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Causes and consequences of time perception differences in overweight and normal weight people.

Three experiments considered whether there are differences between overweight and normal weight subjects in time perception which represent the obese subjects' lack of internal responsiveness as well as heightened external reactivity in a noneating setting. In the first study, no time-relevant cues were provided, and overweight subjects were inaccurate in their temporal judgments and showed significantly higher group variability than did normals. In the second study, the effects of differential temporal information generated by interesting and boring cues was considered. The presentation of these time-relevant external cues reduced the judgment variability of the overweight subjects and influenced their perceived passage of time significantly more than normals. The third study examined the influence, on eating behavior, of differences in perceived passage of time as a consequence of manipulating cues for interest or boredom. When bored, overweight subjects perceived time to pass more slowly than did normals and thus ate sooner. Similarly, they delayed eating, judging time to have passed more quickly than it actually had, when they were attending to interesting cues. The implications of a generalized lack of internal sensitivity for a theory about the development and consequences of obesity are discussed.

Attention↗

Environmental consequences of treating cattle with the antiparasitic drug ivermectin.

Ivermectin (22,23-dihydroavermectin B1) is a recently discovered, persistent, broad-spectrum, antiparasitic drug of unpredecented potency which is now routinely administered to cattle, horses, sheep and pigs in many countries. In cattle, it is an efficient control for parasitic gastrointestinal and respiratory tract nematodes, warble fly, mites, lice and ticks. However, most of the ivermectin dose is ultimately eliminated in the faeces of the treated animals where it has been shown to have an insecticidal effect on the larvae of economically important, dung-breeding, haematophagous Diptera. Nevertheless, the effects of excreted ivermectin on the cowpat fauna as a whole and the wider consequences of such effects have not previously been considered. In field trials reported here, the faeces of calves fitted with rumenal boluses delivering ivermectin at 40 micrograms per kg per day, failed to degrade in the normal way and this failure was associated with the absence of dung-degrading insects. Faeces from placebo-treated controls contained a characteristic dung-degrading invertebrate community and were largely degraded within 100 days. These results indicate that the increasing widespread use of ivermectin may have important environmental consequences for pastureland.

Animals↗

Consequences of changing biodiversity.

Human alteration of the global environment has triggered the sixth major extinction event in the history of life and caused widespread changes in the global distribution of organisms. These changes in biodiversity alter ecosystem processes and change the resilience of ecosystems to environmental change. This has profound consequences for services that humans derive from ecosystems. The large ecological and societal consequences of changing biodiversity should be minimized to preserve options for future solutions to global environmental problems.

Animals↗

Consequences of stabilising selection for polygenic variation.

A number of earlier authors have investigated the consequences for fitness of gene differences affecting the expression of a primary character where stabilising selection is acting in favour of an optimal expression. Assuming that the mean expression must be at or close to the optimum, deviations from the mean have been taken as measures of the deviation from the optimum, and the conclusion reached that, random drift apart, stabilising selection must ultimately lead to fixation of the commoner allele. It is now shown that this approach is incorrect: in an illustrative example the mean cannot be taken as synonymous with the optimum except in the trivial case where they have precisely the same value. Where the mean departs from the optimum, even by sampling variation only, continuing selection for it is effectively self-propagating and directional away from the optimum. Deviation from the optimum itself must be used in investigating the consequences of stabilising selection. The model used here is based on the biometrical description of the effects of a gene difference on a quantitative character as used by Mather and Jinks (1982). This includes a parameter, h, which allows dominance of any magnitude in either direction to be taken into account, and is adapted for the present purpose by introducing an additional parameter, m, measuring the departure from the optimum of the mid-point, or mid-parent, which is used biometrically as the origin for measurement of the gene effects. Assuming random mating and the absence of epistasis in the effects on the primary character, it is shown that stabilising selection acting on a pair of alleles (A and a) can have any one of three possible outcomes depending on the relative values of the m and h which characterise the effects of the gene difference on the primary character, viz: (i) a stable equilibrium in the population where in respect of the primary character Aa is nearer to the optimum than both homozygotes; (ii) fixation of the fitter allele where Aa is intermediate between the homozygotes in its departure from the optimum; (iii) a theoretical unstable equilibrium leading to fixation of the commoner allele, where Aa departs further from the optimum than both homozygotes. Only outcome (i) can lead to the conservation of variation in the population. Preliminary consideration is also given to the interaction in effect on fitness of two gene pairs affecting the same character and segregating simultaneously in the population.(ABSTRACT TRUNCATED AT 400 WORDS)

Alleles↗

Hemodynamic consequences of common carotid artery thrombosis and thrombogenically activated blood in rats.

