Epidemiosurveillance of brucellosis.

Brucellosis is one of the most important infectious diseases worldwide. Nevertheless, since it is not regarded as a priority by national and international health systems in many endemic regions, it is considered to be a neglected zoonosis. Measuresto prevent and control brucellosis rely upon direct approaches aimed at minimising the risk of spreading infection among animals. Collectively, these measures tend to reduce the exposure of animals to Brucella spp. and to increase resistance to infection in susceptible animals. To implement an effective disease control strategy, detailed information about the presence of the pathogen in a specific territory is of fundamental importance. For that reason, particular emphasis should be placed on active surveillance using serological methods. Serological surveillance provides useful information to aid in understanding epidemiological patterns and assess the impact of brucellosis in the targeted area, paving the way to define the most suitable approaches for confining the disease within acceptable limits.

Protective activity and immunogenicity of two recombinant anthrax vaccines for veterinary use.

In this study, the efficacy of two experimental vaccines against Bacillus anthracis toxinaemia was evaluated in the rabbit model. A recombinant Protective Antigen (rPA) mutant and a trivalent vaccine (TV) composed by the rPA, a inactive mutant of Lethal Factor (mLF-Y728A; E735A) and a inactive mutant of Edema Factor (mEF-K346R), both emulsified with mineral oils, were evaluated for their immunogenicity and protective activity in New Zealand white rabbits. Rabbits vaccinated subcutaneously with rPA and TV rapidly produced high level of anti-PA, anti-LF and anti-EF antibodies, which were still present 6 months later. In the efficacy test, these vaccines protected 100% of rabbits challenged with B. anthracis virulent strain 0843 one week after the vaccination. Moreover, all animals vaccinated twice with rPA and TV, resisted B. anthracis infection 6 months later. Our data indicate that rPA and TV could be good vaccine candidates for inducing protection against B. anthracis infection in target animal host. They could successfully be used in an emergency with simultaneous long-acting antibiotics to halt incubating infections or during an anthrax epidemic.

Evaluation of Brucella melitensis B115 as rough-phenotype vaccine against B. melitensis and B. ovis infections.

Brucella melitensis strain Rev1 is used as vaccine for the prophylaxis of brucellosis in sheep and goats. Because of its smooth phenotype, however, it induces antibodies directed to the O-polysaccharide (O-PS) of the lipopolysaccharide (LPS), thus unabling to distinguish between vaccinated and infected animals. It has been speculated that alternative vaccines could be live, attenuated Brucella rough strains, which are devoid of the O-PS. B. melitensis B115 is a natural, attenuated, rough strain. The O-PS is not exposed at the surface but is present in the cytoplasm. We tested the protective activity of B115 against B. melitensis and B. ovis infections in mice, in comparison with that of Rev1. The residual virulence and the humoral response following B115 vaccination were also evaluated. Vaccination with B115 conferred significant protective immunity against B. melitensis 16M and B. ovis challenge strains, equivalent to that provided by Rev1. No interfering antibodies to O-PS were detected, while the B115 vaccination was monitored by a specific B115-based complement fixation test. These promising features suggest further evaluation of B. melitensis B115 as vaccine for target animal hosts.

Brucella melitensis B115-based complement fixation test to detect antibodies induced by Brucella rough strains.

AIMS: To assess the efficiency of a Brucella melitensis B115 rough strain, naturally devoid of anticomplementary activity, used as antigen in a complement fixation test (CFT) to detect antibodies induced by Brucella strains with rough phenotype, such as Brucella abortus RB51, Brucella ovis and Brucella canis. METHODS AND RESULTS: Complement fixation testing was performed on sera from RB51-vaccinated cattle and buffaloes, B. ovis-infected sheep and B. canis-infected dogs using B115, RB51 and the hot saline extract (HSE) as antigens. The B115-based CFT proved highly sensitive and specific in detecting rough antibodies and its efficiency was comparable with that of RB51 and HSE-based CFT. CONCLUSIONS: Brucella melitensis B115 can be successfully used as an antigen in CFT to detect antibodies induced by Brucella rough strains. SIGNIFICANCE AND IMPACT OF THE STUDY: Brucella melitensis B115 antigen may represent an improvement over Brucella rough strains for Brucella antibody detection by CFT, thus enhancing the efficiency of brucellosis surveillance systems. Owing to the absence of anticomplementary activity, it does not require particular growth conditions or modifications and can be accurately standardized. The B115-based CFT may constitute a suitable supplementary test for the diagnosis of human infections owing to rough Brucellae.

