Growth hormone response to clonidine in adversely reared young adult primates: relationship to serial cerebrospinal fluid corticotropin-releasing factor concentrations.

A reduction of the growth hormone (GH) response to the alpha(2) adrenergic agonist clonidine is a neuroendocrine abnormality observed with reasonable consistency among human patients with mood and anxiety disorders. In previous primate studies, in comparison to predictably reared controls, monkeys exposed as infants to maternal variable foraging demand (VFD) rearing exhibited persistent elevations of cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF), as well as other biological disturbances. As CRF has been demonstrated to inhibit GH release, the authors hypothesized that within VFD-reared subjects, animals with relatively high CRF concentrations would exhibit relatively diminished GH responses to clonidine. The current study examined the relationship between the GH response to clonidine in VFD-reared adult primates in relation to a range of both juvenile and follow-up CSF CRF concentrations. Nine bonnet macaques (Macaca radiata) were given ascending dosages of clonidine under ketamine anesthesia. Plasma samples for GH-like immunoreactivity were obtained throughout the session. A significant positive correlation was noted between juvenile CSF CRF concentrations and the levels of the neuropeptide observed in young adults. The mean of the serial CSF CRF concentrations exhibited a significant inverse relationship towards the GH response to clonidine in young adulthood, with relatively high CSF CRF associated with relatively attenuated GH responses to clonidine. These data raise the possibility that a reduced GH response to clonidine may inversely reflect trait-like increases of central nervous system (CNS) CRF activity.

Is chemiluminescent immunoassay an appropriate substitution for radioimmunoassay in monitoring estradiol levels?

OBJECTIVE: To determine the correlation between serum estradiol measurements by chemiluminescent immunoassay (CIA) vs. radioimmunoassay (RIA) in two groups: patients treated with gonadotropins and patients treated with oral estrogen. DESIGN: Prospective study. SETTING: Assisted Reproductive Technology (ART) program based in a university-affiliated hospital in Manhasset, New York. PATIENT(S): Three hundred forty-eight patients undergoing gonadotropin stimulation and 63 patients receiving oral estrogen between July and December, 1997. INTERVENTION(S): Estradiol levels were measured concomitantly on all patients undergoing gonadotropin stimulation for IVF and all patients receiving oral estrogen for a frozen-thaw cycle. MAIN OUTCOME MEASURE(S): RIA:CIA ratio. RESULT(S): In the group undergoing gonadotropin stimulation, the median RIA:CIA ratio was 0.92, RIA = 1.26 x CIA(0.96), r = 0.98. In the group receiving oral estrogen, the median ratio was 3.93, RIA = 2.9 x CIA(1.05), r = 0.89. CONCLUSION(S): Estradiol levels determined by CIA correlate closely with RIA results for patients being treated with gonadotropins. Conversely, for patients receiving oral estrogen, CIA levels are one-third or less of the RIA level.

Vasodilatory state of decompensated cirrhosis: relation to hepatic dysfunction, ascites, and vasoactive substances.

The objective of this study was to determine the relations between the hallmark circulatory finding of decompensated cirrhosis, a reduced systemic vascular resistance (SVR), and the indices of hepatic decompensation, the accumulation of ascites, and the concentrations of various vasoactive substances. At a university-affiliated teaching hospital, eighteen hospitalized patients with cirrhosis and 18 age- and sex-matched healthy subjects were used. This was a case-control study. Measurements included cardiac dimensions and indices derived from echocardiograms and Doppler studies, abdominal ultrasound estimates of ascites, indices of hepatic function, and various serum (S) and urinary (U) substances. Results showed that cirrhotics had increased left atrial and left ventricular dimensions, left ventricular mass, heart rate, cardiac output (CO), transvalvular velocities, and a decreased SVR. SVR was related to hepatic dysfunction, as reflected by an abnormal prothrombin time ratio (r = -0.64, p = 0.006), and also related to overall severity of liver disease as estimated by the Child-Pugh score (r = -0.53, p = 0.044). Although cirrhotics with ascites generally had a reduced SVR, estimates of ascites were directly related to SVR (r = 0.57, p = 0.03) and inversely related to CO (r = -0.53, p = 0.04). Concentrations of S and U digoxin-like immunoreactive substance (DLIS) were also increased, but the concentrations of S glucagon and estradiol were not elevated. The accumulations of S and U DLIS, S glucagon, and S estradiol were all related to hepatic dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Abuse histories in 102 cases of multiple personality disorder.

