Strengthening exercises using swiss ball improve pain, health status, quality of life and muscle strength in patients with fibromyalgia: a randomized controlled trial.

The aim was to evaluate the effectiveness of strengthening exercises using the Swiss ball in patients with fibromyalgia through a randomized controlled trial with intention to treat analyses. A total of 60 patients with fibromyalgia met the inclusion criteria and were randomly allocated to either the Swiss ball exercise group (n=30) or a stretching group (n=30). All patients participated in 40-minute training sessions 3 times per week for 12 weeks. Pain (Visual Analogue Scale 0-100); muscle strength (One Repetition Maximum test); health status (Fibromyalgia Impact Questionnaire Revised); quality of life (Short Form-36 questionnaire) were evaluated at baseline, and after 6 and 12 weeks of training. The Swiss ball group showed a statistically significant improvement in VAS (0-100) (p<0.001), SF-36 (p<0.05) and Fibromyalgia Impact Questionnaire (p<0.001) compared with the stretching group. The results of this study proved that the treatment for fibromyalgia with strengthening exercises and the use of the Swiss ball led to improvement of pain, quality of life, muscle strength and decreased the need for medications for this disease compared to stretching exercises, without negative effects.

Effectiveness of insole use in rheumatoid feet: a randomized controlled trial.

OBJECTIVES: To assess the effectiveness of foot orthoses with regard to pain, function, quality of life, and global perceived effect in patients with rheumatoid arthritis (RA). METHOD: A double-blind randomized controlled trial (RCT) was carried out. Eighty women with RA were randomly assigned to an experimental group (EG) or a control group (CG). The EG used an insole with metatarsal and medial arch supports and the CG used a flat insole for 6 months. Evaluations performed at baseline and after 45, 90, and 180 days by a blinded assessor were: foot pain while walking and at rest, function, quality of life, and global perceived effect with treatment. RESULTS: The groups were homogeneous for all parameters at baseline. A statistically significant improvement (p < 0.001) was found in the EG regarding pain while walking (mean difference: -2.2 for the right foot and -2.1 for the left foot) and at rest (mean difference: -0.3 for the right foot and -0.5 for the left foot) in comparison to CG. There were no differences in any other observed measures. The time of insole use correlated with foot pain and function in the EG. CONCLUSIONS: Foot orthoses with metatarsal and medial arch supports decreases pain during walking and at rest in both feet in patients with RA. Time of insole use correlated with improvements in pain and function.

Secondary bacterial infection in plasma endotoxin levels and the acute-phase response of mice infected with Trypanosoma brucei brucei.

Murine Trypanosoma brucei brucei infection leads to elevated plasma endotoxin-like activity levels not related to parasitaemia levels accompanied by the development of acute-phase response and increased plasma levels of serum amyloid P (SAP) and haptoglobin (Hp). To determine the source of the endotoxin-like activity and role of secondary bacterial infection in the pathogenesis of trypanosomosis, infected mice were treated with the antibiotic ciprofloxacin. Plasma endotoxin-like activity levels, irrespective of treatment, were elevated three- to fourfold, beginning 7 days after infection. Plasma protein concentrations increased markedly following infection from 7 days after infection (DAI). Peak Hp and SAP concentrations in ciprofloxacin-treated and -untreated infected mice were attained 7 and 14 DAI, respectively. Thereafter, both protein levels gradually declined until the end of the experiment, but Hp levels for non-treated mice declined up to 21 DAI and thereafter significantly increased on 28 and 35 DAI. Whole-trypanosome lysate and the membrane-enriched fraction demonstrated endotoxin-like activity, with the former having higher levels. The results suggest that the endotoxin-like activity in trypanosome fractions and plasma of infected mice is due to the trypanosome. Further elevation of haptoglobin during the late stages of infection in non-treated mice suggests the involvement of secondary bacterial infection.

Evaluation of the efficacy of an educational program for rheumatoid arthritis patients.