Pharmacological interventions for spasticity following spinal cord injury: results of a Cochrane systematic review.

UNLABELLED: The aim of this paper was to assess the effectiveness and safety of baclofen, dantrolene, tizanidine and any other drugs for the treatment of long-term spasticity in spinal cord injury (SCI) patients, as well as the effectiveness and safety of different routes of administration of baclofen. A systematic review of randomised controlled trials (RCTs), within the Cochrane Collaboration Injuries Group, was carried out. The Cochrane Injuries Group Specialised Register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE and CINAHL were searched up to July 2006 without language restriction. Drug companies and experts active in the area were also contacted to find other relevant studies. Two investigators independently identified relevant studies, extracted data and assessed methodological quality of studies resolving disagreement by consensus. Nine out of 55 studies met the inclusion criteria. The heterogeneity among studies did not allow quantitative combination of RESULTS: Study designs were: 8 crossover, 1 parallel-group trial. Two studies (14 SCI patients) showed a significant effect of intrathecal baclofen in reducing spasticity (Ashworth score and activities of daily living [ADL] performances), compared to placebo, without any adverse effect. The study comparing tizanidine to placebo (118 SCI patients) showed a significant effect of tizanidine in improving Ashworth score but not in ADL performances. The tizanidine group reported significant rates of adverse effects (drowsiness, xerostomia). For the other drugs (gabapentine, clonidine, diazepam, amytal and oral baclofen) the results do not provide evidence for a clinical significant effectiveness. This systematic review indicates that there is insufficient evidence to assist clinicians in a rational approach to antispastic treatment for SCI. Further research is urgently needed to improve the scientific basis of patient care.

Serologic responses, biosafety and clearance of four dosages of Brucella abortus strain RB51 in 6-10 months old water buffalo (Bubalus bubalis)

Thirty water buffalo were obtained from a brucellosis-free farm in order to evaluate antibody responses, bacterial clearance and safety to Brucella abortus strain RB51 vaccine in a dose response study. The animals were randomly divided into five treatment groups. Groups I–V received the recommended dose of RB51 vaccine (RD) once, RD twice 4 weeks apart, double RD once, double RD twice 4 weeks apart and saline once, respectively. Antibody responses to RB51 were monitored at 2, 4, 6, 8, 10, 12, 16 18, 22, 24 and 27 post-initial-inoculation weeks (PIW). Clearance of RB51 from the prescapular lymph node was evaluated at 2, 4, 6, 12, 18 and 24 PIW for groups 1, III and V and at 6, 8, 10, 16, 22 and 27 PIW for groups II and IV. To evaluate shedding of the RB51 strain, nasal, conjunctival, vaginal or preputial swabs were taken from all experimental animals at 1, 2, 3, 4, 6, 8 and 12 PIW. Sera taken at all PIW were negative for field strain B. abortus by both the buffered plate agglutination test (BPAT) and competitive enzyme-linked immunosorbent assay (c-ELISA). Antibody responses to RB51 were demonstrated in all vaccinates but not in the controls, up to 12 PIW, by complement fixation test (CFT) and the dot-blot assay with an 83.7% agreement for both tests. Clearance of RB51 occurred between 6 and 12 PIW in group I but less than 2 weeks after booster vaccinations in groups II and IV and between 4 and 6 PIW in group III. RB51 was not recovered at any time from swabs obtained from either RB51-vaccinates or non-vaccinates. The results of this study indicate that serologic responses to RB51 vaccination can be monitored by both CFT and dot-blot assay in water buffalo. Our data also indicates that RB51 vaccination does not interfere with brucellosis sero-surveillance and is safe (no serological and bacteriological evidence of spread to non-vaccinates, no adverse clinical signs or detectable abnormalities on haematology and serum biochemistry) for use in water buffalo (AU)

Serologic responses, biosafety and clearance of four dosages of Brucella abortus strain RB51 in 6-10 months old water buffalo (Bubalus bubalis).

