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Biomedical subjects

K M Main

Publications and source records attributed to K M Main.

33 records · Page 2Linked to original sources
PubMed2001

Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects.

Numerous reports have recently focused on various aspects of adverse trends in male reproductive health, such as the rising incidence of testicular cancer; low and probably declining semen quality; high and possibly increasing frequencies of undescended testis and hypospadias; and an apparently growing demand for assisted reproduction. Due to specialization in medicine and different ages at presentation of symptoms, reproductive problems used to be analysed separately by various professional groups, e.g. paediatric endocrinologists, urologists, andrologists and oncologists. This article summarizes existing evidence supporting a new concept that poor semen quality, testis cancer, undescended testis and hypospadias are symptoms of one underlying entity, the testicular dysgenesis syndrome (TDS), which may be increasingly common due to adverse environmental influences. Experimental and epidemiological studies suggest that TDS is a result of disruption of embryonal programming and gonadal development during fetal life. Therefore, we recommend that future epidemiological studies on trends in male reproductive health should not focus on one symptom only, but be more comprehensive and take all aspects of TDS into account. Otherwise, important biological information may be lost.

Androgen Antagonists↗
PubMed2001

Are male reproductive disorders a common entity? The testicular dysgenesis syndrome.

Growing evidence from clinical and epidemiological studies points to a synchronized increase in the incidence of male reproductive problems, such as genital abnormalities, testicular cancer, reduced semen quality, and subfertility. Together these male reproductive problems may reflect the existence of one common entity, a testicular dysgenesis syndrome (TDS). Experimental and epidemiological studies suggest that TDS is a result of disruption of embryonal programming and gonadal development during fetal life. The recent rise in the prevalence of TDS may be causally linked to endocrine disrupters affecting genetically susceptible individuals. We recommend that future epidemiological studies on trends in male reproduction do not focus on one symptom only, but take all aspects of TDS into account. The potential impact of adverse environmental factors and the role of genetic polymorphisms involved in gonadal development requires further research.

Adult↗
PubMed2000

Sweat secretion rates in growth hormone disorders.

BACKGROUND: While increased sweating is a prominent symptom in patients with active acromegaly, reduced sweating is gaining status as part of the growth hormone deficiency (GHD) syndrome. DESIGN AND SUBJECTS: Sweat secretion rate (SSR), as measured by pilocarpine iontophoresis represents the maximal capacity for stimulated sweat secretion in a localized skin area. SSR was studied in 37 patients with a history of acromegaly, 20 adult patients with GHD before and during long-term GH substitution of GHD adults, and 58 control subjects. RESULTS: Acromegaly: Patients with acromegaly had significantly higher SSR than healthy controls (Z-score + 1.9 (+/- 1.1) mean (+/- SD) (P < 0.001)). SSR was increased irrespective of current clinical disease activity. Thus, the SSR Z-scores in 16 clinically inactive patients were + 2.1 (+/- 1.2), in 10 slightly or doubtfully active patients + 1.5 (+/- 0.7) and in 11 active patients + 1.8 (+/- 1.3). There was no correlation between SSR and IGF-I. GHD: Twenty adult patients participated in an 18-month randomised, placebo controlled, double blinded study of physiological dose GH substitution, followed by 18 months of open GH treatment. SSR at baseline was reduced in male but not in female GHD patients. Mean SSR (95% confidence interval) for 11 male patients was 89.0 mg/30 minutes (51.9-126.1) as compared to 133.5 mg/30 minutes (59.2-259.9) (P = 0.01) in 24 male controls, and for 11 female patients 48.2 mg/30 minutes (25.9-70.6) as compared to 49.2 mg/30 minutes (12.6-93. 9) in 34 female controls. GH treatment in physiological substitution doses for up to 36 months had no effect on SSR. CONCLUSION: We have demonstrated that longstanding GH hypersecretion in patients with acromegaly induces irreversible changes of sweat gland function, with persistently elevated SSR despite treatment and clinical cure. In GHD patients, SSR was reduced in males but not in females, which together with the established gender difference in normal controls emphasises the role of androgen deficiency as a cofactor for reduced sweating in hypopituitary patients. Sweat gland development seems to be more susceptible to lack of hormones in childhood and adolescence than in adulthood, whereas growth hormone excess can modify sweat function later in life.