We documented the hemodynamic consequences of nonocclusive common carotid artery thrombosis (CCAT) and tested the hypothesis that vasoactive substances capable of altering local CBF (LCBF) are released into the systemic circulation following cerebrovascular injury. Ten minutes after photochemically induced CCAT, an autoradiographic determination of LCBF was conducted with [14C]iodoantipyrine. In blood transfusion studies using donor and recipient rats, a 1-ml sample of thrombogenically activated blood (TAB) collected downstream from the forming thrombus was reinjected into a recipient rat 15 or 60 min before CBF study. A heterogeneous pattern of abnormal LCBF was documented in the ipsilateral hemisphere of CCAT rats and recipient rats receiving TAB 15 min before CBF study. Acute hemodynamic abnormalities included ischemic (less than 35% of control) and hyperemic (greater than 125% of control) foci and more global reductions (50-80% of control) in cortical and subcortical LCBF. Border zone hyperemia exceeding 2.0 ml/g/min was associated with focal sites of severe LCBF reductions. Although recipient rats that received TAB 15 min before CBF study displayed similar hemodynamic abnormalities, LCBF values in 60-min recipient rats were not significantly different from control despite ischemic foci. Humoral factors generated during CCAT appear to be responsible for the acute LCBF consequences of cerebrovascular thrombosis. Vasoactive substances released from a thrombotic site, capable of regionally affecting vascular reactivity in a time-dependent fashion, might be expected to participate in the pathogenesis of transient ischemic attacks and acute stroke.

Animals↗

Concerns about the consequences of cancer predisposition and relationships with quality of life in young adults with Li-Fraumeni syndrome.

Li-Fraumeni syndrome (LFS) is an inherited condition associated with high multi-organ cancer risks from birth. Young adults (YAs; 18-39 years) with LFS experience psychosocial challenges that may negatively affect health-related quality of life (HRQOL). This study aimed to describe a specific psychosocial challenge, concerns about the consequences of LFS (CC-LFS), and investigate relationships among CC-LFS and HRQOL among YAs. An online survey assessed CC-LFS and HRQOL among YAs with LFS enrolled in a National Cancer Institute study. Regression analyses examined relationships between CC-LFS and HRQOL scores, adjusted for age, cancer, and history of mental health challenges. Of 37 total respondents (78% female; Mage&#x2009;=&#x2009;31 years), 51% had a cancer history. Many reported past mental health challenges, including emotional problems (70%), depression/anxiety disorders (68%), and suicidal ideation (43%). Mean scores for mental (M&#x2009;=&#x2009;65.8), physical (M&#x2009;=&#x2009;67.5), and general (M&#x2009;=&#x2009;63.9) HRQOL were lower than in the general population. Higher CC-LFS scores (M&#x2009;=&#x2009;31/50, SD&#x2009;=&#x2009;7.2) were associated with lower scores for each HRQOL domain. Adjusting for covariates, higher CC-LFS scores were associated with lower physical HRQOL (&#x3b2;&#x2009;=&#x2009;-0.491, 95% CI -0.76, -0.22, p&#x2009;<&#x2009;0.001) and general HRQOL (&#x3b2;&#x2009;=&#x2009;-0.466, 95% CI -0.77, -0.16, p&#x2009;=&#x2009;0.004), but not mental HRQOL (p&#x2009;=&#x2009;0.102). CC-LFS accounted for significant proportions of unique variance in general (R2adj&#x2009;=&#x2009;17.7%, p&#x2009;=&#x2009;0.004) and physical HRQOL (R2adj&#x2009;=&#x2009;20.4%, p&#x2009;<&#x2009;0.001). Findings suggest YAs with LFS may experience substantial concerns, mental health challenges, and diminished HRQOL. Concerns about LFS consequences appear to be a psychosocial risk factor that clinicians and researchers might address through targeted interventions to improve YAs' psychosocial health.

Humans↗

Eighteenth and nineteenth century dental restoration, treatment and consequences in a British nobleman.

