A man with isochromosome Xq Klinefelter syndrome with lack of height increase and normal androgenization

We report on a patient with Klinefelter syndrome (KS) and the homogeneous aneuploidy 47,Xi(Xq)Y, or male trisomy Xq. He had many characteristics of classical KS: small testes, azoospermia, elevated FSH and LH, average intelligence, and normal androgenization, but his stature was not increased, compared with his father's and brothers'. The i(Xq), found in all cells analyzed, was late-replicating, monocentric, and also asymmetric for the RBG-banding of the two arms, indicating a different chronology of DNA synthesis in each arm. When indicated, in the seven previously reported cases, the level of plasma testosterone was always subnormal; it was normal (650 ng/100 ml) in our patient, who had normal masculinization. Thus the level of testosterone among patients with KS is not necessarily lower with an extra Xq. Furthermore, the sharp contrast in the height of KS patients with or without an i(Xq) is striking. It appears definitely possible to associate the isochromosome Xq Klinefelter syndrome with a lack of height increase.     

Effective management of severe cutaneous mastocytosis in young children with omalizumab (Xolair®)

Omalizumab (Xolair^®) is an anti‐IgE monoclonal antibody, which may benefit adults with systemic mastocytosis. We report effective treatment with omalizumab in two toddlers with severe diffuse cutaneous mastocytosis. Our cases offer preliminary evidence to support the safe use of omalizumab in paediatric patients with cutaneous mastocytosis.     

Activation of a serine/threonine kinase signaling pathway by transforming growth factor type beta.

Transforming growth factor type beta (TGF-beta) is a multifunctional factor that regulates proliferation and differentiation of many cell types. TGF-beta mediates its effects by binding to and activating cell surface receptors that possess serine/threonine kinase activity. However, the intracellular signaling pathways through which TGF-beta receptors act remain largely unknown. Here we show that TGF-beta activates a 78-kDa protein (p78) serine/threonine kinase as evidenced by an in-gel kinase assay. Ligand-induced activation of the kinase was near-maximal 5 min after TGF-beta addition to the cells and occurred exclusively on serine and threonine residues. This kinase is distinct from TGF-beta receptor type II, as well as several cytoplasmic serine/threonine kinases of similar size, including protein kinase C, Raf, mitogen-activated protein kinase kinase kinase, and ribosomal S6 kinase. Indeed, these kinases can be separated almost completely from p78 kinase by immunoprecipitation with specific antibodies. Furthermore, using different cell lines, we demonstrate that p78 kinase is activated only in cells for which TGF-beta can act as a growth inhibitory factor. These data raise the interesting possibility that protein serine/threonine kinases contribute to the intracellular relay of biological signals originating from receptor serine/threonine kinases such as the TGF-beta receptors.     

Clinical evidence of the minimal androgenic activity of norgestimate

The goal in improving the progestational component of oral contraceptives (OCs) is to enhance the selectivity of the progestin by achieving a high degree of contraceptive efficacy while decreasing undesirable side effects associated with existing progestational agents. The androgenic activity of current progestins results in changes in lipid metabolism, particularly decreased levels of high-density lipoprotein cholesterol (HDL), which have been associated with an increased risk of coronary heart disease (CHD). A progestin with high antiovulatory activity and minimal androgenicity would offer a clear therapeutic advantage in oral contraception. Norgestimate (NGM) is a new progestin with a unique profile of biological activity that has demonstrated a high level of selectivity in preclinical assays. The present studies were conducted to confirm clinically the low androgenic activity of NGM. Norgestimate (0.25 mg) in combination with 0.035 mg ethinyl estradiol (NGM 0.25/35) was compared with 0.30 mg norgestrel combined with 0.030 mg ethinyl estradiol (Lo/Ovral) in two multicenter clinical studies. In the first study (1,261 women), HDL levels were significantly increased from baseline levels in NGM 0.25/35 subjects but were significantly decreased in Lo/Ovral subjects. Increases in low-density lipoprotein cholesterol (LDL) levels were moderate in the NGM 0.25/35 group and pronounced in the Lo/Ovral group. A favorable lipid profile in NGM 0.25/35 subjects was also reflected in the LDL/HDL ratios, which were significantly lower in the NGM 0.25/35 subjects than in the Lo/Ovral subjects. Sex hormone binding globulin (SHBG) binds androgens, preventing clinical expression of androgenic activity. As a result, elevations in SHBG levels reduce bioactive (unbound) androgen levels and decrease the potential for androgenic side effects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical evidence of the minimal androgenic activity of norgestimate

