Respiratory pathophysiology during sleep in patients with myotonic dystrophy

Myotonic dystrophy is a genetic disorder inherited as an autosomal dominant trait. It is known to be associated with endocrine dysfunction, polar cataracts, cardiac abnormalities and other conditions. Respiratory distress constituents the principal problem in myotonic dystrophy. The author investigated postural change of respiratory function in 12 patients with myotonic dystrophy (MYD), and 7 patients with limb-girdle dystrophy (LG) and overnight polysomnography was performed on 10 patients with MYD and 5 patients with LG. The respiratory function in seated posture showed no significant difference between LG and MYD, but in patients with MYD, the vital capacity and the expiratory reserve volume in a supine posture was reduced in comparison to that during seated posture. However, the respiratory function in patients with LG was not significantly different in seated and supine postures. Also, in patients with MYD, there was a significant decrease in arterial PO2 from the seated posture to the supine posture, without a significant change in the arterial PCO2. However, in patients with LG, there was no significant change in arterial blood gas analysis parameters. It was speculated that these findings concerning respiratory function and blood gas analysis in patients with MYD were caused by the involvement of the diaphragm. In the supine posture, the diaphragm shifted to the cranial position because of the abdominal contents rising into thorax, therefore the lung volume was reduced and the ventilation-perfusion ratio deteriorated. The changes of respiratory function parameters and PaO2 were partly responsible for the hypoxemia observed during sleep in patients with MYD. Overnight polysomnography showed that 9 of the 10 patients with MYD and 1 of the 5 patients with LG presented apneas during sleep, particularly during REM, stage 1 and stage 2. Almost all apneas were central type, with a low percentage of obstructive apneas and the apnea index was 19.0/h (mean) in MYD, 6.5/h in one case of LG. These result strongly suggest that sleep apnea is of central origin, but the distinction between a central and an obstructive etiology is difficult in neuromuscular disease and particularly when a disorder of central ventilatory responsiveness is suspected. The respiratory function of MYD and LG in seated and supine postures was studied and overnight polysomnography performed. It was emphasized that it was important for the respiratory care of neuromuscular disease to consider the influence of postural changes in the respiratory function. The present series of studies revealed central sleep apnea in the patients with myotonic dystrophy.(ABSTRACT TRUNCATED AT 400 WORDS)     

Operant self-control procedure in modifying type A behavior

A multiple-baseline across subjects design was used to evaluate the effects of operant self-control procedure on altering speed/impatient behaviors of the Type A behavior pattern (TABP). The operant-self-control procedure consisted of self-monitoring, self-evaluation, and self-reinforcement. The results demonstrated empirically significant decreases in S/I behaviors of the TABP following transfer to the self-reinforcement condition. Significant reductions in the Jenkins Activity Survey and physical symptoms scores additionally evidenced the effects of the operant self-control procedure. The possibility of pathogenic factors of the TABP varying with culture, and the advantages of the operant self-control procedure are discussed.     

Operative fiberoptic nephroureteroscope--removal of renal and upper ureteral stones

Two types of operative fiberoptic nephroureteroscopes were developed with the cooperation of the Olympus Optical Company mainly to remove the upper urinary tract calculi. Removal of the renal and upper ureteral stones was attempted in nine cases. The ureter was dilated with olive tip, balloon and Teflon dilators alone or in combination. The combination of balloon and Teflon dilators seemed the most promising. As a result of ureteral dilation, operative fiberoptic nephroureteroscopes, 4.5 mm and 3.5 mm in diameter, could be passed into the ureter in all the cases and the stones could be visualized clearly. Four of the 7 upper ureteral stones and 1 of the 2 pelvic stones could be removed. The success ratio was 56%. The method of stone removal still requires improvement. At present, application of the operative fiberoptic nephroureteroscope is indicated for upper ureteral and renal stones less than 1.0 cm in diameter. With the improved techniques of stone removal using this fiberscope, the indications of extracorporeal shock-wave lithotripsy or percutaneous nephrolithotripsy will probably be greatly reduced in the near future.     

Antitumor agents, 119. Kansuiphorins A and B, two novel antileukemic diterpene esters from Euphorbia kansui

The extract of the roots of Euphorbia kansui, which has been widely used in Chinese folk medicine for the treatment of cancer, demonstrated antileukemic activity against the P-388 lymphocytic leukemia in mice. Bioassay-directed fractionation of the active extract led to the isolation and characterization of two novel antileukemic diterpene esters, kansuiphorin A [1] [13-hydroxyingenol-3-(2,3-dimethylbutanoate)-13-dodecanoate- 20- hexadecanoate] and kansuiphorin B [2] [6,7-epoxy-13-hydroxyingenol-3-(2,3-dimethylbutanoate)-13-do decanoate-20- hexadecanoate], whose structures were established from spectral evidence and chemical transformation. Kansuiphorins A and B demonstrated potent antileukemic activity with T/C greater than or equal to 176 and 177% at 0.1 and 0.5 mg/kg, respectively. The selectivity of kansuiphorin A, which inhibits the growth of particular cell types within the disease-oriented human cancer cell line panels, is discussed.     

Exercise testing of the chronic effects of bunazosin hydrochloride on dilated cardiomyopathy

Bunazosin hydrochloride (Detantol) was administrated in 3-mg oral doses to 10 patients (6 males and 4 females, average 49.9 years) with dilated cardiomyopathy (DCM) of class II in the NYHA functional classification. The patients were observed for changes in their hemodynamics at rest, chest X-ray, echocardiography, humoral factors and symptom-limited exercise tolerance with treadmill testing before treatment and 4 and 8 weeks after administration. All but the left ventricular end-diastolic diameter after 8 weeks were unchanged. Of the humoral factors, only aldosterone decreased significantly during the treatment. On the other hand, the duration of symptom-limited exercise was prolonged significantly, and for a given exercise load, a reduction of heart rate and systolic blood pressure as well as a drop in the pressure-rate product occurred at 8 weeks after administration. Therefore, bunazosin appears to improve cardiac function and exercise tolerance in the patients with DCM, at dosages which do not affect hemodynamics at rest.     

Influence of liver damage on antipyrine metabolite formation in rats

1. The effects of three types of liver damage induced by carbon tetrachloride (CCl4), D-galactosamine (Ga1N) and alpha-naphthylisothiocyanate (ANIT) on antipyrine (AP) metabolism was studied in rats. 2. The serum half-life (t1/2) of AP (50 mg/kg, i.p.) was increased and total body clearance (CL) decreased in all three types of liver damage; the apparent volume of distribution (Vd) was relatively unchanged. 3. Rates of formation of AP metabolites (CLm) were lower than those in the control group in all three types of liver damage. 4. Rates of urinary excretion (% dose) of AP metabolites, 3-hydroxymethylantipyrine (HMA) and 3-hydroxymethyl-3-norantipyrine (NORA) were decreased in all three types of liver damage. However, the rate for 4-hydroxyantipyrine (OHA) was lower only in the Ga1N-treated rats. 5. The percentage conjugation of HMA was higher in the ANIT-treated rats than in the control group, and percentage conjugation of NOR was lower only in the Ga1N-treated rats. 6. These results indicate that the pathways of oxidation and conjugation of AP metabolism are not affected to the same extents by different types of liver damage.