Physical workload and the aging worker: a review of the literature

In two groups of epileptic children receiving carbamazepine (CBZ) therapy with or without valproic acid (VPA) comedication, we investigate the drug interactions of VPA on serum CBZ and its metabolites' concentrations, concentration ratios, and level/dose ratios. Serum total and free CBZ-10, 11-epoxide (CBZ-E) concentrations are significantly increased in patients taking CBZ plus VPA, together with higher CBZ-E/CBZ concentration ratios and CBZ-E level/dose ratios. These results reflect the accumulation of CBZ-E. The decreased concentration ratios of trans-10, 11-dihydroxy-10, 11-dihydro-CBZ (CBZ-H)/CBZ-E observed in patients taking CBZ plus VPA suggest an inhibition in the biotransformation from CBZ-E to CBZ-H. Significant negative correlations are found between serum VPA level and CBZ-H/CBZ-E concentration ratios, indicating that the inhibition of CBZ-E hydrolysis by VPA may depend on the concentration of VPA (total or free CBZ-H/CBZ-E concentration ratio = [formula: see text], respectively). VPA concentration also shows significant positive correlations with CBZ-E and CBZ level/dose ratios. Patients taking CBZ plus VPA have significant higher free fractions of CBZ and CBZ-E than do patients on CBZ alone, suggesting a protein-binding displacement by VPA.     

An active-control trial of lamotrigine monotherapy for partial seizures

OBJECTIVE: We report the results of a double-blind, double-dummy, active-control study designed to evaluate the efficacy and safety of lamotrigine (LTG) administered as monotherapy to adult outpatients with partial seizures. BACKGROUND: The effectiveness of LTG as add-on therapy for partial seizures in adults has previously been established. METHODS: After an 8-week baseline during which patients continued their baseline antiepileptic drug (carbamazepine or phenytoin monotherapy), 156 patients were randomly assigned to receive increasing doses of LTG (target 250 mg b.i.d.) or valproic acid (VPA; target low dose of 500 mg b.i.d.) during the first 4 weeks of an 8-week transition period. Carbamazepine or phenytoin was withdrawn over the next 4 weeks; then patients entered a 12-week monotherapy period. Study drug treatment was discontinued in patients who met predetermined escape criteria for seizure worsening. RESULTS: More patients receiving LTG were successfully maintained on monotherapy compared with patients receiving VPA (56% versus 20%; p < 0.001). The time to meet the escape criteria was also significantly longer in LTG-treated patients (median = 168 days) than in VPA-treated patients (median = 57 days; p = 0.001). The incidence of adverse events during the monotherapy period was lower than during the transition period. Four LTG patients and five VPA patients reported serious adverse events. Two of those patients experienced a rash that led to withdrawal soon after adding LTG to carbamazepine. CONCLUSIONS: We conclude that LTG is effective and well tolerated when administered as monotherapy in adult patients with partial seizures.     

Antiepileptic drug therapy and sexual function in men with epilepsy

PURPOSE: To study the effects of antiepileptic drugs (AEDs) on sex hormone levels and sexual activity in a group of men attending a hospital-based epilepsy clinic. METHODS: One hundred eighteen men being treated with AED therapy, 32 with epilepsy but not receiving AEDs, and 34 controls were recruited. All subjects were aged 18-65 years. Blood (20 ml) was removed for hormone assays, after which each subject completed a validated questionnaire [Sexuality Experience Scores (Frenken and Vennix, 1981)] aimed at exploring the individuals' sexual activity and attitudes to sexual morality. RESULTS: Men taking carbamazepine (CBZ) only had significantly higher mean sex hormone-binding globulin (SHBG) levels than the control group. The CBZ group also had a significantly lower mean DHEAS concentration than the control, untreated, and sodium valproate (VPA) monotherapy groups. The phenytoin monotherapy group (PHT) had a significantly higher mean SHBG than both the control and untreated groups, and had a significantly higher mean total testosterone (TT) value than the control untreated, CBZ, and VPA groups, and a significantly lower mean DHEAS than the controls, untreated, and VPA groups. Men receiving more than one AED had significantly higher mean SHBG concentrations compared with control, untreated, and VPA groups. In addition, the polytherapy group's mean TT was significantly higher than the control and VPA groups, although its mean DHEAS concentration was lower than the control, untreated, and VPA groups. There were no significant differences between the study groups in mean FT, Budrostenedione (AND), or estradiol levels. But the CBZ, PHT, and polytherapy groups had significantly lower mean free and rogen index (FAI) than the controls. The CBZ group had a lower mean FAI than the VPA group. The polytherapy group had a lower FAI than the untreated group. Sexuality Experience Scores (SES) showed that those men receiving AEDs embraced a stricter sexual morality than the controls and untreated, and expressed greater satisfaction with their marriages than the control and untreated groups. CONCLUSIONS: Seizure type did not affect SES scores. Multiple regression showed men who had received further education were less accepting of strict sexual morality.     

