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Biomedical subjects

Katharina M Main

Publications and source records attributed to Katharina M Main.

26 records · Page 2Linked to original sources
PubMed2005

Cinacalcet HCl: a novel treatment for secondary hyperparathyroidism in stage 5 chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) alters the regulation of calcium and phosphate homeostasis, leading to secondary hyperparathyroidism, metabolic bone disease, soft tissue calcifications, and other metabolic derangements that have a significant impact on morbidity and mortality. The parathyroid gland is the central organ responsible for regulating these adaptive responses. Suppression of parathyroid hormone (PTH) secretion, hypertrophy, and hyperplasia are a major goal of treatment of CKD. METHODS: Current literature was reviewed and combined with the author's experience to address a number of issues regarding the optimal treatment of secondary hyperparathyroidism in hemodialysis patients. RESULTS: The calcium sensing receptor (CASR) is the most important factor regulating parathyroid gland function, and allosteric modulators of CASR, called calcimimetics, provide a novel drug therapy to suppress PTH secretion. The current use of active vitamin D analogues to suppress PTH is often limited by hypercalcemia and hyperphosphatemia. Clinical trials of cinacalcet HCl, the first calcimimetic to be approved for treatment of secondary hyperparathyroidism in CKD, have demonstrated suppression of circulating PTH levels without increments in the calcium-phosphorus (Ca x P) product, making it easier to achieve the stringent management guidelines proposed for subjects with CKD by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI). CONCLUSION: The management of disordered calcium and phosphate homeostasis in CKD patients is evolving based on our knowledge of the major importance of the calcium sensing receptor (CASR) in controlling parathyroid gland function and the potent actions of calcimimetics to target CASR. The purpose of this presentation is to provide an overview of the role of the CASR in regulation of parathyroid gland function, to examine the mechanisms whereby calcimimetics target the CASR, and to review the clinical trials that support the use of cinacalcet HCl for the treatment of secondary hyperparathyroidism in stage 5 chronic kidney disease (CKD).

Chronic Disease↗
PubMed2005

Decrease in anogenital distance among male infants with prenatal phthalate exposure.

Prenatal phthalate exposure impairs testicular function and shortens anogenital distance (AGD) in male rodents. We present data from the first study to examine AGD and other genital measurements in relation to prenatal phthalate exposure in humans. A standardized measure of AGD was obtained in 134 boys 2-36 months of age. AGD was significantly correlated with penile volume (R = 0.27, p = 0.001) and the proportion of boys with incomplete testicular descent (R = 0.20, p = 0.02). We defined the anogenital index (AGI) as AGD divided by weight at examination [AGI = AGD/weight (mm/kg)] and calculated the age-adjusted AGI by regression analysis. We examined nine phthalate monoester metabolites, measured in prenatal urine samples, as predictors of age-adjusted AGI in regression and categorical analyses that included all participants with prenatal urine samples (n = 85). Urinary concentrations of four phthalate metabolites [monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), and monoisobutyl phthalate (MiBP)] were inversely related to AGI. After adjusting for age at examination, p-values for regression coefficients ranged from 0.007 to 0.097. Comparing boys with prenatal MBP concentration in the highest quartile with those in the lowest quartile, the odds ratio for a shorter than expected AGI was 10.2 (95% confidence interval, 2.5 to 42.2). The corresponding odds ratios for MEP, MBzP, and MiBP were 4.7, 3.8, and 9.1, respectively (all p-values < 0.05). We defined a summary phthalate score to quantify joint exposure to these four phthalate metabolites. The age-adjusted AGI decreased significantly with increasing phthalate score (p-value for slope = 0.009). The associations between male genital development and phthalate exposure seen here are consistent with the phthalate-related syndrome of incomplete virilization that has been reported in prenatally exposed rodents. The median concentrations of phthalate metabolites that are associated with short AGI and incomplete testicular descent are below those found in one-quarter of the female population of the United States, based on a nationwide sample. These data support the hypothesis that prenatal phthalate exposure at environmental levels can adversely affect male reproductive development in humans.

Child, Preschool↗
PubMed2004

Insulin-like growth factor I (IGF-I) and IGF-binding protein 3 as diagnostic markers of growth hormone deficiency in infancy.

BACKGROUND: The diagnosis of growth hormone deficiency (GHD) in infancy is difficult, and no specific cutoff value during GH provocative testing is recommended in early life. METHODS: Serum insulin-like growth factor I (IGF-I) and serum IGF-binding protein 3 (IGFBP-3) levels were evaluated as diagnostic markers of GHD. Measurements of IGF-I and IGFBP-3 during the 1st year of life were analyzed in 11 patients clinically suspected of having GHD (neonatal hypoglycemia, micropenis, or evidence of other pituitary hormone deficiencies), in whom the diagnosis was later verified. A prospective cohort of 51 healthy infants served as controls. RESULTS: The sensitivity of IGF-I as a diagnostic marker of GHD was 90% (10 out of 11 patients) with a cutoff value of -2 standard deviations (SD), and the sensitivity of IGFBP-3 measurements was 81% (9 out of 11 patients) with a cutoff value below -2 SD. One patient had serial measurements before initiation of GH treatment where the IGF-I was fluctuating (3 of 6 slightly above -2 SD), whereas all IGFBP-3 measurements were below -2 SD. CONCLUSIONS: The IGF-I had a high sensitivity in detecting infants with GHD. The combination of IGF-I and IGFBP-3 increased the diagnostic sensitivity. We speculate that assessment of IGF-I and IGFBP-3 may add diagnostic value in infants suspected of having GHD and furthermore that values below -2 SD are highly suggestive of GHD.

Adult↗
PubMed2004

Increased kidney growth in formula-fed versus breast-fed healthy infants.

