Prevalence and factors associated with left ventricular dysfunction in the EULAR Scleroderma Trial and Research group (EUSTAR) database of patients with systemic sclerosis.

OBJECTIVES: To measure the prevalence of, and factors associated with, left ventricular (LV) dysfunction in systemic sclerosis (SSc). METHODS: The EUSTAR database was first searched. A case-control study of a patient subset was then performed to further identify independent factors associated with LV dysfunction by simple and multiple regression. RESULTS: Of 7073 patients, 383 (5.4%) had an LV ejection fraction (EF) of <55%. By multiple regression analysis, age, sex, diffuse cutaneous disease, disease duration, digital ulcerations, renal and muscle involvement, disease activity score, pulmonary fibrosis and pulmonary arterial hypertension were associated with LV dysfunction. In the second phase, 129 patients with SSc with LVEF <55% were compared with 256 patients with SSc with normal LVEF. Male sex (OR 3.48; 95% CI 1.74 to 6.98), age (OR 1.03; 95% CI 1.01 to 1.06), digital ulcerations (OR 1.91; 95% CI 1.05 to 3.50), myositis (OR 2.88; 95% CI 1.15 to 7.19) and use of calcium channel blockers (OR 0.41; 95% CI 0.22 to 0.74) were independent factors associated with LV dysfunction. CONCLUSION: The prevalence of LV dysfunction in SSc is 5.4%. Age, male gender, digital ulcerations, myositis and lung involvement are independently associated with an increased prevalence of LV dysfunction. Conversely, the use of calcium channel blockers may be protective.

Identification of M1 and M2 muscarinic acetylcholine receptors in the cat carotid body chemosensory system.

The carotid body is a major arterial chemoreceptor that senses low O2 tension, high CO2 tension and low pH in the arterial blood. It is generally believed that neurotransmitters, including acetylcholine (ACh), participate in the genesis of afferent neural output from the carotid body and modulate the function of chemoreceptor cells (glomus cells). Previous pharmacological studies suggest that M1 and M2 muscarinic ACh receptors (mAChRs) are involved in these processes. This study was designed to demonstrate the presence and localization of M1 and M2 mAChRs in the carotid body and in the petrosal ganglion of the cat. Since DNA sequences of the cat M1 and M2 mAChRs were not known, we first determined partial DNA sequences. These sequences and deduced amino acid sequences highly resembled those of human and the rat. Subsequent reverse transcription-polymerase chain reaction (RT-PCR)analysis has demonstrated that mRNAs for M1 and M2 mAChRs are present in the carotid body and the petrosal ganglion of the cat. Immunohistochemistry has indicated that the localization of these receptors appears different. Immunoreactivity for M1 mAChR was strong in nerves in the carotid body. Nerve endings positively stained for M1 mAChR appear to innervate glomus cells. Weak staining for M1 mAChRs was seen in glomus cells. On the other hand, M2 receptor protein seems to be present in glomus cells but not on nerve endings. One third of the neurons in the petrosal ganglion showed immunoreactivity for M1 mAChR. Many neurons and nerve fibers in the petrosal ganglion expressed M2 mAChR immunoreactivity. The results were consistent with previous pharmacological studies. Thus, activation of M1 mAChRs on afferent nerve endings may be linked to the increase in neural output during hypoxia. Further, M1 and M2 mAChRs on glomus cells modulate the release of neurotransmitters.

A model of sleep-disordered breathing in the C57BL/6J mouse.

To investigate the pathophysiological sequelae of sleep-disordered breathing (SDB), we have developed a mouse model in which hypoxia was induced during periods of sleep and was removed in response to arousal or wakefulness. An on-line sleep-wake detection system, based on the frequency and amplitude of electroencephalograph and electromyograph recordings, served to trigger intermittent hypoxia during periods of sleep. In adult male C57BL/6J mice (n = 5), the sleep-wake detection system accurately assessed wakefulness (97.2 +/- 1.1%), non-rapid eye movement (NREM) sleep (96.0 +/- 0.9%) and rapid eye movement (REM) sleep (85.6 +/- 5.0%). After 5 consecutive days of SDB, 554 +/- 29 (SE) hypoxic events were recorded over a 24-h period at a rate of 63.6 +/- 2.6 events/h of sleep and with a duration of 28.2 +/- 0.7 s. The mean nadir of fraction of inspired O(2) (FI(O(2))) on day 5 was 13.2 +/- 0.1%, and 137.1 +/- 13.2 of the events had a nadir FI(O(2)) <10% O(2). Arterial blood gases confirmed that hypoxia of this magnitude lead to a significant degree of hypoxemia. Furthermore, 5 days of SDB were associated with decreases in both NREM and REM sleep during the light phase compared with the 24-h postintervention period. We conclude that our murine model of SDB mimics the rate and magnitude of sleep-induced hypoxia, sleep fragmentation, and reduction in total sleep time found in patients with moderate to severe SDB in the clinical setting.

[Ticlopidine-induced neutropenia].

Ticlopidine (TCP) is a drug that inhibits platelet aggregation. Several studies have demonstrated its superiority over aspirin in preventing stroke and other thromboembolic diseases. However, neutropenia occurs in about 2% of TCP-treated patients, which therefore may advance to agranulocytosis, sepsis and death. They should be carefully followed with blood counts. We report 2 patients hospitalized with severe neutropenia while on TCP, despite having had regular blood counts. Their complications underline the need for patient selection and meticulous follow-up when ticlopidine is prescribed.