Thirty water buffalo were obtained from a brucellosis-free farm in order to evaluate antibody responses, bacterial clearance and safety to Brucella abortus strain RB51 vaccine in a dose response study. The animals were randomly divided into five treatment groups. Groups I-V received the recommended dose of RB51 vaccine (RD) once, RD twice 4 weeks apart, double RD once, double RD twice 4 weeks apart and saline once, respectively. Antibody responses to RB51 were monitored at 2, 4, 6, 8, 10, 12, 16 18, 22, 24 and 27 post-initial-inoculation weeks (PIW). Clearance of RB51 from the prescapular lymph node was evaluated at 2, 4, 6, 12, 18 and 24 PIW for groups 1, III and V and at 6, 8, 10, 16, 22 and 27 PIW for groups II and IV. To evaluate shedding of the RB51 strain, nasal, conjunctival, vaginal or preputial swabs were taken from all experimental animals at 1, 2, 3, 4, 6, 8 and 12 PIW. Sera taken at all PIW were negative for field strain B. abortus by both the buffered plate agglutination test (BPAT) and competitive enzyme-linked immunosorbent assay (c-ELISA). Antibody responses to RB51 were demonstrated in all vaccinates but not in the controls, up to 12 PIW, by complement fixation test (CFT) and the dot-blot assay with an 83.7% agreement for both tests. Clearance of RB51 occurred between 6 and 12 PIW in group I but less than 2 weeks after booster vaccinations in groups II and IV and between 4 and 6 PIW in group III. RB51 was not recovered at any time from swabs obtained from either RB51-vaccinates or non-vaccinates. The results of this study indicate that serologic responses to RB51 vaccination can be monitored by both CFT and dot-blot assay in water buffalo. Our data also indicates that RB51 vaccination does not interfere with brucellosis sero-surveillance and is safe (no serological and bacteriological evidence of spread to non-vaccinates, no adverse clinical signs or detectable abnormalities on haematology and serum biochemistry) for use in water buffalo.

Validation of a pXO2-A PCR assay to explore diversity among Italian isolates of Bacillus anthracis strains closely related to the live, attenuated Carbosap vaccine.

Several circulating Bacillus anthracis strains isolated in Italy and belonging to the A1.a cluster, genotype 3 (A1.a-3) are genotypically indistinguishable from Carbosap, a live attenuated vaccine strain, containing both pXO1 and pXO2 plasmids. The genotype was assessed by using eight-locus multilocus variable-number tandem repeat analysis. We describe here the use of a ninth locus able to explore variability among strains that have the same genotype. It is important to be able to genotype the wild isolate of B. anthracis strains from outbreaks of anthrax in areas where Carbosap vaccination of cattle and sheep is common practice. A total of 27 representative field strains isolated in Italy and four vaccinal strains, namely, Carbosap, Sterne, Pasteur I, and Pasteur II, were characterized by a ninth marker, called pXO2-A. Twenty-three field strains were genotype 3 and therefore identical to Carbosap. The marker was in the pXO2 plasmid and is based on the polymorphism of the already-known VX2-3 locus. Detection was obtained by PCR with fluorescence-labeled forward primers in order to produce appropriate fragments for capillary electrophoresis with an ABI 310 genetic analyzer. Genetic relationships showed heterogeneity in all of the examined samples. Interestingly, with respect to genotype 3, samples grouped into eight different subtypes, A to H, and the subtype G, had only two samples indistinguishable from Carbosap. The results of the present study confirm the validity of a hierarchical progressive protocol for discrimination among closely related isolates.

Protective properties of rifampin-resistant rough mutants of Brucella melitensis.

