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S M Pincus

Publications and source records attributed to S M Pincus.

At least 19 recordsLinked to original sources
PubMed1998

Follicle-stimulating hormone is secreted more irregularly than luteinizing hormone in both humans and sheep.

Recently introduced statistical tools capable of discerning differences between the pattern of luteinizing hormone (LH) secretion and that of follicle-stimulating hormone (FSH) could be valuable in understanding ovulation and menopause, and ultimately in making diagnostic decisions and treating infertility and polycystic ovary syndrome. We assessed the validity and scope of the hypothesis that FSH is secreted more irregularly than LH in ewes and fertile women. We compared secretory irregularity of LH to that of FSH in both ovariectomized ewes (n = 7) and women of proven fertility (n = 5) during the follicular and luteal phases of their reproductive cycles. In each sheep, time series from both hypophyseal portal blood (HPB) and peripheral blood were evaluated in 72 samples obtained every 5 min; in each human, both luteal and follicular periods were studied in 192 samples obtained every 7.5 min. To quantify serial irregularity, we used approximate entropy (ApEn), a scale- and model-independent statistic. FSH secretion was consistently more irregular than that of LH in each subject. For sheep HPB, ApEn(FSH) = 1.415+/-0.097 was larger than ApEn(LH) = 0. 822+/-0.213, P < 0.0001 (mean+/-SD, paired t test). This difference persisted peripherally: ApEn(FSHper) = 1.431+/-0.101 > ApEn(LHper) = 1.252+/-0.086, P = 0.024. In women, ApEn(FSH) = 1.467+/-0.217 > ApEn(LH) = 0.923+/- 0.305, P < 0.0001. ApEn(FSH) > ApEn(LH) in 100% of women (peripheral) and sheep HPB. Secretion during the follicular phase was more irregular than during the luteal phase for both FSH and LH (P < 0.01). LH mean level secretion showed a wake/sleep difference in women, P < 0.005, with higher values awake. The consistency and statistical significance of these findings suggest that this LH/FSH difference may be broadly based within higher mammals. Ranges of normative and abnormal regularity values of LH, FSH, and their difference can be used in a number of settings, both (currently) research and (potentially ultimately) clinical milieus.

Animals↗
PubMed1998

Characteristics of luteinizing hormone secretion in younger versus older premenopausal women.

OBJECTIVES: The objectives of this study were to document specific attributes of pulsatile luteinizing hormone secretion in middle-aged women before discernible alterations in their menstrual cycles and to compare the results to corresponding data obtained in younger women. STUDY DESIGN: After documenting normal cycle length, biphasic basal body temperatures, and normal midluteal progesterone in younger and middle-aged women during an initial cycle, daily blood samples and samples withdrawn at 10-minute intervals for 8 hours during the midfollicular phase were obtained during a subsequent cycle. RESULTS: Assessment of luteinizing hormone pulses with the pulse detection algorithm Cluster demonstrated a prolonged interpulse interval and increased pulse width in the older women. Assessment of luteinizing hormone secretory bursts and half-life with the deconvolution analysis procedure demonstrated a prolonged interburst interval and half-life in the older women. Appraisal of approximate entropy revealed greater orderliness of luteinizing hormone release in the older women. CONCLUSIONS: Middle-aged women exhibit alterations in hypothalamic-pituitary function that may account in part for age-related changes in reproductive potential.

Adult↗
PubMed1998

Differential orderliness of the GH release process in castrate male and female rats.

