Evaluation of sleep architecture and cyclic alternating pattern rates in depressed insomniac patients treated with nefazodone hydrochloride.

The standard methods of scoring sleep patterns do not ensure an accurate clinical impression of sleep quality. This is important especially in depressed insomniacs because persistent poor sleep increases the likelihood of recurrent depressive episodes. Changes in cyclic alternating patterns (CAP) in sleep have been shown to reflect corresponding changes in sleep quality. We evaluated the effects of nefazodone on CAP and standard sleep architecture in depressed insomniacs. The study was a single-center, single-blind, 6-week treatment of nefazodone hydrochloride followed by placebo withdrawal in 16 subjects meeting the DSM-IV criteria for depression who had a score of at least 18 on the 17-item Hamilton Depression Rating Scale, with insomnia-related items 4, 5, and 6 having a total score of 3 or greater. A mean daily dose of 339.1 +/- 141.7 mg at endpoint of nefazodone significantly reduced Hamilton Depression Scores from 21.7 +/- 3.0 on baseline to 5.8 +/- 5.3 (P <.05) by the end of the study. Polysomnography showed an improvement in sleep latency and sleep efficiency (P <.05), but no alterations in rapid-eye-movement or slow-wave sleep. Subjective estimates of sleep quality improved throughout the study, but CAP rates did not show a significant improvement. The disparity between CAP rates and sleep quality in depressed insomniacs is discussed.

Outcome evaluation of long-term nasal continuous positive airway pressure therapy in obstructive sleep apnea.

A study was conducted at the Tri-State Sleep Disorders Center of Cincinnati, Ohio, to evaluate both quantitative and qualitative daily function and productivity outcomes of treating obstructive sleep apnea (OSA) with nasal continuous positive airway pressure (NCPAP). This was a prospective outcome study conducted in 316 patients with diagnosed and treated OSA. There were 234 men and 82 women, mean age, 48.79 +/- 0.67 years; weight averaged 250.39 +/- 3.55 pounds; mean pretreatment respiratory disturbance index was 42.9 +/- 1.7 episodes per hour and 2.8 +/- 0.2 episodes per hour with NCPAP treatment. Patients were surveyed by questionnaire, administered on polysomnographic confirmation of OSA and after 6 months of nightly treatment with NCPAP as to their perceptions of their level of daytime functioning and quality of life over the previous 6 months. Main outcome measures included number of incidents of excessive daytime sleepiness; number of headaches on awakening; number of automobile accidents and near-miss automobile accidents; number of days absent from work; number of physician visits; and a series of subjective scales, measuring job productivity, quality of life, general physical and mental condition, short-term memory, and changes in blood pressure. Significant decreases were found in the number of incidents of excessive daytime sleepiness, headaches on awakening, physician visits, days absent from work, and automobile accidents or near misses with NCPAP therapy. Patients also reported subjective increases in productivity, quality of life, physical and mental condition, and short-term memory and reduction in both diastolic and systolic blood pressure. Effective treatment of OSA results in improvement both in preexisting symptoms and in quality of life. Improvement in many of the major problems experienced by patients seeking treatment has important implications for preventive medicine as well as health care cost containment.

Effect of gamma-hydroxybutyrate on pain, fatigue, and the alpha sleep anomaly in patients with fibromyalgia. Preliminary report.

OBJECTIVE: To evaluate the effects of using a gamma-hydroxybutyrate (GHB) administered in divided doses at night in 11 patients previously diagnosed with fibromyalgia (FM). METHODS: Subjects completed daily diaries assessing their pain and fatigue levels and slept in the sleep laboratory before and one month after initiating GHB treatment. Polysomnographic recordings were evaluated for sleep stages, sleep efficiency and the presence of the alpha anomaly in non-REM sleep. RESULTS: There was a significant improvement in both fatigue and pain, with an increase in slow wave sleep and a decrease in the severity of the alpha anomaly. CONCLUSION: Further controlled studies are needed to characterize the clinical improvement and the polysomnographic changes we observed.

Pharmacokinetics of gammahydroxybutyrate (GHB) in narcoleptic patients.

