An Autopsied Case of Interferon Encephalopathy

Abstract: A 78-year-old male with renal carcinoma was treated with a high dose infusion of interferon-alpha (IFN-alpha) for eight months. The patient had evidence of organlc brain syndrome such 88 : dysfunction of memory, slowing of behavior, and development of mental confusion that appeared eight months after the treatment. MRI at the time of mental confusion revealed difise white matter lesions. Neuropathologic findings were compatible to Binswanger's disease and Senile Dementia of Alzheimer Type (SDAT), Preexisting neurologic abnormalities including intracerebral arteriosclerosis and cerebral atrophy may increase susceptibility to unacceptably severe IFN neurotoxicity.     

Whole-Blood Assay to Measure Oxidative Burst and Degranulation of Neutrophils for Monitoring Trauma Patients

AbstractBackground and Purpose: Polymorphonuclear neutrophils (PMNs) protect the host from invading microorganisms, but excessive PMN activation after trauma causes tissue injury. Rapid monitoring of PMN function is critical for the assessment of the inflammatory state of trauma patients. Here, the authors adapted two simple and rapid methods to measure oxidative burst and degranulation of human PMNs in whole blood to avoid potential interference of cell isolation procedures with the assessment of PMN function.Material and Methods: Heparinized blood was drawn from healthy volunteers or trauma patients, preincubated at 37 °C for 5 min, and stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP). Four assays for oxidative burst were tested: (1) cytochrome C; (2) homovanillic acid (HVA); (3) Amplex^® Red; and (4) flow cytometry with dihydrorhodamine 123 (DHR). PMN degranulation was assessed with flow cytometry using antibodies to: (1) CD11b/Mac-1 (CD18); (2) CD63; and (3) CD66b (CD67).Results: With the exception of the DHR method, all methods to measure oxidative burst were found to be unsuitable in whole blood due to interference of plasma proteins and hemoglobin with the fluorimetric or photometric readouts. By contrast, all degranulation methods were suitable for whole-blood studies. However, for the assessment of formyl peptide-induced degranulation, anti-antibodies to CD11b/Mac-1 and CD66b were up to five times more sensitive than antibodies to CD63. Thus, the degranulation and DHR methods were optimized for increased sensitivity, speed, and specificity and their usefulness to measure PMN function in trauma patients was tested.Conclusion: The whole-blood methods based on flow cytometry with DHR, anti-CD11b/Mac-1, and anti- CD66b are rapid, simple, and reliable techniques to assess PMN function for trauma research.     

Posterior instability near extension is related to clinical disability in isolated posterior cruciate ligament deficient patients

The purpose of this study is to evaluate the relationship between the magnitude of knee laxity and posterior instability at different knee flexion angles and clinical disability in isolated posterior cruciate ligament (PCL) deficient patients. Knee laxity at 20° and 70° of knee flexion were evaluated using KT-2000 arthrometer, and the posterior instability at 20°, 45° and 90° of flexion were evaluated using stress radiography. We assessed the differences in the knee laxity and the tibial translation between isolated PCL deficient knees and normal knees, and between the patients with giving-way during activities of daily living (ADL) and without giving-way. There were statistical differences in the knee laxity and the tibial translation at all knee flexion angles between the PCL deficient knees and normal knees. The magnitude of the knee laxity at 20° of flexion measured with KT-2000 arthrometer was significantly larger in the patients with giving-way than those in the patients without giving-way although there was no significant difference in the tibial translation at 70° between the two groups. The tibial translation in both medial and lateral compartments at 20° and 45° measured with stress radiography were significantly larger in the patients with giving-way than those in the patients without giving-way although there was not significant difference at 90° between the two groups. These results suggested that the magnitude of the knee laxity and the posterior tibial translation at shallow knee flexion angles would be related to giving-way during ADL in isolated PCL deficient patients.     