Vaccination against Brucella infections in animals is usually performed by administration of live attenuated smooth B. abortus strain S19 and B. melitensis strain Rev1. They are proven effective vaccines against B. abortus in cattle and against B. melitensis and B. ovis in sheep and goats, respectively. However, both vaccines have the main drawback of inducing O-polysaccharide-specific antibodies that interfere with serologic diagnosis of disease. In addition, they retain residual virulence, being a cause of abortion in pregnant animals and infection in humans. To overcome these problems, one approach is to develop defined rough mutant Brucella strains lacking O antigen of lipopolysaccharide. B. abortus rough strain RB51, a rifampin-resistant mutant of virulent strain B. abortus 2308, is used as a vaccine against B. abortus infection in cattle in some countries. However, RB51 is not effective in sheep, and there is only preliminary evidence that it is effective in goats. In this study, we tested the efficacies of six rifampin-resistant rough strains of B. melitensis in protecting BALB/c mice exposed to B. melitensis infection. The protective properties, as well as both humoral and cellular immune responses, were assessed in comparison with those provided by B. melitensis Rev1 and B. abortus RB51 vaccines. The results indicated that these rough mutants were able to induce a very good level of protection against B. melitensis infection, similar to that provided by Rev1 and superior to that of RB51, without inducing antibodies to O antigen. In addition, all B. melitensis mutants were able to stimulate good production of gamma interferon. The characteristics of these strains encourage further evaluation of them as alternative vaccines to Rev1 in primary host species.

PCR assay to detect Bacillus anthracis spores in heat-treated specimens.

Recent interest in anthrax is due to its potential use in bioterrorism and as a biowarfare agent against civilian populations. The development of rapid and sensitive techniques to detect anthrax spores in suspicious specimens is the most important aim for public health. With a view to preventing exposure of laboratory workers to viable Bacillus anthracis spores, this study evaluated the suitability of PCR assays for detecting anthrax spores previously inactivated at 121 degrees C for 45 min. The results indicate that heat treatment ensures the complete inactivation of B. anthracis spores without significantly affecting the efficiency of PCR assays.

Genetic diversity at alkB locus in Brucella abortus.

DNA polymorphism of the alkB gene, a DNA repair gene, was assessed by PCR on Brucella abortus biovars 1 (strains 99, S19, 45/20, RB51 and 2308), 3 (Tulya strain), 5 (B3196 strain) and 6 (870 strain). A DNA repetitive element, named IS711, was detected in all studied biovars 1 and its complete nucleotide sequence was determined. We found that the element in alkB gene, bounded by 14 bp imperfect inverted repeats (IRs), is 840 bp long and appears to duplicate a consensus target site, CTAG. Analysing its nucleotide sequence of both forward and reverse strands, more than 10 open reading frames (ORFs) were found. Two potential transposase coding regions were chosen comparing all possible ORFs with the database. Comparing IS711 elements isolated from Brucella species, including both those characterized in our work and the published ones, differences in length and in nucleotide composition were observed among Brucella species, members of the same species and within the same strain. Our results confirm the heterogeneity of IS711 elements in Brucella genus and suggest the possibility to use this element to assess gene and genome diversity and to identify new molecular markers for Brucella species.

Combined S99/RB51 antigen for complement fixation test for serological diagnosis of brucellosis in cattle and sheep.

AIMS: To assess the efficiency of a single antigen for the complement fixation (CF) test, prepared by combining Brucella abortus smooth strain 99 (S99) with Brucella abortus rough strain RB51(RB51), in detecting cattle and sheep infected or vaccinated with Brucella spp. METHODS AND RESULTS: Serum samples from B. abortus-infected and RB51-vaccinated cattle were tested by the CF test using S99, RB51 and the combined S99/RB51 as antigens. Likewise, serum samples from Brucella melitensis-infected, RB51-vaccinated and Brucella ovis-infected sheep were tested by the CF test using S99, RB51, hot saline (HS) and combined S99/RB51 as antigens. Comparative analysis of the CF results showed that no reduction of sensitivity or specificity occurs when S99/RB51 antigen is used instead of specific antigens used separately. CONCLUSIONS: The results of this study indicated that combined S99/RB51 antigen used in the CF test, because of its specificity and sensitivity, could be used in animal brucellosis surveillance systems to improve the efficiency of the preliminary screening of herds. SIGNIFICANCE AND IMPACT OF THE STUDY: This study proposes an improved antigen for the CF test for the epidemiological survey of animal brucellosis. It could represent advantages over standard protocols because of its ability to detect antibody responses following infection or vaccination withBrucella strains of rough and smooth phenotype.

