A double blind, randomised, parallel group study to investigate the dose equivalence of Dysport® and Botox® in the treatment of cervical dystonia

OBJECTIVE—This study was designed toestablish whether a ratio of three units of Dysport^® isequivalent to one unit of Botox^® for the treatment ofcervical dystonia.
METHODS—Patients with predominantly rotationalcervical dystonia, and a minimum of four previous Botox treatments,were randomised to receive either the clinically indicated dose ofBotox or three times that dose in Dysport units. Study botulinum toxinwas administered in a double blind fashion, to one or more clinicallyindicated muscles, at one or more sites per muscle. Patients returnedfor assessment two, four, eight, and 12 weeks after treatment.
RESULTS—A total of 73 patients (Dysport, 38;Botox, 35) were entered. The Dysport group received a mean (SD) dose of477 (131) (range 240-720) Dysport units, and the Botox group receiveda mean (SD) dose of 152 (45) (range 70-240) Botox units. The mean(SEM) post-treatment Tsui scores for the Dysport group (4.8 (0.3)) andthe Botox group (5.0 (0.3)) were not statistically different (p=0.66).The study had 91% power to detect a clinically significant differenceof two points. Both groups showed substantial improvement in Tsui scoreby week 2 (mean (SD); Dysport, 46 (28)%; Botox, 37 (28)%), with apeak effect at week 4 (mean (SD); Dysport, 49 (29)%; Botox, 44 (28)%). A similar response profile was seen for other assessments ofefficacy. The duration of effect, assessed by time to retreatment, wasalso similar (mean (SD); Dysport, 83.9 (13.6) days; Botox, 80.7 (14.4)days; p=0.85). During the study 22 of 38 (58%) Dysport patientsreported 39 adverse events, and 24 of 35 (69%) Botox patients reported56 adverse events (p=0.35). A global assessment of efficacy and safetyconsidered that 29 of 38 (76%) Dysport patients and 23 of 35 (66%)Botox patients were treatment successes (p=0.32).
CONCLUSION—Patients with predominantly rotationalcervical dystonia treated with the clinically indicated dose of Botoxor three times that dose in Dysport units show similar improvements anddo not have significantly different safety profiles.

     

Early dissemination of Borrelia burgdorferi without generalized symptoms in patients with erythema migrans

The diagnosis of erythema migrans (EM) is not always easy, and reports of culture- or PCR-confirmed diagnosis as well as reports of EM with simultaneous disseminated disease are few. Characteristics and incidence of EM in addition to frequency of early dissemination of B. burgdorferi were studied in the archipelago of South-Western Finland prospectively using questionnaires, skin biopsies and blood samples. Clinical EM was recognized in 82 patients (incidence 148/100,000 inhabitants/year). Of skin biopsy samples, 35.5% were positive by PCR (the majority B. garinii), and 21.5% by cultivation (all B. garinii). Of blood samples, 3.8% were positive by PCR, and 7.7% by cultivation. Of the patients, 30.9% were seropositive at the first visit, and 52.9% 3 weeks later. Of the patients with laboratory confirmed diagnosis, the EM lesion was ring-like in 31.8% and homogeneous in 65.9%. Dissemination of B. burgdorferi, based on culture or PCR positivity of blood samples, was detected in 11.0% of the patients. The frequency of generalized symptoms was nearly the same in patients with as in those without dissemination (22.2% vs 27.4%). Only 21.4% of the patients with culture-positive EM recalled a previous tick bite at the site of the EM lesion. We conclude that EM lesions are more often homogeneous than ring-like. B. burgdorferi may disseminate early without generalized symptoms.     

Monitoring drug therapy: an applied approach

While it has been agreed that drug therapy monitoring in health care institutions is desirable and necessary, the pharmacists who carry out such programs must have a system that fills their special needs. Pharmaceutical Consultant Services, P.A. has developed a manual monitoring system to provide patient profiles for long-term care patients. This instruction guide explains the system and its application; pharmacists may wish to use this system or simply to learn from it.     

Surfactant protein A and B genetic variants in respiratory distress syndrome in singletons and twins

Interactive genetic and environmental factors may influence the differentiation of surfactant and the risk of respiratory distress syndrome (RDS). DNA samples from 441 premature singleton infants and 480 twin or multiple infants were genotyped for surfactant-specific protein (SP)-A1, SP-A2, and SP-B exon 4 polymorphisms and intron 4 size variants in a homogeneous white population. Distributions of the SP-A and SP-B gene variants between RDS and no-RDS infants were determined alone and in combination. SP-A1 allele 6A2 (p = 0.009) and the homozygous genotype 6A2/6A2 (p = 0.003) were overrepresented in RDS of singletons when the SP-B exon 4 genotype was Thr/Thr, and underrepresented in RDS of multiples when the SP-B genotype was Ile/Thr (p = 0.012 for 6A2 and p = 0.03 for 6A2/6A2) or Thr/Thr (p = 0.12 for 6A2 and p = 0.018 for 6A2/6A2, respectively). The SP-A 6A2 allele in the SP-B Thr131 background predisposed the smallest singleton infants to RDS, whereas near-term multiples were protected from RDS. There was a continuous association between fetal mass and risk of RDS, defined by the SP-A and SP-B variants. Labeled lung explants with the Thr/Thr genotype showed proSP-B amino-terminal glycosylation, which was absent in Ile/Ile samples. Genetic and environmental variation may influence intracellular processing of surfactant complex and the susceptibility to RDS.     

