Peroneal nerve repetitive nerve stimulation test: Its value in diagnosis of myasthenia gravis and Lambert–Eaton myasthenic syndrome

We have developed a repetitive nerve stimulation (RNS) technique for the peroneal nerve. Normal limits for the decremental responses for the anterior tibialis and extensor digitorum brevis muscles are 6–21% at the low rate of stimulation and 44–70% at the high rate of stimulation. These values exceed the normal limits for other commonly tested muscles. This may be due to the lower safety factor for neuromuscular transmission for the anterior tibialis and extensor digitorum brevis muscles. We present 4 cases in which the peroneal nerve RNS test was crucial for the diagnosis of the limb-girdle form of MG or LEMS. Thus, we conclude that, in a small number of patients with neuromuscular transmission disorders, the peroneal nerve RNS test is needed for confirmation of disease. © 1995 John Wiley & Sons, Inc.     

The efficacy and safety of armodafinil as treatment for adults with excessive sleepiness associated with narcolepsy

OBJECTIVE: This study assessed the efficacy and safety of armodafinil, the longer half-life enantiomer of modafinil, for the treatment of excessive sleepiness in patients with narcolepsy. RESEARCH DESIGN AND METHODS: This was a multicenter double-blind study with 196 patients (aged 18-65 years) randomized to receive armodafinil 150 mg (n = 65), armodafinil 250 mg (n = 67), or placebo (n = 64) once daily for 12 weeks. MAIN OUTCOME MEASURES: Efficacy was assessed using the Maintenance of Wakefulness Test (MWT) (six 20-min subtests across the day), the Clinical Global Impression of Change (CGI-C), subjective measures of sleepiness (Epworth Sleepiness Scale), patient diaries, and evaluations of cognitive performance (Cognitive Drug Research) and fatigue (Brief Fatigue Inventory). RESULTS: Armodafinil significantly increased MWT mean sleep latency (at 0900-1500) compared with placebo. The mean change from baseline at final visit for armodafinil was an increase of 1.3, 2.6, and 1.9 min in the 150-mg, 250-mg, and combined groups, respectively, compared with a decrease of 1.9 min for placebo (p < 0.01 for all three comparisons). Mean late-day MWT latency (1500-1900) was also significantly improved (difference of armodafinil combined group relative to placebo at final visit: 2.8 min, p = 0.0358). The proportions of patients who showed at least minimal improvement in the CGIC rating from baseline to final visit in the armodafinil 150-mg, 250-mg, and combined groups were 69%, 73%, and 71%, respectively, compared with 33% for placebo (p < 0.0001). Both doses were associated with statistically significant improvements in memory, attention, and fatigue (p < 0.05). The most common adverse events in patients receiving armodafinil were headache, nausea, and dizziness. CONCLUSIONS: Armodafinil significantly improved ability to sustain wakefulness throughout the day in patients with narcolepsy. Armodafinil also significantly improved overall clinical condition, memory, attention, and fatigue when compared with placebo.     

Adapting Smoking Relapse–Prevention Materials for Pregnant and Postpartum Women: Formative Research

Objective: To decrease smoking relapse among pregnant and postpartum women by adapting existing, validated relapse–prevention materials to meet the unique needs of pregnant and postpartum women. Methods: A series of semi-structured interviews and learner verification activities were conducted with pregnant abstinent, postpartum abstinent, and postpartum relapsed women. Results were used to create new relapse–prevention materials, specific to the needs of pregnant and postpartum women, which are currently being used in a randomized clinical trial. Results: Findings are consistent with the recurrent themes in the literature regarding smoking cessation among pregnant and postpartum women and revealed exceptional needs for coping and stress reduction strategies related to remaining abstinent postpartum. Conflict levels were also high in areas of identity, social support, and reasons for quitting. Conclusion: By interviewing women about their cessation related needs, the current study was able to produce smoking relapse–prevention materials specific to this population. Having pregnant and postpartum women review the modified program materials before starting the clinical trial enhanced the quality, dependability, and validity of the materials. We await the results of the clinical trial to determine if this intervention is indeed more efficacious than previous attempts to intervene with this population.     

Drug monitoring and toxicology: a procedure for the monitoring of levetiracetam and zonisamide by HPLC-UV

This article describes a rapid isocratic high-performance liquid chromatographic (HPLC) method for the simultaneous measurement of the anticonvulsants levetiracetam and zonisamide. Monitoring these drugs is important for detecting potentially toxic concentrations, particularly in patients with renal impairment, but no commercial assays are currently available. Following a liquid-liquid extraction, levetiracetam (5-150 microg/mL) and zonisamide (5-80 microg/mL) are quantitated by HPLC-UV. The assay's limit of quantitation, linearity, imprecision, and accuracy adequately cover the therapeutic range of these drugs. The assay should be attractive to clinical laboratories because the run time for quantification of both drugs is approximately 5 min per sample, and no interferences are currently known.     

