TS patients show high frequency of hypertension in pediatric age. Estrogen therapy is an outbreaking and worsening factor. An estrogen independent role of the renin-angiotensin-aldosterone system in the pathogenesis of TS hypertension is still uncertain.
The inhibition of gonadotropin secrction in childrcn with central precocious puberty trcatcd with LII-RH analogues rcsults in suppression of the pubertal development, including growth vclocity. In some paticnts, a marked slowing of growth is observed. To test whcther this is rclatcd to inhibi ion of GH sccretion, we performed a clonidine test (150 mcg/m5 p.0.) in 9 girls with central prccocious puberty (age range: 4 4/12 to 11 8/12 yrs) treated with D-TRP-6-LH-RH, a supcractivc LH-RII analogue, 6 by daily s.c. injections of an acqucous prcparation, and 3 by monthly i.m. injections of a depot preparation (DecapcptylFerring). The daily dose ranged from 1.5 to 3 mcglkglday and thc trcatmcnt periods were from 10 to 60 months. In all paticnts a normal GH response was found, by a peak valuc of 18 ng/ml or higher. In all, gonadotropin suppression was confirmed by a concomitant i.v. LH-RH test. These data show that GI1 reserve is not affcctcd by the LH-RH analogue therapy and cannot be implicated in the slowing of growth, which is probably duc to lack of sex hormones. P e r i o d i c i n t r a m u s c u l a r i n j e c t i o n o f LRH-M has been shown t o suppress p i t u i t a r y -g o n a d a l a x i s i n c h i l d r e n w i t h precocious p u b e r t y (Roger e t a l . ESPE 1984). I n o r d e r t o assess t h e e f f e c t s o f LRH-M on spermatogenesis, 50 vg/kg were g i v e n t o Fox dogs on days 1 and 21, then e v e r y 28 days. I n t h e a d u l t dogs t r e a t e d f o r 15 weeks spermatogenesis was i n h i b i t e d d u r i n g t h e r a p y and recover e d 90 days a f t e r t h e l a s t i n j e c t i o n . A one-year treatment was s t a r t e d i n 3 adolescent dogs j u s t b e f o r e completion o f puberty.LH l e v e l (ng/ml , Risem) decreased f r o m 4.6 ' 0.6 t o 1.2 + 0.1 on day 21 (p<0.05) and became u n d e t e c t a b l e beyond t h e 5 t h i n j e c t i o n . Normal o r h i g h l e v e l s were recovered 60 days a f t e r t h e l a s t i n j e c t i o n . Mean t e s t o s t e r o n e l e v e l (ng/ml) was 1.6 20.2 i n i t i a ll y , u n d e t e c t a b l e beyond t h e 5 t h i n j e c t i o n and 1 . 3 2 0 . 3 s i x t y days a f t e r t h e l a s t i n j e c t i o n . H i s t o l o g y o f t h e r i g h t t e s t i s on day 371 showed spermatogonia i n a l l tubes, spermatocytes I i n 5 t o 57% o f tubes and absence o f more mature c e l l s . I n i t i a l l y , no spermatozoa were p r e s e n t i n e j a c u l a t e s , b u t i n 2 dogs sperm c e l l s were p r e s e n t f r o m days 56 t o 77 and 64 t o 105 r e s p e c t i v e l y , d i s a p peared t h e r e a f t e r and reappared 92 days a f t e r t h e l a s t i n j e c t i o n . No sperm c e l l s were found i n t h e 3 r d dog throughout t h e study. T h i s work shows t h a t LRH-M induces a r e g r e s s i o n o f spermatogenes i s i n adolescent dogs and t h a t recovery occurs a f t e r treatment. 128 12 hrs urine collections were made in patients presenting with central PP receiving the GnRH agonist B, either subcutaneously (SC) (13 g...
The impact of early donor cell chimerism on outcomes of reduced toxicity conditioning regimens and allogeneic stem cell transplantation (SCT) in myeloid disorders is ill defined. To explore the impact of busulfan pharmacokinetics (Bu PK) on early donor chimerism, we undertook a retrospective analysis of patients with myeloid disorders in the last 10 years who received four days of fludarabine and busulfan (FluBu4) with or without measuring Bu PK and those who got busulfan with cyclophosphamide (BuCy). Methods: Chimerism assay was performed using a quantitative fluorescence-based short tandem repeat-polymerase chain reaction (STR-PCR) with capillary electrophoresis for PCR product resolution. Results: In this study, 75 patients were identified and included. Fifty two patients got FluBu4, of whom 21 had Bu PK measured. BuCy was given in 32 patients. There were 48 males and 27 females with a median age of 59 years. Disease risk index (DRI) was high or very high in 52%, 48% and 60% of patients in the FluBu4 with Pk, no PK and BuCY, respectively. Thirty six patients had matched related donor (MRD), 31 had matched unrelated donor and 8 had mismatched unrelated donor SCT. Total donor cell chimerism analysis showed that the odd ratio (OR) for not having 100% chimerism at day 100 is 4.4 (CI 1.38 to 14.57; P = .01) for FluBu4 without PK compared to BuCY, while OR was 1.4 for FluBu4 with PK compared to BuCy (P = .59). In addition, OR was 3.1 (CI .99 to 10.10, P = .05) for FluB4 without PK to the group with PK. For decreasing total chimerism on day 100, the OR for FluB4 no PK and BuCy was 3 (P = .06) while it was .8 for the group with PK compared to BuCy (P = .86). OR between no PK group and those with PK for decreasing donor chimerism at day 100 was 3.4 (CI 1.00 to 11.63, P = .04). For day 30 chimerism, to have <95% total chimersim, OR FluBu4 no PK compared to BuCy was 1.65 (P = .4) while OR comparing FluB4 with PK to BuCy was .2 (CI .02 to 2.32, P = .2). OR comparing between group without Pkand with PK for <95% at day 30 was 6.9 (P = .07). Relapse rate was 24%, 45% and 57% for FluBu4 with PK, FluBu4 no PK and BuCy respectively, P = .085). Survival distributions of the three treatment groups were not statistically significant (P = .11) Figure 1. Conclusion: In this small cohort, we found that patients with myeloid disorders who got FluBu4 with Bu PK had a trend for higher donor chimerism similar to BuCy at day100. While FluB4 with no PK has tendency to loose donor chimerism by day 100 and has more of <95% donor chimerism on day 30. Previous studies showed that low or decreasing donor chimerism early after SCT is an independent risk factor for relapse and impaired survival. This is especially important in myeloid disorders. These results should be interpreted with caution given the retrospective design of the study, the small number of patients and the need for longer follow up.
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