Efficacy of Zoladex LA (goserelin) in the treatment of girls with central precocious or early puberty

OBJECTIVE: To assess the efficacy of a longer acting preparation of the gonadotrophin releasing hormone (GnRH) analogue goserelin (Zoladex LA, 10.8 mg) in 12 girls with central precocious or early puberty. METHODS: Two girls started treatment de novo; the remainder had been on suppressive treatment for a median duration of 1.5 (range, 0.2-5.6) years. Assessment comprising auxology, pubertal staging, and pelvic ultrasound examination was carried out at weeks 0, 4, 8, 10, and 12 (first cycle) and weeks 8, 10, and 12 (second cycle) to evaluate the required injection frequency. Thereafter, assessment was performed on the day of injection. Zoladex LA was given every 12 weeks unless pubertal progression occurred. RESULTS: Satisfactory control was achieved in eight patients using this regimen, and three patients required more frequent injections. One girl was removed from the study because of clinical progression and extreme mood swings. No serious adverse effects occurred. Mean height velocity during the study period was 4.5 cm/year (range, 3.1-6.6) compared with 6.5 cm/year (range, 3.8-9.6) before treatment in nine patients for whom data were available. CONCLUSIONS: Zoladex LA was effective in controlling precocious puberty in girls when given at intervals of 9-12 weeks and it is recommended that an initial assessment is made eight weeks after beginning treatment.     

Mutation of the p53 tumor suppressor gene in spontaneously occurring osteosarcomas of the dog

Inactivation of the p53 tumor suppressor gene has been implicated in the pathogenesis of numerous human cancers, including osteosarcomas. Appendicular osteosarcomas of the dog appear to be a good model for their human equivalent with regard to biologic behavior, epidemiology and histopathology. We individually screened exons 5-8 of the p53 gene for mutations in 15 canine appendicular osteosarcomas using 'Cold' SSCP to compare the role of this gene in human and canine osteosarcoma tumorigenesis. Seven of the tumors (47%) exhibited point mutations, with one tumor possessing two mutations within different exons. Of these, seven were missense mutations and the eighth was a 'silent' mutation potentially affecting the exon 6-7 splicing region. Five of the missense mutations were located in highly conserved regions IV and V, while another corresponded with the highly conserved codon 220 mutational hotspot located outside the conserved domains. The locations and types of mutations were nearly identical to those reported in human cancer. These findings provide strong evidence of the involvement of p53 mutations in the development of canine appendicular osteosarcomas. Canine osteosarcomas appear to be a promising model for their human equivalent on a clinical, pathologic, and molecular level.      

SOMATIC NEUROPATHY IN DIABETES MELLITUS

One hundred patients of Diabetes Mellitus (70 with and 30 without clinical somatic neuropathy) were studied to correlate clinical severity with the magnitude of nerve conduction abnormalities. Age range was 10-79 years (mean 49) with equal number of males and females. Incidence of neuropathy was more in patients over 40 years of age (60 out of 70 patients) with duration of disease over two years (78.33%). The grades of severity were mild in 22 (31.33%), moderate in 25 (35.71%) and severe in 23 (32.86%) patients. Nerve conduction studies were carried out in 48 (27 with and 21 without clinical neuropathy) patients, using the apparatus Dantec (Cantata TM). The nerves (median, peroneal and sural) were stimulated at two points and the recording of latency; amplitude (micro V) and motor and sensory nerve conduction velocities (m/s) were done under identical environmental conditions. Sensory nerve conduction velocity was more affected than motor velocity. In the 21 patients without clinical neuropathy, 14 showed abnormalities indicating early involvement of peripheral nerves. Reduction of motor nerve conduction velocity was more in patients with moderate and severe grades. The reduction was more in lower than in upper limbs. Nerve conduction abnormality helps in diagnosis in diabetic neuropathy even in preclinical state and correlates with severity, in clinical neuropathy.KEY WORDS: Diabetic neuropathy, Nerve conduction abnormality, Peripheral neuropathy     

FISH Preimplantation Diagnosis of Chromosome Aneuploidy in Recurrent Pregnancy Wastage

Purpose: Our purpose was to detect aneuploidy for chromosomes 13, 16,18, 21, 22, X, and Y in preimplantation embryos from patients with a history of unexplained recurrent miscarriage. Methods: Three patients with a history of unexplained recurrent spontaneous abortion were included in this study. Embryos were biopsied at the eight-cell stage, individually fixed on slides, and processed for fluorescent in situ hybridization (FISH). A multiple FISH protocol for seven chromosomes pairs (13, 16, 18, 21, 22, X, and Y) has been developed. Results: A total of 39 embryos was studied with the multiple FISH protocol developed. Successful analysis of the biopsied embryos was achieved within the time limits usually allowed in a preimplantation diagnosis program. Analysis of the blastomeres showed that 17 embryos were chromosomally normal for the probes used, 16 embryos were aneuploid, and in 6 embryos no informative results were obtained. Conclusions: In the patients studied, a large proportion of embryos (41%) exhibited chromosomal abnormalities for the probes used. Preimplantation diagnosis to screen for chromosome abnormalities could be a feasible approach to improve the possibility of successful pregnancy in these couples.     

Study of daunorubicin cardiotoxicity prevention with pyridoxal isonicotinoyl hydrazone in rabbits.