Magnesium deficiency-dependent audiogenic seizures (MDDASs) in adult mice: a nutritional model for discriminatory screening of anticonvulsant drugs and original assessment of neuroprotection properties

A great many animal models for audiogenic seizures have been described. The extent to which these models may provide insight into neuroscience fields such as abnormal locomotor behavior (wild running), seizures and anticonvulsants, and neuroinsults and neuroprotectors is examined here by our study of magnesium deficiency-dependent audiogenic seizures (MDDASs) in adult mice. MDDASs were induced in all of the eight tested adult murine strains and are presented as a sequence of four successive components (latency, wild running, convulsion, and recovery phase periods). Compared with several classic seizure tests, the nutritional MDDAS model responded to low doses of prototype antiepileptic drugs (AEDs), including phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), valproic acid (VPA), ethosuximide (ESM), and diazepam (DZP). Modulation by AEDs of the four components of MDDAS indicated that this seizure test was discriminatory, distinguishing between phenytoinergic (PHT, CBZ), GABAergic (PB, VPA, DZP), and ethosuximide (ESM) compounds. Suitability of the MDDAS test for evaluation of neuroprotective compounds was also examined: it showed partial (melatonin) and complete (WEB2170, an anti-PAF agent) reduction of recovery phase by non-anticonvulsant doses of test compounds. These neuroprotective responses were compared with neuroprotective potentials determined in a model of neonatal cerebral injury induced by focal injection of ibotenate (a glutamate analog). WEB2170 and melatonin reduced the size of lesions in white matter, but only WEB2170 protected cortical plate against ibotenate-induced lesions. In addition to the original neuroprotective behavior of WEB2170, studies on the neuroprotectors also supported GABAergic anticonvulsant activity of melatonin in the MDDAS test.     

Therapeutic failure, treatment and non-treatment of childhood epilepsy

INTRODUCTION: The classification of epileptic syndromes defines the prognosis and offers some orientation about treatment in childhood epilepsy. OBJECTIVE: To study the medical therapy according to epileptic syndromes in the everyday practice of a hospital based outpatient neuropediatric clinic. METHODS: Survey of the database using an algorithm to define therapeutic failure, treatment and spontaneous evolution, according to syndrome and drug, of all epileptic patients attended at the clinic during 1966. RESULTS: 465 patients with: monotherapy 38%, politherapy 20%, therapeutic success (follow-up after drug discontinuation) 21%, spontaneous evolution 22% (54% of partial idiopathic epilepsies). Most used antiepileptic drugs (VPA > CBZ > VGB > CLB > PB > PHT > LTG > ESM > PRM > GBT) are those with lowest failure rate and highest percentage of patients on monotherapy. Percentages of monotherapy in treated patients and of previous failure out of total number of patients are: idiopathic partial epilepsies: 85% and 10%; remote symptomatic partial: 58% and 43%; cryptogenic partial: 53% and 50%; idiopathic generalized: 83% and 25%; symptomatic-cryptogenic generalized: 34% and 63%; undetermined: 45% and 43%. CONCLUSIONS: Screening of the database serves as a quality control but the use of an algorithm offers only an approximation to reality. In idiopathic partial epilepsy treatment can be avoided in half of the patients and failure is lowest for VPA and CBZ. In idiopathic generalized epilepsies VPA predominance is almost absolute with a very low failure rate. In all other epileptic syndromes the therapeutic failure rate is about 50% regardless of drug, except for VPA which shows a moderately better outcome.     

