The managed care solution: let the patients decide.
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Consumer Behavior↗
Biomedical subjects
J C Goodman
Publications and source records attributed to J C Goodman.
Medisave accounts in Singapore yield positive results.
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Cost Savings↗
Solving the health care crisis: medical savings accounts.
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Cost Control↗
Cowden syndrome and Lhermitte-Duclos disease.
BACKGROUND: Cowden syndrome (CS) is a rare but underdiagnosed autosomal dominant condition also known as "multiple hamartoma-neoplasia syndrome." Patients have multiple tricholemmomas (a type of benign skin appendage tumor) and oral papillomatosis and cutaneous keratoses. They often have goiter, gastrointestinal polyps, and hamartomatous soft tissue lesions. Breast cancer affects approximately one third of women with CS. Lhermitte-Duclos disease (LDD) is a peculiar proliferation of abnormal neuronal elements of the cerebellum that has features of a hamartoma and of a neoplasm. METHODS: The authors described two patients who have both CS and LDD. Also reviewed were 50 of approximately 62 previously described cases of LDD (identified through literature searches) in an effort to find patients with LDD who had other associated lesions. RESULTS: Only one other patient in whom both LDD and CS were recognized has been reported. In addition, a number of patients with LDD who had other neoplasms and/or thyroid lesions have been described. CONCLUSIONS: Given the rarity of these two entities, we believe that their association is not fortuitous. LDD fits into the concept of CS as a hamartoma-neoplasia syndrome. In addition, a number of patients with LDD who had other neoplasms or thyroid lesions have been reported, raising the possibility that CS and LDD are more closely linked than is generally appreciated. We suspect that there are more patients with LDD who have unrecognized CS. Patients with either of the two diseases should be examined and followed up for evidence of the other.
Adult↗
Dietary nonprotein calories and cerebral infarction size in rats.
BACKGROUND AND PURPOSE: Conventional diets may cause hyperglycemia in patients with neurological injuries. The purpose of this study was to examine the effect on the severity of cerebral infarction of replacing carbohydrates as the primary dietary source of nonprotein calories. METHODS: Sixty-nine Long-Evans rats were either fasted for 24 hours, fed isocaloric amounts of a control diet containing 51.5% of the calories as carbohydrates, or fed one of five experimental diets before middle cerebral artery occlusion for 45 minutes. In the experimental diets, 60% of the carbohydrate calories were replaced with one or more of the following substrates: 1,3-butanediol, triacetin, tributyrin, and long- and medium-chain triglycerides. RESULTS: The plasma glucose concentration in the fasted animals was 6.4 +/- 1.1 mumol/ml. In the animals receiving the control diet, which contained the greatest number of carbohydrate calories, plasma glucose was 9.1 +/- 1.4 mumol/ml. The 1,3-butanediol diet resulted in an intermediate plasma glucose concentration averaging 7.8 +/- 1.3 mumol/ml. Plasma beta-hydroxybutyrate levels were elevated in the fasted group and with the 1,3-butanediol diet. Plasma acetate levels were increased with the diets supplemented with triacetin. The smallest infarct volume (53 +/- 43 mm3) was found in the fasted group and the largest (162 +/- 56 mm3) in the control diet group. Infarct volumes that were significantly smaller were found with the 1,3-butanediol diet (98 +/- 41 mm3) and with the triacetin/tributyrin diet (105 +/- 53 mm3). The volume of the infarct was directly related to the plasma glucose concentration before ischemia (n = 69, r = 0.47, p less than 0.01), but not to plasma lactate, ketone body, or acetate levels. CONCLUSIONS: It may be possible to develop a diet for patients with neurological injuries using noncarbohydrate calorie sources, such as 1,3-butanediol, triacetin, or tributyrin, that would supply systemic caloric and protein requirements without the adverse effect of conventional diets.
Animals↗
Blood flow and metabolic therapy in CNS injury.
A hypermetabolic state, consisting of increased resting energy expenditure, excessive protein wasting, and hyperglycemia, occurs in patients with a severe head injury. The hypermetabolism can affect survival by rapidly resulting in protein-calorie malnutrition (increased energy expenditure and protein wasting) and may adversely affect neurological recovery by altering the microenvironment of the injured brain (hyperglycemia).
Animals↗
Respiratory epithelial cyst ventral to the brain stem. Report of a case and review of the literature.
We present the case of a 30-year-old woman who suddenly developed intense occipital headaches. Computed tomography and magnetic resonance imaging demonstrated a cyst located ventrally to the brain stem at the pontomedullary junction. The lesion was resected. Histologically, it was lined by a pseudostratified, ciliated, columnar epithelium indistinguishable from respiratory epithelium. Immunohistochemistry and electron microscopy confirmed the epithelial differentiation of the lining. This case is briefly compared with the few other brain-stem cysts presented in the literature and the concept of their "origin" is discussed.
