HLA-B*27 subtyping by PCR-RFLP in Spanish patients with ankylosing spondyiitis

Abstract: We describe the use of restriction analysis on PCR-amplified DNA for detecting all B*27 subtypes except B*2710 and B*2711 (i.e. from B*2701 to B*2709). After detecting B*27 by Sty I, double digestions consisting of Sty I plus another informative enzyme led to subtype assignment. We used mismatched primers to create restriction sites when necessary. The method avoids group-specific amplifications and other laborious optimization procedures. It was successfully tested on a panel of well characterized cell lines covering different B*27 subtypes. Then, we studied a group of 57 ankylosing spondyiitis patients and 746 controls from the south of Spain. B*27 showed a very strong association with the disease (OR=211.27, P=\0˜7). B*2702 and B*2705 distribution in controls (20% and 77.1%, respectively) differed from previously reported data in the Spanish population. We unexpectedly found the B*2707 allele in our population (one control).     

Partial Adrenalectomy for Renal Cell Carcinoma With Bilateral Adrenal Metastases

Resection of the adrenal glands precludes participation in many immunotherapy protocols for metastatic renal cell carcinoma. We performed radical nephrectomy with adrenalectomy and contralateral partial adrenalectomy, including adrenal vein ligation for a 4 cm. hilar metastasis without perioperative complications or local recurrence after 30 months. Adrenal function, measured by cosyntropin stimulation tests 6 weeks and 10 months postoperatively, was normal. Partial adrenalectomy with preservation of adrenal function is possible.     

Lithium for irritability in Post-Traumatic stress disorder

Irritability is often a problem for patients with Post-Traumatic Stress Disorder (PTSD). We describe two cases that illustrate the use of lithium in the treatment of veterans with PTSD who complained of serious problems with irritability or angry outbursts. These cases are discussed in the context of evidence that lithium may be useful in other patients with disorders of impulse control. The evidence linking disorders of anger and impulse control to a dysregulation in neurotransmitter regulation, particularly in serotonergic pathways, supports a psychopharmacologic approach to treatment. These findings should lead to further study of the role of lithium in the treatment of this symptom complex in patients with PTSD.     

Prevention of early postmenopausal bone loss using low doses of conjugated estrogens and the non-hormonal,bone-active drug ipriflavone

Hormone replacement therapy is the optimal therapeutic choice for postmenopausal syndrome. While low doses of estrogens (0.3 mg/day of conjugated estrogens) can counteract neurovegetative menopausal symptoms, higher doses (0.625 mg/day of conjugated estrogens) are required to prevent bone loss in postmenopausal women. Experimental and clinical studies have shown that ipriflavone, a non-hormonal isoflavone derivative, is effective in the prevention and treatment of postmenopausal osteoporosis. The aim of the present investigation was to evaluate the efficacy and toler-ability of ipriflavone and very low doses of equine conjugated estrogens on bone loss in early postmenopausal women. Eighty-three healthy postmenopausal women (50.3±0.7 years) were enrolled for this 1-year multicenter study. All subjects were randomly allocated to receive: double placebo (n=24; group A), placebo plus conjugated equine estrogens 0.30 mg/day (n=31; group B) or conjugated equine estrogens 0.30 mg/day plus oral ipriflavone 200 mg tris in die at meals (n=28; group C), according to a double-masked design. Among women who completed the treatment period (valid completers), those of group A showed a progressive decrease in forearm bone density (FBD; measured by dual photon absorptiometry) that reached 1.7% after 12 months. The women in group B maintained their FBD in the first 6 months of treatment but, at the end of the study, showed a bone loss of 1.4% compared with basal values. By contrast, women in group C showed a significant increase in FBD after 1 year of treatment (+5.6%;p<0.01). Bothvalid completers andintention to treat analyses revealed a significant difference (p<0.05) between group A and group C over the study period. None of the treatments produced significant changes of biochemical markers of bone turnover, while hot flushes and other climacteric symptoms were significantly reduced after the sixth month of treatment in women receiving estrogens. Adverse events were generally mild, and did not differ among the groups. The results of this study suggest that low doses of estrogens combined with ipriflavone could represent a new therapeutic approach to the treatment of the postmenopausal syndrome.     

Differential inhibition of cyclooxygenase-1 (COX-1) and-2 (COX-2) by NSAIDS: Consequences on anti-inflammatory activity versus gastric and renal safety

The discovery of an inducible isoform of cyclooxygenase (COX-2) requires a refinement of the theory that inhibition of cyclooxygenase activity is responsible for both therapeutic and side-effects of nonsteroidal anti-inflammatory drugs (NSAIDs). Pharmacological results with developmental compounds suggest that COX-2 is the relevant target for the therapeutic (i.e. anti-inflammatory) effects of NSAIDs, whereas gastric and renal side-effects are related to inhibition of constitutive COX-1. However a role of COX-1 in inflammation cannot be excluded. Furthermore, more research effort is needed to investigate the functional relevance of COX-2 in normal tissue.