Acromegaly↗
PubMed2000

A possible role for reproductive hormones in newborn boys: progressive hypogonadism without the postnatal testosterone peak.

Healthy boys have a considerable production of reproductive hormones during the first postnatal months, the biological significance of which is poorly understood. We report on cases of male infants with hypogonadism (hypogonadotropic hypogonadism, n = 1; panhypopituitarism, n = 2) who showed lack of penile growth and involution of the scrotum. In two boys, diagnoses were obtained in early infancy and hormonal measurements at 3-4 months of age showed serum testosterone levels below detection limits in both low inhibin B (37 and 199 pg/mL, respectively; normal range, 193-563 pg/mL) and low to undetectable gonadotropins [LH, undetectable and 0.07 IU/L (normal range, 0.65-2.69 IU/L), respectively; FSH, 0.18 IU/L in both (range, 0.86-2.52 IU/L)]. In a third boy, gonadotropin deficiency was diagnosed at 3 yr of age by undetectable serum levels of FSH and LH both before and after stimulation with GnRH. All cases required hormonal treatment with testosterone, administered as suppositories in daily doses between 1 and 5 mg, which reintroduced male genital development. Our observations suggest that normal phallic and scrotal development in humans is dependent on intact testosterone secretion during early infancy. Additionally, the diagnosis of gonadotropin deficiency may be established in a short-time window postnatally by measurement of spontaneous serum concentrations of reproductive hormones.

Adaptor Proteins, Signal Transducing↗
PubMed1998

The properties of one: facial memory and the isolation effect.

In an experiment testing the extension of the von Restorff/isolation effect to feature recognition, observers viewed a study set of 20 faces with 0, 1, 2, or 4 distinctive stimuli on each face. In Experiments 1 and 2, the stimuli were black spots (simple, distinctive stimuli), and in Experiments 3 and 4 they were inverted es (complex, distinctive stimuli). Observers then viewed a test set containing 20 study-set and 20 distractor faces. In 2 of the experiments (1 & 3), the test sets contained the same distinctive stimuli as the corresponding study set; in the other 2 experiments (2 & 4), the test sets had no distinctive stimuli. In Experiments 1 and 2, faces with 1 spot on them in the study/learning phase were recognized significantly more frequently than those that had 0, 2, or 4 spots. That this one effect was still present when there were no spots on the faces in the test set demonstrates that it is an encoding phenomenon rather than a recall phenomenon. As predicted, that result was not replicated when inverted es were used (Experiments 3 and 4).

Adolescent↗
PubMed1997

Changes in serum concentrations of growth hormone, insulin, insulin-like growth factor and insulin-like growth factor-binding proteins 1 and 3 and urinary growth hormone excretion during the menstrual cycle.

Few studies exist on the physiological changes in the concentrations of growth hormone (GH), insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) within the menstrual cycle, and some controversy remains. We therefore decided to study the impact of endogenous sex steroids on the GH-IGF-IGFBP axis during the ovulatory menstrual cycle in 10 healthy women (aged 18-40 years). Blood sampling and urinary collection was performed every morning at 0800 h for 32 consecutive days. Every second day the subjects were fasted overnight before blood sampling. Follicle stimulating hormone, luteinizing hormone (LH), oestradiol, progesterone, IGF-I, IGFBP-3, sex hormone-binding globulin, dihydroepiandrosterone sulphate and GH were determined in all samples, whereas insulin and IGFBP-1 were determined in fasted samples only. Serum IGF-I concentrations showed some fluctuation during the menstrual cycle, with significantly higher values in the luteal phase compared to the proliferative phase (P < 0.001). Mean individual variation in IGF-I concentrations throughout the menstrual cycle was 13.2% (SD 4.3; range 0.1-18.3%). There were no cyclic changes in IGFBP-3 serum concentrations and no differences in IGFBP-3 concentrations between the luteal and the proliferative phases. Mean individual variation in IGFBP-3 concentrations throughout the menstrual cycle was 8.8% (SD 2.7; range 3.2-14.1). IGFBP-1 concentrations were inversely associated with insulin concentrations, and showed a significant pre-ovulatory increase that returned to baseline at the day of the LH surge. Fasting insulin concentrations showed large fluctuations throughout the menstrual cycle without any distinct cyclic pattern. No cyclic changes in urinary GH excretion during menstrual cycle were detected. We conclude that, although IGF-I concentrations are dependent on the phase of the menstrual cycle, the variation in IGF-I concentrations throughout the menstrual cycle is relatively small. Therefore, the menstrual cycle does not need to be considered when evaluating IGF-I or IGFBP-3 serum values in women suspected to have GH deficiency.