Adult↗
Segmental release of amino acid neurotransmitters from transcranial stimulation.
The present study used microdialysis techniques in an intact rabbit model to measure the release of amino acids within the lumbar spinal cord in response to transcranial electrical stimulation. Dialysis samples from the extracellular space were obtained over a stimulation period of 90 minutes and were examined using high pressure liquid chromatography. Neuronal excitation was verified by recording corticomotor evoked potentials (CMEPs) from the spinal cord. A significant increase in the release of glycine and taurine compared to sham animals was measured after 90 minutes of transcranial stimulation. Glutamate and aspartate release was not significantly elevated. GABA concentrations were consistently low. CMEP components repeatedly showed adequate activation of descending fiber pathways and segmental interneuron pools during dialysis sampling. Since glycine, and to a lesser extent taurine, have been shown to inhibit motor neuron activity and are closely associated with segmental interneuron pools, suprasegmental modulation of motor activity may be, in part, through these inhibitory amino acid neurotransmitters in the rabbit lumbar spinal cord.
Amino Acids↗
Release of segmental amino acid neurotransmitters in response to peripheral afferent and motor cortex stimulation: a pilot study.
The role of amino acid (AA) neurotransmitters in the spinal cord has been primarily studied using in vitro preparations and histochemical methods. The technology necessary to estimate AA levels in an intact animal has only recently become available. Such an investigation could yield valuable information regarding the segmental neurochemical environment. We measured the release of AAs into the rabbit lumbar spinal cord in response to sciatic nerve and transcranial stimulation with stereotaxically placed microdialysis catheters. Samples were obtained periodically during 90 minutes of continuous stimulation of either the left or right sciatic nerve, or motor cortex. Quantification of gamma-amino butyric acid (GABA), aspartate, glutamate, glycine, and taurine was performed using high pressure liquid chromatography (HPLC). Adequate neural excitation was verified by recording somatosensory evoked potentials (SSEPs) or corticomotor evoked potentials (CMEPs). Sensory activation at intensities sufficient to activate small and large diameter peripheral fibers of the ipsilateral (to the microdialysis probe) sciatic nerve produced a significant change only in segmental glycine levels. Contralateral sciatic nerve stimulation failed to evoke a significant elevation of AAs. In addition, a significant increase in the release of glycine and taurine was measured after 90 minutes of transcranial stimulation. SSEP and CMEP components repeatedly showed adequate activation of primary afferent, descending motor fiber pathways, and segmental interneuron pools during dialysis sampling. Our data are consistent with the hypothesis that suprasegmental influence over peripheral afferent and motor activity may be, in part, through these amino acid neurotransmitters in the rabbit lumbar spinal cord.
Amino Acids↗
Recovery of amino acid neurotransmitters from the spinal cord during posterior epidural stimulation: a preliminary study.
Continuous posterior epidural spinal cord stimulation (SCS) has been an effective method for treating spasticity. The mechanisms of SCS include activation of inhibitory segmental neuronal systems and suprasegmental structures that produce inhibitory descending control. The neurochemical correlates of the mechanism of action have not been clearly defined. Microdialysis of the spinal cord extracellular space in an in vivo preparation during continuous epidural SCS was performed. The recovery of amino acid neurotransmitters, aspartate, glutamate, gamma-aminobutyric acid (GABA), glycine, and taurine from stimulated animals was compared to non-stimulated animals. Evoked potentials from the cortex and spinal cord of the stimulated animals were recorded to insure that there had been adequate epidural stimulation and normal segmental cord function. A significant increase in the concentration of glycine was seen after 90 minutes of continuous stimulation. The levels of the other amino acids were not significantly elevated. These results suggest that amelioration of spasticity with epidural SCS may involve enhanced glycine release, the major inhibitory neurotransmitter of the spinal cord.
Amino Acids↗
The effect of glucose administration on carbohydrate metabolism after head injury.