This paper examines unusual eighteenth and nineteenth century dental treatment and its consequences, in a nobleman excavated from beneath St. Nicholas' Church, Sevenoaks, Kent, UK in the early 1990s. This rare archaeological case exhibits erosion of dental enamel on the labial surface of all the anterior dentition. A programme of historical research suggests that this might be attributed to the application of an acid-based dental tincture or the use of an abrasive substance to whiten the teeth. Palliative treatment for the consequence of this application was prescribed by Dr Robert Blake of Dublin. Further, it bears witness to three dental restorations, two of gold and one tin. The two gold (foil) fillings are an occlusal in the upper-right second molar and a cervical on the labial surface of the upper left canine. The tin filling is an occlusal in the upper left second molar. Excavation of the carious tissue appears to have been undertaken using a spoon shaped implement.

Dental Caries↗

Consequences of iron depletion on health in menstruating women.

OBJECTIVE: To examine the consequences of single iron depletion on health in menstruating women, a common but rarely investigated situation in industrialized countries. DESIGN: We studied data issued from the SU.VI.MAX. cohort via a transversal and a longitudinal (2-y follow-up) approach. SUBJECTS AND METHODS: Iron-depleted menstruating women (ferritin &<15 micro g/l, n=472) were compared with iron-sufficient (ferritin 30-80 micro g/l, n=393) menstruating women (aged 35-51 y) in terms of health variables and quality of life (DUKE score) using logistic regression and analysis of variance. RESULTS: The risk of any infection or of specific types of infections was not increased by iron deficiency. Regarding the DUKE health profile, no specific score was significantly different between the two groups: only the scores reflecting 'physical health' (P=0.09) and 'perceived health' (P=0.12) showed a trend toward a lower level, while the best score for 'mental health' (P=0.11) was found in the group of iron-depleted women. The only significant difference between iron-depleted and iron-sufficient women concerned memory disorders, which were significantly less common in iron-depleted women, Odds ratio=0.7 (0.6-0.9; P=0.03). CONCLUSION: There is no conclusive evidence that an absence of iron stores has negative consequences; however, we must consider that in the case of a worsening of the iron balance, it may lead to a rapid decrease in the level of functional compounds. SPONSORSHIP: The laboratory Robapharm, Pierre Fabre, France.

Adult↗

Perceived food intolerance in subjects with irritable bowel syndrome-- etiology, prevalence and consequences.

OBJECTIVES: This study estimates the prevalence of perceived food intolerance and its consequences in subjects with irritable bowel syndrome (IBS), evaluates the utility of common tests for food intolerance, studies the relation between perceived food intolerance and other disorders, and discusses the etiology. DESIGN: Cross-sectional study. SETTING: National health survey. SUBJECTS: A selection of the population (n=11,078) in Oppland county, Norway, was invited to a health screening, and a sample of subjects with IBS were included in the study. INTERVENTIONS: A medical history of food intolerance, musculoskeletal pain, mood disorders and abdominal complaints was taken, and tests were performed for food allergy and malabsorption. A dietician evaluated the dietary habits of the subjects. RESULTS: Out of 4,622 subjects with adequately filled-in questionnaires, 84 were included in the study, 59 (70%) had symptoms related to intake of food, 62% limited or excluded food items from the diet and 12% had an inadequate diet. The mean numbers of food items related to symptoms and the number of foods limited or excluded from the diet were 4.8 and 2.5, respectively. There were no associations between the tests for food allergy and malabsorption and perceived food intolerance. Perceived food intolerance was unrelated to musculoskeletal pain and mood disorders. CONCLUSIONS: Perceived food intolerance is a common problem with significant nutritional consequences in a population with IBS. The uselessness of current antibody tests and tests for malabsorption and the lack of correlation to psychiatric co-morbidity make the etiology obscure.

Cross-Sectional Studies↗

Psychological consequences of predictive genetic testing: a systematic review.

The aim of this systematic literature review is to describe the psychological consequences of predictive genetic testing. Five databases were searched for studies using standardised outcome measures and statistical comparison of groups. Studies were selected and coded by two independent researchers. From 899 abstracts, 15 papers, describing 11 data sets, met the selection criteria for the review. The studies were of predictive genetic testing for Huntington's disease, hereditary breast and ovarian cancer, familial adenomatous polyposis and spinocerebellar ataxia. One involved children; the rest were of adults. None of the 15 papers reported increased distress (general and situational distress, anxiety and depression) in carriers or non-carriers at any point during the 12 months after testing. Both carriers and non-carriers showed decreased distress after testing; this was greater and more rapid amongst non-carriers. Test result (ie being a carrier or non-carrier) was rarely predictive of distress more than one month after testing (predictive in two of 14 analyses). Pre-test emotional state was predictive of subsequent distress in 14 of 27 analyses. There is a lack of informative studies in this field. The studies reviewed suggest that those undergoing predictive genetic testing do not experience adverse psychological consequences. However, the studies are of self-selected populations who have agreed to participate in psychological studies and have been followed up for no more than three years. Most research has been of testing for Huntington's Disease and included follow-up of no more than one year. The results suggest that testing protocols should include a pre-test assessment of emotional state so that post-test counselling can be targeted at those more distressed before testing. None of the studies experimentally manipulated the amount or type of counselling provided. The relationship between counselling and emotional outcome is therefore unclear and awaits empirical study.