New trends in glass-ionomer chemistry

Carbamazepine (CBZ) is an effective anticonvulsant agent. Current literature reports describe several cases of seizure exacerbation and/or EEG worsening due to CBZ with a high prevalence in children and adolescents; we report 10 new cases. Nine patients had epilepsy; one showed delayed psychomotor development and frequent EEG paroxysmal abnormalities. Four patients were on monotherapy, six on polytherapy. All but one had therapeutic CBZ plasma concentrations. Seizures increased in frequency in nine, and in eight patients new seizure types appeared, mostly absences. Cognitive functions/behaviour worsened in eight; EEG recordings showed slowing background activity and increased paroxysmal abnormalities, in six cases diffuse/generalized spike waves were seen and in two continuous spike wave discharges. The mean time of clinical EEG worsening was 1-2 days after introduction of CBZ at therapeutic doses. After CBZ withdrawal clinical EEG improvement was evident in a few days. The underlying pathogenetic mechanism is not yet understood. However, the pathophysiology of seizure exacerbation might be related to the interaction between age-related alterations in the balance of excitation and inhibition in the developing thalamocortical circuitry and the essential activity of CBZ that tends to induce interictal discharges.     

TSH suppression combined with carbimazole for Graves' disease: effect on remission and relapse rates

OBJECTIVE: We studied the influence of TSH suppressive therapy combined with carbimazole (CBZ) on treatment outcome in Graves' disease. DESIGN: Open non-randomized prospective study. SETTING: University Hospital of Montpellier, France. SUBJECTS: Sixty-six consecutive patients without prior treatment were included. All the patients were treated initially with 30 mg of CBZ. After 1 month of treatment, one group continued CBZ alone (n = 23), another group received a combination of CBZ plus T3 (n = 19) and a third group received CBZ and 3,5,3'-triiodothyroacetic acid (Triac, n = 24). Therapy was stopped when remission was obtained based on clinical euthyroidism, normalization of FT4 and of early radioiodine uptake. Nine patients with medical treatment failure or major side effects requiring to stop antithyroid drugs underwent surgery or radioiodine therapy. Nine patients were lost to follow-up. The remaining 48 patients were available for analysis of both remission and relapse. RESULTS: The median duration of therapy was 18 months (range, 4-41 months). Based on clinical examination, goitre size at 4 months decreased more in the CBZ + T3 and CBZ + Triac groups than in the CBZ group (P = 0.02). The overall remission rate tended to be higher in the groups treated with CBZ + T3 and CBZ + Triac than in the group treated with CBZ alone, but the difference did not reach statistical significance (P = 0.17). No difference in the relapse rate was observed between the three groups. CONCLUSION: TSH suppression combined with CBZ has little or no effect on remission and relapse rates in Graves' disease patients.     

Positive and negative psychotropic effects of lamotrigine in patients with epilepsy and mental retardation

PURPOSE: To describe significant positive or negative psychotropic effects of lamotrigine (LTG) observed in epilepsy patients with mental retardation (MR). METHODS: Seven mentally retarded epilepsy patients, [5 with Lennox-Gastaut syndrome (LGS)] who experienced significant behavioral improvements or worsening after addition of LTG to their medication regimen were studied. RESULTS: LTG produced behavioral improvements in 4 patients. Patient 1, a 14-year-old girl, had LTG added to valproate (VPA) and thioridazine, resulting in diminished lethargy, less hyperactivity, and more appropriate speech. In a 17-year-old boy (patient 2) LTG added to VPA, phenytoin (PHT), and gabapentin (GBP) lessened irritability and hyperactivity. In patient 3, a 41-year-old woman, LTG added to PHT, VPA, and carbamazepine (CBZ) diminished lethargy and enhanced her social interactions. In patient 4, a 27-year-old man, LTG monotherapy diminished irritability and hyperactivity. Adverse behavioral effects were noted in 3 patients. In patient 5, a 43-year-old man, LTG added to PHT, phenobarbital (PB), lorazepam, sertraline, and thioridazine produced irritability, hyperactivity, and poor cooperation. In patient 6, a 29-year-old woman, LTG added to VPA produced frequent screaming, temper tantrums, increased rocking movements, and hyperactivity. In patient 7, a 29-year-old man, LTG added to VPA and PHT resulted in severe exacerbation of baseline behaviors, including self-injurious activity, temper tantrums, and failure to obey simple instructions. CONCLUSIONS: In some patients with epilepsy and MR, LTG has significant positive or negative effects on behavior.     

