Mortality in sleep apnea patients: a multivariate analysis of risk factors.

During 1976-1988 we diagnosed sleep apnea syndrome (SAS) in 1,620 adult men and women monitored in the Technion sleep laboratories. Their age at the time of diagnosis ranged between 21 and 79 years. Fifty-seven patients (53 men and 4 women) had died by 1990, 53% due to respiratory-cardiovascular causes. The observed/expected (O/E) mortality rates, calculated for men only, revealed excess mortality of patients under 70 years old. Excess mortality was significant in the fourth and fifth decades (3.33, p < 0.002; 3.23, p < 0.0002, respectively). In patients older than 70 O/E was 0.33 (p < 0.0007). Hierarchical multivariate analysis with four fixed variables [age, body mass index (BMI), hypertension and apnea index] and four additional variables added manually one at a time (heart disease, lung disease, diabetes, apnea duration) was used to determine the predictors of death from all causes, cardiopulmonary causes and from myocardial infarction (MI). All four major variables were found to be significant predictors of mortality from all causes, in addition to lung disease and heart disease. Only age and BMI were significant predictors of cardiopulmonary deaths in addition to lung disease. Age, BMI and hypertension predicted MI deaths in addition to lung disease. These results were interpreted to suggest that SAS affects death indirectly, most probably by being a risk factor for hypertension.

The relationship between the severity of sleep apnea syndrome and 24-h blood pressure values in patients with obstructive sleep apnea.

Automated ambulatory 24-h BP monitoring was made in 38 patients with obstructive sleep apnea syndrome. Stepwise multiple regression analysis revealed that diastolic, systolic, and mean BP values during sleep as well as during wakefulness were significantly related to apnea/hypopnea index and age. Minimal arterial O2 saturation and total sleep time also significantly contributed to diastolic and mean BP values during sleep. Body mass index did not significantly contribute to any of the BP values. These results support a causal relationship between the severity of sleep apnea syndrome and systemic hypertension.

A crossover study comparing the efficacy of continuous positive airway pressure with anterior mandibular positioning devices on patients with obstructive sleep apnea.

OBJECTIVE: This study compared the efficacy of a removable anterior mandibular positioning (AMP) device to continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) using a fully balanced crossover design. DESIGN: Twenty-three male subjects with confirmed OSA were recruited from the Technion Sleep Laboratory in Haifa, Israel, from February 18, 1991 to December 17, 1992. Twenty-one of the 23 subjects enrolled completed all aspects of the study. RESULTS: The mean apnea-hypopnea index (AHI) before treatment was 33.86 +/- 14.30. The mean AHI decreased with CPAP to 59.50%, but decreased only 38.91% with the AMP device. The lowest mean recorded oxygen saturation level for the 21 subjects was 84.30 before treatment, 91.10 after CPAP treatment, and 90.20 after AMP treatment. Sleep data revealed a significant decrease in stage 1 and 2 (p=0.0088) and an increase in rapid eye movement percent (p=0.0066) for both treatments when compared with baseline. Three- to 10-month posttreatment phone interviews showed that 1 subject was not using either device, 1 subject was using CPAP, and 2 subjects were using the AMP device intermittently due to occasional temporomandibular joint pain symptoms. The remaining 17 subjects were all using the AMP device nightly. The symptoms of excessive daytime sleepiness also decreased significantly by both AMP and CPAP. CONCLUSIONS: The AMP device achieved substantial success in most cases, but was less effective than CPAP, especially for the more severe cases. In general, the AMP device was strongly preferred over the CPAP by the subjects of this study.

First- and second-trimester diagnosis of fetal ocular defects and associated anomalies: report of eight cases.

Ocular cataract, hypertelorism, hypotelorism, anophthalmos, and microphthalmos are rare malformations commonly associated with other fetal anomalies. Previously, ocular malformations were detected only after mid-gestation. Transvaginal sonography allows the detection of many structural fetal anomalies. We describe the case reports of eight ocular anomalies among 1600 fetal screenings by transvaginal sonography at 12-18 weeks' gestation. Severe cataract was correctly diagnosed by transvaginal sonography. However, transvaginal sonography failed to detect moderate cataract in a case of repeat cataract in a subsequent gestation. Anophthalmia may sometimes be secondary to a degenerative process in middle and late pregnancy. In five of the eight described cases, the eye malformations were associated with defects of the central nervous system.