Male- and female-specific modes of episodic growth hormone (GH) release are presumptively imposed by sex steroid hormones, and, although typically evident visually, are vividly distinguished quantitatively via a regularity statistic, approximate entropy (ApEn), in both the rat and human. GH secretory patterns may determine GH-stimulated growth and specific hepatic and muscle gene expression in the rat. Consequently, it is important to discern mechanisms that underlie their regulation. Here we have examined the impact of prepubertal gonadal suppression (at 4 wk of age) via surgical or pharmacological [gonadotropin-releasing hormone (GnRH) agonist] intervention on the regularity (ApEn) of GH release in male and female rats (at 10-11 wk of age) sampled at 10-min intervals for 10 h (n = 60 points) during a lights-out (dark) period. We observed a graded hierarchy of mean disorderliness of GH release that was quantifiable by ApEn measures, with maximal to minimal disorderliness in the following rank order: intact female, GnRH agonist-treated female, ovariectomized female, orchidectomized male, GnRH agonist-treated male, and intact male. These observations suggest a continuum of sex steroid actions on the regularity of GH secretion and, by inference, on the interplay among GH-releasing hormone, somatostatin, and GH/insulin-like growth factor I negative feedback.

Animals↗
PubMed1998

Patients with Cushing's disease secrete adrenocorticotropin and cortisol jointly more asynchronously than healthy subjects.

We examined serum concentration time-series for ACTH and cortisol in 20 patients with pituitary-dependent ACTH excess (Cushing's disease) and in 29 age- and gender-matched controls. For each subject, blood samples were obtained at 10-min intervals for 24 h. Joint ACTH-cortisol synchrony was quantified using the recently introduced cross-approximate entropy (cross-ApEn) statistic. In patients, cross-ApEn was greater than in controls (1.686 +/- 0.051 vs. 1.077 +/- 0.039, P = 3.45 x 10(-16), giving a sensitivity of 85%. In control subjects, but not in patients, cross-ApEn was correlated positively with age (r = 0.465, P = 0.011) There was no gender difference in cross-ApEn, nor a relationship between cross-ApEn and the 24-h ACTH and cortisol secretion, in patients or controls. In contrast, the maximal cross-correlation coefficient for the ACTH and cortisol series after detrending the series was 0.394 +/- 0.033 in controls and 0.297 +/- 0.034 in patients with considerable overlap of the subgroups, giving a sensitivity for this index of only 5%. In addition to previous findings of increased individual irregularity of ACTH and cortisol release in Cushing's disease, we can now also demonstrate greater joint asynchrony of the circulating concentrations of these hormones. Thus, Cushing's disease disrupts ensemble network secretory dynamics over individual hormone output. We conclude that, like GH-secreting pituitary and aldosterone-secreting adrenal tumors, ACTH-secreting pituitary tumors exhibit significant loss of orderly hormone release patterns. Moreover, Cushing's disease is marked further by deterioriation of bihormonal synchrony between ACTH and cortisol release, thus suggesting further erosion of within-axis feedback control.

Adolescent↗
PubMed1998

Reduced disorderliness of growth hormone release in biochemically inactive acromegaly after pituitary surgery.

The episodicity of 24 h GH release was studied in 18 patients with active acromegaly, 12 patients 7-10 days after pituitary surgery, 14 patients long after operation (3-17 years), and 21 healthy gender- and age-matched control subjects, using a recently introduced scale- and model-independent regularity statistic, approximate entropy (ApEn). Blood samples were taken at 10-min intervals for 24 h, and plasma GH concentrations were measured by immunofluorometric assay (detection limit 11.5 ng/l). For this study we selected operated patients who were biochemically in remission, defined by normal circulating IGF-I and insulin-like growth factor-binding protein-3 (IGFBP-3) concentrations, normal glucose-suppressed plasma GH concentration (<0.38 microg/l), and the normalization of the paradoxical rise of GH to TRH or GnRH. In patients with active acromegaly ApEn was 1.23+/-0.04, with no overlap with the control subjects (P = 1.2 x 10[-16]), who had an ApEn of 0.40+/-0.04. ApEn in patients shortly after surgery was 0.71+/-0.09 (P < 0.001 vs controls), and long after surgery 0.56+/-0.05 (P < 0.011 vs controls). ApEn values in treated and untreated patients correlated significantly with the plasma concentration of IGF-I (r=0.531) and IGFBP-3 (r=0.598), and the log-transformed 24h GH secretion rate (r=0.749). Shortly after surgery only one-third of the patients had a normal ApEn value, whereas long after surgery about 70% of the patients had a normal ApEn value. Although ApEn eventually normalized in about 70% of the operated patients, the cause of the persistence of abnormal GH release in the remainder of the subjects is not known, and might reflect permanent hypothalamic-pituitary dysfunction or a very early recurrence of the somatotroph adenoma.

