Heart Rate Recovery After 6-min Walking Test Predicts Acute Exacerbation in COPD

Introduction

Abnormalities of autonomic function have been reported in patients with chronic obstructive pulmonary disease (COPD). Our objectives were to identify determinants of abnormal heart rate recovery at 1 min (HRR₁) following completion of the 6-min walk test (6MWT) in COPD and to establish whether abnormal HRR₁ predicts acute exacerbations (AECOPD).

Methods

Hundred one COPD patients (FEV₁ (SD) 53 (19)  % predicted) were prospectively recruited in a multi-center study. HRR₁ after the 6MWT was evaluated as the difference between heart rate at the end of the test and 1 min into the recovery (HRR₁). Linear and logistic regression was used to identify predictors of HRR₁ and AECOPD, respectively. The best HRR₁ cut-off point to predict AECOPD was selected using the receiver operating characteristics (ROC) curves. The follow-up period was 12 months.

Results

Distance covered during the 6MWT (m) and DLco (% predicted) were independently associated with HRR₁ (r ² = 0.51, p = 0.001). Among several potential covariates, HRR₁ emerged as the most significant predictor of AECOPD (Odds ratio [OR], 0.91 per beat of recovery; 95% confidence interval [CI], 0.85–0.97; p = 0.02). The ROC analysis indicated that subjects with HRR₁ less than 14 beats (AUC, 0.71 [CI] 0.60–0.80; p = 0.0001) were more likely to suffer an exacerbation during the follow-up period (for HRR₁, p = 0.004 [log-rank test]).

Conclusions

HRR₁ after the 6MWT is an independent predictor factor for AECOPD. Further studies are warranted to examine the physiological mechanisms associating a delayed HRR and acute exacerbations in COPD patients.

     

Proposed outcome measures for prospective clinical trials in juvenile idiopathic arthritis–associated uveitis: A consensus effort from the multinational interdisciplinary working group for uveitis in childhood

Objective

To develop a set of core outcome measures for use in randomized controlled trials (RCTs) and longitudinal observational studies in juvenile idiopathic arthritis (JIA)–associated uveitis.

Methods

The literature relating to outcome measures used in studies of uveitis in childhood and adolescence was reviewed. A set of core outcomes and domains was established using the Delphi process. This was reviewed by a representative multinational interdisciplinary working group. Nominal group technique consensus was reached on face and content validity of the range and content of the domains. The outcomes and the appropriate instruments for uveitis trials were adapted to the age ranges of patients with JIA‐associated uveitis.

Results

Consensus was reached that data should be reported at defined time points in longitudinal studies with patients stratified by prognostic markers. Visual acuity testing should be age appropriate. The severity of uveitis (measured as anterior chamber cell grade) and duration of active inflammation should be documented. Visually significant structural complications should be recorded and quantified with standard measures. The responses to treatment and corticosteroid‐sparing effects of treatment should be documented. Patient‐reported disease activity and age‐specific uveitis‐related quality of life should be reported using appropriate questionnaires.

Conclusion

The proposed outcome measures in JIA‐associated uveitis should aid in the standardization and comparison of future RCTs of the treatment regimens for this disease. The proposed outcome measures will be verified in a prospective validation study.     

Training depletes muscle glutathione in patients with chronic obstructive pulmonary disease and low body mass index

BACKGROUND: A physiological increase in muscle glutathione after training is not seen in patients with chronic obstructive pulmonary disease (COPD), indicating abnormal peripheral muscle adaptations to exercise. OBJECTIVE: We hypothesized that oxidative stress is primarily associated with low body mass index (BMI). METHODS: Eleven patients with preserved BMI (BMI(N): 28.2 +/- 1.2 kg.m(-2)), 9 patients with low BMI (BMI(L): 19.7 +/- 0.60 kg.m(-2)) and 5 age-matched controls (26.5 +/- 0.9 kg.m(-2)) were studied before and after 8 weeks of high-intensity endurance training. Reduced glutathione (GSH) and gamma-glutamyl cysteine synthase heavy-subunit chain mRNA expression (gammaGCS-HS mRNA) were measured in the vastus lateralis. RESULTS: After training, exercise capacity increased (DeltaVO(2)PEAK, 13 +/- 5.2%; 10 +/- 5.6% and 15 +/- 4.3% in BMI(L), BMI(N) and controls, respectively; p < 0.05 each). GSH levels decreased in BMI(L) (from 5.2 +/- 0.7 to 3.7 +/- 0.8 nmol/mg protein, DeltaGSH -1.5 +/- 0.7 nmol/mg protein, p < 0.05); no changes were seen in BMI(N) (from 5.4 +/- 0.7 to 6.7 +/- 0.9 nmol/mg protein, DeltaGSH 1.3 +/- 0.9 nmol/mg protein), whereas GSH markedly increased in controls (from 4.6 +/- 1 to 8.7 +/- 0.4 nmol/mg protein, DeltaGSH 4.1 +/- 1 nmol/mg protein, p < 0.01). DeltaGSH in BMI(L) was different from DeltaGSH in BMI(N) and controls (p < 0.05, each). Consistent changes were observed in gammaGCS-HS mRNA expression. CONCLUSIONS: GSH depletion after training in BMI(L) may suggest that oxidative stress plays a key role in muscle wasting in COPD patients.     