The role of intravenous infusion of glucose in limiting ketogenesis and the effect of glucose on cerebral metabolism following severe head injury were studied in 21 comatose patients. The patients were randomly assigned to alimentation with or without glucose. Systemic protein wasting, arterial concentrations of energy substrates, and cerebral metabolism of these energy substrates were monitored for 5 days postinjury. Both groups were in negative nitrogen balance, and had wasting of systemic proteins despite substantial protein intake. Blood and cerebrospinal fluid (CSF) glucose concentrations were highest on Day 1, but remained higher than normal fasting levels on all days of study, even in the patients who received no exogenous glucose. Although there were no differences in blood or CSF glucose concentrations in the two groups of patients, the glucose group had higher plasma insulin levels, with a mean +/- standard deviation of 14.8 +/- 7.3 microU/ml compared to 10.3 +/- 4.2 microU/ml in the saline group. The blood concentrations of beta-hydroxybutyrate, acetoacetate, pyruvate, glycerol, and the free fatty acids were higher in the saline group than in the glucose group. Cerebral oxygen consumption was similar in the two groups, while the cerebral metabolism of glucose and of the ketone bodies was dependent on whether glucose was administered. In the glucose group, glucose was the only energy substrate utilized by the brain. In the saline group, the ketone bodies beta-hydroxybutyrate and acetoacetate replaced glucose to the extent of 16% of the brain's total energy production. Cerebral lactate production and CSF lactate concentration were lower in the saline group. These studies suggest that administration of glucose during the early recovery period of severe head injury is a major cause of suppressed ketogenesis, and may increase production of lactic acid by the traumatized brain by limiting the availability of nonglycolytic energy substrates.
3-Hydroxybutyric Acid↗
Spinal cord ischemia-induced elevation of amino acids: extracellular measurement with microdialysis.
Excitatory amino acids have been implicated in the production of calcium mediated neuronal death following central nervous system ischemia. We have used microdialysis to investigate changes in the extracellular concentrations of amino acids in the spinal cord after aortic occlusion in the rabbit. Glutamate, aspartate, glutamine, asparagine, glycine, taurine, valine, and leucine were measured in the microdialysis perfusate by high pressure liquid chromatography. The concentrations of glutamate, glycine, and taurine were significantly higher during ischemia and reperfusion than controls. Delayed elevations in the concentrations of asparagine and valine were also detected. The elevation of glutamate is consistent with the hypothesis that excitotoxins may mediate neuronal damage in the ischemic spinal cord. Increased extracellular concentrations of asparagine and valine may reflect preferential use of amino acids for energy metabolism under ischemic conditions. The significance of increased concentrations of inhibitory amino acid neurotransmitters is unclear.
Amino Acids↗
Elevation of tumor necrosis factor in head injury.
Tumor necrosis factor (TNF) is a cytokine which mediates protein wasting in pathological states by promoting the catabolism of visceral tissues and skeletal muscle. The role that TNF plays in nitrogen wasting following head injury was studied by measuring TNF in the serum of 21 patients with severe head injury. Parallel measurements of TNF and urinary nitrogen excretion were performed on days 1, 3, and 5 after head injury. TNF values after head injury ranged from 65 pg/ml to 7500 pg/ml, with a mean of 1147 pg/ml, compared to control values of serum TNF of less than 38 pg/ml. The mean daily urinary nitrogen loss was 13 g/day with a range of 2.8 to 27.6 g/day, and the mean nitrogen balance was -5.8 g with a range of +4.6 to -19.1 g. While both serum TNF levels and nitrogen loss were increased after head injury, the elevation of TNF did not correlate strongly with nitrogen wasting.
Adult↗
Reduction in spinal cord postischemic lactic acidosis and functional improvement with dichloroacetate.
Pyruvate dehydrogenase complex (PDHC) is a major enzyme of glucose metabolism. Dichloroacetate (DCA) is a noncompetitive inhibitor of PDHC kinase, an enzyme that inactivates PDHC. We examined the effects of DCA on extracellular lactate and pyruvate concentration changes and spinal somatosensory evoked potentials (SSEP) in ischemic rabbit spinal cords. In the first group of 26 animals, the aorta was occluded until postsynaptic SSEP waves were completely suppressed for 10 min, a period of ischemia that causes neurologic deficits in 50% of untreated animals. DCA (25 mg/kg) was given to 13 of these animals before ischemia. In the second group of 24 animals, the aorta was occluded until the postsynaptic SSEP waves were absent for 20 min, a period of ischemia that produces paraplegia in 100% of untreated animals. DCA (25 mg/kg) was given to 16 of these animals just before the aortic occlusion was released. After occlusion, extracellular spinal lactate concentrations increased abruptly while pyruvate concentrations fell. Both lactate and pyruvate concentrations reached a plateau during the ischemic period but increased when the aortic balloon was deflated. DCA-treated animals had lower lactate and pyruvate peak concentrations during reperfusion, as well as more rapid and greater recovery of SSEP at 2 h after reperfusion. DCA did not alter spinal metabolism during the ischemia but appeared to produce a more rapid shift to glucose metabolism on reperfusion. Thus, DCA treatment resulted in better electrophysiological recovery after both moderate and severe ischemia, either by reducing lactic acidosis or by increasing the recovery rate of aerobic energy production.
