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Biomedical subjects

C C Parker

Publications and source records attributed to C C Parker.

33 records · Page 2Linked to original sources
PubMed1998

The management of PSA failure after radical radiotherapy for localized prostate cancer.

An asymptomatic rising serum prostate-specific antigen (PSA) level is the most common form of failure after radical radiotherapy for localized prostate cancer, but there is no consensus as to how it should be managed. This review addresses the following three questions concerning men with PSA failure after radiotherapy: (i) what is the course of the disease without further intervention?; (ii) what is the role of radical treatment, such as salvage prostatectomy?; and (iii) should androgen deprivation be started immediately or should it be delayed until clinical progression occurs? An algorithm for the management of PSA failure after radical radiotherapy for localized prostate cancer is proposed.

Aged↗
PubMed1997

Prospective study of neurological responses to treatment with macrophage-targeted glucocerebrosidase in patients with type 3 Gaucher's disease.

We prospectively evaluated the clinical and biochemical responses to enzyme-replacement therapy (ERT) with macrophage-targeted glucocerebrosidase (Ceredase) infusions in 5 patients (age, 3.5-8.5 years) with type 3 Gaucher's disease. The patients were followed for up to 5 years. Enzyme dosage ranged from 120 to 480 U/kg of body weight/month. Systemic manifestations of the disease regressed in all patients. Neurological deficits remained stable in 3 patients and slightly improved in 1. One patient developed myoclonic encephalopathy. Cognitive deterioration occurred in 1 patient and electroencephalographic deterioration in 2. Sequential cerebrospinal fluid (CSF) samples were obtained during the first 3 years of treatment in 3 patients and were analyzed for biochemical markers of disease burden. Glucocerebroside and psychosine levels were not elevated in these specimens, whereas chitotriosidase and quinolinic acid were elevated in 2 patients. Progressive decrease in the CSF levels of these latter macrophage markers during 3 years of treatment implies a decreased number of Gaucher cells in the cerebral perivascular space. Similar changes were not observed in the patient who had a poor neurological outcome. In conclusion, ERT reverses systemic manifestations of type 3 Gaucher's disease and appears to reduce the burden of Gaucher cells in the brain-CSF compartment in some patients.

Antibodies↗
PubMed1995

Neurofibrillary tangles in Niemann-Pick disease type C.

Niemann-Pick disease type C (NPC) is an autosomal recessive disease, belonging to a clinically heterogeneous group of lipid storage diseases, distinguished by a unique error in cellular trafficking of exogenous cholesterol, associated with lysosomal accumulation of unesterified cholesterol. Unlike Niemann-Pick disease types A and B, there is no primary genetic defect in sphingomyelinase in NPC. During the routine neuropathological study of NPC patients, we found neurofibrillary tangles (NFT) in a series of cases with a slowly progressive chronic course. These were not associated with beta-amyloid deposits. The NFT were most frequent in the orbital gyrus, cingulate gyrus and entorhinal region of the cerebral cortex, but were also frequently found in the basal ganglia, thalamus and hypothalamus. In one of the most severely affected case, the NFT were even found in the neurons in the inferior olivary nucleus and in the spinal cord. The NFT were immunostained with Alz 50, and consisted of paired helical filaments. The distribution of the neurons bearing the NFT was generally similar to that of the swollen storage neurons, and storage neurons often contained NFT in their perikarya and/or in the meganeurites. However, neurons with NFT could be noted without swollen perikarya. The coexistence of neuronal storage and NFT in NPC without amyloid deposits suggests that perturbed cholesterol metabolism and/or lysosomal membrane trafficking may play a role in the formation of NFT, and that amyloid deposits are not necessarily the prerequisite for NFT formation. The results of our study also suggest that NFT formation may be a rather nonspecific cellular reaction of neurons to certain slowly progressive metabolic perturbations of an as yet undefined nature.

Adolescent↗
PubMed1994

Childhood ataxia with diffuse central nervous system hypomyelination.