The authors interviewed 102 individuals with clinical diagnoses of multiple personality disorder at four centres using the Dissociative Disorders Interview Schedule. The patients reported high rates of childhood trauma: 90.2% had been sexually abused, 82.4% physically abused, and 95.1% subjected to one or both forms of child abuse. Over 50% of subjects reported initial physical and sexual abuse before age five. The average duration of both types of abuse was ten years, and numerous different perpetrators were identified. Subjects were equally likely to be physically abused by their mothers or fathers. Sexual abusers were more often male than female, but a substantial amount of sexual abuse was perpetrated by mothers, female relatives, and other females. Multiple personality disorder appears to be a response to chronic trauma originating during a vulnerable period in childhood.

Structured interview data on 102 cases of multiple personality disorder from four centers.

Patients with multiple personality disorder (N = 102) at four different centers were interviewed with the Dissociative Disorders Interview Schedule. The presenting characteristics of the patients at all four centers were very similar. The clinical profile that emerged included a history of childhood physical and/or sexual abuse in 97 (95.1%) of the cases. The subjects reported an average of 15.2 somatic symptoms, 6.4 Schneiderian symptoms, 10.2 secondary features of the disorder, 5.2 borderline personality disorder criteria, and 5.6 extrasensory experiences; their average score on the Dissociative Experiences Scale was 41.4. The results indicate that multiple personality disorder has a stable, consistent set of features.

Schneiderian symptoms in multiple personality disorder and schizophrenia.

We report structured interview data from a series of 102 cases of multiple personality disorder (MPD) diagnosed in four centers. Schneiderian first-rank symptoms of schizophrenia were equally common in all four centers. The average MPD patient had experienced 6.4 Schneiderian symptoms. When these 102 cases are combined with two previously reported series of MPD cases, an average of 4.9 Schneiderian symptoms in 368 cases of MPD is noted. This compares with an average of 1.3 symptoms acknowledged by 1,739 schizophrenics in 10 published series. Schneiderian symptoms are more characteristic of MPD than of schizophrenia.

Reliability and predictive value of salivary theophylline levels.

The reliability and accuracy of salivary theophylline levels as a predictor of serum theophylline levels was investigated in 28 hospitalized chronic asthmatics, free of other chronic diseases, on continuous aminophylline infusion for greater than 24 hours. Twenty paired blood and saliva theophylline levels from 12 patients (group 1) were used to develop a formula for predicting serum theophylline levels from salivary levels. Twenty-one paired blood and saliva theophylline levels from 16 patients (group 2) were used to test the formula obtained. The formula predicted the serum theophylline concentration within 1.51 microgram/mL in 76% of the samples and within 1.88 microgram/mL in 100% of the samples. There was an excellent correlation between the predicted and actual serum theophylline concentrations, r = .93; thus under controlled conditions of steady-state pharmacokinetics in patients free of other diseases, salivary theophylline levels can be used to accurately predict serum levels.

Photoprotection in erythropoietic protoporphyria: mechanism of photoprotection by beta carotene.

Erythropoietic protoporphyria is a genetic disease caused by the accumulation of protoporphyrin IX. This molecule absorbs 400-nm light and its presence is at times associated with severe cutaneous photosensitivity. The only effective treatment for this disease is oral administration of beta carotene. Several possible mechanisms of photoprotection by beta carotene were investigated using the photohemolysis of red blood cells as an in vitro model. Additional studies were done in an in vivo model which involves lethal hematoporphyrin photosensitization of white mice. The photoprotective effects of beta carotene were compared with those of alpha tocopherol, an agent which possesses some but not all the properties that have been implicated in explaining the known effectiveness of beta carotene. In the photohemolysis model, both compounds demonstrated partial protection. In hematoporphyrin-photosensitized mice, tocopherol showed some protection at high doses, while beta carotene showed greater protection at lower concentrations. Although these results suggest that photoprotective was due to free radical scavenging or singlet oxygen quenching, properties common to both agents, they do not rule out the possible role of 400-nm light absorption, a property of beta carotene alone.

The transport of alpha-tocopherol and beta-carotene in human blood.

