Glutamine and vitamin E in the treatment of hepatic veno-occlusive disease following high-dose chemotherapy

PURPOSE: To analyze the nonfatal adverse events (AE) associated with a first episode of status epilepticus (SE). METHODS: We performed a population-based retrospective cohort study to determine the morbidity of SE. Participants included 184 residents of Rochester, Minnesota who experienced nonfebrile SE between 1965 and 1984. RESULTS: The etiology of SE was acute symptomatic in 100 patients and unprovoked in 84 patients. The most common seizure-types were continuous partial (n=56, 30%), generalized convulsive (n=52, 28%), and generalized with focal features (n=32, 17%). Morbidity related to SE was noted in 5 of the 146 patients (3.4%) surviving 30 days. The AE included hemiparesis (n=3), encephalopathy (n=2), mental retardation (n=1), and aphasia (n=1). All patients with morbidity had an acute symptomatic (n=4) or remote symptomatic (n=1) etiology. Thirty-four patients (18.5%) had a second episode of SE. CONCLUSIONS: Based on this retrospective study, significant morbidity related to SE is uncommon and is associated with the underlying etiology.     

Short-term mortality after a first episode of status epilepticus

PURPOSE: Studies evaluating short-term mortality among people who experience status epilepticus (SE) have produced conflicting results. Most studies are derived from clinical series with results affected by unspecified follow-up period and select referral of cases. This study was planned to evaluate short-term mortality after a first episode of SE. METHODS: We performed a population-based retrospective cohort study to determine the short-term mortality following a first episode of SE. Between January 1, 1965 and December 31, 1984, we studied all first episodes of afebrile SE who received medical attention in Rochester, Minnesota. Cases were followed until death or end of the study (February 1996). RESULTS: Mortality within the first 30 days was 19% (38 deaths out of 201 incident SE). Thirty-four deaths (89%) occurred among those with nonfebrile acute symptomatic SE, while 4 deaths (11%) occurred among those with unprovoked SE. Within the acute symptomatic group, after adjusting for age, there was a decreased risk of death in women (RR = 0.4; 95% CI: 0.2-0.9). No effect of duration or seizure type was shown after adjusting for other risk factors. CONCLUSIONS: One out of 5 subjects with SE died within the first 30 days. Short-term mortality is associated with the presence of an underlying acute etiology. Among acute symptomatic cases, women had a decreased risk of dying.     

The influence of diabetes on neurological outcome and mortality in stroke patients

In a retrospective study of diabetic and non-diabetic patients with acute ischaemic stroke, mortality and neurological outcome were assessed. Mortality was determined 4 weeks after admission. The study population consisted of the consecutive patients (n = 609) admitted to the Department of Neurology with acute stroke between January 1994 and December 1995. There were 80 diabetic and 529 non-diabetic patients. The mortality rate was higher in diabetics (36.3%) than in non-diabetics (27%), but the difference was not significant (p = 0.08). The neurological status on admission, age, history of arterial hypertension, atrial fibrillation and coronary arterial disease were used to select groups of 41 diabetics and 84 non-diabetics with similar risk factors and similar onset of stroke. The neurological status on 10-th, 20-th and 28-th day of the hospital stay in both groups was compared. The study showed that insulin-dependent diabetics and older patients (above 65 years of age) with diabetes demonstrated a worse neurological outcome than non-diabetic patients, although the difference was not significant.     

Medical and surgical therapy in diverticular disease: a comparative study

The course of 132 patients with documented acute diverticulitis was analyzed: 99 patients treated medically and 33 patients treated surgically were followed for an average of 9.2 years. Seventy-three per cent of the medical group and 79% of the surgical group had no further symptoms or hospital admissions as a result of their diverticular disease once they were recovered from the acute episode. For three-quarters of the patients, therefore, acute diverticulitis occurred as a single episode that responded to either medical or surgical management. Considering the morbidity and cost to the patient, the treatment of the patient recovered from acute diverticulitis should be medical, with operation reserved for complications.     