A significant number of patients with progressive leukodystrophy do not have a definitive diagnosis. This report describes the clinical, morphological, and biochemical characteristics of 4 unrelated girls with progressive ataxic diplegia of unknown etiology. These patients had normal development until the ages of 1.5 to 5 years. A diffuse confluent abnormality of the white matter of the central nervous system was present on computed tomography and magnetic resonance scans obtained early in the course of the illness. Dementia was not present and peripheral nerves were normal. All patients were evaluated for known metabolic and degenerative diseases and no abnormalities were observed. Light and electron microscopy of open-brain biopsy specimens from 2 girls showed selective white matter abnormalities including hypomyelination, demyelination, and gliosis. Myelin-specific proteins in the subcortical white matter were examined immunocytochemically and by Western blot analysis. They were of normal molecular size but were markedly reduced in quantity in both patients compared to control subjects. Lipid analysis revealed decreased levels of characteristic myelin lipids. When examined by magnetic resonance spectroscopic imaging, all patients showed a marked decrease of N-acetylaspartic acid, choline, and creatine in white matter only. The magnetic resonance spectroscopic imaging profile is a unique diagnostic feature of this clinicopathological syndrome.

Ataxia↗
PubMed1993

Linkage of Niemann-Pick disease type C to human chromosome 18.

We analyzed the involvement of chromosome 18 in Niemann-Pick disease type C (NPC), an autosomal recessive cholesterol-processing disorder. Within affected offspring, the chromosome 18 parental contributions were identified by using allele-specific microsatellite markers. Significant linkage of NPC to an 18p genomic marker, D18S40, was indicated by a two-point lod score of 3.84. Analysis of meiotic chromosomal breakpoint patterns among the affected individuals indicated that the NPC gene is pericentromerically localized on human chromosome 18.

Chromosomes, Human, Pair 18↗
PubMed1993

Use of polyethylene glycol-bound superoxide dismutase, polyethylene glycol-bound catalase, and nimodipine to prevent hypoxic ischemic injury to the brain of newborn pigs.

OBJECTIVE: To determine if polyethylene glycol-bound superoxide dismutase and catalase and nimodipine, alone or in combination, will ameliorate hypoxic ischemic injury to the brain. SUBJECTS: A total of 78 newborn (0 to 3 days) pigs were used. DESIGN: Prospective, blinded, randomized, controlled trial. INTERVENTIONS: The piglets were subjected to hypoxic ischemic brain injury. Carotid arteries were ligated at time 0 and BP was reduced one third by hemorrhage. At 15 mins, FIO2 was reduced to 0.6. At 30 mins, carotids were released, blood was reinfused, and FIO2 was increased to 1.0. Pigs were randomly assigned at time 35 mins to receive either: 10,000 U/kg of polyethylene glycol-bound superoxide dismutase and catalase (group 1); 0.5 mg/kg of nimodipine (group 2); both 10,000 U/kg of superoxide dismutase and catalase and 0.5 mg/kg of nimodipine (group 3); or no drugs (controls). MEASUREMENTS: The time after reoxygenation for return of electroencephalogram, respiration, blink and pain were recorded in minutes as well as a neurologic examination at 1, 2, and 3 days and pathologic examination of the brain at 3 days, both by blinded observers. MAIN RESULTS: There were no significant differences in the four groups. CONCLUSIONS: Polyethylene glycol-bound superoxide dismutase and catalase, and nimodipine, either alone or in combination, do not ameliorate hypoxic ischemic injury to the brain in the newborn pig when given 5 mins after reoxygenation.

Animals↗
PubMed1993

The effect of cholesterol-lowering agents on hepatic and plasma cholesterol in Niemann-Pick disease type C.

Niemann-Pick disease type C (NP-C) is a neurovisceral lipidosis characterized by defective intracellular trafficking of cholesterol and lysosomal accumulation of unesterified cholesterol, believed to be an offending metabolite. We studied the effect of cholesterol-lowering agents on hepatic and plasma cholesterol levels in NP-C by randomly assigning 25 patients with NP-C to one of five treatment regimens containing different combinations of cholestyramine, lovastatin, nicotinic acid, or dimethyl sulfoxide (DMSO). Unesterified cholesterol content was measured in liver biopsies before and after 4 months' treatment. All drug regimens except DMSO alone reduced hepatic and plasma cholesterol levels. Toxicity was limited and did not prevent any patient from completing the study. The combination of cholestyramine, lovastatin, and nicotinic acid lowered cholesterol levels in liver and blood with minimal side effects. A controlled clinical study will be necessary to determine if this regimen influences the rate of neurologic progression.

Adolescent↗
PubMed1992

Fructose-1,6-bisphosphate does not ameliorate hypoxic ischemic injury to the central nervous system in the newborn pig.