Reversible parkinsonism induced by prolonged treatment with valproate

We describe two patients who developed levodopa-responsive parkinsonism without dementia at least 4 years after beginning chronic valproate (VPA) treatment for seizures. Parkinsonism disappeared in less than 3 months after VPA substitution with carbamazepine.     

Quality of life in children with congenital heart defects

PURPOSE: The antiepileptic effects of zonisamide (ZNS) have been well documented experimentally and clinically. The purpose of this study was to examine whether ZNS reduces cerebral damage after transient focal ischemia in rats. METHODS: Ischemia was induced by a transient occlusion of the left middle cerebral artery (MCA) with a 3-0 nylon monofilament for 90 min. Neurological evaluation was performed by measuring the event of neurological deficit of the contralateral forepaw and hindpaw at 10 min and 1 day after MCA occlusion (MCAo). Brain infarct size was determined by measuring triphenyltetrazonium chloride-negative stained area of the serial brain sections 1 day after MCAo. RESULTS: The pre- or postischemic treatment with ZNS [(10-100 mg/kg p.o.), 30 min before and 4 h after or 15 min and 4 h after the occlusion] markedly reduced cerebral damage in the ipsilateral hemisphere and the neurological deficit induced by transient ischemia. The reducing effect on the damage was observed in the cortical and subcortical regions. Preischemic treatment with carbamazepine (CBZ 60 mg/kg p.o. twice 30 min before and 4 h after MCAo) tended to reduce the cerebral damage and neurological deficit, but the lower dose (20 mg/kg p.o. twice) did not. Valproate (VPA 1,000 mg/kg p.o. twice) also had no effect. CONCLUSIONS: ZNS at the anticonvulsant dose, unlike CBZ and VPA, ameliorated the brain infarction and the event of neurological deficit after transient focal cerebral ischemia. These data suggest that ZNS has therapeutic potential in protecting against ischemic cerebral damage, such as stroke.     

Pharmacodynamic interaction between phenytoin and sodium valproate changes seizure thresholds and pattern

1. In this study we used cortical stimulation to assess the effects of phenytoin (PHT), sodium valproate (VPA), and their interaction on total motor seizure and on the constituent elements of the seizure. 2. PHT (40 mg kg(-1)) was administered as an intravenous bolus infusion to animals receiving either a continuous infusion of VPA or saline. VPA plasma concentration was maintained at levels that produced no detectable anticonvulsant effect. 3. Analysis of ictal components (eyes closure, jerk, gasp, forelimb, clonus, and hindlimb tonus) and their durations revealed both qualitative and quantitative differences in drug effects. 4. The anticonvulsant effect is represented by the increase in the duration of the stimulation required to reach a given seizure threshold. PHT significantly increased the duration of the stimulation and of the motor seizure. This increase was greatly enhanced by VPA. In addition, ictal component analysis revealed that the combination of PHT and VPA causes the reduction of a specific seizure component (JERK). 5. Neither the free fraction of PHT nor the biophase equilibration kinetics changes in the presence of VPA. It is concluded that the synergism may be due to a pharmacodynamic rather than a pharmacokinetic interaction.     

Adjustment of carbamazepine dose to offset the effects of the interaction with remacemide hydrochloride in a double-blind, multicentre, add-on drug trial (CR2237) in refractory epilepsy