Sonographic growth measurements in triplet pregnancies.

Sonographic growth curves of biparietal diameter (BPD), head circumference, abdominal circumference, head circumference/abdominal circumference ratio, and femur length were generated from 24 uncomplicated, concordant triplet pregnancies. These were compared with the standard curves derived for singletons used in our medical center. Slowing of BPD, head circumference, and abdominal circumference growth was noted in triplets from the 28th week of gestation, whereas the head circumference/abdominal circumference ratio was similar to that of singletons. Femur growth was parallel to that of singletons, although on the low margin of the two standard deviations. We conclude that the growth patterns of triplets are different from those of singletons. We suggest that femur length derived for singletons may be suitable for the follow-up of triplets. However, when growth retardation is suspected, the growth curves presented herein may be used to identify the growth-retarded fetus.

Treatment of ovarian hyperstimulation syndrome: the physiologic basis for a modified approach.

A case of severe ovarian hyperstimulation syndrome (OHSS) secondary to human menopausal gonadotropin-human chorionic gonadotropin therapy is presented. Draining 4000 ml of exudate by abdominal paracentesis under real-time B-scan imaging induced a marked improvement in the patient's condition. Fluids from the third space were rapidly excreted, renal function improved, and the patient's weight decreased substantially. The underlying physiologic factors responsible for these changes are discussed. Other modes of treatment, including salt and water restriction and the use of volume expanders and diuretics, had no significant effect on the course of the syndrome. Paracentesis has a definite therapeutic value and is recommended in cases of OHSS with tense ascites.

Menstrual asthma: use of a gonadotropin-releasing hormone analogue for the treatment of cyclic aggravation of bronchial asthma.

A new clinical indication for GnRH-a treatment seems to exist in addition to the many indications known so far. The successful treatment of cyclic severe attacks of bronchial asthma during ovulation and the menstrual periods with a GnRH-a is described. A 45-year-old woman with long-standing bronchial asthma was hospitalized because of severe bronchial asthma and status asthmaticus 11 times during the 5 months before her referral. The hospitalizations were either during the ovulatory or menstrual period, and in two of them they were so grave to require artificial ventilation through an endotracheal tube. To induce pituitary-ovarian desensitization and amenorrhea, the patient was put on monthly injections of depot GnRH-a, which she has been receiving for the last 20 months. Subjective improvement was accompanied by a significant improvement in spirometric indices, by lack of hospitalizations, and decrease in glucocorticoid daily dosage. Although a trial of sequential add-back HRT was unsupportable because of respiratory aggravation, low-dose continuous HRT was tolerated by the patient. In light of the dramatic subjective and objective improvement in association with the GnRH-a treatment, we conclude that this new application deserves further experience.

Native gonadotropin-releasing hormone for triggering follicular maturation in polycystic ovary syndrome patients undergoing human menopausal gonadotropin ovulation induction.

OBJECTIVE: To evaluate the role of GnRH administration instead of hCG for triggering follicular maturation in patients with polycystic ovaries (PCO) undergoing hMG ovulation induction when the late follicular 17-beta-E2 levels are > 1,600 pg/mL (> 6,000 pmol/L). DESIGN: Prospective study. SETTING: Infertility outpatient clinic of Rambam Medical Center (general hospital), Haifa, Israel. PATIENTS AND INTERVENTIONS: High serum E2 concentrations from 1,600 to > 3,600 pg/mL (2,800 +/- 68, mean +/- SD [6,000 to > 13,000 pmol/L, 10,279 +/- 2,500]) were experienced in 44 hMG cycles. The number of preovulatory follicles visualized by transvaginal sonography was between 8 and 25. An IV injection of 200 micrograms GnRH was administered for triggering final follicular maturation and ovulation, instead of 10,000 IU IM hCG, usually injected for this purpose, when the E2 levels are < or = 1,600 pg/mL (6,000 pmol/L). Serum E2 and P levels were monitored in the luteal phase. In cycles where E2 decreased to < or = 1,360 pg/mL (5,000 pmol/L), 2,500 IU hCG was administered once or twice at 3-day intervals for luteal support. MAIN OUTCOME MEASURES: Pregnancy and abortion rates and the rate of ovarian hyperstimulation syndrome (OHSS). RESULTS: Ten pregnancies were generated by the hMG and GnRH co-treatment in 32 patients (31.2%), in 44 cycles (23%). Two pregnancies aborted (20%), and eight generated eight healthy neonates. Ovarian hyperstimulation syndrome occurred in two cycles of patients who were both pregnant. All but two of these PCO patients also have undergone 69 hMG and hCG cycles. Only 7 patients conceived (23%) 10 times (10/69, 14.5%); 5 of these pregnancies (50%) were multiple gestations (3 twins, 1 sextuplet, and 1 heptuplet gestation). The pregnancy wastage rate was 30% (3/10). CONCLUSION: The use of native GnRH to trigger ovulation in PCO patients with late follicular E2 levels > 1,600 pg/mL (6,000 pmol/L) appears to be comparable with prior hMG and hCG cycles in terms of pregnancy rate, pregnancy wastage, risk of multiple gestation, and incidence of severe ovarian hyperstimulation. Unlike hMG and GnRH-agonist, which is associated with luteal phase dysfunction, hMG and GnRH offers a preferable alternative due to the ability of hCG luteal support and rescue, providing the E2 levels are not dangerously increased.