The concentrations and distributions of major lipids (cholesterol, phospholipid, and triglyceride), tocopherol and carotenoids were determined in the plasma lipoprotein fractions (VLDL, LDL, and HDL) of (1) normal human subjects, (2) patients with hyperlipoproteinemia, and (3) patients with erythropoietic protoporphyria treated with oral beta-carotene and/or alpha-tocopherol. The distribution of tocopherol (in percent) was most closely correlated with the distribution of total lipids in the individual lipoproteins, while the major portion of beta-carotene was present in the low density lipoproteins, irrespective of the lipid distribution in the lipoproteins (except for one subject with hyperchylomicronemia). The alpha-tocopherol and beta-carotene concentrations of plasma and RBC in patients treated with tocopherol and carotene were determined periodically for a one-year period. Plasma and RBC tocopherol concentrations showed a rapid, parallel increase in response to tocopherol supplementation. In contrast, the plasma and RBC carotene concentrations showed a much slower and nonparallel increase in response to carotene administration. When carotene supplementation was stopped, the elevated carotene levels in both plasma and RBC persisted for several months; the elevated plasma carotene level persisted longer than the raised RBC carotene levels. These results suggest that alpha-tocopherol and beta-carotene are transported differently in the circulation and that the tissue storage and mobilization of these compounds are different.

Comparison of exchange of alpha-tocopherol and free cholesterol between rat plasma lipoproteins and erythrocytes.

The simultaneous exchange of (3h)tocopherol and (14C)cholesterol between rat plasma, rat plasma lipoproteins, and RBC was studied in vitro to compare quantitavely (a) the fractional exchange rates and (b) the half-times for isotope equilibration. In all incubations of RBC with plasma or with plasma lipoprotein fractions, (14C)cholesterol approached equilibrium more rapidly than (3H)tocopherol. When the RBC contained the initial radioactivity, the half-times for equilibration with plasma of cholesterol and of tocopherol were 1.0 and 2.2 hr, respectively. However, the fractional exchange rates (KRBC leads to plasma) were 0.097/hr for cholesterol and 0.188/hr for tocopherol, indicating that the RBC tocopherol pool is turning over almost twice as rapidly as the RBC cholesterol pool. The rat plasma lipoproteins were separated into five fractions by successive ultracentrifugation. Only two fractions, the high density lipoproteins (d 1.063-1.21) and the very low density lipoproteins (d is less than 1.006), participated to a significant extent in the exchange of either tocopherol or cholesterol with RBC. Cholesterol exchange between individual rat plasma lipoproteins and RBC had the same half-times for isotope equilibrium for the very low and high density lipoproteins, and the RBC fractional exchange rates were proportional to the amount of cholesterol in the lipoproteins. In tocopherol exchange between individual rat plasma lipoproteins and RBC, the very low density lipoprotein tocopherol did not equilibrate completely with the RBC. However, the initial rate of tocopherol exchange appeared to be the same for very low and high density lipoproteins. The very low density lipoproteins were disrupted by repeated freezing and thawing or by dehydrating and rehydrating, and analysis of the resulting lipoproteins indicated that free cholesterol was associated more closely than tocopherol with the phospholipid-protein portion of the molecule, which is thought to be on the surface. This difference in distribution of tocopherol and free cholesterol within very low density lipoproteins could account for their different rates of exchange and for the nonequilibrium of tocopherol between RBC and very low density lipoproteins.

Spectrophotometric method for determination of tocopherol in red blood cells.

A relatively rapid procedure is described for the spectrophotometric determination of total tocopherol in red blood cells (RBC) based on a modification of the original Emmerie-Engel reaction. The critical feature in this method is the presence of a large amount of an added antioxidant, pyrogallol or ascorbic acid, during the saponification and extraction stages and the use of thin-layer chromatography for tocopherol purification. The total tocopherol levels of plasma and erythrocytes were determined for a number of human subjects, for patients with abetalipoproteinemia, and for rats. It was found that these levels had a wide range in normal human subjects but that the ratio of RBC to plasma tocopherol was relatively constant and equal to 0.18, uncorrected, and 0.21 when both RBC and plasma values were corrected to 100% recovery. The RBC-to-plasma ratio for rats was 0.39. The accuracy of this ratio determined by the spectrophotometric procedure was verified by measuring the distribution of [(14)C]tocopherol in RBC and plasma when radioactive vitamin E was introduced into the blood by both in vitro and in vivo techniques. The addition of radioactive tocopherol to RBC or plasma at the initial stage of the analysis permits an accurate determination of the total tocopherol in RBC or plasma by calculations based on the recovery of the added isotope. This procedure for erythrocyte tocopherol analysis is compared with a gas-liquid chromatographic method in current use.