for 2 hours at a rate of 10 microliters/min. Force required to produce the pain response was significantly increased after glycine administration and reduced using strychnine, a specific glycine receptor (Gly l) antagonist. Strychnine blocked the response to glycine when infused together. Administration of the non-specific NMDA receptor MK-801 antagonist and 5,7-DKA, a specific glycine-NMDA receptor (Gly 2) antagonist, however, failed to block the response to glycine. Our results provide evidence for the use of glycine and related compounds to treat neuropathic pain.

Animals↗
PubMed1996

Paraganglioma of the thoracic spinal cord.

Paraganglioma arising in the thoracic extradural space is an uncommon tumor, with only four cases previously reported. The authors review the clinical and pathological features of thoracic paraganglioma and compare them to the more common paraganglioma of the cauda equina.

Adult↗
PubMed1996

The role of glycine in spinal shock.

Suppression of increased muscle tone by epidural spinal cord stimulation, an invasive method for treating spasticity, increases segmental concentrations of inhibitory amino acid neurotransmitters, particularly glycine. The role of glycine in spasticity and spinal shock was explored further in rabbits with ischemic spinal cord injuries that produced spastic paraparesis or flaccid paraplegia. H-reflexes were monitored following posterior tibial nerve stimulation and plantar surface recording. Spasticity was quantified by using H/M ratios. Spastic animals were intrathecally infused with 100 mmol/l solutions of glycine and related compounds. Glycine agonists suppressed tone whereas glycine antagonists increased tone. In addition, microdialysis sampling from the cord was done in injured, non-infused animals and aspartate, GABA, glutamate, glycine and taurine were measured. Flaccid animals had glycine levels two-three times higher than spastic or control animals. High concentrations of glycine within spinal cord segments is associated with spinal shock. Glycine and related compounds may be useful as treatment for excessive tone.

Amino Acids↗
PubMed1996

Secondary insults increase injury after controlled cortical impact in rats.

Secondary ischemic insults are common after severe head injury and contribute to poor neurological outcome. To study the increased vulnerability of the traumatized brain to secondary insults, bilateral carotid occlusion was produced after a controlled cortical impact injury in rats. The injury produced by either the impact injury or the bilateral carotid occlusion was mild to moderate when studied individually. The 1 and 3 m/sec impact injuries alone caused no detectable contusion at the impact side and minimal neuronal loss in the hippocampus. The 5 m/sec impact injury alone resulted in a small contusion with a median volume of 5.4 mm3. The 40-min period of bilateral carotid occlusion alone caused no cortical injury and no neuronal loss in the CA1 region of the hippocampus. When the 40 min of bilateral carotid occlusion was produced 1 h after the impact injury, there was an increase in the damage produced. The contusion volume was significantly larger after the 3 and 5 m/sec impact injuries and the hippocampal neuronal loss was significantly greater after the 1 and 3 m/sec impact injuries. When varying durations of bilateral carotid occlusion were produced 1 h after a 3 m/sec impact injury, contusion volume was significantly larger after bilateral carotid occlusion duration of 40 min, and CA1 neuronal loss was significantly greater after bilateral carotid occlusion durations of 30 and 40 min. When 40 min of bilateral carotid occlusion was produced at different time intervals after a 3 m/sec injury, the increased contusion volume was maximal when bilateral carotid occlusion occurred at 4 h after the impact injury, and the increased neuronal loss in the CA3 region of the hippocampus was maximal when bilateral carotid occlusion occurred at 1 h after the impact injury. By 24 h after the impact injury, 40 min of bilateral carotid occlusion had minimal consequences, similar to the effect in sham-injured animals. These results mimic the clinical situation where secondary insults of a severity that would not cause permanent neurological damage in a normal person are associated with a marked worsening of neurological outcome after head injury and where the injured brain is most susceptible to secondary insults in the first few hours after injury.

Animals↗
PubMed1996

Evaluation of a carbohydrate-free diet for patients with severe head injury.