Inability of human sperm to change their orientation in response to external chemical stimuli.

OBJECTIVE: To investigate whether human sperm can respond to external chemical stimuli by orienting themselves toward chemoattractants or withdrawing from hostile environments. DESIGN: Controlled laboratory assays. SETTING: Normal human sperm and two other flagellated micro-organisms were exposed to various potential chemoattractant or chemorepellent substances. INTERVENTION: Human sperm, Euglena viridis, and Escherichia coli were exposed to various substances from the female reproductive system or to various toxic agents by placing them within tiny wells in a sealed minichamber. They were followed by microscopic observation and by intermittent photography. MAIN OUTCOME MEASURE: Images of photographed micro-organisms were analyzed for signs of attraction to or withdrawal from the test substances. RESULTS: Human sperm neither changed their orientation toward nor accumulated next to the well that contained cervical mucus, uterine cavity and follicular fluid, cumulus cells, or intact nonfertilized human eggs. Contrary to other micro-organisms that turned away from sources of hydrochloric acid, sodium hydroxide, ethanol, or glutaraldehyde, human sperm did not withdraw from these solutions. They swam along the ascending chemical gradient, facing ahead while becoming immobilized by these agents. CONCLUSION: It may be implied from the observation that they did not turn away from a hostile environment when expected to do so or turn toward chemoattractants that human sperm do not respond to external chemical stimuli and, most probably, chemotaxis between human sperm and ova in nature does not exist.

Transvaginal sonography in infertility and assisted reproduction.

This review on transvaginal sonographic uses in the diagnosis and treatment of infertility evolves from the plethora of data acquired due to the renewed technology of TVS. A combination of its advantages: 1) closer proximity to the pelvic organs and therefore clearer images as compared to abdominal ultrasound, 2) the avoidance of the necessity of full bladder made the TVS gain much popularity in obstetrics and gynecology. Its value is recognized not only by opening a door to early detection of common pathologies of pregnancy--ectopic gestation and fetal malformations, multiple fetuses, and spontaneous fetal reduction ("vanished twin"), but also made visualization of the enlarged fallopian tubes, uterine cervix and corpus and ovarian follicles an almost indispensible adjunct to modern gynecologic infertility workup. The value of TVS seems to increase tremendously not only as an indispensible diagnostic tool but also as a modern means of replacing laparotomy or laparoscopy for follicular aspiration and eggs retrieval for IVF/ET, GIFT and assisted reproduction, reduction of the number of multiple fetuses, and for treatment of most cases of ectopic pregnancy. Its value in the diagnosis and treatment of the infertile couple seems invaluable now and indispensible tomorrow.

[Gestation and spontaneous delivery in hydrocephalus with ventriculoperitoneal shunt].

The number of hydrocephalic patients reaching the reproductive age has increased in recent years due to improvement in the therapeutic armamentarium and the increased use of unidirectional ventriculo-peritoneal or ventriculo-atrial shunts for drainage of cerebrospinal fluid. 15 pregnancies in 14 patients with hydrocephalus and draining shunts have been reported. A patient with hyperprolactinemia and ventriculo-peritoneal shunt for hydrocephalus, who conceived after treatment and delivered spontaneously, is presented. It is concluded that gestation does not change the rate of complications and that most of these women conceive and deliver spontaneously.

