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Biomedical subjects

D Schoenfeld

Publications and source records attributed to D Schoenfeld.

At least 55 records · Page 3Linked to original sources

Suppression by the sumatriptan analogue, CP-122,288 of c-fos immunoreactivity in trigeminal nucleus caudalis induced by intracisternal capsaicin.

1. The effects of an intravenously administered sumatriptan analogue were examined on c-fos-like immunoreactivity (c-fos-LI), a marker of neuronal activation, evoked within trigeminal nucleus caudalis (TNC) and other brain stem regions 2 h after intracisternal injection of the irritant, capsaicin (0.1 ml, 0.1 mM), in pentobarbitone-anaesthetized Hartley guinea-pigs. 2. C-fos-LI was assessed in eighteen serial sections (50 microns) using a polyclonal antiserum. A weighted average, reflecting total expression within lamina I, IIo of TNC was obtained from three representative levels (i.e., at -0.225 mm, -2.475 mm and -6.975 mm.). 3. Capsaicin caused significant labelling within lamina I, IIo, a region containing axonal terminations of small unmyelinated C-fibres, as well as within the nucleus of the solitary tract, area postrema and medial reticular nucleus. A similar distribution of positive cells was reported previously after intracisternal injection of other chemical irritants such as autologous blood or carrageenin. 4. Pretreatment with a conformationally restricted sumatriptan analogue (with some selectivity for 5-HT1B and 5-HTID receptor subtypes) CP-122,288, reduced the weighted average by approximately 50-60% (P < 0.05) in lamina I, IIo at > or = 100 pmol kg-1, i.v., but did not decrease cell number within area postrema, nucleus of the solitary tract or medial reticular nucleus. A similar pattern was reported previously following sumatriptan, dihydroergotamine or CP-93,129 administration after noxious meningeal stimulation. 5. We conclude that modifications at the amino-ethyl side chain of sumatriptan dramatically enhance the suppression of c-fos expression within TNC, a finding consistent with its remarkable potency against neurogenic plasma protein extravasation within dura mater. CP-122,288 and related analogues may serve as an important prototype for drug development in migraine and related headaches.

Animals↗

Accuracy, precision, and utility of spine and whole-skeleton mineral measurements by DXA in rats.

We evaluated the precision and accuracy of dual-energy x-ray bone densitometry (DXA) in 38 male and female rats aged 1-10 months. The coefficients of variation (CV) estimated from same-day paired measurements of bone mineral content (BMC) were 1.26% at the lumbar spine and 0.69% at the whole skeleton, and the corresponding CV for BMC corrected for projected bone area (i.e., bone mineral density, BMD) were 0.57 and 0.66%. BMC, measured in vivo, correlated closely with the subsequently determined ash weights (spine r2 = 0.94, whole-skeleton r2 = 0.97). The long-term CV for BMC measurements, assessed by measuring a frozen animal daily for 4 weeks, were 1.28% for the spine and 1.03% for the whole skeleton; for BMD the corresponding CV were 0.88 and 1.15%. To examine the utility of serial DXA measurements we followed female rats subjected to ovariectomy (OVX) or sham operation at 10 months of age and male rats given daily subcutaneous injections of hPTH-(1-34) or vehicle starting at 10 months of age every 3 weeks for 15 weeks. In the OVX rats a progressive decrease in spine BMC was observed that was most rapid during the first 6 weeks. By 15 weeks the mean spine BMC decreased by 17% in the OVX rats (p < 0.007 versus sham operation). OVX did not affect the accuracy of DXA measurements as assessed by comparison with the ash weight at the end of the 15 week study. PTH treatment increased spine BMC by a mean of 32% and increased whole-skeleton BMC by a mean of 19% within 15 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

R-PEP-27, a potent renin inhibitor, decreases plasma angiotensin II and blood pressure in normal volunteers.