Adolescent↗
PubMed1997

Influence of gender on the correlation between plasma growth hormone profiles and urinary growth hormone excretion.

A lot of interest has been directed towards the measurement of urinary growth hormone (GH) excretion instead of plasma GH profiles or provocation tests. We investigated the factors influencing the relationship between 24- and 3-hour plasma GH profiles and urinary GH excretion in a cohort of 113 pediatric patients with growth disorders and healthy volunteers. Plasma and urinary GH were measured by polyclonal immunoassays differing in cross-reactivity with 20 kD GH (100 versus 46%), but not with 22-kD, dimer, deamidated and pituitary GH. In the 24-hour urine samples, only urinary GH excretion expressed as nanograms per 24 h correlated with plasma GH parameters, whereas the correlations for short-term samples were strongest if urinary GH excretion was expressed as nanograms per gram creatinine (r = 0.70-79, p < 0.00005-0.0001). In short-term samples urinary GH excretion depends on urinary volume and should thus be expressed in nanograms per gram creatinine, whereas 24-hour samples correlate best when urinary GH is expressed as nanograms per period. We found a significant sex difference (p < 0.02) in the correlation between 24-hour plasma GH profiles and urinary GH excretion with strong correlations in the female group (r = 0.63-0.78, p < 0.00005-0.0002) and a lack of correlation in the male group. The sex difference in the correlations between serum and urinary GH may reflect sex differences in GH profiles and metabolism, with urinary GH better reflecting the basal and slowly clearing portion of plasma GH than spontaneous GH peaks. The difference in cross-reactivities of molecular GH forms in polyclonal assays may have an impact on the correlation between plasma and urinary GH. Thus, the diagnostic value of urinary GH measurement as compared to serum GH profiles needs to be further evaluated.

Adolescent↗
PubMed1995

[Body proportions of Danish children. Curves for sitting height ratio, subischial length and arm span].

No previous Danish growth charts have been published for sitting height, subischial leg length, armspan or the ratio of sitting height to stature. These growth charts are useful in the evaluation of dysproportional growth retardation. Foreign standards have previously been used. However, due to population-specific differences and "the secular trend", the construction of Danish growth charts was found to be appropriate. We examined 1977 children (927 boys and 1050 girls) from the Copenhagen area, aged six to 20 years. Height, sitting height and armspan were measured. Growth charts were constructed using local linear regression and smoothing of residuals. We found sitting height values in Danish children to be comparable to English and Norwegian children. Sitting height values were lower than values of Dutch children, but higher than values of Swiss and Swedish children. The extremities of Danish children were 3-4 cm longer than the extremities of English children, but Dutch children had 2-3 cm longer armspan than the Danish boys and girls. Growth charts for sitting height, sitting height ratio, subischial leg length and armspan are presented. These charts should be useful when evaluating dysproportionality in growth retarded children and when assessing the effect of growth modulating therapy in children.

Adolescent↗
PubMed1995

Automatic needle insertion diminishes pain during growth hormone injection.

Non-compliance in children receiving growth hormone (GH) treatment is often caused by pain on injection and difficulties in administration of GH. It has been suggested that automatic needle insertion diminishes pain perception. We quantitatively measured pain intensity on injection with two prototype pens for GH administration, providing either manual or automatic sc needle insertion, using a combined visual analogue/facial scale and a five-item scale in 18 children. With the automatic pen there was a significantly lower maximum pain score compared with the manual pen (median 28.5 versus 52.0 mm) as well as a lower mean pain score (mean 13.7 versus 23.5 mm). The five-item scale revealed that automatic needle insertion was significantly less painful than manual insertion and 13 patients chose to continue treatment with the automatic pen. In conclusion, pain during GH injection can be significantly diminished by automatic needle insertion, which may improve compliance in long-term GH treatment.

Adolescent↗
PubMed1995

Massive weight loss restores 24-hour growth hormone release profiles and serum insulin-like growth factor-I levels in obese subjects.

