Genomic instability in scleroderma.

Scleroderma is an enigmatic rheumatic disorder of uncertain etio-pathogenesis. Cancer has an approximately two-fold higher incidence in scleroderma patients than in the general population. There are preliminary data of acquired genetic damage in scleroderma but the significance of these observations are uncertain. To determine somatic mutation frequency at the glycophorin-A (GPA) locus in patients with limited and diffuse cutaneous scleroderma. The GPA assay measures the total somatic mutation frequency (Vf), composed of gene inactivating mutations (NO) and mutations arising from mitotic recombination (NN) in individuals heterozygous for the GPA MN blood group. Mutation frequency was determined using a validated GPA flow cytometric assay using fluorescent labeled monoclonal antibodies specific for the GPA blood groups M and N. This assay detects and enumerates progeny of red blood cell (rbc) precursor cells which have acquired genetic damage resulting in a loss of expression of one of the GPA alleles. It was found that patients with scleroderma (n = 23) had significantly elevated Vf as compared with young healthy controls (p < 0.001) and elderly controls (p = 0.03). Patients with diffuse scleroderma had higher mean Vf as compared with limited scleroderma (p = 0.055). In comparison with controls, patients with scleroderma exhibit a higher proportion of mitotic recombinant mutations than inactivating mutations (p < 0.002). There was no correlation between Vf and disease duration, age at onset or autoantibody status. We have documented evidence of acquired genetic damage at the GPA locus in scleroderma. Evidence of acquired genetic damage in this disorder may be importance in explaining both the etio-pathogenesis of scleroderma and the association of scleroderma with cancer.

Induccion de ovulacion y embarazo con pulsos de LRH en amenorrea primitiva hipotalamica. / Ovulation induction in pregnancy with pulses of LHR in primary hypothalamic amenorrhea

El mejor conocimiento de la fisiologia del eje hipotalamo-hipofisario ha permitido el uso clinico del LHRH bajo la forma de pulsos endovenosos circhorarios con muy buenos resultados bajo la forma de ovulaciones y embarazos en pacientes con amenorreas de origen hipotalamico. Se refiere el caso de una paciente con amenorrea normogonadotrofica hipoestrogenica, que recibio 16 pulsos diarios de LHvRH (10 ugr. IV cada 90 m) ovulando a los 14 dias de estimulo seguido de 5000 UI de HCG en los dias 1, 3 y 5 postovulatorio y embarazando en ese ciclo. El desarollo folicular fue controlado por determinaciones hormonales (LH, FSH, E2), moco cervical y monitoreo ecografico, la fase lutea por determinaciones de progesterona plasmatica y la evolucion del embarazo por dosajes semanales de B-HCG y monitoreo ecografico de la gestacion. Esta observacion demuestra la utilidad clinica de la administracion pulsatil intravenosa de LHRH para inducir ovulacion y embarazo en un caso de amenorrea de aparente origen hipotalamico, observandose la induccion de un ciclo cuyas fases folicular y luteal no son diferentes a aquellas registradas durante un ciclo normal