Current management of acute leg ischaemia: results of an audit by the Vascular Surgical Society of Great Britain and Ireland

BACKGROUND: Management of acute leg ischaemia has changed in recent years. This study aimed to elucidate current practice throughout the UK and Ireland. METHODS: Surgeons and audit departments were asked to return a questionnaire about every episode of acute leg ischaemia seen in the hospital between 1 January and 31 March 1996. RESULTS: A total of 539 episodes were reported in 474 patients (248 men) aged 19-96 (median 73) years. Common causes were thrombosis in situ (41 per cent), embolism (38 per cent) and graft or angioplasty occlusion (15 per cent). Vascular surgical advice was requested in 95 per cent of cases. Initial management was: immediate embolectomy in 21 per cent, anticoagulants in 13 per cent and no vascular intervention in 10 per cent. Arteriography was done in 56 per cent, followed by 186 endovascular and 165 surgical interventions. At 30 days, 70 per cent of limbs were definitely viable and 16 per cent had been amputated. The mortality rate was 22 per cent. Cases were reported by 86 of 182 hospitals contacted, but some referred no patients, and a supplementary audit of 54 cases (10 per cent size of the original sample) from non-contributing hospitals showed no important differences. CONCLUSION: Patients with acute leg ischaemia are generally treated by vascular specialists, with modern methods and acceptable results. This is being achieved despite insufficient vascular surgeons and radiologists for formal emergency rotas in most hospitals.     

Recommendations of the Brain Tumor Subcommittee for the reporting of trials. SIOP Brain Tumor Subcommittee. International Society of Pediatric Oncology

Depression was examined in 45 patients evaluated within 2 months of diagnosis of MS. At the time of testing, 40% of the MS sample met the diagnostic criteria for major depression, 22% had adjustment disorder with depressed mood and 37% showed no evidence of mood disorder. Personal and family history of depression in patients with MS was also examined and compared with a sample of patients with chronic low back pain (CLBP) who were matched for age, gender, marital and employment status and current level of depression. Fifty-two per cent of patients with MS reported experiencing a depressive episode before the onset of MS compared with 17% of patients with CLBP (P < 0.001). Sixteen patients with MS (35%) reported family history (parent or sibling) of treatment for depression compared with seven (15%) of patients with CLBP (P < 0.05). MS patients with a history of depression reported more initial symptoms than MS patients without a history of depression. Clinical and theoretical implications of the findings are discussed.     

Similarities between pleuropulmonary blastoma and Askin tumor

AIM: The purpose of the study was to determine the risk of postoperative complications and the functional outcome after a hand-sewn ileal pouch-anal anastomosis (IPAA) for ulcerative colitis using a single J-shaped pouch design. METHODS: Preoperative function, operative morbidity and long-term functional outcome were assessed prospectively in 1310 patients who underwent IPAA between 1981 and 1994 for ulcerative colitis. RESULTS: Three patients died after operation. Postoperative pelvic sepsis rates decreased from 7 per cent in 1981-1985 to 3 per cent in 1991-1994 (P = 0.02). After mean follow-up of 6.5 (range 2-15) years, the mean number of stools was 5 per day and 1 per night. Frequent daytime and nighttime incontinence occurred in 7 and 12 per cent of patients respectively, and did not change over a 10-year period. The cumulative probability of suffering at least one episode of 'clinical' pouchitis was 18 and 48 per cent at 1 and 10 years and the cumulative probability of pouch failure at 1 and 10 years was 2 and 9 per cent respectively. CONCLUSION: These results indicate that increased experience decreases the risk of pouch-related complications and that with time the functional results remain stable, but the failure rate increases.     