Sodium gammahydroxybutyrate (GHB) is an endogenous compound that has been under investigation in the management of narcolepsy for about two decades. The data confirm that GHB treatment decreases daytime sleepiness and episodes of cataplexy, sleep paralysis, and hypnagogic hallucinations. The current study evaluated the pharmacokinetics of GHB, given twice in one night to six narcoleptic patients who had been chronically taking GHB nightly on a similar basis. Results confirmed earlier reports and showed nonlinear pharmacokinetics. Maximum concentrations were reached in 40 +/- 6.2 and 35.7 +/- 7 minutes after the first and second dose respectively. Mean AUCinf was 17731.6 +/- 4867 mg/mL/m. Mean GHB T1/2 was 53 +/- 19 minutes. GHB elimination appears to be capacity-limited in some patients when administered at a fixed dose of 3 g twice nightly at a 4-hour interval.

Effects of estrogen replacement therapy on rates of cyclic alternating patterns and hot-flush events during sleep in postmenopausal women: a pilot study.

The objective of this pilot study was to evaluate the effects of conjugated estrogens on the rates of cyclic alternating patterns of sleep (CAPS) and nocturnal hot flushes in symptomatic postmenopausal women. Seven postmenopausal or posthysterectomy women aged 45 to 60 years with nocturnal diaphoresis and/or hot flushes participated in this study. The study was conducted with a single-masked design using a matching placebo. The placebo baseline was followed by a 4-week, single-masked treatment of conjugated estrogens 0.625 mg taken 4 hours before bedtime. Each patient's sleep was monitored in the laboratory for 3 consecutive nights during placebo baseline and again for 3 consecutive nights after an at-home period of at least 24 days of estrogen replacement therapy. Estrogen therapy resulted in a statistically significant decrease in the overall number of hot flushes and the number of hot hot flushes associated with awakenings, as well as improvement in sleep efficiency and a reduction in the rate of CAPS. These data confirm earlier well-established reports that estrogens reduce the frequency of hot flushes and suggest that the frequency of nocturnal arousals decreases and sleep quality improves in conjunction with a reduction in the rate of CAPS.

Comparative effects of sleep on a standard mattress to an experimental foam surface on sleep architecture and CAP rates.

The comparative effects of sleep patterns and rates of cyclic alternating patterns (CAP rate) in a high quality innerspring mattress were compared to those on a unique foam support mattress in 10 normal subjects. Results showed no differences in sleep stages, number of wakes, or total sleep time between the two conditions. CAP rates were significantly reduced on the foam surface. CAP rate was sensitive to the first-night effect on both surfaces, but was blunted on the foam mattress.

First Report of Black Sigatoka in Bolivia.