Acromegaly↗
PubMed1998

Glucagon-like peptide 1 increases mass but not frequency or orderliness of pulsatile insulin secretion.

Glucagon-like peptide 1 (GLP-1) is a peptide hormone that is released from the gut after luminal stimulation. The hormone is a potent insulin secretagogue and is a potential novel pharmaceutical adjuvant in the treatment of NIDDM. Insulin is secreted as a series of punctuated secretory bursts superimposed on a basal insulin release. Recently, the contribution of these secretory bursts to overall insulin secretion has been evaluated, and studies using catheterization across the pancreas in a canine model and studies using deconvolution in humans have revealed that the majority of insulin is released during these secretory bursts. Moreover, the main regulation of insulin secretion is through perturbation of mass and frequency of these secretory bursts. The mode of delivery of insulin into the circulation seems important for insulin action, and it is therefore important to know the impact of a potential therapeutic insulin secretagogue on the mode of insulin secretion. To assess the effects of GLP-1 on the mass, frequency, amplitude, and overall contribution of pulsatile insulin secretion, we used a recently validated deconvolution model to examine these variables before and during infusion of GLP-1 in eight healthy men (age 28 +/- 2 years; BMI 24 +/- 2 kg/m2). At a constant glucose infusion (2.5 mg x kg-1 x min-1), near-steady state was reached at 75 min, and sampling was performed every minute at t = 75-115 and 145-185 min. At t = 115 min, an infusion of saline or GLP-1 (50 pmol x kg-1 x min-1) was given. The regularity of insulin secretion was measured by approximate entropy, a recently developed mathematical statistic, applied herein to assess the regularity in a hormone concentration time series. After GLP-1 infusion, there was an abrupt increase in the peripheral concentrations of serum C-peptide (696 +/- 65 vs. 1,538 +/- 165 pmol/l) and insulin (49 +/- 8 vs. 138 +/- 21 pmol/l) concentrations. This increase was mainly due to an increase in the pulsatile component of insulin secretion that was achieved by a fourfold increase in secretory burst mass (28.2 +/- 4.4 vs. 100.1 +/- 15.8 pmol x l-1 x pulse-1; P < 0.001), and amplitude (12.7 +/- 2.2 vs. 4.3 +/- 7.7 pmol x l-1 x min-1; P < 0.002), whereas the secretory burst frequency was not affected by GLP-1 (11.5 +/- 0.7 vs. 12.6 +/- 0.6 pulses/h; P = 0.4). As a consequence, the detected contribution of pulsatile to overall insulin secretion was increased from 56 +/- 4 to 77 +/- 4% (P < 0.005). The orderliness of the insulin release process was not deteriorated by short-term GLP-1 infusion as assessed by approximate entropy (1.19 +/- 0.04 vs. 1.18 +/- 0.04; P = 0.7).

Adult↗
PubMed1997

Preliminary evidence for the evolution in complexity of heart rate dynamics during autonomic maturation in neonatal swine.

