In vivo biological validation and biophysical modeling of the sensitivity and positive accuracy of endocrine peak detection. II. The follicle-stimulating hormone pulse signal

Despite interest in the in vivo control of gonadotropin release, valid assessment of the physiological regulation of the pulsatile secretion of the gonadotropin FSH has been hampered by the uncertain validity and reliability of available FSH peak detection algorithms. Difficulties in identifying FSH peaks accurately are believed to arise in part because of the slow metabolic clearance of this glycoprotein hormone. Here, we have used two complementary strategies to test the validity of FSH pulse detection. First, by means of a computer-assisted mathematical model for simulating episodic hormone secretion, we evaluated the effects of various putative FSH secretory pulse amplitudes and half-lives on the sensitivity and positive accuracy of peak detection. Secondly, we used an in vivo primate animal model, in which presumptively true FSH pulses were evaluated independently by continuous electrophysiological monitoring of mediobasal hypothalamic multiunit activity. These two approaches allowed us to define optimal pulse analysis parameters that yield maximal sensitivity and positive accuracy for detecting FSH peaks in synthetic and biological time series. We found (as predicted intuitively) that increasing half-times of hormone disappearance decrease both the sensitivity and positive accuracy of peak detection for any given peak detection thresholds and hormone secretory amplitudes. However, adequately sampled episodic FSH time series could be analyzed for FSH pulsatility by an appropriately constrained, objective computerized algorithm with reasonable (less than 10-15%) false negative and false positive errors, such that resultant sensitivity and positive accuracy exceed 85-90%. Of interest, computer simulations and the in vivo animal model exhibited similar discriminative capabilities. We conclude that increasing half-times of hormone (e.g. FSH) removal do impair hormone peak detection sensitivity and positive accuracy. Nevertheless, gonadotropin time series can be analyzed for FSH pulsatility in a valid manner with adequately constrained false negative and false positive error rates.     

Traumatic spinal cord injury: unusual recovery in 3 children

We report on 3 children with traumatic spinal cord injury. All of them had normal x-rays of the vertebral column. There were no abnormalities of the spinal cord in myelography or magnetic resonance imaging. Although these situations are often associated with a poor neurological prognosis, we observed very unusual recoveries in these 3 cases.     

Lynestrenol induced therapeutic amenorrhea: effects of dose reduction on serum sex-hormones and lipids.

The effect of reducing the dose of peroral lynestrenol by half on serum sex-hormone, lipid and lipoprotein status was studied in 21 mentally retarded women with therapeutic amenorrhea (TA). They had previously received 5 or 10 mg peroral lynestrenol daily for periods ranging from 32 to 196 months. Dose halving of lynestrenol resulted in an increase in serum total testosterone (T) by 16% (p less than 0.05), sex-hormone binding globulin (SHBG) by 39% (p less than 0.01) and high-density lipoprotein cholesterol (HDL-C) by 28% (p less than 0.001). Both the mean serum total and free concentrations of norethisterone (NET and fNET) decreased by 60% (p less than 0.001). The serum concentrations of 17-beta-estradiol (E2), its free fractions (fE2) and free T (fT) were not significantly altered. Significant correlations were observed between the change in HDL-C and the change in T (r = 0.45, p less than 0.05), between the change in SHBG and the change in T (r = 0.62, p less than 0.01), fT (r = 0.43, p less than 0.05) and E2 (r = 0.51, p less than 0.05). The elevation of HDL-C was probably caused by the reduced serum NET concentrations. This also resulted in an increase in serum SHBG concentration, which is regarded as an indicator of the overall estrogen/androgen ratio.     

Nitrosamine excretion in patients with continent ileal reservoirs for urinary diversion.

Adenocarcinomas are a recognized complication following ureterosigmoidostomy for which the endogenous formation of N-nitroso compounds may be a risk factor. As an alternative means of urinary diversion, the continent ileal reservoir has recently been developed. Microbiological and chemical investigations on the urine of patients with an ileal reservoir showed the presence of bacteria, nitrate, nitrite and N-nitrosamines formed endogenously in the ileal pouch. The role of nitrosamines in carcinogenesis in these patients as a late stage complication resulting from the use of a continent ileal reservoir is discussed.     

Dioxin concentrations in the blood of workers at municipal waste incinerators.

OBJECTIVES--Increased concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzo-furans (PCDFs) in pooled blood samples from workers at municipal waste incinerators have been reported. This study was undertaken to confirm these results in individual blood samples from potentially exposed and unexposed workers at municipal waste incinerators compared with matched unexposed controls and compared with concentrations in the slag and fly ash from the municipal waste incinerators. METHODS--Concentrations of PCDDs and PCDFs were determined in the blood of 10 workers from an old municipal waste incinerator without adequate pollution controls, 11 workers from a newer incinerator with modern pollution controls, and 25 controls from the general population group matched for age (+/- 10 years), sex, and race, and in the slag and fly ash from the older incinerator. RESULTS--Significant increases of certain PCDDs and PCDFs were found in the blood of the workers from the older incinerator compared with the controls as follows: octaCDD (1051 (438) v 637 (344), P < 0.001), hexaCDF (52.3 (28.7) v 30.2 (18.2), P < 0.01), heptaCDF (43.9 (30.4) v 22.7 (12.4), P < 0.001), total PCDDs (1262 (484) v 825 (454), P < 0.001), total PCDFs (133.0 (68.1) v 93.7 (36.7), P < 0.05), and total PCDD/Fs (1395 (537) v 918 (437), P < 0.001). The workers from the older incinerator with the greatest exposure were found to have the most significant increases of the blood PCDDs and PCDFs, and the pattern of increased PCDD and PCDF congeners in the blood corresponded to the pattern in the incinerator slag and ash. No significant differences were found between the blood concentrations of the workers at the newer incinerator and the controls. CONCLUSION--Occupational exposure to slag and fly ash from municipal waste incinerators may increase the blood concentrations of PCDDs and PCDFs. Modern pollution control technology in new incinerators may be able to minimise potential exposure to slag and fly ash and thus the absorption of PCDDs and PCDFs from this source.     

Behavioral risk factors for injury among rural adolescents.

This 3-year, longitudinal, prospective study examined behavioral risk factors for medically attended injuries among a cohort of 758 rural students from Maryland's Eastern Shore region who were 12-14 years of age in 1987. Students were surveyed annually in the eighth, ninth, and tenth grades with a self-administered questionnaire. Information was obtained on the number of injuries experienced, risk-taking behaviors, delinquency, alcohol and drug use, physical exercise and sports, parental supervision, and work experience. Information on the parents' education was obtained from a parental interview. Slightly more than half (53.5%) of the students reported having experienced one or more injuries in the eighth grade as compared with one-third of the students in ninth grade, and 38% of those in the tenth grade. Poisson regression analyses were conducted to examine the association of eighth grade variables with ninth grade injuries and ninth grade variables with tenth grade injuries. Results from these analyses indicated that, in addition to sex and race, a high degree of risk taking, frequent cruising, and having high and low parental supervision in the eighth grade significantly increased the number of injuries in ninth grade. In the tenth grade, risk taking continued to be associated with injuries. In addition, students who reported disciplinary problems in school, working 1-10 hours per week, drinking on 1-2 days during the past month, lifetime use of marijuana equal to 1-5 occasions, and involvement in sports experienced greater numbers of injuries in the tenth grade.