A high protein intake results in increased kidney growth and glomerular filtration rate in human adults and young rats. It is unknown whether kidney size in young infants is influenced by increased protein intake in formula-fed compared with breast-fed infants. We investigated the effect of formula versus breast feeding on kidney growth in a cohort of 631 healthy children examined at birth, and at 3 and 18 months of age. Kidney size was determined by ultrasonography and related to gender, age, body size, and feeding category (fully breast fed, partially breast fed, or fully formula fed at 3 months). Serum urea nitrogen, serum creatinine, and estimated creatinine clearance were measured at 3 months of age. Kidney growth and serum urea nitrogen were significantly increased in partially or fully formula-fed 3-month-old infants. This effect was more pronounced in boys than in girls. The changes in relative kidney size were temporary, as they did not persist at 18 months of age, when all children received a normal mixed diet. The immediate renal effects of formula feeding should be taken into consideration for recommendations concerning infant feeding. Whether there are any long-term effects of early increased protein intake on later kidney function remains to be seen.

Blood Urea Nitrogen↗
PubMed2004

Kidney growth in 717 healthy children aged 0-18 months: a longitudinal cohort study.

Kidney size is an important parameter in the evaluation of children with renal disease. However, reference materials for kidney size in healthy children have been limited beyond the neonatal period. We performed a longitudinal cohort study of 717 healthy children born at term with normal birth weight. Kidney size and shape were determined by ultrasonography and related to gender, age, and body size (weight, length, body surface area, skinfold thickness) at 0, 3, and 18 months of age. Gender-differentiated reference charts were established. Boys had significantly larger kidney volumes than girls ( P<0.001) and larger relative volumes (kidney volume/weight) at 0 and 3 months ( P<0.001), but not at 18 months of age. The best single predictor of gender-differentiated kidney volume was weight. Relative kidney volume changed with increasing age and height in a two-phase pattern: an initial decrease until a height of 65-70 cm was reached followed by a stable level. In conclusion, kidney size was significantly influenced by gender, age, and body composition. Relative kidney volume decreased with increasing age and height in a two-phase pattern. These characteristic changes in kidney volume indicated that infant kidney growth might be influenced by sex steroids and growth hormone in addition to body composition.

Cohort Studies↗
PubMed2002

Longitudinal study of serum placental GH in 455 normal pregnancies: correlation to gestational age, fetal gender, and weight.

Placental GH is thought to be responsible for the rise in maternal IGF-I during pregnancy and is considered to be important for fetal growth. In this prospective longitudinal study of healthy pregnant women, we investigated determinants of placental GH in maternal serum. Serum was obtained from 455 women with normal singleton pregnancies at approximately 19 and 28 wk gestation. Serum placental GH concentrations were measured by a highly specific immunoradiometric assay, and fetal size was measured by ultrasound. Data on birth weight, gender, prepregnancy body mass index (BMI), parity, and smoking habits were obtained from medical records. Serum placental GH concentrations were detectable in serum from all women as early as 14 wk gestation and increased during pregnancy in all individuals (P < 0.001). Placental GH levels at second examination were found to be higher in women carrying female fetuses [median, 9.0 ng/ml; 95% confidence interval (CI), 4.7-23.0] compared with women carrying male fetuses (median, 8.2 ng/ml; 95% CI, 3.96-19.4; P = 0.004). Similarly, the increase in placental GH between 19 and 28 wk gestation was significantly larger in female fetus bearers than in male fetus bearers (P = 0.002). Placental GH at second examination was positively correlated with gestational age (P = 0.002) and negatively correlated with prepregnancy BMI (P = 0.039). Placental GH correlated with fetal weight at approximately 28 wk gestation (P = 0.002) but did not predict birth weight at term. Our study supports the role of maternal placental GH in the regulation of fetal growth. In conclusion, we found that 1) placental GH levels correlated significantly with fetal size at 28 wk gestation; 2) GH levels were measurable in serum from all women as early as 14 wk gestation; 3) maternal prepregnancy BMI and smoking were determinants of placental GH levels, although their specific effects on the serum maternal levels of placental GH remain to be seen; and 4) women carrying female fetuses have significantly higher placental GH levels compared with women carrying male fetuses at 28 wk gestation.

Female↗
PubMed2002

Early postnatal treatment of hypogonadotropic hypogonadism with recombinant human FSH and LH.

BACKGROUND: Patients with hypogonadotropic hypogonadism may be diagnosed shortly after birth because of micropenis and cryptorchidism, combined with subnormal LH and FSH concentrations during the postnatal period. OBJECTIVE: To investigate whether treating these patients with gonadotropins postnatally, to mimic the physiological development, would improve testicular growth and fertility potential later in life. DESIGN: Our patient presented with micropenis. Serum hormone concentrations were measured monthly after delivery: LH and testosterone were undetectable, and FSH and inhibin B were below the normal range (0.05-0.17 IU/l and 79-112 pg/ml respectively). METHODS: From 7.9 to 13.7 months of age, the patient was treated with recombinant human LH and FSH in doses of 20 and 21.3 IU s.c. twice weekly respectively. RESULTS: During treatment concentrations of LH, FSH, inhibin B and estradiol increased to values within normal limits (0.7-1.88 IU/l, 0.17-3.24 IU/l, 121-268 pg/ml and 40-55 pmol/l respectively), whereas serum testosterone remained undetectable. Penile length increased from 1.6 to 2.4 cm and testicular volume, assessed by ultrasound, increased by 170%. No significant adverse events were observed. CONCLUSIONS: Gonadotropin treatment in an infant with hypogonadotropic hypogonadism succeeded in inducing an increase in inhibin B and testicular growth.

Follicle Stimulating Hormone↗