Autosomal dominant myopathy with proximal weakness and early respiratory muscle involvement maps to chromosome 2q.
Two Swedish families with autosomal dominant myopathy, who also had proximal weakness, early respiratory failure, and characteristic cytoplasmic bodies in the affected muscle biopsies, were screened for linkage by means of the human genome screening set (Cooperative Human Linkage Center Human Screening Set/Weber version 6). Most chromosome regions were completely excluded by linkage analysis (LOD score <-2). Linkage to the chromosomal region 2q24-q31 was established. A maximum combined two-point LOD score of 4.87 at a recombination fraction of 0 was obtained with marker D2S1245. Haplotype analysis indicated that the gene responsible for the disease is likely to be located in the 17-cM region between markers D2S2384 and D2S364. The affected individuals from these two families share an identical haplotype, which suggests a common origin. (+info)
Outcome for cancer patients requiring mechanical ventilation.
PURPOSE: To describe hospital survival for cancer patients who require mechanical ventilation. MATERIALS AND METHODS: A prospective, multicenter observational study was performed at five academic tertiary care hospitals. Demographic and clinical variables were obtained on consecutive cancer patients at initiation of mechanical ventilation, and information on vital status at hospital discharge was acquired. RESULTS: Our analysis was based on 782 adult cancer patients who met predetermined inclusion criteria. The overall observed hospital mortality was 76%, with no statistically significant differences among the five study centers. Seven variables (intubation after 24 hours, leukemia, progression or recurrence of cancer, allogeneic bone marrow transplantation, cardiac arrhythmias, presence of disseminated intravascular coagulation, and need for vasopressor therapy) were associated with an increased risk of death, whereas prior surgery with curative intent was protective. The predictive model based on these variables had an area under the receiver operating characteristic curve of 0.736, with Hosmer-Lemeshow goodness-of-fit statistics of 7.19; P = .52. CONCLUSION: This model can be used to estimate the probability of hospital survival for classes of adult cancer patients who require mechanical ventilation and can help to guide physicians, patients, and families in deciding goals and direction of treatment. Prospective independent validation in different medical settings is warranted. (+info)
Effects of acute prolonged exposure to high-altitude hypoxia on exercise-induced breathlessness.
The direct effects of hypoxia on exercise-induced breathlessness are unclear. Increased breathlessness on exercise is known to occur at high altitude, but it is not known whether this is related to the hypoxia per se, or to other ventilatory parameters. To examine the role of high-altitude hypoxia in exercise-induced breathlessness, studies were performed in 10 healthy, normal subjects at sea level and after acute exposure to an altitude of 4450 m. Although the perception of hand weights did not alter between sea level and high altitude, the intensity of exercise-induced breathlessness increased significantly at high altitude. This was associated with a higher minute ventilation and respiratory frequency for any given exercise level, whereas tidal volume was not significantly altered from sea level values. The increased intensity of breathlessness with exercise did not change significantly over the 5 days at high altitude. These results suggest that the increased intensity of exercise-induced breathlessness at high altitude is not related to peripheral mechanisms or the pattern of ventilation, or to the level of hypoxia per se, but to the level of reflexly increased ventilation. (+info)
Microscopic polyangiitis: clinical and laboratory findings in eighty-five patients.
OBJECTIVE: To retrospectively analyze the clinical symptoms, laboratory findings, and outcomes in patients with microscopic polyangiitis (MPA) who were enrolled in various clinical trials conducted by the French Vasculitis Study Group. METHODS: A cohort of 85 patients meeting the Chapel Hill criteria for MPA participated in the study. Seventy-one of them were included in prospective therapeutic trials. Eighty-one diagnoses were biopsy proven. In the other patients, diagnosis was based on clinical findings. RESULTS: Forty-seven men and 38 women, with a mean +/- SD age of 56.8 +/- 14.6 years, met the criteria for MPA. Their main clinical symptoms were renal manifestations (78.8%), weight loss (72.9%), skin involvement (62.4%), fever (55.3%), mononeuritis multiplex (57.6%), arthralgias (50.6%), myalgias (48.2%), hypertension (34.1%), lung involvement (24.7%; alveolar hemorrhage 11.8%), and cardiac failure (17.6%). The mean +/- SD serum creatinine level before treatment was 2.59 +/- 2.96 mg/dl; 47 patients had renal insufficiency (serum creatinine > 1.36 mg/dl). Eight patients underwent dialysis at the time of diagnosis, and long-term dialysis was necessary for 10 patients. Antineutrophil cytoplasmic antibodies (ANCA) were present in 38 of 51 patients (74.5%), of whom 33 had a perinuclear staining pattern (pANCA) and 5 had a cytoplasmic pattern. Antibodies to proteinase 3 were present in 4 patients and antibodies to myeloperoxidase were detected in 31, as determined by enzyme-linked immunosorbent assay. Of the 30 patients who underwent renal and celiac angiography, 4 had microaneurysms. Of the 29 patients (34.1%) who had relapses, 8 died during or after the relapse. During followup, 28 of the 85 patients (32.9%) died. The mean +/- SD duration of followup of the group was 69.9 +/- 60.6 months. Deaths were less frequent when patients had been treated with steroids and immunosuppressive drugs (13 patients [24.1%]) than with steroids alone (15 patients [48.4%]) (P < 0.01). The 5-year survival rate was 74%. CONCLUSION: This study demonstrated that MPA is a multisystemic disease in which renal symptoms are frequent, but the disease is also associated with general symptoms, arthritis, mononeuritis multiplex, and other manifestations that are also seen in various vasculitides. The rarity of abnormal angiogram findings and the high frequency of pANCA are characteristic of MPA. In most cases, the outcome is comparable with those of other systemic vasculitides, but relapses are frequent. (+info)
Frequency of arrhythmias and other cardiac abnormalities in fulminant hepatic failure.
