Prognosis of the middle-aged and aged patients with obstructive sleep apnea syndrome

Abstract The long-term natural course of obstructive sleep apnea syndrome (OSAS) is studied in order to determine whether severity of nocturnal oxygen desaturation associated with apnea/hypopnea, body mass index (BMI), and hypertension influence survival in young (<40 years), middle-aged (40–64 years), and aged (65 years) using a questionnaire survey. One hundred and forty-eight patients with OSAS aged 17–78 years (136 men, 12 women, mean 52.0±12.3 yean), who were diagnosed by standard polysomnography (PSG) between 1983 and 1993, participated in the study. The survey revealed 15 deaths and 101 survivors; 32 subjects could not be located. The survival rate was 71.4% (95% confidence interval:55.6–87.2%). The survival rate in patients with OSAS was significantly lower than that in the age and sex-adjusted control Japanese population (87.6%). In the young group, only one death (a 19–year-old woman) occurred unexpectedly during sleep. The patient showed an apnea/hypopnea index (AHI) of 33 per h and the length of time that the nocturnal oxygen saturation (SaO₂) fell below 90% (time of SaO₂ < 90%) of 205 min. The survival rate in middle-aged patients with OSAS was significantly lower than that in the age and sex-adjusted control Japanese population (79.2 vs 91.0%), but this pattern was not seen among the aged. Time of SaO₂ <90% was significantly longer in the middle-aged patients than in the aged patients, but AHI did not differ between the two groups. Moreover, it was significantly correlated with AHI in middle-aged patients, but not in the aged patients. The survival rate was significantly lower in patients with hypertension than in the patients without such complications in the middle-aged group (57.9 vs 90.4%). Cox proportional-hazard regression model including age, hypertension, BMI, AHI, lowest SaO₂, and time of SaO₂ <90% showed that hypertension was only significantly associated with lower survival rate in total group and middle-aged patients, but not in the young or aged patients. The prognosis in patients with OSAS may differ among the generations. The prognosis in the middle-aged population may depend on the role of OSAS on the complications of hypertension or severity of oxygen desaturation, but not on AHI only.     

INSULIN AND GLUCAGON SECRETION IN HEPATIC GLYCOGENOSES

ABSTRACT. Okada, S., Seino, V., Kodama, H., Yutaka, T., Inui, K., Ishida, M., Yabuuchi, H. and Seino, Y. (Department of Pediatrics, Osaka University Hospital, Fukushima-ku, Osaka and The Third Division, Department of Medicine, University of Kobe, Kobe, Japan). Insulin and glucagon secretion in hepatic glycogenoses. Acta Paediatr Scand 68: 735, 1979.—Insulin and glucagon secretion was investigated in ten patients with hepatic glycogenosis, types I and III, in order to understand the relationship between hypoglycemia and pancreatic function. In all patients, both oral glucose tolerance and intravenous arginine infusion tests revealed hypoinsulinemia. Decreased urinary C-peptide levels with standard food intake also supported hypofunction of pancreatic beta cells. On the contrary, the normal secretion pattern of glucagon in both types indicated in the arginine loading test, intact alpha cells in the pancreas. Persistent hypoinsulinism, which is apparently an adaptation to hypoglycemia, could be an important cause of nutritional dwarfism in both types of glycogenosis. The usefulness of the measurement of urinary C-peptide, which evaluates the pancreatic function and provides management for normal body growth, is discussed.     

Pharmacokinetics and pharmacodynamics of ()-sotalol in healthy male volunteers

1 We investigated the pharmacokinetics and pharmacodynamics of (±)-sotalol administered orally to healthy male volunteers in single doses of 40, 80 and 160 mg and in multiple doses of 80 mg twice daily for 7 consecutive days.
2 In the single dose studies, the half-life of (-)-sotalol (7.2-8.5 h) was significantly ( P < 0.01) shorter than that of (+)-sotalol (9.1-11.4 h) while the renal clearance of (-)-sotalol (110.6-126.4 ml min^-1) was significantly ( P < 0.01) faster than that of (+)-sotalol (102.2-110.1 ml min^-1). In the multiple dose studies, similar differences in the pharmacokinetics of (+)- and (-)-sotalol were observed. In addition, the pharmacokinetics of both (+)- and (-)-sotalol on day 4 were shown to be essentially the same as those on day 7.
3 In pharmacodynamic examinations, (±)-sotalol prolonged QTc intervals on electrocardiograms dose-dependently after single doses of 80 and 160 mg (3.81 ± 2.96%, 13.23 ± 5.66%). The correlation between the plasma concentration of (±)-sotalol and prolongation of QTc intervals was nearly linear, and showed no hysteresis.
4 In conclusion, we demonstrated that QTc interval was prolonged with a linear correlation to the plasma concentration of (±)-sotalol. In addition, our study suggested that differences in the pharmacokinetics of (+)- and (-)-sotalol may be attributable to faster urinary excretion of (-)-sotalol.     

