Impaired redox status and cytochrome c oxidase deficiency in patients with polymyalgia rheumatica.

OBJECTIVE: To evaluate redox status and muscular mitochondrial abnormalities in patients with polymyalgia rheumatica (PMR). METHODS: Prospective evaluation of deltoid muscle biopsy in 15 patients with PMR. Fifteen subjects matched for age and sex, with histologically normal muscle and without clinical evidence of myopathy, were used as controls. Cryostat sections of muscle were processed for conventional dyes, cytochrome c oxidase (COX), usual histochemical reactions, and Sudan black. A total of 300-800 fibres was examined in each case. Blood lactate, pyruvate, and lactate/pyruvate ratio were determined in all patients. RESULTS: Ragged red fibres were found in eight patients with PMR and accounted for 0-0.5% of fibres. Focal COX deficiency was found in 14 (93%) of 15 patients and in nine (60%) of 15 controls. COX deficient fibres were more common in patients with PMR (range 0-2.5%; mean 0.9%) than in controls (range 0-1.2%; mean 0.3%) (paired t test, p=0.001). Seven (47%) of 15 patients had high blood lactate levels (1.50-2.60 mmol/l) or high blood lactate/pyruvate ratios (22-25). CONCLUSIONS: PMR is associated with mitochondrial abnormalities not solely related to the aging process.

Zidovudine-induced mitochondrial disorder with massive liver steatosis, myopathy, lactic acidosis, and mitochondrial DNA depletion.

Zidovudine is known to be responsible for a mitochondrial myopathy with ragged-red fibres and mitochondrial DNA depletion in muscle. Lactic acidosis alone or associated with hepatic abnormalities has also been reported. A single report mentioned the concomitant occurrence of muscular and hepatic disturbances and lactic acidosis in a patient receiving zidovudine, but muscle and liver tissues were not studied. A 57-year-old man with AIDS, who had been treated with zidovudine for 3 years, developed fatigue and weight loss. Serum creatine kinase and hepatic enzyme levels were high. Lactic acidosis was present. Liver biopsy showed diffuse macrovacuolar and microvacuolar steatosis. After withdrawal of zidovudine, creatine kinase, aspartate aminotransferase, and alanine aminotransferase levels normalised within 5 days, and lactacidaemia decreased. Acidosis persisted. The patient became confused and febrile and died 8 days after detection of high blood lactic acid. A muscle sample obtained at autopsy showed mitochondrial abnormalities with ragged-red fibres and lipid droplet accumulation. Southern blot analysis showed depletion of mitochondrial DNA, affecting skeletal muscle and liver tissue. No depletion was found in myocardium and kidney. This case emphasises that zidovudine treatment can induce mitochondrial multisystem disease, as revealed in our case by myopathy, liver steatosis and lactic acidosis.

Effects of different mechanical treatments on nasal resistance assessed by rhinometry.

The goal of this study was to compare the effectiveness of three treatments aiming to reduce nasal airflow resistance (NR): an external nasal strip device (Respir+), an internal nasal mechanical dilator (Nozovent), and a topical decongestant (Pernazène). NR was estimated by active posterior rhinometry at both a 0.5 L/s flow (NRF) and a 1 cm H2O pressure (NRP), under four conditions: in the basal state, with Respir+, with Nozovent, and after treatment with Pernazène. The efficacy of each treatment was assessed by the percentage changes in NRF and NRP (%NRF and %NRP, respectively). The study was performed in 15 healthy subjects. The efficacy of the treatments was significantly different, depending on whether it was evaluated by NRF or by NRP (p<0.02), with %NRF and %NRP values, respectively, equal to the following: 88+/-20% and 91+/-14% with Respir+, 58+/-17% and 70+/-13% with Nozovent, and 55+/-29% and 69+/-22% with Pernazène. NRF remained unchanged with Respir+, whereas it significantly decreased with Nozovent and Pernazène (p<0.0001). No significant difference was observed between the effects of the two latter treatments. These results demonstrate that Nozovent, which involves no risk of side effects or drug interactions, is an effective treatment to improve nasal breathing. Nozovent might therefore be recommended as an alternative to topical decongestants, for certain subjects presenting with nasal obstruction.

Nasal airflow resistance measurement: forced oscillation technique versus posterior rhinomanometry.

This study was designed to determine whether nasal airflow resistance (Rn) which is nonlinear during tidal breathing, can be assessed by the forced oscillation (FO) technique. Rn values obtained by the FO technique and extrapolated to 0 Hz (Rn,FO) were compared to those assessed by posterior rhinomanometry at maximal tidal inspiratory flow (Rn,m), at a 0.5 L x s(-1) flow (Rn,F), and at a 1 hPa transnasal pressure (Rn,P). All Rn estimates were derived from the same inspiratory and expiratory nasal flow and transnasal pressure signals obtained during tidal nasal breathing whilst a forced flow was applied at the nose via a rigid nasal mask in 23 healthy volunteers, of whom 14 had additional measurements after vasoconstrictor treatment. In the basal state, no significant difference, and significant correlations (p<0.0001) were found between Rn,FO and the other Rn estimates. Only the regression line of Rn,FO versus Rn,m was not significantly different from the identity line. After nasal decongestion, Rn,P became significantly higher than the other Rn estimates (p<0.005). The regression line of Rn,FO versus Rn,m remained nonsignificantly different from the identity line. Similar results were observed regarding the percentage values of the different Rn estimates after decongestant treatment. This study shows that, despite its nonlinearity, Rn can be assessed by the FO technique, and that Rn,FO and Rn,m could be indifferently used as physiological indices of nasal patency. As the FO technique is more difficult to implement than the conventional rhinomanometry, its interest in rhinology appears not to be obvious.