Morphine-3-glucuronide: hyperglycemic and neuroendocrine potentiating effects

The greater potency of morphine-6-glucuronide (M6G) as well as the inactivity of morphine-3-glucuronide (M3G) with respect to the antinociceptive effects of the parent molecule, morphine (MOR), have been well established. It has been suggested that M3G is an antagonist of MOR's antinociceptive and respiratory depressive effects. The present study addressed the central nervous system (CNS) interaction of these opiate metabolites on their metabolic and hormonal effects. Whole body glucose kinetics were assessed on conscious, chronically catheterized, unrestrained rats. M3G (5 μg) or H₂O (5 μl) was injected intracerebroventricularly (i.c.v.) 15 min prior to the bolus administration of H₂O (5 μl), M6G (1 μg), or MOR (80 μg). i.c.v. M3G (5 μg) resulted in behavioral excitation, hyperglycemia (+50%), stimulation of glucose rate of appearance (R_a; +100%), glucose rate of disappeaance (R_d; +70%), and metabolic clearance rate (MCR; +33%) within 30 min after injection with no alterations in hormone concentrations. i.c.v. M6G and MOR produced progressive hyperglycemia with significantly high catecholamine and corticosterone levels. M3G pretreatment resulted in enhanced elevations in plasma glucose levels (+52% and +18%), plasma lactate (+138% and +108%), norepinephrine (+96% and +30%), and epinephrine (+62% and +67%) in response to both i.c.v. MOR and M6G administration. These findings suggest a non-opiate and non-hormonal mechanism for M3G-induced hyperglycemia. In contrast, the metabolic and hormonal responses to i.c.v. M6G and MOR are associated with elevations in catecholamine and corticosterone levels, which are remarkably enhanced by M3G pretreatment, most likely through accelerated catecholamine release. Our findings suggest a modulatory role for MOR glucuronidation, not only by rendering it inactive, as in the case of M3G, but by an interplay of the metabolic effects of the parent molecule and its metabolite     

What are “clinical practice guidelines”?

Journal of Neurology - An evidence-based approach to the development of clinical practice guidelines has attracted significant attention from physicians' groups as well as from the public....     

Effect of myasthenic IgG on degradation of junctional acetylcholine receptor

We investigated the effect of the lgG from patients with myasthenia gravis (MG) on the degradation of normal rat junctional acetylcholine receptor (AChR) labeled with ¹²⁵l-α-bungarotoxin (BuTx) and calculated the degradation rate (DR). The DR for the lgG from these patients was significantly higher than that from healthy volunteers and patients with other autoimmune diseases. For MG, DR was significantly correlated with the severity of the disease but not with anti-AChR antibody titer. DR was accelerated by lgG from patients with generalized MG whose antibody titers were in the normal range and by lgG from patients with ocular MG. These results indicate that measurement of the DR of junctional AChR in normal rats is more closely correlated with the severity of the disease than is measurement of anti-AChR antibody and that the former is a sensitive and confirmatory method for evaluating MG. © 1993 John Wiley & Sons, Inc.     

Unilateral sudden deafness as a primary symptom of brainstem and cerebellar infarction]

We report a case with a unilateral sudden sensorineural hearing loss caused by an infarction of brainstem and cerebellum. The patient was a 74-year-old male presented with a sudden onset of hearing loss and tinnitus in the right ear and dizziness. Steroid was administered on suspicion of idiopathic sudden deafness. However, the initial symptoms were deteriorated approximately 2 weeks later. He newly complained of the numbness of the right face and double vision, and he was transferred to our hospital for further evaluation. Neurological examination demonstrated horizontal nystagmus, diminution in the right facial sensation, right peripheral facial palsy, right hearing loss and cerebellar ataxia. Urgent MRI disclosed fresh infarctions of the right middle cerebellar peduncle and cerebellum localized in the territory of anterior inferior cerebellar artery. In general, idiopathic sudden deafness and Meniere's disease are frequent diagnosis in cases of sudden hearing loss with vertigo, but these symptoms may rarely be caused by cerebrovascular disorder. In patients with risk factors for arteriosclerosis, cerebrovascular disorder should be taken into consideration even if idiopathic sudden deafness may be suspected clinically. We emphasize the diagnostic importance of careful observation on neurological findings and early detection of radiological abnormalities on MRI.     

A Case of Postbulbar Duodenal Ulcer with Jaundice

Abstract: A 63-year-old man was hospitalized because of jaundice and anorexia. An upper gastrointestinal series and hypotonic duodenography revealed circumferential sclerosis and stenosis of the duodenal wall. Endoscopic examination disclosed an ulcer, the upper margin of which was located at the papilla of Vater. The papilla was situated in the base of the ulcer. Endoscopic retrograde cholangiopancreatography disclosed mild dilatation of the common bile, intrahepatic bile and pancreatic ducts, but with neither severe stenosis nor occlusion. Nevertheless, there was some degree of circumferential compression and mild stenosis of the terminal portions of the bile and pancreatic ducts, as potential causes of obstructive jaundice in this patient. Computed tomographic examination of the abdomen revealed a tumorous lesion at the duodenal bulb. Because malignancy in the duodenum could not be ruled out, a pancreatoduodenectomy was performed. Histopathological examination showed a postbulbar duodenal ulcer, associated with inflammation of the papillary orifice and fibrosis of the region near the papilla. There was no evidence of a tumorous lesion. In this case, a postbulbar duodenal ulcer may have caused obstructive jaundice.