PURPOSE: The efficacy of remacemide hydrochloride (REM) as an antiepileptic drug (AED) was tested in a double-blind, add-on trial in patients with refractory epilepsy. Concurrent drugs included carbamazepine (CBZ). The interfering effects of the pharmacokinetic interaction between REM and CBZ were offset by the monitoring of plasma CBZ concentration and the appropriate reduction of CBZ dose by an unblinded observer. METHODS: Patients taking CBZ entered a 4-week run-in period to stabilise their dosage regimen to Tegretol tablets and blinded capsules containing Tegretol tablets. They then entered an 8-week baseline period during which variation of plasma CBZ concentration was used to derive an individual Shewart Control Chart for each patient. These charts were used to define the threshold for CBZ dose reduction after the addition of trial drug. Where necessary the unblinded observer adjusted that portion of the daily dose of CBZ concealed in the opaque capsules, thereby maintaining the blind for the investigator and the patient. RESULTS: CBZ dosage reductions ranging from 14 to 50% were required by 63% of patients who received REM. Substantial increases in plasma CBZ concentration, which would have confounded the results of the trial, were thus avoided. The small increases in CBZ concentration that occurred in spite of this procedure were of similar magnitude in responders (patients who experienced > or =50% reduction in seizure frequency during treatment) and nonresponders, and in both groups the mean increase was <1 mg/L. CONCLUSIONS: The method is offered as a model solution for problems caused by pharmacokinetic interactions in add-on trials.     

Study on the suitability of a rat model for tardive dyskinesia and the preventive effects of various drugs

1. Male Sprague-Dawley rats (weighing 260-300 g) were administered 1.5 mg/kg of haloperidol (HPD) intraperitoneally once daily for 28 days to produce an animal model for tardive dyskinesia (TD). The daily administration of HPD significantly increased the frequency of involuntary orofacial movements (chewing movements, tongue protrusions and buccal tremors). 2. Its suitability as a model for TD was assessed in terms of the therapeutic effects of 6 drugs [trihexyphenodyl hydrochloride(THP), clonazepam(CZP), sodium valproate(VPA), alpha-tocopherol(Vit E), ritanserin(RS) and propranolol hydrochloride(PPL)]. These drugs were also used concomitantly with HPD to study their preventive effect. 3. As for the therapeutic effects of the drugs, both the single and the 14-day daily administrations of CZP as well as of VPA significantly suppressed the chewing movements. The results were mostly consistent with the effect of each drug on human TD, indicating this would be an excellent model for TD in terms of the drug responsiveness. 4. The concomitant administration of RS from the start of HPD administration significantly suppressed the appearance of chewing movements. The concomitant administration of Vit E for 42 days also suppressed chewing movements and buccal tremors. On the other hand, the concomitant administration of THP tended to aggravate these involuntary movements. 5. The fact that the therapeutic and preventive effects of the drugs on this model differed suggested that the development and recovery of the movements might also differ, at least in part.     

Antiepileptic effects of tiagabine, a selective GABA uptake inhibitor, in the rat kindling model of temporal lobe epilepsy

PURPOSE: We determined the antiepileptic profile of tiagabine (TGB), a selective gamma-aminobutyric acid (GABA) uptake inhibitor, in the rat kindling model of temporal lobe epilepsy (TLE). METHODS: The anticonvulsant and adverse effects of TGB were examined in amygdala- or hippocampal-kindled rats and compared with those of other GABA uptake inhibitors (SKF89976A and NNC-711) and conventional antiepileptic drugs [AEDs: valproate (VPA) and carbamazepine (CBZ)]. In addition, the antiepileptogenic effects of TGB on amygdala kindling development were examined. RESULTS: TGB (2.5-40 mg/kg intraperitoneally, i.p.) had potent and dose-dependent anticonvulsant effects on both amygdala- and hippocampal-kindled seizures. The order of anticonvulsant potency of the three GABA uptake inhibitors tested was: NNC-711 > TGB > SKF-89976A and paralleled the in vitro GABA uptake efficacy. In addition, daily treatment with TGB 10 mg/kg for 10 days significantly retarded kindling development. Although adverse effects of TGB on motor systems were significantly less than those of VPA and CBZ, high toxic doses of TGB often caused EEG paroxysm and myoclonus. CONCLUSIONS: Our results indicate the clinical usefulness of TGB for treatment of drug-resistant TLE.     