The hemodynamic and humoral effects of the specific human renin inhibitor R-PEP-27 were studied in six normal human subjects on low and high sodium intake diets. An intravenous infusion of R-PEP-27 (0.5 to 16 micrograms/min/kg body wt) reduced blood pressure in a dose-dependent fashion; the mean arterial blood pressure at the end of the infusion fell from 128 +/- 4/83 +/- 4 to 119 +/- 3/71 +/- 3 mm Hg (mean +/- SEM) (P < .01) during the low sodium intake diet. R-PEP-27 had no effect on blood pressure during the high sodium intake diet. R-PEP-27 significantly reduced plasma angiotensin II and aldosterone concentrations. The temporal response to R-PEP-27 suggests that it is a short-lived although highly potent competitive inhibitor of renin; this peptide is a valuable and specific physiologic probe of the renin-angiotensin system.

Adult↗

Effects of a small quantity of omega-3 fatty acids on cardiovascular risk factors in NIDDM. A randomized, prospective, double-blind, controlled study.

OBJECTIVE: To study the effects of a low dose of omega-3 fatty acids on platelet function and other cardiovascular risk factors in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: We performed a randomized, prospective, double-blind, controlled study of a low dose of omega-3 fatty acids (2.5 g/day) in 20 ambulatory subjects with NIDDM. Subjects ingested five 1-g fish oil capsules each containing 0.5 g omega-3 fatty acids or five 1-g safflower oil capsules per day for 6 weeks followed by a 6-week washout period. RESULTS: Nine subjects completed the study in each group. Both groups exhibited moderate control of glucose levels; modest elevations in baseline total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride (TG) levels; and normal blood pressure values. In the fish oil group, plasma omega-3 fatty acid levels increased significantly. Fish oil significantly reduced the slope of the dose-response curves for collagen-induced platelet aggregation to one-third the value observed with safflower oil. No difference was observed in collagen-induced production of thromboxane A2 (TXA2, measured as the stable derivative TXB2), or in adenosine-5'-diphosphate- (ADP) induced platelet aggregation or TXA2 generation. Patients with high initial collagen-induced platelet TXA2 production showed a significantly larger drop after fish oil than safflower oil. Fish oil significantly reduced TG levels by 44 mg/dl and decreased upright systolic blood pressure (sBP) by 8 mmHg compared with safflower oil. Fish oil caused a significant but small increase in HbA1c (0.56%) and total cholesterol (20 mg/dl) but had no effect on fasting glucose, high-density lipoprotein cholesterol, or LDL-cholesterol levels. CONCLUSIONS: Small doses of fish oil inhibit platelet aggregation and TXA2 production, reduce upright sBP and TG levels, and have only a small effect on glucose and cholesterol levels in patients with moderately controlled NIDDM. Small quantities of omega-3 fatty acids or dietary fish are safe and potentially beneficial in NIDDM patients.

Adult↗

Subsets of glioblastoma multiforme defined by molecular genetic analysis.

Glioblastoma multiforme is a clinically and histologically heterogeneous lesion; however, to date, it has not been possible to subdivide glioblastomas on a clinical, histopathological or biological basis. Previous studies have demonstrated that loss of portions of chromosomes 10 and 17 and amplification of the epidermal growth factor receptor (EGFR) gene are the most frequent genetic alterations in glioblastoma. We therefore examined 74 glioblastomas from 67 patients for loss of heterozygosity on chromosomes 10 and 17, and for amplification of the epidermal growth factor receptor gene, to determine whether glioblastomas can be subtyped on a genetic basis. Using Southern blot analysis we were able to detect different patterns of genomic alterations. Eighteen of 67 informative patients were characterized by a loss of heterozygosity on the short arm of chromosome 17 in the tumor tissue. Forty-five of 64 informative patients showed a loss of heterozygosity on chromosome 10. Amplification of the epidermal growth factor receptor gene was noted in 25 of 67 patients and was restricted to those glioblastomas that had lost portions of chromosome 10. Epidermal growth factor receptor gene amplification occurred significantly more often in patients without chromosome 17p loss than in patients with chromosome 17p loss (p = 0.01). In addition, those glioblastomas with a loss of chromosome 17p occurred in patients significantly younger than those with glioblastomas characterized by EGFR gene amplification (p = 0.001). These data emphasize the genetic heterogeneity of glioblastoma and suggest the division of glioblastoma into genetic subsets.

Adolescent↗

Regulation of growth-plate chondrocytes by insulin-like growth-factor I and basic fibroblast growth factor.