Rimantadine Therapy of Influenza A Infection in Mice

Eighty per cent of mice infected with a mouse-adapted strain of influenza virus died within 3 to 8 days after infection. Rimantadine given at maximum protective doses reduced mortality to 10%. This protection is dose related and can be demonstrated with doses from 4.5 to 24 mg per kg per day. Significant survival rates are shown by delaying treatment as long as 48 hr after infection. Lungs of treated mice have significantly less virus than those of controls at 24, 48, and 72 hr after infection. Antibody production as measured by hemagglutination inhibition is not different in treated and controlled mice. These results indicate that rimantadine is an effective prophylactic and therapeutic agent and that its activity is associated with decreased viral titers.     

Validity of activity monitors in health and chronic disease: a systematic review

ABSTRACT: The assessment of physical activity in healthy populations and in those with chronic diseases is challenging. The aim of this systematic review was to identify whether available activity monitors (AM) have been appropriately validated for use in assessing physical activity in these groups. Following a systematic literature search we found 134 papers meeting the inclusion criteria; 40 conducted in a field setting (validation against doubly labelled water), 86 in a laboratory setting (validation against a metabolic cart, metabolic chamber) and 8 in a field and laboratory setting. Correlation coefficients between AM outcomes and energy expenditure (EE) by the criterion method (doubly labelled water and metabolic cart/chamber) and percentage mean differences between EE estimation from the monitor and EE measurement by the criterion method were extracted. Random-effects meta-analyses were performed to pool the results across studies where possible. Types of devices were compared using meta-regression analyses. Most validation studies had been performed in healthy adults (n = 118), with few carried out in patients with chronic diseases (n = 16). For total EE, correlation coefficients were statistically significantly lower in uniaxial compared to multisensor devices. For active EE, correlations were slightly but not significantly lower in uniaxial compared to triaxial and multisensor devices. Uniaxial devices tended to underestimate TEE (12.07 (95%CI; -18.28 to 5.85) %) compared to triaxial (6.85 (95%CI; -18.20 to 4.49) %, p = 0.37) and were statistically significantly less accurate than multisensor devices (3.64 (95%CI; -8.97 to 1.70) %, p<0.001). TEE was underestimated during slow walking speeds in 69% of the lab validation studies compared to 37%, 30% and 37% of the studies during intermediate, fast walking speed and running, respectively. The high level of heterogeneity in the validation studies is only partly explained by the type of activity monitor and the activity monitor outcome. Triaxial and multisensor devices tend to be more valid monitors. Since activity monitors are less accurate at slow walking speeds and information about validated activity monitors in chronic disease populations is lacking, proper validation studies in these populations are needed prior to their inclusion in clinical trials.     

Culture of Plasmodium berghei with the short life span in mouse erythrocytes: evaluation of chloroquine resistance in three strains of the malaria parasite

This comparative study was made to examine chroloquine inhibition of C14-hypoxanthine incorporation (preferably nucleic acid precursor for plasmodium) in the short-living red blood cell cultures in mice infected with P. berghei strains differently sensitive to the agent 24 hours after incubation. These included 1) chloroquine-sensitive H strain; 2) LNK-65 strain having a spontaneously 2-3-fold decreased sensitivity to the agent; 3) strain LNK-65 ChR selected for high resistance to chloroquine. IC50 (chloroquine concentrations that ensure 50% inhibition of the incorporation of nucleic acid precursor into the cells of the parasite) was estimated for 3 P. berghei strains that were differently sensitive to chloroquine. These in vitro values adequately reflect the sensitivity of these strains to the agent in vivo.     

Psammomacarcinoma of the peritoneum.

Psammomacarcinoma is a rare histologic subtype of serous carcinoma originating in the ovary or peritoneum, characterized by massive psammoma body formation, invasiveness, and low-grade differentiation. Its clinical behavior appears similar to that of serous borderline tumors rather than that of typical invasive serous carcinomas. Peritoneal psammomacarcinoma is even rarer than its ovarian counterpart with only 10 cases have previously been documented in the literature. A case of F.I.G.O. stage IIIC peritoneal psammomacarcinoma is described. Optimal debulking surgery, including omentectomy, total abdominal hysterectomy, bilateral adnexectomy, and resection of segment of jejunum, was performed. The patient received adjuvant chemotherapy with taxol and cisplatin, and to date, 15 months after surgery, she is alive and with no evidence of disease. It is concluded that peritoneal psammomacarcinoma is a very rare tumor that behaves less aggressively than typical serous carcinoma. The mainstay of treatment is surgical debulking. The role of adjuvant chemotherapy has as yet not been established.