In the present study, we 1) determined whether the impaired spontaneous 24-h GH secretion as well as the blunted GH response to provocative testing in obese subjects are persistent disorders or transient defects reversed with weight loss and 2) investigated 24-h urinary GH excretion and basal levels of insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3), as well as insulin in obese subjects before and after a massive weight loss. We studied 18 obese subjects (age, 26 +/- 1 yr; body mass index, 40.9 +/- 1.1 kg/m2); 18 normal age-, and sex-matched control subjects; and 9 reduced weight obese subjects after a diet-induced average weight loss of 30.3 +/- 4.6 kg. Twenty-four-hour spontaneous GH secretion was estimated by obtaining 3240 integrated 20-min blood samples using a constant blood withdrawal technique and computerized algorithms. Body composition was determined using anthropometric measurements and dual energy x-ray absorptiometry scanning (DXA). In the obese subjects, 24-h spontaneous GH release profiles and the GH responses to insulin-induced hypoglycemia and L-arginine as well as basal IGF-I levels and the IGF-I/IGFBP-3 molar ratio were decreased, whereas insulin levels were elevated compared to those in normal subjects. In obese subjects, 24-h spontaneous GH secretion and serum IGF-I levels were inversely related to abdominal fat (r = -0.67; P < 0.01) and percent body fat (r = -0.69; P < 0.01), respectively. The decreased 24-h spontaneous GH release profiles, the decreased GH responses to insulin-induced hypoglycemia and L-arginine, the decreased basal IGF-I levels and IGF-I/IGFBP-3 molar ratio, as well as the elevated insulin levels were returned to normal after a massive weight loss in the obese subjects. In conclusion, the present study has shown reversible defects in 24-h spontaneous GH release profiles, basal IGF-I levels, and the IGF-I/IGFBP-3 molar ratio in obese subjects. The recovery of the 24-h GH release points to an acquired transient defect rather than a persistent preexisting disorder.

Adult↗
PubMed1994

The impact of gender and puberty on reference values for urinary growth hormone excretion: a study of 3 morning urine samples in 517 healthy children and adults.

Some recent studies have indicated that measurement of urinary GH (U-GH) excretion may be a useful tool for the evaluation of GH insufficiency in children with growth disorders, although some investigators are skeptical about the diagnostic value of U-GH. Most current assays are only available for specific laboratories or require time-intensive pretreatments of the specimens. This limits the possibility for many centers to compare their patients' data with others or to establish their own reference ranges for U-GH excretion. Therefore, we investigated the performance of a commercially available kit, which allows direct measurement of U-GH in untreated urine specimens. We established a reference range for the geometric mean of 3 morning urine samples in 446 healthy children and 71 adults. U-GH could be determined in all but 9 of 1526 samples (99.4%). U-GH excretion was significantly dependent on pubertal maturation (P < 0.001) and sex (P < 0.001), whereas age had no significant influence in the prepubertal group (P > 0.3). Peak values occurred in Tanner stages 3 and 4 (369 and 391 pg/h in females; 503 and 882 pg/h in males), corresponding to an age interval of 11-18 yr in boys and 9-15 yr in girls. Short collection periods (< 6 h) were related to low values for U-GH excretion (nanograms per night; P < 0.02). This time effect disappeared if U-GH excretion was expressed as picograms per h. If U-GH was related to creatinine output, there was a decrease in U-GH excretion during prepuberty, a blunting of the pubertal peak, and lower values in adults than in prepubertal children (P < 0.0002). The intraindividual variation in U-GH excretion (picograms per h) ranged from 40-61%, constituting approximately two thirds of the interindividual variation. This variation was not lowered by relating U-GH to creatinine. We conclude that the assay was suitable for measurement of U-GH excretion in virtually all healthy volunteers. Sex and pubertal stage as well as urinary volume and clock times for collection periods should be registered when establishing a reference range for U-GH excretion and applying it for clinical purposes. Our reference values may be useful for further studies of patients with GH disorders.

Adolescent↗
PubMed1993

Serum concentrations of type I and III procollagen propeptides in healthy children and girls with central precocious puberty during treatment with gonadotropin-releasing hormone analog and cyproterone acetate.