Sequence analysis of the genes encoding for the major virulence factors of Bacillus anthracis vaccine strain 'Carbosap'.

AIMS: This study was performed to analyse the molecular characteristics of genes encoding for the major virulence factors in Bacillus anthracis vaccine strain 'Carbosap' compared with the wild B. anthracis strain, to evaluate the basis of attenuation. METHODS AND RESULTS: The molecular characteristics of the B. anthracis 'Carbosap' vaccine strain, used as vaccine in Italy, were analysed in comparison with a B. anthracis virulent strain. Despite the presence of the two virulence plasmids pXO1 and pXO2, the 'Carbosap' strain proved to be protective for cattle. The presence of the regulatory genes atxA and pagR and the gerX operon, known to be involved in the virulence, was verified. In addition, all genes were sequenced. The results showed that no molecular differences between 'Carbosap' and the virulent strain were evident. CONCLUSIONS: The results of this study indicate that the attenuation of the 'Carbosap' vaccine strain is not due to the lack of virulence genes or to modifications occurring on the sequence of these genes. Therefore, other virulence factors, still unknown, could be involved in the pathogenic mechanisms. SIGNIFICANCE AND IMPACT OF THE STUDY: This paper adds new information regarding the molecular characteristics of the vaccine strain 'Carbosap' and highlights the need to better understand the virulence factors involved in the pathogenicity of B. anthracis strains.

Mouse cytokine profiles associated with Brucella abortus RB51 vaccination or B. abortus 2308 infection.

This study indicated that mice immunized with Brucella abortus RB51 bacteria and subsequently challenged with B. abortus 2308 were protected from reinfection. After vaccination, both Th1 and Th2 cytokine patterns were observed. Of those, the early production of gamma interferon seems to have the prominent role in inducing an immunologically based protection.

Detection of anthrax vaccine virulence factors by polymerase chain reaction.

In Italy, an attenuated Bacillus anthracis strain, named 'Carbosap', is used for immunization against ovine and bovine anthrax. Analysis on 'Carbosap', Sterne vaccine strain F34 and Pasteur vaccine strain SS104, were performed using primers specific for the sequences, encoding the toxic factors, located on plasmids pXO1 and pXO2 and primers specific for the chromosome. The results obtained from polymerase chain reaction (PCR) assay revealed the presence of both plasmids pXO1 and pXO2 in 'Carbosap' strain. This study showed that the 'Carbosap' vaccine strain has a different plasmid pattern in comparison to Pasteur vaccine strain SS104 and Sterne vaccine strain F34.

Use of polymerase chain reaction to identify Brucella abortus strain RB51 among Brucella field isolates from cattle in Italy.

Brucella abortus strain RB51, a rough mutant of the B. abortus 2308 virulent strain, was recently approved in the United States as the official vaccine for brucellosis in cattle. Following recent evidence of unauthorized use of RB51 vaccine in Italy, where the use of vaccines for brucellosis is no longer allowed, the suitability of an RB51-specific polymerase chain reaction assay for identifying the RB51 strain among Brucella field isolates from cattle in Italy was investigated. The oligonucleotide primers used in this study, belonging to a six-primer cocktail for Brucella species previously described by other authors, allowed the amplification of a 364-base pair (bp) fragment specific for RB51 and its parent strain 2308, and a 498-bp product specific for B. abortus. In addition, unresolved bands ranging from 600 to 700 bp were observed from RB51 strain. Brucella abortus biovars 1, 2 and 4 have only one specific sensitive 498-bp band. The B. abortus biovars 3, 5 and 6 did not give any signal. The 498-bp product from a reference Brucella strain was sequenced and submitted to EMBL with the accession number AJ271969 while the 364-bp fragment from RB51 strain was submitted to EMBL database with accession number AJ271968. The sequence studies confirmed the specificity of the detected fragments. No amplification was obtained by testing DNA from strains antigenically related to Brucella, such as Yersinia enterocolitica O:9, Escherichia coli O:157, Salmonella urbana and Pasteurella multocida. The results of this study indicate that this technique, in combination with specific serological tests, could be a useful diagnostic method to verify the use of RB51 vaccine and can contribute to the creation of a databank of circulating strains.