A study was performed in order to investigate the possible functional roles of insulin-like growth-factor I (IGFI) and basic fibroblast growth factor (bFGF) in the regulation of mitotic and metabolic activity of growth-plate chondrocytes. Chondrocytes from the distal radial growth plates of calves and the costal physeal cartilage of rats were exposed to these factors, individually and in combination, in primary monolayer culture, to assess their effects. The data showed that bFGF had both a greater potency and a greater efficacy as a mitogen for bovine growth-plate chondrocytes than did IGF-I. The maximum incorporation of 3H-thymidine by bFGF was 8.3 times that in serum-free (control) cultures; the maximum stimulation of incorporation by IGF-I was 2.5 times that in the control medium. In contrast, IGF-I stimulated a maximum incorporation of 35S-sulfate into glycosaminoglycans that was 2.6 times that in the IGF-I serum-free control cultures, while bFGF had no effect or was mildly inhibitory. When used together, these two factors acted synergistically. Incorporation of 3H-thymidine was more than two times greater than the sum of the effects of the growth factors when used alone and 20.5 times greater than that of the growth factor-free control cultures. Physeal chondrocytes from six-day-old rats were mitotically more responsive to bFGF than to IGF-I, but they were more responsive to IGF-I when they had been derived from twenty-eight-day-old rats. Interaction between bFGF and factors in the serum enhanced the mitotic activity of the rat chondrocytes, but bFGF did not interact with IGF-I under the same experimental conditions. In the presence of bFGF, there was a reduction in the stimulation by IGF-I of incorporation of 35S-sulfate and a decrease in the percentage of chondrocytes containing alkaline phosphatase. These growth factors also influenced cellular morphology in culture. In the presence of IGF-I or serum, the rat chondrocytes manifested the polygonal morphology typical of chondrocytes in culture, while bFGF promoted a more elongated spindle shape. Removal of bFGF and replacement by IGF-I restored the polygonal morphology, indicating that this transition is reversible.

Alkaline Phosphatase↗

An antispasticity effect of threonine in multiple sclerosis.

To determine whether the naturally occurring amino acid threonine, a potential precursor for glycine biosynthesis in the spinal cord, has an effect on spasticity in multiple sclerosis, 26 ambulatory patients were entered into a randomized crossover trial. Threonine administered at a total daily dose of 7.5 g reduced signs of spasticity on clinical examination, although no symptomatic improvement could be detected by the examining physician or the patient. In contrast to the side effects of sedation and increased motor weakness associated with antispasticity drugs commonly used for the treatment of multiple sclerosis, no side effects or toxic effects of threonine were identified. Levels of threonine were elevated in serum and cerebrospinal fluid during treatment, but glycine levels did not change. Enhancement by threonine of glycinergic postsynaptic inhibition of the motor reflex arc in the spinal cord may represent a non-sedating, nontoxic approach to the management of spasticity in multiple sclerosis.

Adult↗

Ovulation and menstrual function of adolescent girls with central precocious puberty after therapy with gonadotropin-releasing hormone agonists.

Chronic GmRH agonist (GnRHa) administration has been shown to suppress pituitary-gonadal function in children with central precocious puberty (CPP), but long term data after the reactivation of gonadarche posttherapy are not yet available. This study evaluated the menstrual function of 46 girls with CPP who had been treated for at least 2 yr with GnRHa (deslorelin or histrelin, sc, daily) and were up to 7 yr posttreatment, including 21 postmenarcheal girls who collected weekly overnight urine samples for 12 consecutive weeks to assess rates of ovulation by urinary pregnanediol-3 beta-glucuronide measurements. Menarche occurred at age 12.1 +/- 1.0 yr (mean +/- SD), on the average 1.2 +/- 0.8 yr posttherapy (range, 0.1-4.3 yr). Menstrual cycle lengths became increasingly regular, with cycles of 25- to 35-day duration reported by 41% of the girls in the first year postmenarche and 65% of the girls studied 3 or more years postmenarche. Ovulation was demonstrated in 50% of the girls studied within 1 yr of menarche and in 90% of the girls studied 2 yr or more postmenarche, including 5 girls who reported pregnancies. The development of regular ovulatory menstrual function in these girls with CPP is in accord with previously documented patterns in normal adolescents. While these data provide further evidence supporting the safety of long term GnRHa therapy, continued studies will be necessary to characterize fully the reproductive function in CPP patients through adolescence and adulthood.