OBJECTIVE: To evaluate the efficacy of an educational program for patients with rheumatoid arthritis in relation to their knowledge about the disease and to their psychosocial and physical health status. MATERIALS AND METHODS: The study included patients with rheumatoid arthritis classified according to the American College of Rheumatology criteria without any previous participation in disease-specific educational programs. The patients were randomly assigned to an educational program intervention or a waiting list. The intervention was a 6-week educational program consisting of weekly sessions lasting 1 hour each. Evaluations by a blind assessor were made prior to intervention and after 45, 90 and 180 days. The main outcome variables were the Patient Knowledge Questionnaire and the Short-form Health Survey (SF-36) quality of life questionnaire. Secondary outcome variables were the Health Assessment Questionnaire, Visual Analogue Pain Scale, Beck Depression Inventory and State-Trait Anxiety Inventory. RESULTS: Patients in the intervention group (n=28) had significant improvement in disease-specific knowledge compared to patients in control group (n=30). There was no significant difference between the groups in terms of pain, depression, anxiety or functional capacity, but the "general health perception" subscale of SF-36 showed a significant improvement in the intervention group (p=0.041). There was a positive correlation between improvement of disease-specific knowledge and schooling. CONCLUSION: Patients who attended the educational program had significant improvement in disease-specific knowledge and general health perception. No harmful effects on their psychosocial status were noticed. The acquisition of knowledge was also found to be proportional to schooling.

Lipopolysaccharide binding protein in the acute phase response of experimental murine Trypanosoma brucei brucei infection.

Cellular responses to lipopolysaccharide (LPS) are enhanced by LPS-binding protein (LBP). The present study investigated the acute phase response of LBP during Trypanosoma brucei brucei infection in mice. Mean plasma concentrations of LBP increased two-fold by the seventh day following infection, but decreased to intermediate levels by the 14th day. There were no significant differences in LBP concentrations of infected/antibiotic-treated and infected/untreated mice. At 35 days post-infection, the infected mice were treated with the anti-trypanosomal diminazine aceturate (Berenil). LBP levels of the mice then decreased to pre-infection levels within one-week. This demonstrated that LBP is an acute phase protein during murine trypanosomosis. Furthermore, opportunistic secondary bacterial infection during trypanosomosis did not seem to play an important role in the changes in plasma LBP levels. We speculate that the marked concomitant increases in plasma LBP and endotoxin-like activity following murine trypanosome infection might play an important role in the pathogenesis of trypanosomosis.

Effectiveness of a back school program in low back pain.

OBJECTIVES: To evaluate the effectiveness of a back school program in pain, functional status, quality of life, and in anxiety and depression in patients with non-specific low back pain. METHODS: Sixty patients with low back pain were randomized to an intervention and control group. The intervention group underwent a five-weekly back school program. The control group was seen in weekly medical visits, without educative approaches. Both groups took acetaminophen as analgesic medication. All subjects were evaluated by a blind physiotherapist after randomization, 30, 60 and 120 days. Rolland-Morris, SF-36, STAI and Beck questionnaires, pain visual analogical scale and Schober's test were applied. Non-steroidal anti-inflammatory drugs (NSAID) consumption was considered co-intervention. The statistical analyses were performed using Pearson's Chi-Square analysis and Student's t-test to compare the baseline characteristics of the groups and the analysis of variance (ANOVA) with repeated measures to assess changes inter/intra groups. RESULTS: There were no significant differences in the baseline characteristics between the two groups. Fifty-five patients completed the study. The intervention group showed a significant improvement in the general health domain, assessed by SF-36, and also in the reduction of acetaminophen and NSAID intake. There was no significant difference between the groups in pain, functional status, anxiety or depression. CONCLUSION: The back school program was more effective than any educational intervention in general health status and in decreasing acetaminophen and NSAID intake. It was ineffective in the other quality of life domains, in pain, functional status, anxiety and depression.

Acute phase response in mice experimentally infected with Trypanosoma congolense: a molecular gauge of parasite-host interaction.

Mice infected with Trypanosoma congolense developed a severe anaemia 1 week after infection, which persisted till treatment with diminazine aceturate when the packed cell volume (PCV) recovered to pre-infection levels. This was accompanied by a marked increase in the plasma levels of the acute phase proteins (APP), serum amyloid P-component (SAP) and haptoglobin (Hp). The initial peak levels of Hp and SAP were attained 7 and 12 days post-infection (DPI), respectively. Thereafter SAP levels decreased significantly to near pre-infection levels, but later increased even after treatment to give a second peak 34 DPI after which there was a decline till the study was terminated. The Hp levels on the other hand decreased to an intermediate level after the initial peak increasing to a second peak 22 DPI. Thereafter Hp decreased significantly following diminazine aceturate treatment to reach pre-infection levels within 5 days post-treatment. This indicates that T. congolense-infected mice develop severe anaemia accompanied by an acute phase response leading to an increase in SAP and Hp but that following treatment divergent responses occurred indicating differences in the pathways for stimulation of the APP. Haptoglobin was shown to be an earlier indicator of infection and a better marker in monitoring the response to treatment.