Serum levels of type I and III procollagen propeptides (s-PICP and s-PIIINP) were measured in 466 healthy school children and in 23 girls with central precocious puberty (CPP) during GnRH analog and cyproterone acetate therapy, using two commercially available RIAs. In normal children, s-PICP and s-PIIINP changed significantly with age and pubertal development stages. For s-PIIINP, a peak was seen at 12 yr for girls and 13 yr for boys; no peak could be discerned for s-PICP. The prepubertal (Tanner stage 1) s-PICP value (mean +/- SD) for girls was 374 +/- 132 micrograms/L, the midpubertal value (stage 3) was 442 +/- 135 micrograms/L, and the postpubertal value (stage 5) was 203 +/- 103 micrograms/L. The mean s-PIIINP levels for girls were 9.1 +/- 2.4, 15.0 +/- 4.3, and 6.8 +/- 3.1 micrograms/L, respectively. For boys, levels were 362 +/- 119, 544 +/- 138, and 359 +/- 256 micrograms/L for s-PICP and 8.5 +/- 2.2, 14.5 +/- 5.0, and 8.6 +/- 3.8 micrograms/L for s-PIIINP (P < 0.001 for both propeptides in both boys and girls). There was, however, a large variation in normal values for both propeptides within the age groups and pubertal stages. There was a significant correlation of s-PICP and s-PIIINP levels to height velocity in girls (r = 0.35; P < 0.001 and r = 0.33; P < 0.001, respectively), while in boys, only s-PIIINP showed significant correlation to height velocity (r = 0.40; P < 0.001). In untreated girls with CPP, serum levels of s-PIIINP were elevated [PIIINP SD score (SDS), 2.13]. Levels of s-PICP were normal (PICP SDS, 0.39). Levels of both propeptides decreased within 2 months after initiation of therapy and remained below initial values (P < 0.01). The decrease in s-PIIINP after 2 months of therapy showed a significant correlation with the fall in height velocity SDS for chronological age after 6 months of therapy (r = 0.64; P < 0.01). We conclude that s-PIIINP and, to a lesser degree, s-PICP reflect growth in normal children, but due to the large variation, both propeptides seem unsuitable as markers for screening of growth disorders in children.

Adolescent↗
PubMed1993

Decreased sweating in seven patients with Laron syndrome.

Previous studies have shown that sweat secretion was reduced in patients with GH deficiency and increased during GH treatment, indicating an influence of GH on sweat gland function. Thus, patients with GH deficiency have impaired thermoregulation. We report on sweat secretion rates (SSRs) in seven patients with Laron syndrome, measured by pilocarpine iontophoresis. The patients had significantly lower SSRs than healthy children matched for sex and pubertal stage (P < 0.00005) and moderately, but significantly, elevated sweat electrolyte concentrations (P < 0.00005 for potassium; P < 0.01 for sodium). These observations further supported the hypothesis that sweat gland function in humans is under the influence of the GH-insulin-like growth factor-I axis. It remains to be seen whether the decrease in SSR also leads to altered thermoregulation in patients with Laron syndrome.

Adolescent↗
PubMed1993

Urinary growth hormone excretion in acromegaly: diagnostic value in mild disease activity.

The biochemical assessment of disease activity in acromegaly still presents a problem, especially in treated patients with mild clinical symptoms. We therefore examined the diagnostic value of the measurement of urinary growth hormone (GH) excretion in seventy unselected patients with acromegaly of different activity by comparing it to serum GH, serum insulin-like growth factor I (IGF-I) and clinical activity. There were highly significant, positive correlations between urinary GH and serum GH, serum IGF-I as well as clinical activity score (p < 0.00005), although some overlap between the groups was observed. In seven patients with low serum GH values (< 2.0 micrograms/l) discordant results were found. Two of the seven patients were clinically mildly active, but only IGF-I was either elevated or within the upper normal range; in three other patients who appeared clinically cured either IGF-I (N = 1) or urinary GH (n = 2) alone were increased. In the remaining two patients elevated serum IGF-I and urinary GH as well as activity score suggested disease activity. Thus, in the majority of cases, urinary GH was significantly correlated to the other three parameters, but added little information to that obtained by serum IGF-I. In conclusion, urinary GH measurements in difficult cases may provide a more direct information on the GH status than IGF-I.

Acromegaly↗