Adaptation, Psychological↗

Health consequences of obesity in the elderly: a review of four unresolved questions.

Obesity prevalence is growing progressively even among older age groups. Controversy exists about the potential harms of obesity in the elderly. Debate persists about the relation between obesity in old age and total or disease-specific mortality, the definition of obesity in the elderly, its clinical relevance, and about the need for its treatment. Knowledge of age-related body composition and fat distribution changes will help us to better understand the relationships between obesity, morbidity and mortality in the elderly. Review of the literature supports that central fat and relative loss of fat-free mass may become relatively more important than BMI in determining the health risk associated with obesity in older ages. Weight gain or fat redistribution in older age may still confer adverse health risks (for earlier mortality, comorbidities conferring independent adverse health risks, or for functional decline). Evaluation of comorbidity and weight history should be performed in the elderly in order to generate a comprehensive assessment of the potential adverse health effects of overweight or obesity. The risks of obesity in the elderly have been underestimated by a number of confounders such as survival effect, competing mortalities, relatively shortened life expectancy in older persons, smoking, weight change and unintentional weight loss. Identification of elderly subjects with sarcopenic obesity is probably clinically relevant, but the definition of sarcopenic obesity, the benefits of its clinical identification, as well as its relation to clinical consequences require further study. Studies on the effect of voluntary weight loss in the elderly are scarce, but they suggest that even small amounts of weight loss (between 5-10% of initial body weight) may be beneficial. In older as well as in younger adults, voluntary weight loss may help to prevent the adverse health consequences of obesity.

Adipose Tissue↗

Neurobehavioral and immunological consequences of prenatal immune activation in rats. Influence of antipsychotics.

Increasing evidence suggests that pre- or perinatal events that influence the immune system contribute to the development of behavioral or neuropsychiatric disorders. For instance, exposure of pregnant rats to the bacterial endotoxin lipopolysaccharide (LPS) disrupts sensorimotor information processing, as assessed by the prepulse inhibition test (PPI), and also the immune function in adult offspring, which might be of particular relevance as regards schizophrenia. However, the consequences of maternal LPS exposure during pregnancy on synaptic functioning in adult offspring and, more importantly, the therapeutic opportunity to re-establish PPI and immune function have still to be demonstrated. In this work, we analyzed the consequences of prenatal LPS exposure on dopaminergic neurotransmission and presynaptic markers in adult brain areas related to PPI circuitry. In addition, we tested whether oral treatment with the typical antipsychotic drug haloperidol (HAL) could reinstate PPI performances and cytokine serum levels in six-month-old male rats with prenatal LPS exposure. Both sensory information processing deficits and immune anomalies induced by prenatal exposure to LPS were accompanied by changes in dopaminergic neurotransmission and synaptophysin expression. It is important to note that PPI disruption and serum increases in cytokines induced by prenatal LPS exposure were both reversed by HAL. Taken together, these results demonstrate the critical influence of prenatal immune events on the functioning of adult nervous and immune systems, in association with the putative role of the immune system in the development of behavior relevant to schizophrenia.

Analysis of Variance↗

Functional consequences of tumorigenic missense mutations in the amino-terminal domain of Smad4.