Maternal use of antiepileptic drugs and the risk of major congenital malformations: a joint European prospective study of human teratogenesis associated with maternal epilepsy

PURPOSE: To quantify the risks of intrauterine antiepileptic drug (AED) exposure in monotherapy and polytherapy. METHODS: Data from five prospective European studies totaling 1,379 children were pooled and reanalyzed. Data were available for 1,221 children exposed to AED during pregnancy and for 158 children of unexposed control pregnancies. RESULTS: Overall, when comparing a subgroup of 192 children exposed to AED with 158 children of matched nonepileptic controls, there was an increased risk of major congenital malformations (MCA) in children exposed to AED during gestation [relative risk (RR) 2.3; 95% confidence interval (CI): 1.2-4.7]. A significant increase in risk was found for children exposed to valproate (VPA) (RR 4.9; 95% CI: 1.6-15.0) or carbamazepine (CBZ) (RR 4.9; 95% CI: 1.3-18.0) in monotherapy. When comparing different AED regimens during all 1,221 pregnancies, risks of MCA were significantly increased for the combination of phenobarbital (PB) and ethosuximide (RR 9.8; 95% CI: 1.4-67.3) and the combination of phenytoin, PB, CBZ, and VPA (RR 11.0; 95% CI: 2.1-57.6). Offspring of mothers using > 1,000 mg VPA/day were at a significantly increased risk of MCA, especially neural tube defects, compared to offspring exposed < or =600 mg VPA/day (RR 6.8; 95% CI: 1.4-32.7). No difference in risk of MCA was found between the offspring exposed to 601-1,000 mg/day and < or =600 mg/day. CONCLUSIONS: This reanalysis shows that VPA is consistently associated with an increased risk of MCA in babies born to mothers with epilepsy. Significant associations were also observed with CBZ. Larger prospective population-based studies are needed to evaluate the risks of many other less frequently prescribed treatment regimens, including newly marketed AEDs.     

Primary intracerebral small lymphocytic non-Hodgkin''s lymphoma with plasmacytoid differentiation, associated with prominent extracellular proteinaceous deposits

Surgical treatment is increasingly used for patients with medically re fractory seizures. Valproate (VPA) is an effective, widely used anticonvulsant in this patient population, but believed by some researchers to increase surgical bleeding because of quantitative thrombocytopenia and functional defects in platelet aggregation. Because we have observed no clinical evidence that perioperative administration of VPA increases blood loss or complications related to postoperative bleeding in patients undergoing temporal lobectomy at our institution, we sought to test this hypothesis. We made a retrospective review of the medical records of all patients who underwent epilepsy surgery at the University of California, San Francisco Medical Center, from September 1986 through January 1993. Patients who had a temporal lobectomy and whose medical records documented preoperative platelet counts and pre- and postoperative hematocrit and hemoglobin values were included. We excluded patients who had cranial surgery before temporal lobectomy and those with intracranial neoplasms or vascular malformations. Patients were divided into two groups: those who received VPA in the immediate preoperative period and those who had not received VPA recently. We compared the estimated surgical blood loss and the estimated change in red blood cell (RBC) volume between groups by unpaired t tests. The charts of 87 consecutive patients qualified for inclusion in the study. Patients in the VPA group had relative (but not absolute) thrombocytopenia preoperatively (235 +/- 64 vs. 277 +/- 69 k in the No-VPA group). There were no differences in the estimated blood loss, RBC volume, or in the incidence of postoperative transfusion. VPA apparently does not increase complications of hemostasis during therapeutic surgical resections for epilepsy. Therefore, we do not recommend routinely discontinuing VPA before craniotomy.     

Carbamazepine reduces dopamine-mediated behavior in chronic neuroleptic-treated and untreated rats: Implications for treatment of tardive dyskinesia and hyperdopaminergic states.

Chronic treatment with neuroleptic drugs such as haloperidol (HAL) can result in a syndrome of abnormal involuntary movements known as tardive dyskinesia (TD). The authors have obtained evidence that TD in humans is reduced in patients also taking anticonvulsant drugs, primarily carbamazepine (CBZ). To test for a causal role of CBZ in this effect, the authors quantified abnormal movements elicited by dopamine (DA) receptor stimulation in rats (Rattus norvegicus) withdrawn from chronic treatment with HAL or CBZ alone or in combination. The expected increased behavioral responsiveness to combined D1/D2 stimulation in rats treated with HAL for 8 weeks was significantly attenuated by chronic CBZ, which also attenuated behavioral responsiveness in otherwise untreated rats. Striatal D2 DA receptor density was elevated in rats treated chronically with HAL but unaffected by CBZ. Striatal D1 DA receptor density was elevated by chronic CBZ but unaffected by HAL. These findings suggest that by reducing DA supersensitivity, CBZ may be useful in treating TD and other hyperdopaminergic states. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Involvement of c-myc in the resistance of non-obese diabetic mice to glucocorticoid-induced apoptosis