Black Sigatoka, caused by Mycosphaerella fijiensis, is the most important disease of banana worldwide (1). It affects cultivars of the Cavendish subgroup that are used for export and important, locally consumed cooking and dessert bananas and plantains, reducing yields by 50% or more. Black Sigatoka first appeared in the Western Hemisphere in 1972 in Honduras, and has spread to all other countries in Central America (1980), Mexico (1980), and the following islands in the Caribbean: Cuba (1992), Hispanola (Dominican Republic) (1996), and Jamaica (1994). In South America, the disease has spread to Colombia (1981), Ecuador (1986), Venezuela (1992), and Peru (1994) (1). In June 1996, symptoms of the disease were observed in the San Carlos area in the western Chapare region of Bolivia. During surveys conducted in March and June 1997, several Cavendish clones, Dulce Cajita (Pisang mas), Guineo (Silk), Morado (Red), and Platano (French and Horn plantain) were affected. In each of eight major banana-producing areas in the region, disease incidence and severity were recorded at several representative sites on Cavendish cultivars, which were the most widely spread and susceptible clones in the region. Disease incidence was 100% in all areas from San Carlos to Ingavi B, 30 km to the east, and disease severity, rated as the youngest leaf spotted (YLS), ranged from means of 4.5 to 8 in the same areas. The disease was less common or rare in the Valle Sajta area, 60 km east of San Carlos, the reserve of the Yuqui indigenous group at the confluence of the Rio Chimore and Rio Useuta, 15 km northeast of San Carlos, and the southernmost settlements of the Yuracare indigenous group on the Rio Chapare, 20 km north of Ingavi B (incidences = 0 to 50%). Symptoms began as brown streaks on the abaxial leaf surface, 1 to 3 mm in length, and became visible on the adaxial surface and enlarged to wet, dark brown streaks, 1 to 2 × 10 to 20 mm, with chlorotic haloes. Ultimately, large portions of the leaf became blackened and watersoaked. The presence of the disease in the San Carlos, Ingavi B, and Senda B areas and the Yuqui reserve was confirmed after microscopic examination of the anamorph, Paracercospora fijiensis, on affected leaf tissue: scars were present on the base of conidia, and only simple conidiophores were found (2). This is the first report of black Sigatoka in Bolivia, and represents the southernmost extent of the disease on the South American continent. High rainfall in western portions of the Chapare (4 to 7 meters per year) makes it unlikely that the disease could be controlled effectively or economically in the region with fungicides. We believe this is the closest approach of the disease to Brazil (ca. 700 km), the last major banana-producing country in which black Sigatoka has not been reported. Moreover, the outbreaks in the northern Chapare are thought to be the first across the colonist frontier to indigenous Amazonian populations that rely on plantains and bananas as staple foods. References: (1) X. Mourichon and R. A. Fullerton. Fruits 45:213, 1990; (2) N. Pons. Trans. Br. Mycol. Soc. 89:120, 1987.

Effects of an external nasal dilator on sleep and breathing patterns in newborn infants with and without congestion.

BACKGROUND: We recently demonstrated that the use of an external nasal dilator reduced subjective snoring levels and improved sleep quality. Our study polysomnographically evaluated the effects of this device on the frequency of obstructive airway events during sleep in infants with and without congestion. METHODS: We used a crossover study to monitor 20 infants between the ages of 2 and 4 months (15 infants without congestion and 5 with congestion). Monitoring was conducted during two daytime sleep sessions in a crossover study in which infants slept with or without a cutdown version of an external nasal dilator (Breathe Right Nasal Strips, CNS, Inc., Bloomington, Minn.) in the first session with crossover to the other condition in the second session. A respiratory disturbance index consisting of apneas (pauses in respiration of at least 8 seconds) or hypopneas (decreased airflow resulting in oxygen desaturation of at least 3%) was determined. RESULTS: Babies without congestion showed a greater than 50% reduction in respiratory disturbance index from 3.2 +/- 2.8 to 1.2 +/- 1.2 events per hour (p < 0.005). Congested infants showed a decrease from 6.9 +/- 2.9 to 1.5 +/- 1.6 events per hour (p < 0.05). Babies with the greatest number of events showed the greatest improvement. CONCLUSION: The use of an external nasal dilator reduces the frequency of obstructive respiratory events in infants.

Biological activities of melanotropic peptide fatty acid conjugates.

Four fatty acids (FA, palmitic, myristic, decanoic, hexanoic) were individually conjugated to the N-terminus of the alpha-MSH fragment analog, H-Asp5-His6-D-Phe7-Arg8-Trp9-Lys10-NH2. This resulted in enhanced potency of the conjugates (compared to the unconjugated melanotropin analog) as determined in the lizard skin bioassay and in the mouse melanoma cell tyrosinase bioassay. The shorter conjugates of hexanoic and decanoic acid were at least equipotent to alpha-MSH in the lizard skin bioassay, whereas the longer myristoyl and palmitoyl analogs were 100 times less active. The myristoyl and palmitoyl conjugates exhibited a "creeping" potency in the lizard skin bioassay-that is, potency of the peptides increased with time in contact with the skins. These observations may be related to the more lipid nature of these FA-conjugates. In the tyrosinase assay, the conjugates were 10-100 times more active than alpha-MSH or the unconjugated analog. Each of the FA-melanotropic peptide conjugates exhibited prolonged (residual) melanotropic activity in both the lizard skin and melanoma cell bioassays. In other words, after removal of the melanotropin conjugates from contact with the skins or cells, responses were still manifested for hours or days thereafter. As little as 1 hr of contact with melanoma cells resulted in enhanced enzyme activity as measured 48 hr later. Since the conjugates, but not H-[Asp5, D-Phe7, Lys10]alpha-MSH5-10-NH2, exhibited prolonged activity, the conversion of reversible agonists to irreversible agonists was demonstrated.