Field validation of the use of RB51 as antigen in a complement fixation test to identify calves vaccinated with Brucella abortus RB51.

In order to confirm the efficiency of an experimental RB51-based complement fixation (CF) test in identifying cattle vaccinated with Brucella abortus strain RB51, 831 sera from 110 vaccinated and 48 unvaccinated Hereford heifers of Iowa, collected for studies conducted in different years, were sent to Italy without coding to be tested in a CF test using RB51 as antigen. Most of the calves, aged from 3 to 10 months, were vaccinated subcutaneously with the recommended dosage of 10(10) CFU of RB51 commercial vaccine, while only six calves received 10(9) CFU of the same vaccine. Serum samples for serologic testing, collected until 16 postinoculation weeks (PIW), were also tested by routine surveillance tests for brucellosis such as rose bengal plate and CF tests performed with B. abortus smooth strain 99 as control antigen. RB51 CF test results obtained by testing sera from cattle vaccinated in 1999 indicate that the sensitivity of the reaction is 97% at 2 to 3 PIW and 90% until 8 PIW and decreases to 65% at 12 PIW, the specificity remaining at 100%. Collectively, the results of this study confirm that serologic standard tests fail to detect antibodies to RB51 while the RB51-based CF test is able to monitor antibody responses to RB51 until 15 to 16 PIW with a specificity of 100%. In addition, unlike the RB51-based dot blot assay, which is the only test currently used to monitor antibody responses to RB51, the CF test also detected specific responses following vaccination with 10(9) CFU of RB51, although seroconversion was only 50% at 8 PIW. In conclusion, because of high specificity and sensitivity, the CF test described here can be used to efficaciously monitor serologic responses following RB51 vaccination in cattle and could also be employed to detect RB51 infection in humans exposed to this strain.

Brucella abortus RB51 and hot saline extract from Brucella ovis as antigens in a complement fixation test used To detect sheep vaccinated with Brucella abortus RB51.

The efficacy of Brucella abortus RB51 and hot saline extract (HSE) from Brucella ovis as antigens in complement fixation (CF) tests was comparatively evaluated in detecting immune responses of sheep vaccinated with B. abortus strain RB51. For this study, four 5-month-old sheep were vaccinated subcutaneously with 5 x 10(9) CFU of RB51, and two sheep received saline. Serum samples collected at different times after vaccination were tested for the presence of antibodies to RB51 by a CF test with RB51 as antigen, previously deprived of anticomplementary activity, and with HSE antigen, which already used as the official antigen to detect B. ovis-infected sheep. The results showed that vaccinated sheep developed antibodies which reacted weakly against HSE antigen and these antibodies were detectable for 30 days after vaccination. However, antibodies to RB51 could be detected for a longer period after vaccination by using homologous RB51 antigen in CF tests. In fact, high titers were still present at 110 days postvaccination with RB51 antigen. Sera from sheep naturally infected with B. ovis also reacted to RB51 but gave lower titers than those detected by HSE antigen. As expected, all sera from RB51-vaccinated sheep remained negative when tested with standard S-type Brucella standard antigens.

Pharmacological interventions for spasticity following spinal cord injury.

