Depression of ventilatory responses to hypoxia and hypercapnia after pentamorphone.

Pentamorphone is a novel, potent opiate with rapid onset and short duration of action that has been reported to produce analgesia with limited depression of ventilation. We quantified the effects of pentamorphone (0.08, 0.24, and 0.60 micrograms/kg, IV) on ventilatory responses to hypercapnia and hypoxia in 12 healthy volunteers. Normoxic hypercapnia and isocapnic hypoxia were induced through a rebreathing method. During each test we recorded ventilation (VE), end tidal carbon dioxide tension (PETCO2), and arterial oxygen saturation (SO2) using a pulse oximeter. Using linear regression analysis of the relationships between VE and PCO2 during hypercapnia and VE and SO2 during hypoxia, we determined the slope (slope CO2) and intercept (V55), both at PCO2 55 mm Hg, and the slope (slope O2) and intercept (V80) at SO2 80%. Pentamorphone produced dose-related reductions in the ventilatory responses to both hypercapnia and hypoxia. Maximal depression occurred 15 min after injection of pentamorphone with all doses; the highest dose (0.60 micrograms/kg) produced 48% and 53% reductions in slope CO2 and V55, and 42% and 22% reductions in slope O2 and V80, respectively, relative to parallel saline controls. The respiratory depressant actions of pentamorphone were short-lived, as all parameters returned to baseline levels within 45 min. Testing was continued for 180 min after injection, but no delayed ventilatory effects were detected, and minimal side effects were reported, even at the highest dose. The findings confirm previous reports that pentamorphone has limited ventilatory depressant effects in humans in doses that (in other studies) have been associated with clinically effective analgesia.     

An oncogenic cell line inducing transplantable metastasizing adenocarcinomas in Xenopus borealis

Three epithelioid cell lines were initiated from stage 35 tadpolesof Xenopus borealis. Cell strain XB693-M1 was obtained by incubationof one of these cell lines in MNNG. The strain is hypotetraploidwith a modal chromosome number of 62. It is tumorigenic when4 ? 10⁶ cells are injected into hosts belonging to a partiallyhistocompatible family. The tumors are very invasive, metastazingadenocarcinomas that kill the host within 5 to 38 weeks. Thetumor can be propagated in vivo by serial transplantation.     

A possible role for electron microscopy in detection of carriers of Duchenne type muscular dystrophy

Five carriers of the gene of Duchenne type muscular dystrophy are described. Muscle histology was minimally to moderately abnormal in two and normal in three. Electron microscopy was abnormal in all five and showed massive aggregates of subsarcolemmal mitochondria, paracrystalline mitochondria, Z line streaming, central nuclei, dilated sacs of sarcoplasmic reticulum, focal loss of myofilaments, and lipid lysosome bodies. The electron microscopic literature on the carrier state is reviewed and analysed. The possible role of electron microscopy in detection of carriers is discussed.     

Effects of short-term, single and combined exposure to low-level NO2 and O3 on lung tissue enzyme activities in rats

To examine the pulmonary effects of relatively low levels of NO2 and O3, and test for any possible interaction in their effects, we exposed 3-mo-old male Sprague-Dawley rats, free of specific pathogens, to either filtered room air (control) or 1.20 ppm (2256 micrograms/m3) NO2, 0.30 ppm (588 micrograms/m3) O3, or a combination of the two oxidants continuously for 3 d. We studied a series of parameters in the lung, including lung weight, and enzyme activities related to NADPH generation, sulfhydryl metabolism, and cellular detoxification. The results showed that relative to control, exposure to NO2 caused small but nonsignificant changes in all the parameters; O3 caused significant increases in all the parameters except for superoxide dismutase; and a combination of NO2 and O3 caused increases in all the parameters, and the increases were greater than those caused by NO2 or O3 alone. Statistical analysis of the data showed that the effects of combined exposure were synergistic for 6-phosphogluconate dehydrogenase, isocitrate dehydrogenase, glutathione reductase, and superoxide dismutase activities, and additive for glutathione peroxidase and disulfide reductase activities, but indifferent from those of O3 exposure for other enzyme activities.     