The aim for improving the progestogen component of oral contraceptives is both to increase their selectivity by obtaining a highly effective contraceptive action and to decrease the side effects related to the existing progestogens. The androgenic activity of the existing progestogens modifies the lipid metabolism, particularly a decrease in the high density lipoprotein (HDL) level, which increases the risks of cardiovascular diseases. Thus, the discovery of a progestogen with good anti-ovulatory and minimal androgenic properties would constitute an important progress in the field of oral contraception. Norgestimate (NGM) is a new progestogen presenting an exceptional profile of biological activity, and has proved to be extremely selective, as observed during the clinical trials. The studies described below have been carried out in order to confirm clinically the low androgenic activity of NGM. In two clinical trials, Norgestimate (0.25 mg) associated with 0.035 mg of ethinyloestradiol (NGM 0.25/35) was compared to norgestrel (0.30 mg) associated with 0.030 mg of ethinyloestradiol (Lo/Ovral). In the first trial (1,261 women), the following observations were made: an important increase in the HDL level compared to the base levels in the subjects taking NGM 0.25/35, and an important decrease in the HDL level in those taking Lo/Ovral. The low density lipoprotein (LDL) level increased slightly in the NGM 0.25/35 group, while a higher increase was observed in the Lo/Ovral group. Moreover, the LDL/HDL ratio translates a more favourable lipid profile in the NGM 0.25/35 group, since the values are lower than those observed for the Lo/Ovral group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hormone study in a case of Klinefelter syndrome with an isochromosome Xq

We investigated the endocrine function of a patient with Klinefelter syndrome in which the extra chromosome was an isochromosome Xq. This man was azoospermic but with normal secondary sex characteristics; smallness of the testes was the only abnormal physical finding. High follicle-stimulating hormone (FSH, 70 mIU/mL) and moderately elevated luteinizing hormone (LH, 40 mIU/mL) were found; the FSH and LH response to LH-RH was exaggerated. Androgen and estrogen levels were normal. The insulin test (measure of glycemia, growth hormone, and corticol) and the test with TRH (measure of TSH and prolactin) gave normal results. We conclude that the presence of additional long arms of the X chromosome is sufficient to cause Klinefelter syndrome and that the presence of two extra Xq does not intensify the degree of androgenic insufficiency.     

Localization of cholesteryl sulfate in human spermatozoa in support of a hypothesis for the mechanism of capacitation.

Cholesteryl sulfate is a normal constituent of human spermatozoa. The in vitro uptake of tritiated cholesteryl sulfate resulted in the labeling of all spermatozoa as demonstrated by light-microscope radioautography. The binding of the sterol sulfate was localized mainly in the head and midpiece. Radioautography at the level of the electron microscope revealed that the sterol sulfate is localized on the plasma membrane, mostly in the region of the acrosome. Further proof of this localization was obtained by selective dissolution of the plasma membrane and acrosome of the spermatozoa with low concentrations of Triton X-100. This treatment resulted in the simultaneous removal of tritiated cholesteryl sulfate bound to the spermatozoa. A hypothesis is presented concerning the role of cholesteryl sulfate as a membrane stabilizer and enzyme inhibitor during the maturation of spermatozoa in the epididymis. According to this hypothesis, the cleavage of the sulfate moiety within the female reproductive tract triggers a cascade of events leading to sperm capacitation and fertilization.     

Asynchronous bilateral ovarian torsion

Background

Pediatric ovarian torsion (OT) is a serious condition, especially in cases of asynchronous bilateral ovarian torsion (ABOT). The authors sought to evaluate the predisposing factors for ABOT and to evaluate the most appropriate treatment for ovarian torsion.

Methods

The authors retrospectively reviewed the charts of patients with ovarian torsion between 1980 and 2002. Data collected included age at presentation, type and duration of symptoms, ultrasound scan findings, interval to surgery, procedures, pathology report, and follow-up.

Results

Seventy-six patients had adnexal torsion confirmed at surgery, 4 of whom had ABOT. The mean age was 10 years. The mean duration of complaints before hospitalisation and interval to surgery were 56 and 33 hours, respectively. Thirty-five patients had simple tubo-ovarian torsion (46%), including all the patients with ABOT (11.4%), and 41 had an ovarian pathology (54%). All patients with ABOT underwent salpingo-oophorectomy at the first episode. They presented earlier for the second episode and had a shorter interval to surgery where detorsion with oophoropexy was performed. Follow-up ultrasound scan showed perfusion and follicles in the remaining ovary.

Conclusions

The diagnosis of ovarian torsion often is delayed, especially when a solid tumor is suspected. Conservative management should be strongly considered when there is no underlying ovarian pathology. Furthermore, oophoropexy of the ipsilateral and contralateral ovary should be considered to prevent a potentially devastating recurrence.     

Auditory neuropathy in siblings with Waardenburg's syndrome

We report two siblings with a family history of Waardenburg's syndrome (WS) for whom the audiological profile corresponds to auditory neuropathy (AN). They have; (1) bilateral severe to profound hearing loss, (2) robust oto-acoustic emissions (OAEs) in both ears, and (3) no auditory evoked responses at 95 dBnHL bilaterally. Electrocochleography (ECochG) and auditory middle and late latency potentials were performed in one of the children. Results showed cochlear and neural activities in both ears. Central auditory responses were not conclusive. These children did not have any history of neonatal illness and one child was diagnosed with AN at the age of 3 weeks and the other at the age of 11 months.