Risk of cardiotoxicity is the most serious drawback of the clinical usefulness of anthracycline antineoplastic antibiotics, which however, remain among the most powerful and widely employed anticancer drugs. In this study we have used daunorubicin-induced cardiomyopathy in rabbits as a model to investigate possible cardioprotective effects of pyridoxal isonicotinoyl hydrazone (PIH)-a principal representative of a novel group of aroylhydrazone iron chelators. Three groups of animals were used: a control group (n=11; i.v. saline), daunorubicin-treated animals (n=11; 3mg/kg, i.v.), and animals pretreated with PIH (n=9, 25 mg/kg, i.p.) 60 min before daunorubicin administration. All substances were administered once weekly for 10 weeks. Repeated administration of daunorubicin caused premature death in four animals and induced conspicuous histopathological changes in the myocardium, progressive and significant impairment of systolic heart function (a decrease in left ventricular dP/dt(max), ejection fraction, an increase in the pre-ejection period/left ventricular ejection time index), and a gradual increase in cardiac troponin T plasma concentrations. On the contrary, all the PIH-treated animals have survived all daunorubicin applications. Furthermore, in this group, the daunorubicin-induced cardiac changes were in most functional, biochemical as well as morphological parameters less pronounced than in the group receiving daunorubicin alone. Hence, PIH and other aroylhydrazones merit further investigation as potentially protective agents against anthracycline-induced cardiotoxicity.     

The usefulness of ovarian volume, antral follicle count and age as predictors of menopausal status.

OBJECTIVE: To compare the accuracy of ovarian volume, antral follicle count and age in predicting menopausal status in healthy women. METHODS: The cross-sectional study was set in the Gynecology Division at the Leonor Mendes de Barros Maternity Hospital, S?o Paulo, Brazil. The subjects of this study were premenopausal (n = 121) and postmenopausal (n = 71) healthy women aged between 40 and 55 years. They were submitted to a medical interview and transvaginal ultrasound examination. The ovarian volume (cm3), antral follicle count and chronological age were recorded in both groups and the accuracies of these parameters in predicting menopausal status were compared. RESULTS: Premenopausal women presented larger ovaries than postmenopausal women (p < 0.01). Premenopausal women had a higher number of antral follicles than postmenopausal women (p < 0.01). The receiver operating characteristic curves showed that ovarian volume, age and antral follicle count had similar sensitivities and specificities in predicting menopausal status. The best cut-off points were observed when ovarian volume was <4 cm3, age was > or =48 years and antral follicle count was < or = two follicles. CONCLUSIONS: Ovarian volume, antral follicle count and chronological age are all individually predictive of menopausal status, with similar accuracies.     

Needlescopic thoracic sympathectomy: treatment for palmar hyperhidrosis

BACKGROUND: Open thoracic sympathectomy has been the established option for patients with essential hyperhidrosis. Recently, video-assisted endoscopic sympathectomy has provided a simple, safe, reliable, and cost-effective alternative to the earlier technique. With advances in instrumentation, performing the procedure through 2-mm and 3-mm needlescopic ports is now possible. The authors evaluate the effectiveness of so-called needlescopic thoracic sympathectomy for the treatment of primary hyperhidrosis. METHODS: Thirty five consecutive patients with a mean age of 24 years, including 23 men and 12 women, underwent bilateral needlescopic thoracic sympathectomies at the National University Hospital of Singapore. RESULTS: The mean operative duration was 56 minutes, and the mean hospital stay was 1.2 days. In no patient did Horner's syndrome or significant pneumothorax develop. The rate of success, defined as completely dry hands, was 97%. Two patients had unilateral recurrences that responded well to repeat needlescopic sympathectomies. We performed a total of 72 sympathectomies. CONCLUSIONS: Our study demonstrates that the use of miniature port access sites produces excellent medical and cosmetic results and is associated with a short hospital stay and low risk of complications.     

Permeabilisation and solubilisation of soybean phosphatidylcholine bilayer vesicles, as membrane models, by polysorbate, Tween 80.

To understand better the wide-spread pharmaceutical use of non-ionic surfactant Tween 80 (TW), the colloidal properties of the surfactant alone and in combinations with the common phospholipid, phosphatidylcholine (PC), were studied. Static and dynamic light scattering revealed that TW solubilises PC at TW/PC approximately 2.75/1 mol/mol and that TW micelle disintegration occurs on time-scale of 2.5 min, independent of amphipath concentration. This is up to nearly 300-times faster than the TW caused dissolution of PC containing unilamellar vesicles. The apparent dissolution time of TW/PC mixed aggregates, in contrast, decelerates from >700 min to <5 min upon increasing starting total amphipath concentration, with thermal activation energy > or =24 (< or =80) kJ mol(-1). The aggregate dissolution rate in highly concentrated TW/PC suspensions reflects the dissolved polysorbate-aggregate exchange rate (approximately 6.7 x 10(-3)s(-1)) rather than TW flip-flop rate across a bilayer (>0.2 min(-1)). PC solubilisation proceeds linearly with the square-root of time, and is kinetically governed by the speed of surfactant diffusion through the bulk (D approximately 2.8 x 10(-11)m2 s(-1)). Creation of small Tween-phosphatidylcholine mixed micelles is typically preceded by pre-solubilisation structures, first in the form of deformable, strongly fluctuating, bilayer vesicles and then of elongated, presumably thread-like, mixed micelles. TW/PC mixed micelles become smaller with growing surfactant/lipid molar ratio, whereas TW/PC mixed vesicles become more and more leaky with increasing surfactant concentration. Our results highlight the molecular and kinetic aspects of polysorbate-membrane interactions and provide a rationale for the popularity of Tween surfactants in pharmaceutical products: such surfactants can solubilise fatty molecules and bilayer membranes but need quite a long time for this, which is available in pharmaceutical preparations but normally not in vivo; this makes Tweens relatively efficient and safe. Furthermore, our data could help design better ultra-deformable mixed lipid-surfactant vesicles for the non-invasive transdermal drug delivery across the skin.