Previous studies suggest that the autonomic nervous system plays an important role in the generation of complex heart rate dynamics. Therefore, we hypothesized that the complexity (irregularity) of cardiac interbeat intervals would evolve with the maturation of autonomic innervation to the heart. Twelve healthy newborn piglets were implanted with ECG transmitters and studied at one or more different ages up to 33 days of age, the period during which pigs develop functional sympathetic innervation of the heart from the stellate ganglia. Three animals underwent right stellate ganglionectomy, two a left stellate ganglionectomy, two a right cardiac vagotomy and five a sham procedure. The statistic, approximate entropy (ApEn), was used to quantify the regularity of interbeat interval fluctuations. Sham-operated animals showed an increase in the standard deviation (SD) and irregularity (ApEn) of cardiac interval fluctuations with increasing age. Right stellate ganglionectomized piglets had lower interbeat interval ApEn values, but similar SD's by 26-27 days of age compared to sham-operated animals. Left stellate ganglionectomy, which affects cardiac inotropy rather than chronotropy, had no effect on cardiac interval irregularity, while vagotomy had an indeterminant effect. The increasing irregularity of interbeat interval dynamics during autonomic maturation and the apparent attenuation of heartbeat irregularity when right stellate ganglion innervation is interrupted, provides empirical support for the notion that complex heartbeat dynamics in the mature animal are the result of a network of autonomic neural pathways that enables an organism to adapt to stress.

Aging↗
PubMed1997

Disorderly and nonstationary insulin secretion in relatives of patients with NIDDM.

To further explore the role of the beta-cell as a pathogenic factor behind non-insulin-dependent diabetes mellitus (NIDDM), insulin secretion at modest hyperglycemia was examined in 15 healthy first-degree relatives of NIDDM patients and 13 anthropometrically and age-matched controls. The oral glucose tolerance test was normal in all, but the relatives had impaired insulin-stimulated glucose uptake (P < 0.05). During a constant intravenous glucose infusion we performed a time-series analysis of serum insulin in samples obtained at 1-min intervals for 75 min (60-135 min). The recently introduced scale- and model-independent statistic approximate entropy (ApEn) and the coefficient of variation for a 6- (9 and 15) point moving average (MA) were applied to test regularity and stationarity, respectively, of insulin secretion. Both ApEn and 6-point MA were able to significantly discern the insulin time series of the two groups (P < 0.05), demonstrating a higher degree of irregularity and nonstationarity among the offspring. Moreover, when the two complementary sets of statistics were combined into a single "index of nonpulsatility," an even more notable distinction was available (P < 0.01). No relationship was found between altered insulin secretion and insulin resistance. In conclusion, this experimental and statistical model demonstrates that the stimulated insulin secretion of glucose-tolerant relatives of NIDDM patients is characterized by disorderliness. Whether the model can predict the risk for developing a clinically important beta-cell dysfunction remains to be clarified.

Adult↗
PubMed1997

Effects of age on the irregularity of LH and FSH serum concentrations in women and men.

We evaluated an apparent distinction between follicle-stimulating hormone (FSH) and luteinizing hormone (LH) dynamics: visually, it appears that the pattern of serum concentrations of FSH is more irregular than that of LH in younger human females. We studied healthy humans, with LH and FSH serum samples obtained every 10 min for 24 h. Three groups were studied: 24 young females [8 early follicular (EFol), 8 late follicular (LFol), and 8 midluteal (MLut)]; 8 postmenopausal females; and 17 males 21-79 yr of age. To quantify serial irregularity, we utilized approximate entropy (ApEn), a scale- and model-independent statistic. For young females, FSH was consistently more irregular than LH per subject: among the younger subjects, ApEn(FSH) - ApEn(LH) = 0.342 +/- 0.270; ApEn(FSH) > ApEn(LH), P < 0.00001; ApEn(FSH) > ApEn(LH) for 23 of 24 subjects. For each cycle stage, pairwise ApEn(FSH) > ApEn(LH): P < 0.005 for both LFol and MLut, P < 0.01 for EFol. Notably, for the postmenopausal women, the irregularity difference vanished:ApEn(FSH) - ApEn(LH) = 0.008 +/- 0.205. Males exhibited qualitatively similar results: ApEn(FSH)- ApEn(LH) was significantly and negatively correlated with age (r = -0.75, P = 0.0006). The capability to quantify (the extent of) differences between FSH and LH release, beyond the general 1:1 correspondence between primary LH and FSH pulses, suggests a means to assess bihormonal changes as a clinical marker of altered reproductive status in a variety of settings, e.g., a perimenopausal milieu. Mechanistically, the erosion of unequal FSH-LH regularity with age is consistent with a loss of synchrony control within the integrated hypothalamo-pituitary-gonadal axis.