In a series of 106 patients with fulminant hepatic failure and grade 4 encephalopathy, cardiac arrhythmias and other abnormalities occurred in 92 per cent. The most common was sinus tachycardia (75%) and this was the only abnormality in 22 per cent of the patients. Sudden cardiac arrest occurred in 25 per cent, various ectopic beats in 20 per cent, and heart block or bradycardia in 18 per cent. Other electrocardiographic abnormalities, mostly of the T wave and ST segment, were found in 31 per cent. Cardiac and respiratory arrests were usually unrelated to each other and both frequently occurred without warning. Only 7 out of 71 patients with arrhythmias other than sinus tachycardia survived, compared with 15 out of 31 patients without them (P less than 0-005). During the latter part of the series when an arrhythmia computer was used to monitor 38 patients, it was shown that significantly lower arterial oxygen levels occurred in those with arrhythmias, other than sinus tachycardia, than in those without. They were also found to be more acidotic and hyperkalaemic, and a higher number required dialysis and ventilation. Macroscopical cardiac abnormalities including scattered petechial haemorrhages, small pericardial effusions, and fatty, pale, and flabby ventricles, were found at necropsy in 64 per cent of the patients examined. Combinations of these macroscopical abnormalities occurred, particularly in the paracetamol overdose group. Another necropsy finding of possible significance in the pathogenesis of arrhythmias was cerebral oedema, present in 48 per cent of the patients examined, and often associated with coning of the brain stem. However, 7 of the 16 patients who suffered asystolic cardiac arrests had no macroscopical abnormality of either heart or brain. In the management of patients with fulminant hepatic failure continuous cardiac monitoring is essential. Correction of the biochemical and coagulation defects may decrease the frequency of arrhythmias but studies of the mechanism and control of cerebral oedema and its relation to cardiovascular function are urgently needed. (+info)
Impact of nasal ventilation on survival in hypercapnic Duchenne muscular dystrophy.
BACKGROUND: Respiratory failure is the commonest cause of death in patients with Duchenne muscular dystrophy (DMD). Life expectancy is less than one year once diurnal hypercapnia develops. This study examines the effects of nasal intermittent positive pressure ventilation (NIPPV) on survival in symptomatic Duchenne patients with established ventilatory failure. METHODS: Nocturnal NIPPV was applied in 23 consecutive patients with DMD of mean (SD) age 20.3 (3.4) years who presented with diurnal and nocturnal hypercapnia. RESULTS: One year and five year survival rates were 85% (95% CI 69 to 100) and 73% (95% CI 53 to 94), respectively. Early changes in arterial blood gas tensions following NIPPV occurred with mean (SD) PO2 increasing from 7.6 (2.1) kPa to 10.8 (1.3) kPa and mean (SD) PCO2 falling from 10.3 (4.5) kPa to 6.1 (1.0) kPa. Improvements in arterial blood gas tensions were maintained over five years. Health perception and social aspects of SF-36 health related quality of life index were reported as equivalent to other groups with nonprogressive disorders using NIPPV. CONCLUSIONS: Nasal ventilation is likely to increase survival in hypercapnic patients with Duchenne muscular dystrophy and should be considered as a treatment option when ventilatory failure develops. (+info)
Speed of onset and offset and mechanisms of ventilatory depression from sevoflurane: an experimental study in the cat.
BACKGROUND: Inhalational anesthetics depress breathing dose dependently. The authors studied the dynamics of ventilation on changes in end-tidal sevoflurane partial pressure. To learn more about the mechanisms of sevoflurane-induced respiratory depression, the authors also studied its influence on the dynamic ventilatory response to carbon dioxide. METHODS: Experiments were performed in cats anesthetized with alpha chloralose-urethane. For protocol 1, step changes in end-tidal sevoflurane partial pressure were applied and inspired ventilation was measured. Breath-to-breath inspired ventilation was related to the sevoflurane concentration in a hypothetical effect compartment based on an inhibitory sigmoid Emax model. For protocol 2, step changes in the end-tidal partial pressure of carbon dioxide were applied at 0, 0.5, and 1% end-tidal sevoflurane. The inspired ventilation-end-tidal partial pressure of carbon dioxide data were analyzed using a two-compartment model of the respiratory controller, which consisted of a fast peripheral and slow central compartment. Values are the mean +/- SD. RESULTS: In protocol 1, the effect-site half-life of respiratory changes caused by alterations in end-tidal sevoflurane partial pressure was 3.6+/-1.0 min. In protocol 2, at 0.50% sevoflurane, the central and peripheral carbon dioxide sensitivities decreased to 43+/-20% and 36+/-18% of control. At 1% sevoflurane, the peripheral carbon dioxide sensitivity decreased further, to 12+/-13% of control, whereas the central carbon dioxide sensitivity showed no further decrease. CONCLUSIONS: Steady state inspired ventilation is reached after 18 min (i.e., 5 half-lives) on stepwise changes in end-tidal sevoflurane. Anesthetic concentrations of sevoflurane have, in addition to an effect on pathways common to the peripheral and central chemoreflex loops, a selective effect on the peripheral chemoreflex loop. Sevoflurane has similar effects on ventilatory control in humans and cats. (+info)
Pulmonary alveolar proteinosis in a patient with chronic myelogenous leukemia.
We describe the case of a 53-year-old Philadelphia-chromosome-positive woman with chronic myelogenous leukemia, who developed pulmonary alveolar proteinosis (PAP). The possible mechanism involved in the pathogenesis of PAP are discussed based on the clinical and laboratory data for this patient as well as on experimental and clinical data reported in the literature. (+info)