Brazil Patient Knowledge Questionnaire (PKQ) and evaluation of disease-specific knowledge in patients with rheumatoid arthritis.

OBJECTIVE: To create a Brazilian version of the Patient Knowledge Questionnaire--PKQ, an instrument for measuring the knowledge of patients with rheumatoid arthritis (RA) as regards their disease, and through the use of this instrument, also measure the knowledge of RA patients from reference hospitals in the city of São Paulo. METHODS: Two teachers of English translated the PKQ into Portuguese in order to obtain a single version, which was then translated back into English to evaluate its equivalence to the original version (back translation). The final version in Portuguese was applied to 20 patients with RA for adaptation to cultural issues, and questions not understood by 20% or more patients were subsequently modified. Inter- and intraobserver reliability and the constructive validity of the PKQ were tested. The questionnaire was then applied to 100 RA patients, selected in four outpatient clinics at reference hospitals in the city of São Paulo. RESULTS: Three of the PKQ questions were modified to adapt to cultural issues. Intraclass correlation coefficients used for the reliability and validity of the PKQ were between were between 0.62 and 0.94, therefore, statistically significant (p< 0.05). The mean PKQ score was 12.96 and the mean test application time was 10.3 minutes, for the 100 patients assessed. The lowest scores were observed in the domains of medications and joint protection/energy conservation. PKQ scores showed a positive correlation with the level of education (r=0.40) and a negative correlation with the patients' age (r= -0.32) and with HAQ (r= -0.28). CONCLUSION: The Brazilian version of the PKQ that was created and proved to be a reliable and valid instrument. Patients' knowledge of RA is poor, particularly in the domains regarding medications and joint protection/energy conservation.

Titration of KATP channel expression in mammalian cells utilizing recombinant baculovirus transduction.

A variety of transfection approaches have been used to deliver plasmids encoding ion channel genes into cells. We have used the baculovirus transduction system, BacMam, to demonstrate transient expression of multi-subunit KATP channels in CHO-K1 and HEK-293 EBNA cells using sulfonylurea receptor 1 (SUR), SUR2A, SUR2B, and KIR 6.2 genes. [3H]-glyburide binding, patch clamp, and DiBAC4(3) measurements of membrane potential changes were used to monitor channel expression. BacMam delivery of each SUR isoform with KIR6.2 was demonstrated based on its pharmacological profiles. Expression levels of SUR1 and KIR6.2 were titrated by varying the viral concentration or time of virus addition, with functional activity measured in as little as 4-6 hours posttransduction. Further increases in BacMam virus induced sufficient KATP expression to dominate membrane potential without pharmacological opening of the channel. Independently altering treatment with virus containing either the SUR1 or KIR6.2 gene revealed interactions among subunits during formation of functional channels in the plasma membrane. This study demonstrates the utility and versatility of BacMam as a valuable gene delivery tool for the study of ion channel function.

Synthesis and evaluation of 7-substituted-3-cyclobutylamino-4H-1,2,4-benzothiadiazine-1,1-dioxide derivatives as K(ATP) channel agonists.

A series of 7-substituted-3-cyclobutylamino-4H-1,2,4-benzothiadiazine-1,1-dioxide derivatives has been synthesized and evaluated as K(ATP) channel agonists using the inside-out excised patch clamp technique. The most active compounds were approximately 20-fold more potent than diazoxide in opening K(ATP) channels. A linear relationship exists between the potency of the compound and the sigma value of the 7-substituent with electron-withdrawing groups exhibiting higher activity. These compounds may be useful in modulating insulin release from pancreatic beta-cells and in diseases associated with hyperinsulinemia.

An industrial perspective on utilizing functional ion channel assays for high throughput screening.

The ability to apply large-scale screening formats to measures of ion channel function offers immense opportunities for drug discovery and academic research. Technologies have been developed over the last several years that now provide the ability to screen large numbers of compounds and natural products on ion channel function to find novel drugs. Application of these technologies has vastly improved the capabilities of ion channel drug discovery and provides an avenue to accelerate discoveries of ion channel biology. These advances have largely arisen from the development and application of instruments and reporters of membrane potential and ion movements in cells used to measure functional activity of ion channels. This article endeavors to describe the practical applications of these technologies in developing, validating, and implementing high throughput screening assay formats to different types of ion channels.