Hypoxic-ischemic encephalopathy in newborn infants. Acute period and outcome

Ninety four neonates with hypoxic ischemic encephalopathy HIE attended at the University of Ribeir?o Preto since 1982 were studied in terms of the neurological alterations during the acute phase and outcome over a mean period of 47 months. From 43 newborns with HIE I, 40 recovered within 96 hours and 3 died. Among 40 infants with HIE II, 37.5% recovered within the first week, and the others continued abnormal beyond the 7th day. All 11 infants with HIE III died before the second month of life. The HIE I group had no motor sequelae. Among the HIE II group, 34.5% showed cerebral palsy and 17.7% neuromotor retardation. 80.0% of those with sequelae persisted abnormal beyond 7th day of life, during the acute phase of the HIE. Epilepsy occurred in 17.5% of cases with HIE grade II, only among those with neuromotor sequelae. The IQ test did not show statistically significant difference between the HIE I, II without motor sequelae and the control groups. The authors reaffirm the value of the findings in the acute phase of HIE on the outcome of these patients.     

Natural history of adhesional small bowel obstruction: counting the cost

BACKGROUND: The aim of this study was to identify patients admitted with adhesional obstruction to determine if there was an identifiable pattern to the type of initial operation, the type of treatment used for the obstructive episode and the subsequent need for further treatment. METHODS: Patients with adhesional obstruction were identified retrospectively in a cross-sectional study using ICD codes relating to admissions in the years 1990 to 1996. The case notes were used to assess their outcome. RESULTS: Fifty-nine case notes from a total of 175 identified initially satisfied the inclusion criteria. These patients had a mean age at presentation of 51 (range 16-88) years and had undergone a total of 122 operations. Thirty-one patients (53 per cent) had a single previous operation with a median time to presentation with obstruction of 5.5 years (range 11 days to 34.7 years); 33 patients (56 per cent) were treated conservatively on their first admission. There was no statistically significant difference in the outcome in patients who received either conservative or surgical treatment. The length of stay in patients treated surgically (median 11 (range 2-47) days) was significantly longer than that for those treated conservatively (median 6 (range 1-39) days) (P< 0.001). A flow chart was constructed demonstrating the eventual outcome of the patients in the study, enabling the cost of adhesional obstruction to be calculated. CONCLUSION: This type of approach could be used to assess the potential effect of different treatment strategies for adhesional obstruction.     

Extracranial neuroblastomas and neurological complications

Between October 1989 and March 1997, 25 pediatric inpatients were treated for primary extracranial neuroblastoma (NB; n=20) or ganglioneuroblastoma (GNB; n=5) at the University of Istanbul, Institute of Pediatric Oncology, and these children were the subjects of this retrospective study. Seventeen (68%) of these patients experienced 19 neurological complications during the course of their disease. Fourteen had nervous system metastases or invasion. Nonmetastatic complications, including CNS infections (n=3) and new onset of seizures (n=2) secondary to metabolic encephalopathy were seen in 5 cases. By the time of the final analysis of the results, 8 of the 17 patients with neurological complications had died, 7 had either been lost to follow-up (n=4) or were in the terminal stage of their disease (n=3), and 2 were in remission. Both of the patients who were in remission had dumbbell neuroblastoma (DNB), and 1 of them, with congenital DNB, also had neurological sequelae, characterized by paraplegia and neurogenic bladder. Neurological complications occurred in 68% of NB and GNB cases. Metastatic complications were more common than nonmetastatic complications and had a poor prognosis. Neurological complications were the primary cause of mortality in this study, mortality being related to neurological complications in 63% of cases, and the final outcome was worse than expected. However, regardless of any differences in social, economic and geographic factors and different treatment protocols for NB in different pediatric oncology institutions, neurological complication rates in pediatric NB are similar in all.     

Disorders of granulocytes induced by toxic agents

In 152 consecutively selected patients with detrusor hyperreflexia (DH) 96 (63 per cent) had neurological disorders. Thirty-two patients did not show any primary neurological or urological cause for DH. This group was chosen to elucidate the evaluation of possible neurological symptoms in relation to the urological symptomatology. Nine had died and one failed to appear to the neurological examination. Twelve (63 per cent) of the 22 examined patients showed signs of lesions in different parts of the central nervous system, particularly cerebrovascular diseases and myeloneuropathy. Six had had neurological symptoms for years. In two the urological symptoms were first to appear. In the group with no neurological complaints the urological symptoms had existed for 2-30 years. No essential difference was found in the degree of voiding disturbance whether or not neurological signs were disclosed. It is concluded that the discovery of DH should be followed by a neurological examination to disclose further signs of lesions in CNS. Likewise, an extended urological examination with demonstration of DH might help in the evaluation of an obscure neurological disease.     