CASE REPORT: Insulin - like growth factor II expression in hepatocellular carcinoma with alcoholic liver fibrosis accompanied by hypoglycaemia

This case of hepatocellular carcinoma (HCC) with alcoholic liver fibrosis, which was not associated with hepatitis viruses, was accompanied by hypoglycaemia. The immunoreactive insulin level was low and other hormonal examinations were almost normal. Immunohistochemical studies showed a high level of insulin-like growth factor II (IGF2) peptide in the HCC section and the size heterogeneity of serum IGF2 investigated by western blot revealed a large form at approximately 15 kDa. These results suggest that the HCC with alcoholic liver fibrosis produced IGF2 and that the hypoglycaemia was caused by tumour-associated IGF2.     

Is interval from an initial biopsy a significant predictor of prostate cancer at repeat biopsies?

BACKGROUND: Currently, there are no clear criteria for indicating repeat biopsies in patients with negative results at an initial biopsy of the prostate. The aim of the present study is to determine the clinical and pathological parameters which predict prostate cancer at repeat biopsies with special attention to the interval between biopsies in addition to prostate specific antigen (PSA) and its derivatives. METHODS: We reviewed 100 patients who underwent an initial biopsy that proved negative for prostate cancer and required repeat biopsies between November 1996 and November 2003. Clinical parameters such as age, PSA and its derivatives, interval between biopsies, number of cores taken and initial biopsy histology were analyzed. RESULTS: In total, 31 patients (31.0%) were found to have prostate cancer, 18 (25.7%) of 70 patients by the second biopsy and 13 (46.4%) of 28 patients by the third biopsy. Two patients underwent the fourth biopsy, which revealed no prostate cancer. The patients with a positive biopsy had a significantly longer interval between the biopsies than the patients with a negative biopsy (P=0.0036). Furthermore, in both univariate and multivariate logistic regression analysis, only the interval between the biopsies proved to be an independent predictor of positive results at repeat biopsies (P=0.0094 and 0.0019). CONCLUSIONS: Only the biopsy interval was a significant predictor of prostate cancer at repeat biopsies in both univariate and multivariate analysis.     

Clinical outcome of conservative therapy for stage T1, grade 3 transitional cell carcinoma of the bladder

BACKGROUND: The objective of this study was to retrospectively investigate the effectiveness of transurethral resection of bladder tumor (TURBT) and intravesical instillation therapy for stage T1, grade 3 (T1G3) transitional cell carcinoma (TCC) of the urinary bladder. METHODS: Between January 1995 and December 1997, 97 patients with T1G3 TCC of the urinary bladder were treated by TURBT and adjuvant intravesical instillation with bacillus Calmette-Guérin (BCG) or other anticancer agents. The recurrence-free survival rates were evaluated according to several clinicopathological factors. The cases that progressed to muscle invasive disease were also analysed. RESULTS: In this series, the median follow-up period was 25 months (range, 5- 41) after the initial TURBT. Intravesical recurrence was noted in 44 patients (45%), and the 1, 2, and 3 year recurrence-free survival rates were 72%, 58%, and 42%, respectively. Multivariate analyses revealed that the risk of intravesical recurrence was significantly higher for patients who did not receive BCG therapy, irrespective of age, gender, tumor size, multiplicity, pathological stage, concomitant carcinoma in situ, and lymphovascular involvement. Moreover, after a median of 10 months, disease progression occurred in seven patients (7%), of which only one patient was treated by BCG therapy after initial TURBT. CONCLUSION: These findings suggest that intravesical instillation with BCG combined with TURBT is an effective conservative treatment for T1G3 TCC of the bladder. Patients with negative prognostic factors should be treated by BCG rather than other anticancer agents after TURBT.