Child↗

Asymptomatic primary hyperparathyroidism.

Of 118 consecutive white patients referred for asymptomatic primary hyperparathyroidism, the diagnosis was clinically confirmed in 100, of whom 85 adults had a serum calcium less than 3.0 mM (12 mg/dl) and no skeletal, rheumatic, or significant neuropsychiatric symptoms, azotemia, or other significant illnesses. Among these 85, 68 had both asymptomatic and medically uncomplicated hyperparathyroidism, whereas 17 had historical, radiographic, or ultrasonic evidence of renal stone disease. The 20% with past or present renal calculi concentrated their urine significantly better than the 68 others (p = 0.05), but these two groups were otherwise not distinguished by the tests we performed, so all 85 patients were analyzed together. Systolic and diastolic blood pressures were normal, but premature osteopenia and/or impaired renal function were present in 29-36% of the patients. Micrometer measurements of metacarpal radiographs and 125I photon absorptiometry at the shaft of the radius revealed cortical osteopenia. Osteopenia was equally significant in the distal radius (cortical plus trabecular bone). These quantitative measurements were superior to routine bone radiography, and ROC analysis showed that 125I absorptiometry at either site was superior (p less than 0.01) to metacarpal cortex measurements for detecting premature osteopenia, which was present in more than a third of these patients. Creatinine clearances (24 h) and maximum urine concentrating capacity (overnight dehydration plus the synthetic vasopressin analog DDAVP) were each significantly reduced, despite all patients' normal BUN and serum creatinine levels. Sequential performance of a 24 h creatinine clearance and a urine concentration test revealed abnormalities in the renal function of 27 of 74 patients (36%), with a specificity of 95% and a higher sensitivity than either test alone (27-29%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Idazoxan treatment in progressive supranuclear palsy.

To confirm the preliminary report that increases in norepinephrine neurotransmission improve motor performance, we administered the investigational drug idazoxan (IDA) to nine patients with progressive supranuclear palsy (PSP) according to a double-blind crossover protocol. There were seven women and two men, whose mean age was 70 years and mean duration of illness 4 years. All had an advanced parkinsonian syndrome, supranuclear ocular motor palsies, and poor responses to dopaminergic drugs. During administration of 40 mg tid of IDA, the total score and the motor subscale score of the United Parkinson's Disease Rating Scale significantly decreased. Features that improved most included mobility, balance, gait, and measures of digital dexterity. There were no significant changes in any measure during placebo administration. Corticobulbar manifestations and eye movements were not significantly improved during treatment. Side effects of IDA included transient hypertension, tachycardia, action tremor, flushing, and sweating, but none was so severe that any patient withdrew from the study. Among the few attempted treatments of PSP, IDA is the first medication shown in a double-blind study to improve aspects of motor function.

Adrenergic alpha-Antagonists↗

T-lymphocyte changes linked to autoantibodies. Association of insulin autoantibodies with CD4+CD45R+ lymphocyte subpopulation in prediabetic subjects.

The onset of insulin-dependent (type I) diabetes is predictable before hyperglycemia by the presence of islet cell autoantibodies (ICAs) and competitive insulin autoantibodies (CIAAs). CIAA+ICA+ first-degree relatives of individuals with type I diabetes have increased numbers of CD4 cells bearing the CD45R antigen and reciprocal depressions of the CD4 cells bearing the CD29 determinant. In addition, depressed CD4/CD8 ratios are present. In this study, we investigated the correlation between autoantibody levels and T-lymphocyte changes in the prediabetic state. The data demonstrate a clear linear relationship between rising CIAA levels, a marker of disease rate, and rising elevations in the CD4+CD45R+/CD4+CD29+ ratio in 37 CIAA+ICA+ and CIAA+ICA- relatives (r = 0.93). In marked contrast, the degree of CD4/CD8 depression found in individuals with prediabetes or long-term diabetes failed to correlate with either CIAA (r = 0.32) or ICA (r = 0.29) levels. The investigation of T-lymphocyte changes in siblings of individuals with type I diabetes with different stable autoantibody patterns (CIAAs and/or ICAs), and thus varying risks for diabetes, revealed differences in the prediabetic groups. Fifteen CIAA+ICA- relatives with high CIAA levels (greater than 80 nU/ml) had high CD4+CD45R+/CD4+CD29+ ratios (P = 0.03) and depressed CD4/CD8 ratios (P = 0.008). In contrast, CIAA+ICA- relatives with low CIAA levels (39-80 nU/ml), and thus low risk of diabetes, had no alteration in their CD4/CD8 ratio (P = 0.75) or CD4+CD45R+/CD4+CD29+ ratio (P = 0.33). Nineteen CIAA-ICA+ siblings with a predicted intermediate risk for diabetes showed heterogeneity in the presence of T-lymphocyte abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗

Osteopenia in women with hypothalamic amenorrhea: a prospective study.

Hypothalamic amenorrhea, a common disorder associated with abnormalities in gonadotropin pulsatility and subsequent estrogen deficiency, is usually transient, and treatment indications are unclear unless fertility is desired. To determine whether this disorder is associated with progressive bone loss, we studied 24 women with primary or secondary amenorrhea related to stress or simple weight loss, compared with 31 normal women of the same age. Amenorrheic women had significantly lower (P = .01) body fat (26.4 +/- 7.3 versus 30.6 +/- 4.7%) and higher (P = .0001) urine free cortisol levels (250 +/- 100 versus 140 +/- 50 nmol/day) than normals. Trabecular bone density in women with hypothalamic amenorrhea as assessed by spinal computed tomography was significantly (P = .001) lower than in normals (140.2 +/- 27.3 versus 175.1 +/- 24.6 mg K2HPO4/mL, respectively). Twenty of the 24 amenorrheic women had initial spinal bone density below the mean in normals, and in eight it was 2 standard deviations or more below the normal mean. Initial bone density correlated negatively with duration of amenorrhea (r = -0.489, P = .02) and positively with serum free testosterone levels (r = 0.517, P = .02). Prospective evaluation showed a decline in spinal bone density in those who were amenorrheic for fewer than 5 years. The slope of change in bone density correlated with initial weight, percent ideal body weight, and percent body fat (R2 = 0.597, P = .0003; R2 = 0.549, P = .0007; and R2 = 0.618, P = .0002, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Tyrosine for depression: a double-blind trial.

We treated 65 outpatients with RDC major depression in a randomized, prospective, double-blind comparison of oral L-tyrosine, 100 mg/kg/day, imipramine, 2.5 mg/kg/day, or placebo for 4 weeks. Tyrosine increased and imipramine decreased 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion significantly, but there was no evidence that tyrosine had antidepressant activity. The only side effect to achieve statistical significance was greater dry mouth with imipramine. MHPG excretion and plasma amino acid concentrations failed to predict or correlate with clinical improvement.

Adult↗

Issues in the design of drug trials for AIDS.

Although the fundamental principles that drive the design, conduct, and analysis of clinical trials are as applicable to AIDS as to other diseases, there is no question that we have been confronted with unusually difficult challenges in studying therapeutic approaches in this disease area. Treatments are being developed that show great promise, but when investigated further some may be seen to offer no clinical benefit and others may do active harm through toxicity. A group of biostatisticians, meeting in association with the AIDS Clinical Trials Group (ACTG), has discussed and written a report on a number of issues, primarily related to principles of study design, with the goal of stimulating thought on new study designs and the timely implementation of well-designed trials to identify effective treatment strategies for HIV-infected populations. These issues include (1) progression of clinical trials through phases, (2) choices of outcomes, (3) breadth and complexity of clinical trials (eligibility criteria and "low-tech" trials, (4) alternative designs to be used in randomized trials, and (5) the concept of randomized clinical trials as a desirable option, both for patients and for science. The current HIV epidemic makes the requirements of obtaining valid scientific comparisons more important, not less so, but the challenge is to expedite this process.

Acquired Immunodeficiency Syndrome↗

Phase II trial of spirogermanium and vindesine in malignant glioma.