Hyperglycemia, which may be caused or exacerbated by conventional diets, may worsen the neurological outcome from severe head injury, especially if secondary ischemic insults occur. The purpose of this study was to evaluate an experimental diet intended to replace systemic caloric and protein requirements without producing hyperglycemia. In initial studies in the laboratory, 5 experimental diets were employed in a middle cerebral artery temporary occlusion model. The effects of the diets on blood biochemistry and on infarction volume were compared in fasted animals and in animals fed a control diet. Animals fed the experimental diets had a significantly lower preischemia blood glucose concentration, a higher blood concentration of ketone bodies, and a smaller infarct volume than the animals fed a control diet. One diet chosen from the laboratory study was then evaluated in a clinical study as a randomized, open-label trial. Twenty severely head-injured patients were randomly assigned to be fed the experimental diet, EN-9305, or the control diet, Osmolyte HN, for the first 2 weeks after injury. Both treatment groups had similar blood glucose concentrations, averaging 6.33 +/- 0.21 mumol/mL (114 +/- 4 mg/dL), on day 1 prior to starting the assigned diet. Blood glucose concentration increased in the control diet group to a peak of 8.37 +/- 0.94 mumol/mL (151 +/- 17 mg/dL) on day 7 as the infusion rate of the diet was increased to the final rate. In the experimental diet group, the blood glucose concentration remained unchanged from fasting levels as the diet was advanced. Blood lactate concentration was lower, and blood ketone body concentrations were higher in the patients fed the experimental diet. Urinary nitrogen balance was better in the experimental diet group, but measures of visceral protein sparing, including serum albumin, plasma retinol binding protein, and total lymphocyte count, were not significantly different in the 2 treatment groups. Measures of cerebral anaerobic metabolism, including CSF lactate concentration and cerebral lactate production, were not significantly different in the 2 treatment groups. These studies suggest that a carbohydrate-free diet such as EN-9305 might have advantages for patients with severe head injury by replacing systemic caloric and protein requirements without producing hyperglycemia.

Adult↗
PubMed1996

Lactate and excitatory amino acids measured by microdialysis are decreased by pentobarbital coma in head-injured patients.

Primary traumatic brain injury and secondary ischemic/hypoxic injury are being increasingly characterized at the neurochemical level. Neurochemical monitoring using microdialysis has shown that these forms of tissue damage share many common features. In particular, anaerobic glycolysis with increased lactate production and release of excitatory amino acids into the extracellular space are seen in both conditions. Clinical microdialysis studies have heretofore focused on methodological issues, establishment of basal analyte values, and clinico-neurochemical correlation. Here we report the neurochemical consequences of therapeutic intervention in head injury. Specifically, induction of thiopental coma to manage severe increased intracranial pressure in seven patients was associated with a 37% reduction of lactate, 59% reduction of glutamate, and 66% reduction in aspartate in the extracellular space of the brain.

Adolescent↗
PubMed1995

Adenovirus-mediated gene therapy for experimental spinal cord tumors: tumoricidal efficacy and functional outcome.

We evaluated the efficacy of adenoviral-mediated gene therapy of experimental spinal cord tumors and the functional outcome after this treatment. Spinal cord tumors were generated in the thoracic region of the spinal cord in Fischer 344 rats by stereotaxic intramedullary injection of 1 x 10(4) 9L gliosarcoma cells. Seven days after tumor cell injection, a replication-defective adenoviral vector carrying the herpes simplex virus thymidine kinase gene (ADV-tk) or a control adenoviral vector carrying the beta-galactosidase gene (ADV-beta gal) was injected into the tumors. Beginning 12 h later the animals were treated with the antiviral drug ganciclovir (GCV; 50 mg/kg) or saline twice a day for 6 days. The neurological performance of the animals was assessed during and following treatment. Eighteen days after tumor cell injection, all of the control animals had paraplegia and large tumors. In contrast, no tumors were detected in animals treated with ADV-tk and GCV. In long-term studies, two of the 5 animals treated with ADV-tk and GCV remained tumor-free and remained neurologically intact at 6 months whereas all animals in the control groups became paraplegic within 18 days.

Animals↗
PubMed1995

The influence of glycine and related compounds on spinal cord injury-induced spasticity.

Spasticity is a frequent and complex sequel to spinal cord injury. The neurochemical basis for the origin of spasticity is largely unknown. Glycine is among the most abundant neurotransmitters in the spinal cord. However, the role of glycine and related compounds in spasticity have received little attention. An ischemic spinal cord injury was created in rabbits, by an intraaortic balloon occlusion technique, which produced lower limb spasticity. A catheter was inserted into the cisterna magna and the spinal cord was bathed with 100 microM solutions of glycine, strychnine, D-serine, beta-alanine, MK-801, or artificial CSF for 4 hours at a rate of 10 microliters/min. H-reflexes were monitored before and during infusion by stimulating the posterior tibial nerve and recording from the plantar surface of the foot. Glycine, D-serine, and MK-801 depressed the H wave, strychnine produced a heightened H wave, and beta-alanine caused no significant changes. These results indicate that glycine and related compounds may influence spasticity.

Animals↗