We conducted a multicentered, retrospective review of clozapine's (CZP) effects on a range of psychiatric, sleep, cognitive, motor, and sensory disorders in Parkinson's disease (PD). Therapeutic outcomes and adverse events were compared with varying prescribing practices at participating sites. The medical records of 172 consecutive PD patients treated with CZP at four movement disorder clinics were reviewed. Low-dose CZP improved psychiatric symptoms of psychosis, anxiety, depression, hypersexuality, sleep disturbance, and akathisia. Tremor, torticollis, limb dystonia, and pain showed modest rates of improvement. Twenty-three percent of patients withdrew as a result of adverse events or treatment failure. Inpatient CZP initiation did not improve therapeutic efficacy, or reduce adverse events or the withdrawal rate. Low-dose CZP in the outpatient setting is generally an effective and well-tolerated treatment for many of the psychiatric, sleep, motor, and sensory disturbances common to late-stage PD.     

Incidence of retinal detachment after cataract surgery and neodymium: YAG laser capsulotomy

The objective of this retrospective study was to determine the incidence of retinal detachment (RD) in patients following cataract extraction with intraocular lens placement and after neodymium:YAG (Nd:YAG) laser capsulotomy. This study comprised 1092 patients (1168 eyes) who had cataract extraction and related procedures between January 1986 and December 1992 identified from the coding and billing database. Of the 1092 patients, 215 (244 eyes) had had Nd:YAG laser capsulotomy. Their charts were reviewed for incidence of RD, and these data were correlated with age, sex, axial length, surgical complications, and other surgical procedures done at the time of cataract extraction. The incidence of RD following phacoemulsification alone was 0.75% (6/799), with a mean time between cataract extraction and RD of 11.6 months. The cases of RD after extracapsular cataract extraction, combined phacoemulsification and trabeculectomy, combined extracapsular cataract extraction and penetrating keratoplasty, and combined phacoemulsification and anterior vitrectomy were too few to draw any conclusions. The incidence of RD following Nd:YAG laser capsulotomy was 0.82% (2/244), with a mean time of 32 months between cataract surgery and capsulotomy and 13.5 months between capsulotomy and RD. There was a statistically significant higher incidence of RD after posterior capsule rupture and anterior vitrectomy than after uncomplicated phacoemulsification (2/12 versus 6/799). In conclusion, the rate of RD after uncomplicated phacoemulsification was less than or similar to the rate found in other recent studies. It was not statistically different from the rate following phacoemulsification and Nd:YAG laser capsulotomy (0.82%). This study confirms the increased risk of RD following posterior capsule rupture and anterior vitrectomy.     

Bispectral EEG index during nitrous oxide administration

Recent reports suggest an increased incidence of cytomegalovirus (CMV) infection in recipients of unrelated donor (UD) bone marrow transplantation (BMT). In this study we have collated the incidence of CMV infection and disease in sequential UD (n = 119) and related donor (RD; n = 79) BMT performed in a single institution over a 7-year period. Low-risk patients (CMV seronegative recipient and donor) accounted for 51% of UD BMT (n = 61) and 62% of RD BMT (n=49), with CMV excretion documented in one RD BMT only. The remaining high-risk patients received identical prophylaxis regimens with aciclovir and intravenous immunoglobulin (IVIG). Two groups consisting of 58 UD BMT (median age 9.0 years, range 0.7-45.3 years) and 30 RD BMT (median age 13.6 years. range 1.6-47.6 years) were analysed. CMV reactivation/re-infection was documented in 15 UD BMT (26%) and 10 RD BMT (33%) (P = 0.72), and CMV disease in four UD BMT (8%) and four RD BMT (13%) (P = 0.533). In this series the risk of CMV excretion and disease following UD BMT was similar to that following RD BMT.