Fermentative 2‐carbon metabolism produces carcinogenic levels of acetaldehyde in Candida albicans

Acetaldehyde is a carcinogenic product of alcohol fermentation and metabolism in microbes associated with cancers of the upper digestive tract. In yeast acetaldehyde is a by‐product of the pyruvate bypass that converts pyruvate into acetyl‐Coenzyme A (CoA) during fermentation. The aims of our study were: (i) to determine the levels of acetaldehyde produced by Candida albicans in the presence of glucose in low oxygen tension in vitro; (ii) to analyse the expression levels of genes involved in the pyruvate‐bypass and acetaldehyde production; and (iii) to analyse whether any correlations exist between acetaldehyde levels, alcohol dehydrogenase enzyme activity or expression of the genes involved in the pyruvate‐bypass. Candida albicans strains were isolated from patients with oral squamous cell carcinoma (n = 5), autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) patients with chronic oral candidosis (n = 5), and control patients (n = 5). The acetaldehyde and ethanol production by these isolates grown under low oxygen tension in the presence of glucose was determined, and the expression of alcohol dehydrogenase (ADH1 and ADH2), pyruvate decarboxylase (PDC11), aldehyde dehydrogenase (ALD6) and acetyl‐CoA synthetase (ACS1 and ACS2) and Adh enzyme activity were analysed. The C. albicans isolates produced high levels of acetaldehyde from glucose under low oxygen tension. The acetaldehyde levels did not correlate with the expression of ADH1, ADH2 or PDC11 but correlated with the expression of down‐stream genes ALD6 and ACS1. Significant differences in the gene expressions were measured between strains isolated from different patient groups. Under low oxygen tension ALD6 and ACS1, instead of ADH1 or ADH2, appear the most reliable indicators of candidal acetaldehyde production from glucose.     

Association between bone mineral density and lumbar disc degeneration

Objectives

Higher vertebral bone mineral density (BMD) has been found to be related with lumbar disc degeneration (LDD), while relationship between femoral neck BMD and LDD remains controversial. The aim of our research was to study the relationship between LDD and BMD of the lumbar spine and femoral neck.

Study design

The study population consisted of 168 postmenopausal women (aged 63.3–75.0 years, mean 68.6 years) from the prospective OSTPRE and OSTPRE-FPS study cohorts. The severity of LDD was graded from T2-weighted MRI images using the five-grade Pfirrmann classification. Four vertebral levels (L1-L4) were studied (total 672 discs). The association between lumbar BMD and Z-score and the severity of LDD was studied separately for each vertebral level with AN(C)OVA analysis, using potential confounders as covariates.

Results

Higher lumbar BMD and Z-score were associated with more severe LDD at all studied levels (L1-L4): between L4-L5 disc and L4 BMD (p = 0.044) and L4 Z-score (p = 0.052), between L2-L3 disc and L3 BMD (p = 0.001) and at all other levels (p < 0.001). The mean degeneration grade of the studied discs was associated with the mean L1-L4 BMD and Z-score (p < 0.001). Statistical significance of any result did not alter after controlling for confounding factors. There was no significant association between femoral neck BMD and LDD.

Conclusions

Higher lumbar BMD/Z-score were associated with more severe LDD. There was no significant association between femoral neck BMD and disc degeneration. Femoral neck BMD may be a more reliable measurement for diagnosing osteoporosis in postmenopausal women with degenerative changes in the lumbar spine.     

Aetiological diagnosis of brain abscesses and spinal infections: application of broad range bacterial polymerase chain reaction analysis

OBJECTIVE: To evaluate the usefulness of the broad range bacterial rDNA polymerase chain reaction (PCR) method combined with DNA sequencing in the aetiological diagnosis of intracranial or spinal infections in neurosurgical patients. METHODS: In addition to conventional methods, the broad range bacterial PCR approach was applied to examine pus or tissue specimens from cerebral or spinal lesions in patients treated in a neurosurgical unit for a clinical or neuroradiological suspicion of bacterial brain abscess or spondylitis. RESULTS: Among the 44 patients with intracranial or spinal lesions, the final diagnosis suggested bacterial disease in 25 patients, among whom the aetiological agent was identified in 17. A causative bacterial species was identified only by the rDNA PCR method in six cases, by both the PCR methodology and bacterial culture in six cases, and by bacterial culture alone in five. All samples in which a bacterial aetiology was identified only by the PCR approach were taken during antimicrobial treatment, and in three patients the method yielded the diagnosis even after >/= 12 days of parenteral treatment. One case also identified by the PCR approach alone involved a brain abscess caused by Mycoplasma hominis, which is not readily cultured by routine methods. CONCLUSIONS: In patients with brain abscesses and spinal infections, the broad range bacterial rDNA PCR approach may be the only method to provide an aetiological diagnosis when the patient is receiving antimicrobial treatment, or when the causative agent is fastidious.