Smads, the intracellular effectors of transforming growth factor-beta (TGF-beta) family members, are somatically mutated at high frequency in particular types of human cancers. Certain of these mutations affect the Smad amino-terminal domain, which, in the case of Smad3 and Smad4, binds DNA. We investigated the functional consequences of four missense mutations in the Smad4 amino-terminal domain found in human tumors. The mutant proteins were found to have impaired abilities to bind DNA although they were fully capable of forming complexes with Smad3. All four Smad4 mutants showed decreased protein stability compared to wild-type Smad4. Two of the Smad4 mutants (G65V and P130S) were translocated to the nucleus and were capable of transactivating a Smad-dependent promoter in a ligand-dependent manner. In contrast, the L43S and R100T mutants were not translocated efficiently to the nucleus and consequently resulted in severely defective transcriptional responses to TGF-beta. Moreover, we demonstrate here the critical importance of two basic residues in the beta-hairpin loop of Smad3 or Smad4 for DNA binding, consistent with predictions from the Smad3 crystal structure. In addition, our results reveal that in the TGF-beta-induced heteromeric signaling complex, loss of DNA binding of Smad4 can be compensated by Smad3, however, both Smad3 and Smad4 are needed for efficient DNA binding and signaling. In conclusion, mutations in the amino-terminal domain of Smad4, that are found in cancer, show loss of multiple functional properties which may contribute to tumorigenesis.

Amino Acid Sequence↗

Theoretical analysis of the consequences of cyclic nucleotide phosphodiesterase negative co-operativity. Amplification and positive co-operativity of cyclic AMP accumulation.

Most tissues contain multiple forms of cyclic nucleotide phosphodiesterases (3':5'-cyclic-nucleotide 5' nucleotidohydrolase, EC 3.1.4.17). Consequently, in most, if not in all, tissues, substrate-velocity curves deviate from Michaelian kinetics and exhibit an apparent negative co-operativity. We have studied the possible theoretical consequences of this property on the quantitative features of cyclic AMP accumulation in response to activation of adenylate cyclase. Negative co-operativity of phosphodiesterases tends to generate a "positively co-operative" cyclic AMP accumulation curve. It amplifies the stimulation of cyclic AMP accumulation as compared with the stimulation of cyclic AMP synthesis. It enhances the sensitivity of cyclic AMP accumulation to slight variation of phosphodiesterase maximal velocity. It tends to shift the cyclic AMP accumulation curve to higher concentrations of stimulator as compared with the adenylate cyclase activation curve. This accounts for much of the data in the literature of hormonal effects on phosphodiesterase activity. It shows that the characteristics of cyclic nucleotide phosphodiesterases are as important as those of adenylate cyclase in determining the response of the system.

3',5'-Cyclic-AMP Phosphodiesterases↗

The functional consequences of mis-sense mutations affecting an intra-molecular salt bridge in arylsulphatase A.

Metachromatic leukodystrophy is a lysosomal storage disorder caused by the deficiency of arylsulphatase A. We describe the functional consequences of three mis-sense mutations in the arylsulphatase A gene (Asp-335-Val, Arg-370-Trp and Arg-370-Gln), affecting an apparent intramolecular Asp-335 to Arg-370 salt bridge, and interpret the effects and clinical consequences on the basis of the three-dimensional structure of arylsulphatase A. Asp-335-Val and Arg-370-Trp substitutions each cause a complete loss of enzyme activity and are associated with the most severe form of the human disease, whereas the Arg-370-Gln-substituted enzyme retains some residual activity, being found in a patient suffering from the milder juvenile form of the disease. Detailed analysis reveals that formation of the apparent salt bridge depends critically on the presence of aspartic acid and arginine residues at positions 335 and 370, respectively. Substitution by various other amino acids, including glutamic acid and lysine, affects enzyme function severely. Biosynthesis and immunoprecipitation studies indicate that the Asp-335-Val substitution affects folding of arylsulphatase A more severely than either the Arg-370-Trp or Arg-370-Gln substitutions. In vitro mutagenesis data show that clinical severity correlates with the space occupied by residue 370. The combination with structural data suggests that the bulky tryptophan residue broadens the cleft held together by the apparent salt bridge, whereas the smaller glutamine residue still allows the cleft to close, yielding a less severely affected enzyme. The position of residue 370 in the three-dimensional structure of the enzyme provides a plausible explanation for the differing severities in loss of enzyme function caused by the mutations and thus the clinical phenotype.

Adolescent↗

Functional consequences of perforin gene mutations in 22 patients with familial haemophagocytic lymphohistiocytosis.