Bilateral loss of vestibular function: clinical findings in 53 patients

The clinical presentations and aetiologies of a series of 53 cases of bilateral vestibular failure (BVF) seen by the authors over a decade were evaluated by retrospective review of the medical records. Thirty-nine per cent of patients had associated neurological disease; 13% had a progressive cerebellar syndrome with disabling gait ataxia, abnormal eye movements and cerebellar atrophy on neuro-imaging. BVF was usually unsuspected. Nine per cent had cranial or peripheral neuropathies and in this group there was no abnormality of brain stem/cerebellar oculomotor function, but hearing loss was common. Eleven per cent revealed BVF and hearing loss secondary to meningitis, and 6% had other neurological disorders. Idiopathic BVF was found in 21% of cases, characterised by paroxysmal vertigo and/or oscillopsia, but no abnormal clinical signs. Gentamicin ototoxicity accounted for a further 17%, while autoimmune disease was present in 9% of patients. Otological or neoplastic disease was diagnosed in the remaining 13% of patients. It was concluded that neurological, audiological and ocular motor assessments allow the probable cause of BVF to be defined in approximately 80% of cases. A group of BVF related to autoimmune pathologies is reported for the first time, indicating the need for immunological screening. Idiopathic BVF may present with only minor visual or vestibular symptoms, while in patients with cerebellar degeneration, BVF may be unsuspected and, thus, underdiagnosed.     

Large ice crystals in the nucleus of rapidly frozen liver cells

Twenty-one infants who had virologically confirmed exanthem subitum and central nervous system (CNS) complications were studied to elucidate the clinical features, laboratory and virological findings, and outcome. The primary infection with human herpesvirus 6 was confirmed by isolation of the virus from blood, a significant rise in the antibody titers to the virus, or both. All convulsive seizures (15 generalized and 6 focal) occurred during the pre-eruptive stage of exanthem subitum. Four infants with encephalitis/encephalopathy had more severe clinical features with abnormalities demonstrated on electroencephalograms and cerebral computed tomograms. All infants except those with encephalitis/encephalopathy recovered without any sequelae. One infant with encephalitis/encephalopathy developed epilepsy and another one died. Human herpesvirus 6 DNA amplified by the nested polymerase chain reaction method was detected in the cerebrospinal fluid of 6 infants, including 3 with encephalitis/encephalopathy, of 11 patients examined by the fifth day of the illness. These findings suggest that CNS complications including encephalitis/encephalopathy occur at the pre-eruptive stage of exanthem subitum, that human herpesvirus 6 invades the CNS in some patients, and that the outcome is not always benign.     

Liver failure in children with hepatitis A

There have been very few reports dealing with liver failure related to hepatitis A in children. Moreover, the criteria usually used for selecting patients with fulminant hepatitis A for liver transplantation have not been evaluated in children. Therefore, the current study was conducted retrospectively in a single French urban pediatric liver transplantation center to serve as a reminder of the potential severity of hepatitis A in children and to identify predictors of outcome. Children were selected by chart review using a data base system and were grouped according to outcome for analyses purposes. Over a 15-year period, 24 children with hepatitis A showed evidence of liver failure, including 6 children who did not develop hepatic encephalopathy, 7 children in whom encephalopathy occurred but resolved spontaneously, and 11 children in whom death or liver transplantation was the outcome. The mean age at onset was 6.5 years. Those with the most rapid onset of liver failure from onset of jaundice had the best chance of recovery without developing encephalopathy. Otherwise, no predictive factors of outcome were found at onset of liver failure. Among the 18 children who developed encephalopathy, the best early prognostic indicator of a poor outcome irrespective of the grade of encephalopathy, appeared to be a prothrombin time level below 21% of normal combined with a serum bilirubin level above 400 micromol/L. Therefore, these two prognostic indicators may be helpful in deciding liver transplantation in children with hepatitis A-induced fulminant liver failure.     