BACKGROUND AND METHODS: Fructose-1,6-bisphosphate has been shown to improve the outcome of hypoxic ischemic brain injury in adult rabbits. We wished to see if these results could be extended to a newborn animal. Twenty-four 0- to 3-day-old piglets were randomized to receive 300 mg/kg of fructose-1,6-bisphosphate 5 mins before injury, followed by a continuous infusion of 15 mg/kg/min of fructose-1,6-bisphosphate for the next 90 mins, or the equivalent volume of normal saline. Hypoxic ischemic central nervous system damage was induced by ligating both carotid arteries and reducing their BP to two thirds of the normal value for 30 mins. In the last 15 mins of this 30 mins, the FIO2 was reduced to 0.6. At 30 mins, the piglets were resuscitated with an FIO2 of 1.0, the carotid ligatures were released, and the removed blood was reinfused. RESULTS: The neurologic examination scores at 1, 2, and 3 days after injury and pathologic examination scores at 3 days after injury were not different in the fructose-1,6-bisphosphate-treated and the control animals. CONCLUSION: Fructose-1,6-bisphosphate does not ameliorate hypoxic ischemic brain injury in the newborn pig.

Animals↗
PubMed1991

MK-801 does not protect against hypoxic-ischemic brain injury in piglets.

BACKGROUND AND PURPOSE: The excitatory amino acid inhibitor MK-801 has been shown in many animals species to protect against hypoxic-ischemic brain injury. We sought to determine whether hypoxic-ischemic injury to the newborn pig's brain could be prevented by the use of MK-801. METHODS: Hypoxic-ischemic injury to the brain was induced in forty 0-3-day-old piglets. They were randomized to receive either 3 mg/kg MK-801 (MK-801 group, n = 20) or vehicle (control group, n = 19) prior to insult. At time 0, the carotid arteries were ligated and the blood pressure was reduced by one third by hemorrhage. At 15 minutes, inspired oxygen was reduced from 50% to 6%. At 30 minutes, inspired oxygen was changed to 100%, carotid ligatures were released, and the withdrawn blood was reinfused. An additional 14 piglets received 3 mg/kg MK-801 but not hypoxic-ischemic injury (drug-only group), and a final group of 11 piglets were subjected to only a sham operation (sham group). RESULTS: Neurological examination scores at 24, 48, and 72 hours showed that MK-801 and drug-only piglets were significantly worse than the controls. Pathological examination of the brains at 72 hours showed significantly greater damage in the brains of the MK-801 and control pigs relative to the sham and drug-only groups. No differences were found between the control and the MK-801 groups. No differences were found between the sham and drug-only groups. CONCLUSIONS: MK-801, at a dose of 3 mg/kg, causes neurological dysfunction in piglets lasting at least 72 hours, but neither causes brain damage nor ameliorates the effects of hypoxic-ischemic injury to the brain of the newborn pig.

Animals↗
PubMedDate not supplied

Mistaken diagnoses in continuous muscle fiber activity of peripheral nerve origin.

The syndrome of continuous muscle fiber activity of peripheral nerve origin has manifestations that resemble those of many other more common neurologic disorders during childhood and infancy. This similarity often leads to misdiagnosis when an adequate index of suspicion is not entertained and a comprehensive electromyographic examination is not performed. Two affected patients from 1 family are reported to illustrate the type of diagnostic errors that were made before the establishment of the correct diagnosis.

Arthrogryposis↗
PubMedDate not supplied

Prematurity and early-onset juvenile myasthenia gravis.

A child manifested ocular myasthenia gravis at age 16 months which progressed to bulbar and mild systemic weakness over a 3-year period. The medical history was significant for premature birth at 32 weeks gestation and birth weight 940 gm. A review of reported patients with juvenile myasthenia gravis with adequate documentation of the birth history, noncongenital onset, typical clinical course and diagnostic findings, and elevated titers of antiacetylcholine receptor antibodies revealed that 55% with onset before age 3 years had a history of prematurity. This association of myasthenia gravis and prematurity may provide insights to the pathogenesis of the disease.

Autoantibodies↗
PubMedDate not supplied

MRI of multiple platyspondyly in Gaucher disease: response to enzyme replacement therapy.

Vertebra plana and multiple platyspondyly are complications of aggressive Gaucher disease. Magnetic resonance imaging readily identifies vertebra plana and secondary spinal cord compression. We present a case of a 2-year-old boy with clinically aggressive Type 1 Gaucher disease in whom MRI showed partial reconstitution of the height of a collapsed lumbar vertebral body after 16 months of enzyme replacement therapy.

Child, Preschool↗