Nocturnal home hemodialysis in North America.

Nocturnal home hemodialysis (NHD) was made possible in the 1960s by fail-safe monitoring, the Scribner shunt, and low-resistant Kiil dialyzer allowing hemodialysis without a blood pump. In London, Sheldon was the first to use overnight home hemodialysis. The Lynchburg NHD program and Lisa Murphy, a dietician in Bender's NHD program in Kansas City, developed a questionnaire for short daily hemodialysis and NHD. The questionnaire was sent to all known daily hemodialysis programs in North America. Some advances in nocturnal home hemodialysis since 1994 include: improvement in teaching methods, preventing disconnects and air emboli, preventing catheter infections, and using arteriovenous fistulas and grafts for access. As of January 2001, there were 13 centers in North America performing daily nocturnal home hemodialysis caring for 115 patients. Since 1997, all programs performing NHD have validated Pierratos' reported results, showing improvement in quality of life, better blood pressure control with fewer medications, reduced Epogen usage, reduced hospitalizations, control of phosphorous without binders, and a greater sense of hope for patients. Even though this new modality is safe and better for selected patients with ESRD, dialysis providers in Canada and the United States cannot afford to offer NHD within the present reimbursement scheme.

Nightly home hemodialysis: improvement in nutrition and quality of life.

In September, 1997, we began a Nightly Home Hemodialysis Program modeled after a program in Toronto, Canada. We have assessed nutritional parameters and quality of life indicators before initiation of the program, and at 3, 6, 12, and 18 months. Data suggest that patients have improved overall quality of life as measured by the CHOICE Health Experience Questionnaire. Three-day dietary recalls at 0, 3, 6, 12, and 18 months also show patients are eating healthy and maintaining adequate kilocalorie and protein intakes, as well as maintaining adequate dry weight and protein stores.

The role of the polyamine inhibitor eflornithine in the neuropathogenesis of experimental murine African trypanosomiasis.

The treatment of late-stage human African trypanosomiasis is complicated by a post-treatment reactive encephalopathy, also referred to as a 'reactive arsenical encephalopathy', that may be fatal. This study used a well established experimental mouse system to assess the use of the trypanostatic drug, eflornithine, in the management of this post-treatment reaction. Female CD-1 mice infected with an eflornithine-resistant trypanosome stabilate and treated with the trypanocidal compound diminazene aceturate on or after day 21 post-infection develop a reactive encephalopathy and relapsing parasitaemia. If these animals are re-treated with diminazene aceturate, a severe encephalopathy develops histologically comparable with that of human cases and characterized by a severe meningoencephalitis and astrogliosis. Histopathological and immunocytochemical examination shows that administration of eflornithine before or after the development of this reactive encephalopathy prevented or ameliorated the inflammatory reaction. Since an eflornithine resistant stabilate was used, this effect appears to be independent of the drug's trypanostatic action and illustrates an important, previously unrecognized, pharmacological property of eflornithine. Consideration can now be given to the use of eflornithine for the management of human trypanosomiasis cases, even where trypanosome resistance to eflornithine exists.

A substance P antagonist, RP-67,580, ameliorates a mouse meningoencephalitic response to Trypanosoma brucei brucei.

Mice infected with the protozoan parasite Trypanosoma brucei brucei and treated subcuratively with the trypanocidal drug diminazene aceturate develop an acute inflammatory meningoencephalitis with associated astrocytic proliferation. This reaction is very similar to that seen in the fatal posttreatment reactive encephalopathies that can occur in human African trypanosomiasis. The 11-amino acid neuropeptide substance P (SP) has recently been identified as a mediator in many inflammatory responses, and the development of potent, highly specific, nonpeptide SP antagonists has provided a new opportunity to investigate the possible involvement of SP in a variety of pathological conditions. We therefore postulated that SP may play a role in the development of the posttreatment inflammatory encephalopathy found in this experimental mouse model of African trypanosomiasis. In the present study RP-67,580, a SP antagonist that binds specifically to NK-1 receptors, was given intraperitoneally at a dose of 2 mg/kg twice daily to mice in which a severe meningoencephalitis had been produced. A significant reduction in both the severity of the inflammatory response (P = 0.0001) as well as the degree of astrocyte activation (P < 0.001) was found in the brains of these animals as compared with control mice that had not received RP-67,580. An inactive enantiomer of this SP antagonist, RP-68,651, had no effect on the central nervous system inflammatory reaction. We conclude from these findings that the neuropeptide SP plays a key role in the development of the severe central nervous system inflammatory response associated with African trypanosomiasis.