Adult↗
PubMed1997

Estrogen and testosterone, but not a nonaromatizable androgen, direct network integration of the hypothalamo-somatotrope (growth hormone)-insulin-like growth factor I axis in the human: evidence from pubertal pathophysiology and sex-steroid hormone replacement.

Activation of the gonadotropic and somatotropic axes in puberty is marked by striking amplification of pulsatile neurohormone secretion. In addition, each axis, as a whole, constitutes a regulated network whose feedback relationships are likely to manifest important changes at the time of puberty. Here, we use the regularity statistic, approximate entropy (ApEn), to assess feedback activity within the somatotropic (hypothalamo-pituitary/GH-insulin-like growth factor I) axis indirectly. To this end, we studied pubertal boys and prepubertal girls or boys with sex-steroid hormone deficiency treated short-term with estrogen, testosterone, or a nonaromatizable androgen in a total of 3 paradigms. First, our cross-sectional analysis of 53 boys at various stages of puberty or young adulthood revealed that mean ApEn, taken as a measure of feedback complexity, of 24-h serum GH concentration profiles is maximal in pre- and mid-late puberty, followed by a significant decline in postpubertal adolescence and young adulthood (P = 0.0008 by ANOVA). This indicates that marked disorderliness of the GH release process occurs in mid-late puberty at or near the time of peak growth velocity, with a return to maximal orderliness thereafter at reproductive maturity. Second, oral administration of ethinyl estradiol for 5 weeks to 7 prepubertal girls with Turner's syndrome also augmented ApEn significantly (P = 0.018), thus showing that estrogen per se can induce greater irregularity of GH secretion. Third, in 5 boys with constitutionally delayed puberty, im testosterone administration also significantly increased ApEn of 24-h GH time series (P = 0.0045). In counterpoint, 5 alpha-dihydrotestosterone, a nonaromatizable androgen, failed to produce a significant ApEn increase (P > 0.43). We conclude from these three distinct experimental contexts that aromatization of testosterone to estrogen in boys, or estrogen itself in girls, is likely the proximate sex-steroid stimulus amplifying secretory activity of the GH axis in puberty. In addition, based on inferences derived from mathematical models that mechanistically link increased disorderliness (higher ApEn) to network changes, we suggest that sex-steroid hormones in normal puberty modulate feedback within, and hence network function of, the hypothalamo-pituitary/GH-insulin-like growth factor I axis.

Adolescent↗
PubMed1997

Greater disorderliness of ACTH and cortisol release accompanies pituitary-dependent Cushing's disease.

We investigated the episodicity of 24-h ACTH and cortisol secretory profiles in 16 patients with Cushing's disease and 25 healthy matched controls, with a recently introduced scale- and model-independent regularity statistic, approximate entropy (ApEn). The mean (+/-S.E.M.) ApEn value for plasma ACTH concentrations in Cushing's disease was 1.3817 +/- 0.033, and in controls 0.8394 +/- 0.049 (P < 10(-10)); for plasma cortisol concentrations the values were 1.4575 +/- 0.052 and 0.8637 +/- 0.020 respectively (P < 10(-10)), implying greater irregularity of release for both hormones in Cushing's subjects. The calculated sensitivity and specificity of ApEn for ACTH profiles were 94% and 100% respectively. For cortisol the sensitivity and specificity were both 100%. ApEn was not correlated with sex, age, or the total 24-h secretion rate of ACTH and cortisol in patients and controls. The increased ApEn in patients with Cushing's disease points to an increased disorderliness of ACTH and cortisol secretion compared with healthy controls. In conjunction with the available literature, we hypothesize more generally that autonomous endocrine tumors may be typified by reduced regularity, orderliness, or synchrony of the time structure of hormone release.