Cerebrocortical oxygenation and ventilatory response during sustained hypoxia

Cerebrocortical oxygenation was monitored in 8 healthy adults during exposure to sustained isocapnic hypoxia. Subjects were maintained at an arterial oxygen saturation (SaO2) of 80% for 12 min with a rebreathing circuit while cerebrocortical oxygenation was assessed non-invasively using near-infrared (NIR) spectroscopy to measure changes in the oxidation state of cytochrome a,a3 (Cyt a,a3) and changes in cortical blood volume (tBV). During sustained hypoxia, subjects demonstrated a biphasic ventilatory response. The mean minute ventilation (VE) peak response was 255% of baseline at an average of 3.4 +/- 0.5 min (mean +/- SE) after the initiation of hypoxia. A subsequent significant attenuation of VE to 163% (P less than 0.05) of baseline occurred after an additional 8.6 min. NIR monitoring revealed a significant (P less than 0.05) decrease in oxidized Cyt a,a3 as well as a significant (P less than 0.05) increase in tissue blood volume (tBV) at the time of peak VE. Both Cyt a,a3 and tBV remained stable during the remainder of the hypoxic period, despite attenuation of VE during sustained hypoxia. The data suggest that cerebrocortical oxygenation and blood flow remain constant when the ventilatory attenuation is observed during sustained hypoxia.     

Modulation of cholestasis-induced antinociception by CCK receptor agonists and antagonists.

Acute cholestasis is associated with increased activity of the endogenous opioid system. Agonists and antagonists of cholecystokinin (CCK) receptors are known to modulate opioid-induced antinociception. In the present study, the effect of the CCK receptor agonist caerulein and the antagonist proglumide on antinociception induced during acute cholestasis was investigated in rats using the tail-flick test. A significant increase in nociception threshold was observed in bile duct ligated (BDL) rats compared to sham-operated controls that was maximum on day 7 after the operation and decreased thereafter. Proglumide (40 mg/kg, i.p.) did not affect nociception in unoperated and sham-operated animals, but exerted a significant potentiation of antinociception in cholestatic rats in a way similar to its potentiation effect on unoperated morphine-treated (2 mg/kg, s.c.) animals. Caerulein (0.005, 0.001, 0.01 and 0.02 mg/kg, s.c.), which did not change nociception per se or in sham-operated animals, also significantly potentiated the antinociception in BDL rats as well as in morphine-treated unoperated controls. Caerulein-induced potentiation of antinociception in BDL animals was completely reversed by proglumide pretreatment. Our findings show that, in cholestatic animals, modulation of nociception by the CCK system is different from normal subjects and resembles the state observable in morphine-administered subjects.     

Prevalence of Alzheimer's disease in a retirement community

In a white, predominantly middle class southern California retirement community, 817 adults aged 65-99 years were evaluated in 1980-1982 in a study designed to assess prevalence of early Alzheimer-type senile dementia. Based on 162 neurologically diagnosed cases, the age- and sex-adjusted prevalence of Alzheimer's disease in the target population was 15.3% (95% confidence interval = 13.0-17.5) among persons aged 65+ years and 35.8% among persons aged 80+ years. Age-adjusted correction for false negatives not detected by a screening procedure yields an estimated prevalence of 16.4% in persons aged 65+ years. Validity of the diagnostic approach was confirmed by a follow-up study. These rates far exceed past prevalence estimates for this disease. Since prevalence of mid- or later stages of Alzheimer's disease may have been underestimated, the high rates in this study may reflect a considerable community burden of early disease. Observed prevalence of Alzheimer-type senile dementia was higher among men than women after adjustment for age, 19.1% and 13.1%, respectively. The female predominance reported in many past clinical surveys may be peculiar to late disease and reflect care-seeking and care-utilization behaviors, rather than differences in incidence.