Familial haemophagocytic lymphohistiocytosis (FHL), an inherited form of haemophagocytic lymphohistiocytosis (HLH) syndrome, is characterized by the overwhelming activation of T lymphocytes and macrophages invariably leading to death in the absence of treatment. FHL is a heterogeneous autosomal recessive disorder, with one known causative gene which codes for perforin, a cytotoxic effector protein. In this study, we have characterized the genotype and phenotype of 14 unrelated families with perforin deficiency. Four new missense mutations of the perforin gene were identified. In every case, perforin gene mutations led to undetectable intracellular perforin expression within cytotoxic cells, while some residual T-cell cytotoxic activity could be associated with certain missense mutations. Clinical and biological analyses did not differentiate between patients with nonsense or missense mutations, although age at diagnosis, which tended to be similar within members of the same family, was delayed in patients from two families belonging to the second group. In one case, consequences of perforin deficiency, diagnosed at birth, could be assessed prior to onset of clinical manifestations. No evidence for T-cell activation could be shown, suggesting that an exogenous event is required to trigger the disease manifestation. Control assessment of perforin expression and cytotoxic assays by lymphocytes from young children led to the conclusion that perforin content of natural killer cells could be a reliable diagnostic test at any age. Altogether, these data enabled a better characterization of perforin deficiency and its consequences, and defined reliable diagnostic tools.

Codon, Nonsense↗

Consequences of vitamin D receptor gene polymorphisms for growth inhibition of cultured human peripheral blood mononuclear cells by 1, 25-dihydroxyvitamin D3.

OBJECTIVE: In the vitamin D receptor (VDR) gene a BsmI restriction fragment length polymorphism (RFLP) in intron 8 and a translational start-site polymorphism, identified as a FokI RFLP, have been described. Crucial for a proper interpretation of these polymorphisms in association studies is the knowledge whether they have direct consequences for 1,25-(OH)2D3 action at cellular level. The present study was designed to assess functional significance of the FokI and BsmI VDR gene polymorphisms in peripheral blood mononuclear cells (PBMC) with a natural occurring VDR genotype for cell growth inhibition by 1,25-(OH)2D3. DESIGN: PBMC of women were isolated, VDR genotyped and in vitro inhibition by 1,25-(OH)2D3 of Phytohemagglutinin (PHA)-stimulated growth of PBMC was examined in relation to VDR genotype. RESULTS: PHA-stimulated growth and maximal growth inhibition were independent of VDR genotype. However, the FF genotype had a significant lower ED50 than the Ff genotype corresponding to an allele dose effect of 0.32 nM per f allele copy (P = 0.0036). For BsmI genotypes no differences in ED50 were observed. CONCLUSION: The present study demonstrates for the first time in cells with a natural VDR genotype a direct functional consequence of the VDR gene translational start-site polymorphism for the action of 1,25-(OH)2D3. Especially under conditions of vitamin D insufficiency these findings might have clinical implications.

Aged↗

Endocrine consequences of premature pubarche in post-pubertal Caucasian girls.

BACKGROUND: It has been postulated that intrauterine undernutrition may predispose to serious endocrine consequences, including precocious pubarche (PP), functional ovarian hyperandrogenism and insulin resistance syndrome. OBJECTIVE: The aim of this study was to determine whether a history of PP was associated with the development of hyperandrogenism and/or metabolic consequences and to evaluate the effect of birth weight on this association. PATIENTS: The study population comprised 27 Caucasian girls with a history of PP and 25 healthy girls of similar age (17.4 +/- 1.3 vs. 17.7 +/- 0.9 years). RESULTS: Gynecological age, irregular menses and oral contraceptive use were similar in the two groups. PP girls showed an increased Ferriman-Gallway Score [median (range) 8 (4-17) vs. 6 (2-10), P = 0.02] and tended to have more previous history of acne. No statistical differences were found between the groups for mean testosterone (1.7 +/- 0.7 vs. 1.4 +/- 0.7 nmol/l, P = 0.49) and dehydroepiandrosterone sulphate concentrations (7.2 +/- 3.7 vs. 5.8 +/- 2.0 micromol/l, P = 0.15), but mean Delta4-androstenedione concentrations (7.3 +/- 2.4 vs. 4.9 +/- 2.1 nmol/l, P = 0.007) and free androgen index (8.5 +/- 9.7 vs. 3.6 +/- 3.9 IU, P = 0.003) were significantly increased in the PP group. All girls showed normal glucose tolerance with an oral glucose tolerance test. Derived insulin resistance parameters were not statistically different between the two groups and fasting lipids were comparable in both groups. There was no significant effect of birth weight on androgen levels in the PP girls. Moreover, none of the PP girls demonstrated the above-described association. CONCLUSIONS: Precocious pubarche could be the first sign of future functional ovarian hyperandrogenism but a link between this condition and intrauterine undernutrition or insulin resistance could not be demonstrated in this study.

Adolescent↗