Adrenocorticotropic Hormone↗
PubMed1996

Older males secrete luteinizing hormone and testosterone more irregularly, and jointly more asynchronously, than younger males.

New statistical perspectives on the secretory patterns of both luteinizing hormone (LH) and testosterone (T) may prove useful in further understanding the aging process, and possibly ultimately in improving the diagnosis and treatment of spermatogenetic failure and loss of sexual interest. We examined serum concentration time-series for LH and T in 14 young (21-34 years of age) and 11 aged (62-74 years of age) healthy men. For each subject, blood samples were obtained at 2.5-min intervals during a sleep period, with an average sampling duration of 7 hr. For each of LH and T, we used the model-independent statistic approximate entropy (ApEn) to quantify the irregularity of the serum concentration time-series; to quantify joint LH-T secretory asynchrony, we employed the recently introduced cross-ApEn. Although mean (and SD) LH and T concentrations were indistinguishable in the two age groups (P > 0.25), for LH, aged subjects had greater ApEn values (1.525 +/- 0.221) than younger individuals (1.207 +/- 0.252), P < 0.003, indicating more irregular secretion in the older cohort. For T, aged subjects also had greater ApEn values (1.622 +/- 0.120) than younger counterparts (1.384 +/- 0.228), P < 0.004. In young, but not older men, ApEn(T) significantly exceeded ApEn(LH), P < 0.02. Aged subjects had greater cross-ApEn values (1.961 +/- 0.121) than younger subjects (1.574 +/- 0.249), P < 10(-4), with nearly 100% sensitivity and specificity, indicating greater LH-T asynchrony in the older group. In conjunction with previous findings of greater irregularity of growth hormone release with increasing age, we propose that increased secretory irregularity with advancing age may be a widespread hormonal phenomenon. Finally, theoretically, we clarify the need for quantifications such as ApEn and cross-ApEn via a study of a "variable lag" pulsatile process, and empirically note the potential wide applicability of cross-ApEn to quantify asynchrony in interconnected (hormonal) networks.

Adult↗
PubMed1996

Generation of activated natural killer (A-NK) cells in patients with chronic myelogenous leukaemia and their role in the in vitro disappearance of BCR/abl-positive targets.

Activated natural killer (A-NK) cells, a subset of CD56(dim)CD3- lymphocytes, are obtained from PBMC of normal donors by adherence to plastic and culture in the presence of IL2. In this study we tested the feasibility of generating A-NK cells in patients with Ph+ chronic myeloid leukaemia (CML). Cultures obtained from patients with early chronic phase (ECP; n=7) contained a mean (+/-SD) of83 +/- 7% of CD3- cells, and those from patients with advanced chronic phase (ACP; n=7) contained 27+/-33% CD56+CD3- cells. In three patients with leukaemia in a blastic phase (BP) it was only possible to obtain one culture enriched in CD56+CD3- cells (81%). Cellular aggregates of myeloid cells and large granular lymphocytes were observed in early A-NK cell cultures. Paired freshly-adherent and cultured A-NK cells were tested for the presence of BCR/abl mRNA by RT-PCR. The BCR/abl+ cells were detected in all 12 preparations of the freshly adherent A-NK cells tested. In 6/12 the BCR/abl+ cells were no longer detectable by RT-PCR on day 14 of culture. Both proliferation and antileukaemic cytotoxicity were significantly higher (P=0.002 and P=0.029, respectively) in the BCR/abl- cultures than those in the six BCR/abl+ cultures. 5/6 BCR/abl- cultures were highly enriched in A-NK cells on day 14, and 1/6 contained predominantly CD56+CD3+ cells. Only 2/6 BCR/abl + cultures were enriched in A-NK cells on day 14, but they had poor cytotoxicity and a low proliferative index. Myeloid cells (CD33+) were more frequently detected in the BCR/abl+ than BCR/abl- A-NK cell cultures (P=0.028). These observations suggest that: (1) populations of benign A-NK cells can be generated from the peripheral blood of CML patients; (2) the ability to generate A-NK cells is impaired in patients with advanced CML; and (3) the ability to generate A-NK cells with antileukaemic activity correlates with the disappearance of BCR/abl+ cells from these cultures.