The importance of 2,3-dimercaptopropinol (British anti-lewisite, BAL) in the trypanocidal activity of topical melarsoprol.

Both melarsomine dichlorhydrate (mel Cy, Cymelarsan) and melarsen oxide can be dissolved in dimethylsulfoxide and converted into a gel by the addition of hydroxypropylcellulose. When Trypanosoma brucei brucei-infected mice are treated topically with these gels the circulating trypanosomes are rapidly cleared from the circulation but the infections relapse soon after the last application. However, when these two compounds are allowed to react with 2,3-dimercaptopropinol (British anti-lewisite, BAL) and form "melarsoprol" their efficacy, especially in the case of mel Cy, is restored to that of commercial melarsoprol (Arsobal) and trypanosomes in the central nervous system (CNS) can be eliminated. This would indicate that the dimercaptopropinol portion of the molecule does not act solely as an "antidote" to arsenic toxicity, but also plays an important role in the absorption of melarsoprol through the skin and/or blood-brain barrier into the CNS and/or into the trypanosome.

Topical chemotherapy for experimental murine African CNS-trypanosomiasis: the successful use of the arsenical, melarsoprol, combined with the 5-nitroimidazoles, fexinidazole or MK-436.

The 5-nitroimidazoles, MK-436 and fexinidazole dissolved in dimethylsulphoxide can be converted by the addition of hydroxypropylcellulose into gels which facilitates the ease and accuracy of administration. When these gels are used in combination with melarsoprol gel they are capable of curing experimental murine CNS-trypanosomiasis with a one-day treatment. The use of melarsoprol/MK-436 was more efficient than melarsoprol/fexinidazole gels. Thus while a single treatment with 0.1 ml 3.6% melarsoprol gel with 0.1 ml (14.3 mumol) fexinidazole gel cured the infected mice, the same dose of melarsoprol gel with 0.1 ml (4.0 mumol) of MK-436 gel was equally effective. It was also possible to prepare a combined melarsoprol/MK-436 gel which cured experimental CNS-trypanosomiasis with a single treatment. Topical treatment with this melarsoprol/MK-436 gel mixture also resolved clinically the hind leg paralysis which is associated with post-treatment reactive encephalopathy caused by non-curative treatment of CNS-trypanosomiasis.

Topical chemotherapy for experimental African trypanosomiasis with cerebral involvement: the use of melarsoprol combined with the 5-nitroimidazole, megazol.

Megazol, one of a number of related 5-nitroimidazoles, can be dissolved in dimethylsulphoxide and the solution can be converted into a gel by the addition of hydroxypropylcellulose which facilitates the ease and accuracy of administration. This megazol gel, when used in combination with melarsoprol (3.6%) in propylene glycol gel, will cure experimental CNS-trypanosomiasis in mice. A single application of 0.1 ml of melarsoprol (3.6%) gel plus 0.1 ml of either 8 or 16 mg/ml megazol gel successfully treated experimental CNS-trypanosomiasis while two consecutive days' treatment with 0.05 ml melarsoprol and 0.1 ml of 16 or 32 mg/ml megazol gels also produced satisfactory cures.

The effect of spiroarsoranes on Trypanosoma brucei brucei and T. b. rhodesiense.

Topical application and intraperitoneal administration of spiroarsoranes were carried out to cure central nervous system (CNS) trypanosomiasis in the chronic Trypanosoma brucei GVR 35 mouse model. Topical application appeared more efficient than intraperitoneal injection. The periods of aparasitaemia after treatment were longer but none of the mice was permanently cured. Combination treatment with eflornithine (DFMO) and the spiroarsoranes failed to show any synergistic effect. In addition, spiroarsorane I was evaluated against the T. b. rhodesiense KETRI 2634 strain, whereby 60-mg/kg treatment produced a noticeable prolongation of the life span of trypanosome-positive animals. These in vivo results suggests that the spiroarsoranes have difficulty in crossing the blood-brain barrier (BBB) and clearing the parasites from the CNS or, alternatively, that these strains are less sensitive to pentavalent arsenicals than the T. b. brucei CMP fast strain, which in the present study was more sensitive to spiroarsoranes whose lipophilicity corresponded to a log-P value ranging from 2.5 to 3.7.