Acetates↗
Autoradiographic assessment of the sequence of cellular proliferation in postpneumonectomy lung growth.
To determine the extent and sequence of proliferation of the various types of cells in postpneumonectomy lung growth, 4-wk-old male Sprague-Dawley rats were injected with tritiated thymidine prior to sacrifice on days 2, 4, 7, and 10 after left pneumonectomy. Autoradiography of sections from each lobe of the remaining lung was performed and compared to controls. All of the cell types studied, both parenchymal and nonparenchymal, participated in postpneumonectomy lung growth. Mesothelial cell labeling peaked on day 2 and declined thereafter. Labeling of alveolar endothelial cells, alveolar interstitial cells, types I and II pneumonocytes, bronchial epithelium, and nonparenchymal endothelium occurred in parallel, peaking on day 4. The different lobes had equal percentages of dividing cells, suggesting that a global stimulus such as an endocrine factor has a dominant role in postpneumonectomy lung growth.
Animals↗
Alterations in the corticomotor evoked potential following spinal cord ischemia.
A simple yet reliable model of spinal cord ischemia has been previously developed by inserting a Swan-Ganz catheter into the abdominal aorta of rabbits and inflating the balloon just inferior to the renal arteries. Recent investigations have shown that paraplegia is consistently reproduced if the balloon remains inflated for 20 min after loss of the N3 component of the somatosensory evoked potential. Because of its high reliability, this model has been frequently and successfully used to determine the efficacy of pharmacological agents thought to provide protection against spinal cord ischemia. Results from the present report demonstrate that a similar degree of reliability can be achieved in this model for testing motor activity. A simple method of evoking highly reproducible motor potentials, that can be percutaneously recorded from the spinal cord in response to cortical stimulation, was developed. Predictable and repeatable changes in the configuration of the corticomotor evoked potential were found during spinal cord ischemia and reperfusion. With this added dimension of functional assessment, future application of the current spinal cord ischemia model have been greatly expanded.
Action Potentials↗
Autosomal dominant familial angiolipomatosis clinically mimicking neurofibromatosis.
The autosomal dominant form of familial angiolipomatosis may be mistaken for peripheral neurofibromatosis (NF-1) due to the similarity of the family history and the occurrence of multiple subcutaneous masses, but histopathological examination of the tumors readily distinguishes these two diseases. We report here a case of familial angiolipomatosis, which was initially though to be neurofibromatosis, and the occurrence in this patient of a granular cell tumor similar to such tumors occasionally seen in neurofibromatosis. A review of the literature discloses intriguing parallels between familial angiolipomatosis and neurofibromatosis, suggesting that similar pathogenetic mechanisms may operate in both diseases.
Adult↗
Alterations in cerebral availability of metabolic substrates after severe head injury.
Cerebral and systemic metabolism of oxygen, glucose, lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, and amino acids were studied in 27 comatose patients during the first 7 days after a head injury. Systemic oxygen consumption was elevated initially and gradually returned toward normal over the week of study. In contrast, cerebral oxygen consumption was depressed and decreased further over the week of study. Cardiac output and cerebral blood flow were increased with respect to systemic and cerebral metabolic requirements, and remained elevated for the entire week of study. Systemic hyperglycemia and lactic acidosis were present. The injured brain often made a sizeable contribution to the lactic acidosis. The arterial concentrations of pyruvate, beta-hydroxybutyrate and acetoacetate were low. The early postinjury arterial amino acid profile was typically an increased level of alanine, taurine, glutamic acid, and a reduced concentration of valine, leucine, isoleucine, threonine, serine, ornithine, and arginine. At 3-4 days postinjury, as the early abnormalities were returning toward normal, glutamine, lysine, phenylalanine, tyrosine, and methionine became elevated. These late increases in amino acids occurred at the time of the peak in plasma catecholamine concentrations. The net cerebral flux of amino acids followed the same general pattern of evolution over time as did the arterial concentration of amino acids. On days when the availability of the individual amino acid was increased, the net cerebral flux tended to be positive; when the availability was decreased, the net cerebral flux was zero or there was a net efflux of the amino acid. There was a significant linear relationship between the arterial concentration and the net flux of 13 of the 17 amino acids studied. Unlike the fasting state in normal man, in which beta-hydroxybutyrate and acetoacetate are important metabolic substrates, cerebral metabolism after head injury is almost totally dependent upon the aerobic and anaerobic metabolism of glucose. This is at least in part due to injury-induced limitations in the variety of substrates that are available for the brain to extract.
Adolescent↗