BACKGROUND: Spasticity is a major health problem for patients with a spinal cord injury (SCI) that limits patients' mobility and affects independence in activities of daily living and work. Spasticity may also cause pain, loss of range of motion, contractures, sleep disorders and impair ambulation in patients with an incomplete lesion. The effectiveness of available drugs is still uncertain and they may cause adverse effects. Assessing what works in this area is complicated by the lack of valid and reliable measurement tools. The aim of this systematic review is to critically appraise and summarise existing information of the effectiveness of available treatments and to identify areas where further research is needed. OBJECTIVES: To assess the effectiveness and safety of Baclofen, Dantrolene, Tizanidine and any other drugs for the treatment of long term spasticity in SCI patients as well as the effectiveness and safety of different routes of administration of Baclofen. SEARCH STRATEGY: We searched the Injuries Group specialised register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE and CINHALH up to 1998. Drug companies and experts active in the area were also contacted. SELECTION CRITERIA: All parallel and crossover RCTs including spinal cord injury patients complaining of "severe spasticity". Studies where less than 50% of patients had a spinal cord injury were excluded. DATA COLLECTION AND ANALYSIS: Methodological quality of studies (allocation concealment, blinding, patients characteristics, inclusion and exclusion criteria; interventions; outcomes; lost to follow up) was independently assessed by two investigators. The heterogeneity among studies did not allow quantitative combination of results. MAIN RESULTS: Nine out of 53 studies met the inclusion criteria. Study design was: 8 cross over, 1 parallel-group trial. Two studies (14 SCI patients), showed a significant effect of intrathecal baclofen in reducing spasticity (Ashworth Score and ADL performances), compared to placebo, without any side effect. The study comparing tizanidine to placebo (118 SCI patients) showed a significant effect of tizanidine in improving Ashworth Score but not in ADL performances. Tizanidine group reported significant rates of adverse effects (drowsiness, xerostomia). For the other drugs (Gabapentine, Clonidine, Diazepam, Amytal and oral Baclofen ) the results do not provide evidence for a clinical significant effectiveness. REVIEWER'S CONCLUSIONS: There is insufficient evidence to assist clinicians in a rational approach to antispastic treatment for SCI. Further research is urgently needed to improve the scientific basis of patient care.

Chest physical therapy in patients with acute exacerbation of chronic bronchitis: effectiveness of three methods.

OBJECTIVE: To compare the short-term effects of postural drainage (PD), oscillating positive expiratory pressure (using the FLUTTER device), and expiration with the glottis open in the lateral posture (ELTGOL) on oxygen saturation, pulmonary function, and sputum production in patients with an acute exacerbation of chronic bronchitis. DESIGN: A prospective, randomized study. SETTING: A clinical ward. PATIENTS: Ten patients with chronic bronchitis exacerbation received PD, FLUTTER, and ELTGOL by the same respiratory therapist at about the same time of day on separate days and in random order. MAIN OUTCOME MEASURES: Oxygen saturation and pulmonary function were measured before, immediately after, and 15 minutes and 1 hour after each treatment. Improvement in sputum production was measured by total sputum wet weight immediately after and for 1 hour after treatment. INTERVENTIONS: PD consisted of positioning the patients in a posture that allows bronchial drainage by gravity. FLUTTER is a device that is claimed to combine oscillating positive expiratory pressure with oscillations of the airflow. ELTGOL is an airway clearance technique that uses lateral posture and different lung volumes to control expiratory flow rate to avoid airway compression. The total time spent for treatments was 30 minutes. RESULTS: All techniques were well tolerated, and oxygen saturation and pulmonary function did not change significantly during and after treatments. Thirty minutes after the beginning of treatment, sputum production increased significantly with all techniques, but during the 1 hour after the end of treatment, it was significantly larger with FLUTTER (from 15.0 +/- 8.6g to 19.0 +/- 9.3g, p < .01) and ELTGOL (from 17.0 +/- 7.0g to 20.6 +/- 6.9g, p < .02) than with PD (from 15.5 +/- 4.0g to 17.5 +/- 3.7g, NS). CONCLUSIONS: All three treatments were safe and effective in removing secretions without causing undesirable effects on oxygen saturation, but FLUTTER and ELTGOL techniques were more effective in prolonging secretion removal in chronic bronchitis exacerbation than was the PD method.