Tumor necrosis factor blockade in actively induced experimental autoimmune encephalomyelitis prevents clinical disease despite activated T cell infiltration to the central nervous system

Recently, we demonstrated that experimental autoimmune encephalomyelitis (EAE) in the rat, passively transferred using myelin basic protein (MBP)-reactive encephalitogenic CD4+ T cells, was preventable by administration of a p55-tumor necrosis factor-IgG fusion protein (TNFR-IgG). This was despite quantitatively and qualitatively normal movement of these MBP-specific T cells to the central nervous system (CNS). To extend these findings, the effect of TNFR-IgG on EAE actively induced by injection of MBP in complete Freund's adjuvant was examined. This form of EAE in the rat typically involves an acute, self-limiting neurological deficit, substantial CNS inflammation, but minimal demyelination. Here we show that administration of TNFR-IgG prior to onset of disease signs completely prevented the neurological deficit or markedly reduced its severity. This blockade of clinical disease was dissociated from weight loss which occurred at the same tempo and magnitude as in control rats exhibiting neurological signs of disease such as paralysis. The timing of TNF blockade was critical as established clinical disease was relatively refractory to TNFR-IgG treatment. Activated CD4+ T cells expressing normal or elevated levels of VLA4, major histocompatibility complex class II, MRC OX40 and CD25 were isolated from or immunohistochemically localized in the CNS of clinically healthy rats treated before disease onset. There was a reduction of the amount of other inflammatory leukocytes in the CNS of these treated animals but, more importantly, the activation state of inflammatory leukocytes, as well as that of microglia isolated from treated animals, was reduced. Thus, TNFR-IgG, when administered before disease onset, appears to act by inhibiting an effector function of activated T cells and possibly other inflammatory leukocytes necessary to bring about the neurological deficit. However, while TNF is a critically important cytokine for the early events leading to initiation of EAE, it is not a necessary factor in the acute neurological deficit characteristic of this form of EAE, once disease onset has occurred.     

Generalized tonic-clonic status epilepticus: causes, treatment, complications and predictors of case fatality

We retrospectively reviewed the clinical course of 66 patients treated for generalized tonic-clonic status epilepticus at the Ege University neurological intensive care unit from 1988 to 1997. Seventy-two per cent of the study group had a pre-existing seizure disorder, and antiepileptic drug withdrawal was the most prominent cause of status epilepticus. The other causes included drug toxicity, central nervous system infection, cerebrovascular disease, tumour and trauma. Seventy-three per cent of all patients responded to the first-line therapy (diazepam and/or phenytoin), and the remainder were considered to have refractory status epilepticus and required pentobarbital anaesthesia. Overall case fatality was 21%, but death could be attributed directly to status epilepticus and/or treatment complication in 10% of the study group. Major determinants of fatal outcomes were: increasing age, longer duration of status epilepticus before initiation of therapy and central nervous system infection as a causal factor.     

Effect of exercise on acid-base status and ventilatory kinetics

OBJECTIVES: To study the clinical spectrum of an acute severe encephalopathy occurring in 2 patients after recovery from falciparum malaria infection and to compare it with the reported clinical features of the postmalaria neurological syndrome. DESIGN: Case report. SETTING: Tertiary care hospital. PATIENTS: Two patients presented with acute onset of fluctuating motor aphasia, severe generalized myoclonus, and postural tremor. Additional signs were cerebellar ataxia, and in 1 patient, generalized epileptic seizures. Magnetic resonance imaging of the brain revealed patchy white matter lesions in 1 patient. Clinically, the patients' conditions continued to worsen until corticosteroids were introduced, the use of which induced a rapid, albeit incomplete, recovery. CONCLUSIONS: We describe a new, severe variant of the still poorly defined postmalaria neurological syndrome. We propose a preliminary classification of this syndrome, according to its clinical characteristics, as follows: a mild or localized form, characterized by isolated cerebellar ataxia or postural tremor; a diffuse, but relatively mild encephalopathic form, characterized by acute confusion or epileptic seizures; and a severe, corticosteroid-responsive encephalopathy that is characterized by motor aphasia, generalized myoclonus, postural tremor, and cerebellar ataxia.     