[Early prenatal detection of trisomy 18 by transvaginal sonography].

A case of very early sonographic detection of trisomy 18 is presented. It is the second most common autosomal aneuploidy in newborns and the most common anomaly in stillborns. More than 130 features of this trisomy have been detailed. Combinations of findings highly suggestive of the diagnosis can be detected in early stages of pregnancy using transvaginal sonography. Identification of these anomalies may be an indication for early amniocentesis.

[Diagnosis of acute appendicitis by transvaginal sonography].

Acute appendicitis is the most common indication for laparotomy. Nevertheless, diagnostic specificity is low and rates of false positive and false negative diagnoses are high, since there is no direct technique for visualizing the appendix. The ultrasonic appearance of appendicitis has recently been described. We present the first case of acute appendicitis identified via high frequency transvaginal sonography, in a 26-year-old woman. Because of the proximity to pelvic organs, transvaginal sonography may improve the diagnosis rate of acute appendicitis, especially in young women in whom the correct diagnosis is more difficult.

[Ambulatory blood pressure in obstructive sleep apnea syndrome].

38 patients with obstructive sleep apnea syndrome underwent automated ambulatory 24-hour blood pressure monitoring. Systolic, diastolic and mean pressure values were significantly correlated with the apnea index (AI) during sleep, as well as during wakefulness. A significant negative correlation was found between minimal arterial O2 saturation in sleep and diastolic blood pressure values during waking hours. The contribution of the AI to blood pressure during sleep and wakefulness was significant, while the contribution of body mass index (BMI) was negligible. These results support the causal relationship between the severity of sleep apnea syndrome and systemic hypertension, independent of BMI.

[Treatment of obstructive sleep apnea with anterior mandibular positioning device].

The efficacy of the anterior mandibular positioning (AMP) device in obstructive sleep apnea syndrome was assessed. This device advances the mandible anteriorly by approximately 5-7 mm. 29 patients were examined and questioned about temporomandibular (TM) and facial pain before and after treatment with the device. Polysomnographic sleep studies were performed on all before, and 2 weeks after continuous use of the AMP device. 10 of the patients also underwent polysomnographic follow-up after 1 year. The mean apnea index (AI) before treatment was 40.1, which decreased to 24.3 (p < 0.0001) after 14.3 days of treatment with the AMP device. O2 saturation also increased, from 84.2% before, to 89.2% after treatment (p < 0.002). In 10 patients the mean AI after 1 year was 24.9, not different from that after only 2 weeks of treatment, but significantly different from their mean AI before treatment (39.8). Use of the AMP device did not change blood saturation levels; neither did it affect dental status, action of the masticatory muscles, nor did it cause TM joint dysfunction. 21 patients (72.4%) have now been fitted with an AMP device, and the mean follow-up is 13.4 months (range 2-22); 3 have been using the AMP only intermittently for TM joint pain or discomfort. We conclude that the AMP device helps the majority of patients and is an alternative, nonsurgical method for treating obstructive sleep apnea syndrome.

First-trimester and early second-trimester diagnosis of nuchal cystic hygroma by transvaginal sonography: diverse prognosis of the septated from the nonseptated lesion.

Fetal cystic hygroma is a congenital malformation of the lymphatic system appearing as a single or multiloculated fluid-filled cavity, most often in the nuchal region. The malformation is believed to arise from failure of the lymphatic system to communicate with the venous nuchal system. Sometimes the lesion progresses to fetal hydrops, causing fetal death. To further delineate the cause and natural history of this disorder, we have prospectively studied eight cases of cystic hygroma of the neck, detected at gestational ages of 9 to 15 weeks by transvaginal sonography. Three of the eight fetuses survived (37.5%) and were normal at birth. Either hydrops fetalis or intrauterine fetal death occurred in the other five fetuses. In one of these five, therapeutic abortion was induced because of trisomy 21. In another fetus of these five, trisomy 18 was diagnosed by amniocentesis. This pregnancy ended in intrauterine fetal death. The ultrasonic evaluation of the cystic hygromas revealed that those that were reabsorbed in the three ultimately normal viable fetuses were nonseptated cysts, whereas all the four cystic hygromas ending in fetal death or associated with aneuploidy were septated, multilocular hygromas. In another fetus with nonseptated hygroma, nonimmune hydrops developed, which resulted in premature delivery and early neonatal death.