Antigens, CD↗
PubMed1996

High-dose cyclophosphamide, carboplatin, and etoposide with autologous stem cell rescue in patients with breast cancer.

This study was designed to establish the toxicity and response rates o observed with a combination of high-dose cyclophosphamide, carboplatin, and etoposide with stem cell rescue in patients with breast carcinoma. Eligibility criteria included metastatic or locally advanced breast carcinoma ; aged < or equal to 60 years; performance status Eastern Cooperative Oncology Group (ECOG) 0-1; and creatinine clearance > or equal to 65 ml/min. Chemotherapy consisted of cyclophosphamide 25 mg/kg i.v. X 4 days, etoposide 400 mg/m(2) i.v. X 4 days, and carboplatin 375 mg/m(2) X 4 days. Bone marrow or peripheral blood stem cells were reinfused 48 h after completion of chemotherapy. Seventeen patients were treated in this study. The major toxicity was gastrointestinal (grades I and II). Fevers associated with neutropenia were observed in all the patients, but no episodes of bacteremia were documented. Hematopoietic toxicities were acceptable. No toxic deaths were observed. Six patients had chemotherapy-sensitive disease at time of transplant, nine had refractory disease, and two were untested. A response rate of 62% with 18% complete response (CR) was achieved. Two patients are free of disease at +7 and +9 months after transplantation. The combination of high-dose cyclophosphamide, carboplatin, and etoposide is well tolerated with a response rate comparable to previously reported high-dose chemotherapy regimens. However, in a poor prognostic risk group, namely patients with chemoinsensitive disease, this therapeutic approach seems to be of no advantage over standard chemotherapy.

Adult↗
PubMed1996

Females secrete growth hormone with more process irregularity than males in both humans and rats.

In humans, serum growth hormone (GH) concentrations are significantly higher in women than in men, but the neuroendocrine mechanisms that underlie such gender differences are not known. We compared normal episodic GH secretion in males and females in three distinct settings: two human studies employing quite different assay techniques (immunoradiometric assay and a high-sensitivity immunofluorimetric method) and a rat study. To quantify the amount of regularity in data, we utilized approximate entropy (ApEn), a scale- and model-independent statistic. In each study, females exhibited significantly greater statistical irregularity in GH concentration series than their male counterparts (P < 10(-3) for each human study, P < 10(-6) for the rat study), implying that mass and mode of GH secretion are regulated differently in males and females. The regularity comparisons indicated complete gender separation (100% specificity and sensitivity) for the rat study and nearly complete separation for the immunofluorimetric assay study. The consistency and statistical significance of these findings suggest that this gender difference may be broadly based within higher animals and that this may be readily evaluated objectively by analysis of ApEn.

Adult↗
PubMed1994

Greater signal regularity may indicate increased system isolation.

Numerous calculations in diverse biological settings associate greater regularity and decreased complexity of experimental time series with disease and pathology, often accompanied by claims that such calculations indicate chaotic behavior. While the claims of chaos are unresolved, it nonetheless seems important to determine a unifying theme suggesting greater signal regularity in myriad complicated physiologic systems. Our major hypothesis is that in many systems, greater regularity corresponds to greater component autonomy and isolation. The idea is that healthy systems have good lines of communication, whereas crucial biologic messages in diseased states are either slow to transmit and receive or unable to arrive. We employ ApEn, approximate entropy, to quantify regularity and confirm the hypothesis via analysis of several very different, representational mathematical model forms, conferring a robustness to model form of the hypothesis. This hypothesis is experimentally verifiable in settings where some of the crucial network nodes and connections are known.

Animals↗