The Journal of clinical endocrinology and metabolism
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J. Clin. Endocrinol. Metab. · Jul 2002
Genetic or enzymatic disruption of aromatase inhibits the growth of ectopic uterine tissue.
Aromatase P450 (P450arom) is the key enzyme for the biosynthesis of estrogen that is essential for the growth of human endometriosis, a pathology characterized by endometrium-like tissue on the peritoneal surfaces of abdominal organs manifest by pelvic pain and infertility. Surgically transplanted autologous uterine tissue to ectopic sites on the peritoneum in mice has been used as an animal model to study endometriosis. Using this mouse model, we evaluated the roles of the P450arom gene and aromatase enzyme activity in the growth of endometriosis represented by ectopic uterine tissues in mice. ⋯ As tissue controls, the effects of these conditions on normally located (eutopic) uterine tissue were evaluated. The effects of disruption of the P450arom gene and treatments with letrozole and estrogen seemed to be more profound on ectopic tissues, suggesting that ectopic tissues might be more sensitive to estrogen for growth. We conclude that both an intact P450arom gene and the presence of aromatase enzyme activity are essential for the growth of ectopic uterine tissue in a mouse model of endometriosis.
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J. Clin. Endocrinol. Metab. · Jun 2002
A family of autosomal dominant hypocalcemia with a positive correlation between serum calcium and magnesium: identification of a novel gain of function mutation (Ser(820)Phe) in the calcium-sensing receptor.
To date about 20 activating mutations in the calcium-sensing receptor (CaR) gene have been identified to cause autosomal dominant hypocalcemia (ADH) or sporadic hypoparathyroidism. We report a novel activating mutation in the CaR gene in a Japanese family with ADH. The proband, a 15-yr-old boy, and 5 other patients in 3 generations were asymptomatic, except for the proband's grandmother who had a history of seizures. ⋯ The concentration-response curve of the mutant receptor was left-shifted, and its EC(50) (2.5 mM) was significantly (P < 0.05) lower than that of the wild-type CaR (3.3 mM). We conclude that the Ser(820)Phe mutation in the CaR caused ADH in this family. The positive correlation between serum calcium and magnesium levels observed in this family may support the concept that renal CaR acts as a magnesium sensor as well as a calcium sensor.
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J. Clin. Endocrinol. Metab. · Jun 2002
Nine novel mutations in maturity-onset diabetes of the young (MODY) candidate genes in 22 Spanish families.
The aims of this study were to estimate the prevalence of major maturity-onset diabetes of the young (MODY) subtypes in Spanish MODY families and to analyze genotype-phenotype correlations. Twenty-two unrelated pediatric MODY patients and 97 relatives were screened for mutations in the coding region of the glucokinase (GCK), hepatic nuclear factor- HNF-1alpha and HNF4alpha genes using PCR-single strand conformation polymorphism and/or direct sequencing. In families carrying GCK mutations, the influence of genetic defects on fetal growth was investigated by comparing the birth weights of 32 offspring discordant for the mutations. ⋯ Mutations in the GCK/MODY2 gene are the most common cause of MODY in our population as recruited from pediatric and adolescent index patients. The inheritance of GCK defects by the fetus results in a reduction of birth weight. Clinical expression of MODY3 and MODY1 mutations, the second and third groups of defects found, was more severe, including the frequent development of chronic complications.
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J. Clin. Endocrinol. Metab. · Mar 2002
Randomized Controlled Trial Multicenter Study Clinical TrialAdditive effects of raloxifene and alendronate on bone density and biochemical markers of bone remodeling in postmenopausal women with osteoporosis.
Both raloxifene (RLX) and alendronate (ALN) can treat and prevent new vertebral fractures, increase bone mineral density (BMD), and decrease biochemical markers of bone turnover in postmenopausal women with osteoporosis. This phase 3, randomized, double-blind 1-yr study assessed the effects of combined RLX and ALN in 331 postmenopausal women with osteoporosis (femoral neck BMD T-score, less than -2). Women (aged < or = 75 yr; > or = 2 yr since their last menstrual period) received placebo, RLX 60 mg/d, ALN 10 mg/d, or RLX 60 mg/d and ALN 10 mg/d combined. ⋯ RLX and ALN increased lumbar spine and femoral neck BMD, and decreased osteocalcin and C-telopeptide corrected for creatinine in an additive and independent manner, because the interaction effects were not significant. Although the ALN group had changes in BMD and bone markers that were approximately twice the magnitude as in the RLX group, it is not known how well these changes correlate to the clinical outcome of fracture. RLX+ALN reduced bone turnover more than either drug alone, resulting in greater BMD increment, but whether this difference reflects better fracture risk reduction was not assessed in this study.
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J. Clin. Endocrinol. Metab. · Mar 2002
Hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes.
Admission hyperglycemia has been associated with increased hospital mortality in critically ill patients; however, it is not known whether hyperglycemia in patients admitted to general hospital wards is associated with poor outcome. The aim of this study was to determine the prevalence of in-hospital hyperglycemia and determine the survival and functional outcome of patients with hyperglycemia with and without a history of diabetes. We reviewed the medical records of 2030 consecutive adult patients admitted to Georgia Baptist Medical Center, a community teaching hospital in downtown Atlanta, GA, from July 1, 1998, to October 20, 1998. ⋯ In addition, new hyperglycemic patients had a longer length of hospital stay, a higher admission rate to an intensive care unit, and were less likely to be discharged to home, frequently requiring transfer to a transitional care unit or nursing home facility. Our results indicate that in-hospital hyperglycemia is a common finding and represents an important marker of poor clinical outcome and mortality in patients with and without a history of diabetes. Patients with newly diagnosed hyperglycemia had a significantly higher mortality rate and a lower functional outcome than patients with a known history of diabetes or normoglycemia.