Lubeluzole treatment of acute ischemic stroke. The US and Canadian Lubeluzole Ischemic Stroke Study Group

BACKGROUND AND PURPOSE: Lubeluzole is a novel benzothiazole compound that has shown neuroprotective activity in preclinical models of ischemic stroke. The present multicenter, double-blind, placebo-controlled study was conducted to assess the efficacy and safety of lubeluzole in the treatment of ischemic stroke. METHODS: Seven hundred twenty-one patients with clinical symptoms of acute ischemic stroke were randomized to receive either lubeluzole (7.5 mg over 1 hour, followed by a continuous daily infusion of 10 mg for up to 5 days) or placebo. Treatment was initiated within 6 hours of symptom onset. Mortality at 12 weeks was the primary efficacy end point. Secondary efficacy end points included neurological recovery (based on the National Institutes of Health Stroke Scale [NIHSS]), functional status (based on the Barthel Index), and level of disability (based on the Rankin Scale). Safety assessments included standard and continuous electrocardiographic monitoring, physical examination, measurements of vital signs, clinical laboratory evaluation, and adverse events reports. RESULTS: The overall mortality rate at 12 weeks for lubeluzole-treated patients was 20.7% compared to 25.2% for placebo-treated patients (NS). Controlling for relevant covariates, the degree of neurological recovery (NIHSS) at week 12 significantly favored lubeluzole over placebo (P = .033). Lubeluzole treatment similarly resulted in significantly greater improvements in functional status (Barthel Index) (P = .038) and overall disability (Rankin Scale) (P = .034) after 12 weeks. A global test statistic confirmed that lubeluzole-treated patients had a more favorable clinical outcome at 12 weeks (P = .041). The safety profile of lubeluzole resembled that of placebo. CONCLUSIONS: Treatment with lubeluzole within 6 hours of the onset of ischemic stroke had a nonsignificant effect on mortality and resulted in improved clinical outcome compared with placebo, with no safety concerns.     

EEG diagnostic and predictive value on HIV infection in childhood

This prospective study evaluated the electroencephalographic (EEG) diagnostic and prognostic value in childhood HIV infection. It was carried out on 125 subjects and included all Piemonte's seropositive children. The EEG was repeated every three months during the first 15 months of life, and then, at least, annually in the P1 and P2 group. Data of group P2 was compared blindly to that of the seroconverted control group of the same age and risk. EEG results were normal in P0, P1 and control patients. In group P2, EEG was abnormal in 35.5% of subjects, of these 54.6% developed an encephalopathy with a delay of 2.5 months to 2 years 11 months. EEG is therefore useful to evaluate early CNS damage and to identify onset features and evolution of encephalopathy in P2 patients.     

Effects of aspirin treatment on survival in non-insulin-dependent diabetic patients with coronary artery disease. Israeli Bezafibrate Infarction Prevention Study Group

We studied seizures that occur during the acute phase of aseptic and bacterial meningitis in childhood. Of the 108 children with aseptic meningitis, five had seizures (4.7%). Four patients developed them within 24 hours of the onset of the initial symptom (fever in 3 cases), and three had repeated seizures on the first day. One case had SIADH complication, but another neurologic abnormalities were not observed. On the 18 children with bacterial meningitis, three cases (16.7%) had seizure, which occurred on the second day of illness. Disturbance of consciousness and cerebral hypertension were observed in 2 cases each, and abnormal cerebral CT findings in all the three. The NSE level in the cerebrospinal fluid was elevated in 2 cases. Thus, seizures occurring in the acute phase of aseptic meningitis may reflect transient cerebral functional abnormality accompanying fever or SIADH, whereas those in bacterial meningitis may result from neural tissue damage due to encephalopathy or angitis. In aseptic and bacterial meningitis, the presence of seizures in the acute phase was not correlated with the neurological outcome.