Health care-associated Staphylococcus aureus bloodstream infections: a clinical quality indicator for all hospitals

Staphylococcus aureus bloodstream (SAB) infections are common and serious causes of morbidity and mortality that incur considerable health care costs and are potentially preventable, Australia. It should be relatively easy for hospitals to collect data on the incidence of SAB episodes, to determine whether infections were acquired in hospital or in the community, and to establish whether they were health care associated. The proportion of SAB infections caused by methicillin-resistant S. aureus strains should be a useful indicator of the level of control of antibiotic resistance in the community and in the health care setting. Continuous monitoring of infection incidence would enable health care facilities to determine the effectiveness of interventions designed to minimise SAB infections.     

Lipoprotein (a) in pregnancy: a critical review of the literature

In this article the literature on lipoprotein (a) during normal pregnancy and pregnancy complicated by preeclampsia or intrauterine growth restriction is reviewed. MEDLINE, from January 1966 to May 2003, was searched to locate relevant articles in English. Additional publications were identified by reviewing references in selected articles. Studies were reviewed by predefined and strict criteria. It appeared that methodology and results of studies on lipoprotein (a) during normal and complicated pregnancy were very diverse. Lipoprotein (a) increased with advancing gestation or remained unaltered during normal pregnancy. Women with preeclampsia had higher, unaltered or lower lipoprotein (a) concentrations as compared to normal pregnant controls. Only few studies were in agreement with most of the review criteria. In conclusion, published studies on lipoprotein (a) in pregnancy differ substantially in the used methods to measure lipoprotein (a), sample size, study design and ethnicity of the study population. Therefore, these studies yielded conflicting results and no unequivocal view on the role of lipoprotein (a) in normal and complicated pregnancy. Recommendations for future studies are amongst others: the use of an apo(a) independent method for measuring Lp(a), inclusion of sufficient numbers of patients, the use of a longitudinal study design when the objective is to study the changes of Lp(a) during pregnancy and selection of a study population that is ethnically representative for the general population.     

Development and regeneration of motor systems under the influence of ACTH peptides

ACTH peptides exert quantitative and qualitative influences on the formation and maturation of motor units in developing and regenerating neuromuscular systems. ACTH 4–10, administered daily (10 μg/kg.s.c.) from the day of birth, accelerated the rate at which muscle strength developed in the immature rat, the effect of this peptide being most marked in animals 11–15 days old. A similar increase in grasping time occurred in ACTH 4–10 treated animals, indicating that the peptide affects neuronal maturation at a time in development when organization and maturation of the neuromuscular system is most active. The synthetic analogue of ACTH 4–9 (Org 2766), administered in the same dosage, had little effect on these parameters, indicating a differential sensitivity to these similar peptides. Elevated circulating titers of ACTH, whether exogenous (0.2 U ACTH 1–39 IP daily), or endogenous (adrenalectomy), stimulated the formation of more functional motor units, as indicated by increased amplitude of muscle action potentials and tetanic tension following nerve stimulation. ACTH appears to favor the recovery of high threshold, small-size motor units. Fine control of muscle function in peptide-treated animals is partially restored, as indicated by the return of stepwise recruitment to an extent not seen in the reinnervated, saline-treated controls.     

Regulatory considerations for novel gene therapy products: a review of the process leading to the first clinical lentiviral vector

This review is intended to exemplify the roles and responsibilities of the two agencies under the Department of Health and Human Services, the National Institutes of Health and the Food and Drug Administration, that have oversight for human gene transfer clinical protocols, as seen through our experience of bringing a first-in-its-class lentiviral vector to clinical trials. In response to the changing circumstances in gene therapy research between 1999 and 2002, the concerns of these agencies regarding gene therapy have been evolving. This review provides an overview of the major safety concerns regarding insertional oncogenesis, the generation of a replication- competent lentivirus (RCL), and vector mobilization thought to be related to lentiviral vectors, which had to be addressed during the regulatory review process before initiating the clinical trial. Specific monitoring assays to address these concerns were established to test for RCL generation, vector mobilization, persistence of vector-modified cells, and abnormal clonal expansion of modified cells. We hope to provide a basic understanding and appreciation of the regulatory process and major safety concerns, toward providing useful insight to those presently embarking on the development of clinical application of lentiviral vectors.