Fifty-four adults with recurrent malignant glioma were treated on an Eastern Cooperative Oncology Group (ECOG) trial. All had previous radiation therapy, and 70% had previous chemotherapy. They were assigned to either vindesine 3 mg/m2 weekly or spirogermanium 80 mg/m2 three times weekly with escalation to 120 mg/m2. The response was 4% to vindesine, and 8% to spirogermanium. The duration of response was 53 days for a patient who had clinical improvement only, but greater than 151 days and greater than 1066 days for two patients who had achieved a greater than 50% reduction in tumor size by computed tomography (CT). The toxicities were hematologic for vindesine and neurologic for spirogermanium. Neither agent seems to have sufficient efficacy to warrant further trials in previously treated glioma patients.

Adult↗

Combined antibody and ganciclovir treatment of murine cytomegalovirus-infected normal and immunosuppressed BALB/c mice.

The efficacy of treatment with ganciclovir (DHPG) and antibody activity-containing ascitic fluid (AF) separately and in combination was studied in normal and immunosuppressed BALB/c mice challenged intraperitoneally with a lethal dose (10(6) PFU) of murine cytomegalovirus (CMV). With combination therapy, lower doses of both DHPG and AF were often as effective as a higher dose of either agent given singly. For instance, the survival rate of murine CMV-challenged immunosuppressed mice was doubled when 4 mg of DHPG per kg and a 1:16 dilution of AF were both administered in contrast to when each was used alone. In both groups of animals, combination therapy was shown to be more effective than either therapy individually, even when initiation of therapy was delayed as long as 48 h. Such an approach holds promise for decreasing the expense associated with antibody use and the dose-related toxicity associated with DHPG use while maintaining or possibly increasing the efficacy of prophylaxis and therapy of serious CMV disease in humans.

Animals↗

Early natural history of regional left ventricular dysfunction after experimental myocardial infarction.

Existing studies provide conflicting information concerning the natural history of regional dysfunction after subacute myocardial infarction. The purpose of this study was to use quantitative computer-assisted two-dimensional echocardiography to define the natural history of abnormal wall motion in a subacute canine infarct model within individual short-axis echocardiographic planes, and in the entire ventricle as well. Serial short-axis echocardiograms were obtained from 10 closed-chest dogs before occlusion and at 0.5, 6, 24, 48, and 72 hours after ligation of the circumflex (six dogs) or left anterior descending (four dogs) coronary artery. The circumferential extent of abnormal wall motion was quantified by two different computer-assisted methods: the first, a derived correlation method, examined wall motion throughout the systolic contraction sequence; the second method examined the fractional radial change in endocardial ray length from end-diastole to end-systole. The study shows that for individual planes there is a slight but not statistically significant increase in the circumferential extent of abnormal wall motion from 0.5 to 72 hours after coronary artery occlusion; however, when the total extent of left ventricular asynergy was used to define a global functional infarct size, we observed a small (3.6% to 5.4%) but significant increase in the circumferential extent of abnormal wall motion.

Analysis of Variance↗

Neuroendocrine-gonadal axis in men: frequent sampling of LH, FSH, and testosterone.

Previous studies of episodic hormone secretion of the hypothalamic-pituitary-gonadal axis in normal men have produced conflicting results due to examinations of small cohorts of subjects or to limited sampling techniques. We evaluated gonadotropin and testosterone (T) secretory patterns in 20 normal men by sampling blood at 10-min intervals for luteinizing hormone (LH) and follicle-stimulating hormone (FSH). T concentrations were also analyzed at 20-min intervals in 10 subjects. A previously unappreciated spectrum of gonadotropin and T secretory patterns was observed in normal men. Both mean LH concentrations and mean LH pulse amplitudes varied fourfold between individuals. LH interpulse intervals varied from 30 to 480 min (mean 119 +/- 32). Results also suggested a relative refractory period at the level of the hypothalamus or pituitary. In three subjects, a striking nighttime accentuation of LH pulsations was noted. Through use of Fourier analysis, a diurnal variation in LH was observed in the population (P less than 0.02). Mean FSH levels showed marked variation between individual subjects, with discrete pulses rarely observed. No diurnal variation in FSH secretion was noted. Serum T concentrations determined at 6-h intervals ranged from 105 to 1,316 ng/dl between subjects. When T was measured at 20-min intervals, marked intermittent declines in the T concentrations to levels well below the normal range were observed in 3 of 10 subjects. T secretion was found to lag behind LH secretion by approximately 40 min (P less than 0.02).

Adult↗