Quantitation of prolactin-dependent responses in porcine mammary explants.

A system was developed to quantitate prolactin-dependent responses in porcine mammary tissue obtained from pregnant gilts. Metabolic responses to prolactin (Prl) and cortisol (C) in the presence of varying doses of insulin (I) were examined in mammary explants cultured on the surface of the medium or submerged in medium, under an atmosphere of humidified air. Explants suspended on grids at the surface of medium oxidized 45% more glucose (P less than .05) and incorporated 67% more glucose into lipids (P less than .05) than explants submerged in culture medium. In explants cultured on grids, both 100 and 1,000 ng I/ml increased glucose oxidation (by 50%) and glucose incorporation into lipids (by 150%) compared with 10 ng/ml (P less than .05), but responses to 100 and 1,000 ng I/ml were not different. Therefore, in subsequent studies, explants were cultured on grids with 100 ng I/ml. Rates of glucose metabolism for mammary explants cultured with I + C for 48 or 72 h were not different from those in fresh tissue. However, addition of Prl (200 or 1,000 ng/ml) increased oxidation rate 130% and fat synthesis 400% compared with I + C (P less than .05). Addition of triiodothyronine to I + C + Prl further increased rate of fat synthesis by 87%. Dose-dependent responses to Prl were demonstrated and were within the concentrations of Prl found in blood of gestating gilts. These studies demonstrate that the lactogenic complex of I, C and Prl induces metabolic activity in porcine mammary tissue from late pregnancy.

Plasma somatotropin response to exogenous growth hormone releasing factor in lambs.

Two experiments were performed to examine the ability of human pancreatic growth hormone releasing factor (hGRF) administration to stimulate endogenous growth hormone (GH) secretion in lambs. Each study utilized eight Dorset wether lambs in replicated 4 X 4 Latin square experiments. Growth hormone response (integrated area under the curve for 150 min post-injection) for 0, 1, 5 and 10 micrograms hGRF/kg body weight averaged 13, 23, 92 and 134 units, respectively. While the 1-microgram hGRF dose was not different (P greater than .05) than the response to saline injection, there was an increased (P less than .01) GH response to 5 or 10 micrograms hGRF. Overall the GH response increased in a log dose-response fashion. There was distinct variation between lambs in their response to hGRF. Study II examined the optimal method to administer 40 micrograms hGRF/kg body weight to maximize GH concentration over 24 h. Continuous infusion (CI) was compared with eight (8X), four (4X), or two (2X) injections/d. Hourly blood samples were obtained from all lambs. Growth hormone response (area under the curve for 24 h) was 162, 305, 306 and 220 units for CI, 8X, 4X and 2X, respectively. Growth hormone response to CI was inferior to discrete injections, and the GH response to 4X or 8X was superior to 2X/d. Results demonstrate that, in spite of lamb-to-lamb variation, one can utilize exogenous hGRF to enhance GH secretion in lambs. Thus, the ability of exogenous hGRF to enhance growth performance merits further study.

Rat placentae gamma-glutamyltransferase activity changes during pregnancy.

gamma-Glutamyltransferase (D-gamma-glutamyl transpeptidase, EC 2.3.2.2) activity in rat placentae changes during gestation. The enzyme activity reaches a peak during the second trimester on a per gram of tissue basis and coincides with the greatest placental growth (hyperplasia) period. However, the enzyme activity on a per placenta basis shows two peak activity periods. One coincides with the peak of activity determined on a per gram basis. The second peak occurs in the third trimester and appears to coincide with the period of greatest fetal growth. The occurrence of these enzyme changes supports the concept of a developmental role for gamma-glutamyltransferase in providing amino acids from glutathione to the placenta and fetus.