An aldosterone synthase gene variant is associated with improvement in left ventricular ejection fraction in dilated cardiomyopathy

OBJECTIVE: To assess whether renin-angiotensin-aldosterone (RAA) system gene polymorphisms shown to be associated with alterations in the activity of the system, may predict cardiac function changes subsequent to initiating medical therapy in heart failure. METHODS: The impact of RAA system genotypes on left ventricular ejection fraction (LVEF) following therapy to patients with idiopathic dilated cardiomyopathy (IDC) and class II-III heart failure was assessed. In 107 patients LVEF and LV dimensions were determined using radionuclide ventriculography and echocardiography prior to and subsequent to receiving furosemide, digoxin and angiotensin-converting enzyme (ACE) inhibitor therapy. Patients and controls were genotyped for variants of the ACE (insertion-deletion polymorphism), angiotensinogen (AGT; M235T polymorphism) and the aldosterone synthase (CYP11B2, C-344T polymorphism) genes. RESULTS: RAA system genotypes were not significantly associated with LVEF prior to initiating medical therapy. However, the CYP11B2 gene variant (P=0.0064 on covariate analysis [adjusted for multiple genotyping] with a 1-2% chance of false positive data), but neither the ACE, nor the AGT variants, predicted improvement in LV ejection fraction in patients on medical therapy. CONCLUSION: A CYP11B2 gene variant predicts the variable improvement in LV ejection fraction that occurs subsequent to initiating medical therapy in IDC. These data suggest a role for the aldosterone synthase locus in regulating the progression of heart failure.     

Unusual pattern of beta-phenylethylamine deamination in the rat heart

The present study was aimed to determine type A and B MAO activities in rat heart and renal cortex homogenates and evaluate the sensitivity of deamination of 3H-5-HT and 14C-beta-PEA to selective MAO-A and MAO-B inhibitors, respectively Ro 41-1049 and lazabemide. Deamination of beta-PEA in the rat heart was not affected (Vmax = 53+/-10 vs 42+/-6 nmol mg protein(-1) h(-1)) by lazabemide (250 nM), but was significantly reduced (Vmax = 10+/-1 nmol mg protein(-1) h(-1)) by Ro 41-1049 (250 nM). Deamination of beta-PEA in the rat heart is a low affinity process (when compared with that in the kidney) with high Km values (244+/-98 vs 18.6+/-5.8 microM). On the other hand, deamination of 5-HT in the rat heart and renal cortex revealed high Km values, which were similar to those for beta-PEA in the heart. Deamination of beta-PEA (1000 microM) in the rat heart was inhibited in a concentration-dependent manner by Ro 41-1049 with a Ki value of 32 nM (22, 48; 95% confidence limits), but not by the selective MAO-B inhibitor lazabemide (up to 500 nM). Inhibition of 5-HT (1000 microM) deamination in the rat heart by Ro 41-1049 was also a concentration-dependent process with a Ki value of 21 (16, 26) nM. Deamination of 5-HT (1000 microM) in the rat renal cortex, was inhibited in a concentration-dependent manner by Ro 41-1049 with a Ki value of 12 (8, 17) nM. Deamination of beta-PEA in the renal cortex was inhibited by lazabemide with a Ki of 5 (3, 7) nM. In the rat heart, in contrast to that in the renal cortex, the specific MAO-B substrate beta-PEA is deaminated by a form of MAO which most probably corresponds to MAO-A.     

Outcome of apparent ureteropelvic junction obstruction identified by investigation of fetal hydronephrosis

OBJECTIVES: The purpose of the study was to evaluate the outcome of prenatally detected ureteropelvic junction obstruction (UPJO) managed with a more conservative protocol. METHODS: The records and imaging studies of 77 consecutive neonates with UPJO identified by fetal hydronephrosis were reviewed. A nonoperative approach was attempted in patients with mild/moderate pelvic dilatation, renal units with good function as ascertained by DMSA scan and a non-obstructed pattern on DTPA. Otherwise, the patients were managed surgically by pyeloplasty. Both groups were prospectively followed and the imaging studies were performed before and after the initial approach and at one-year intervals thereafter. RESULTS: Of the 77 infants (85 units), 39 were submitted to surgery (33 pyeloplasty and 7 nephrectomy) and 38 were conservatively managed. During follow-up, 9 (24%) of 38 patients in the non-operative group presented renal function deterioration and 3 presented with urinary infections and were submitted to pyeloplasty. Of the 39 patients surgically managed, 76% presented improvement of hydronephrosis and 90% showed a non-obstructed pattern on diuretic renography. The differential renal uptake, as measured by DMSA scan, remained stable in the three groups analyzed (conservative, initial pyeloplasty, and delayed pyeloplasty). There was a minimal improvement in those units submitted to pyeloplasty with impaired renal function at baseline (< 40%). Mean renal uptake was 28.6% at admission and 33.9% at the end of follow-up. CONCLUSION: There was a wide spectrum of ureteropelvic junction stenosis. Surgical intervention in a subgroup of patients with severe hydronephrosis and impaired function may possibly improve or preserve renal parenchyma. Conversely, conservative management and clinical follow-up are safe and desirable for the subgroup with mild/moderate pelvic dilatation and preserved renal function.     

The right to love: the desire for parenthood among men living with HIV

Drug regimens and procedures now exist that will prevent parents from transmitting HIV to infants, and the ethical and legal obligation to promote and protect the reproductive rights of those living with HIV should form part of training for HIV/AIDS care and prevention. This paper reports a study that investigated issues of sexuality and reproduction with 250 Brazilian men living with HIV in S?o Paulo. We asked whether they wished to have children and whether health professionals in HIV/AIDS treatment clinics that they attended were supportive of their wishes. Health professionals were not considered by most participants to be supportive enough or even impartial about HIV-positive people having children, and paid little attention to men's fathering role. 80% of the men had sexual relationships, and 43% of them wanted children, especially those who had no children, in spite of expectations of disapproval. Few of the men received information about treatment options that would protect infants, however. In previous studies with HIV-positive women attending the same clinics, by comparison, greater knowledge about prevention of perinatal HIV transmission was reported, but women had fewer sexual relationships, fewer desired to have children, and they expected even more disapproval of having children from health professionals. We conclude that the rights of those with HIV to found a family depend as much on curing the ills of prejudice and discrimination, including among health professionals, as on medical interventions.     

Only limited support for a role of psychosomatic factors in psoriasis. Results from a case-control study

OBJECTIVE: To investigate the role of stressful events, social support, attachment security and alexithymia in triggering or exacerbating psoriasis. METHODS: Outpatients experiencing a recent onset or exacerbation of psoriasis (n=40) were compared with outpatients with skin conditions in which psychosomatic factors are regarded as negligible (n=116). Stressful events during the last year were assessed with Paykel's Interview for Recent Life Events. Attachment style, alexithymia and perceived social support were assessed with the ECR questionnaire, the TAS-20 and the MSPSS, respectively. RESULTS: The mean number of recently experienced life events, or of undesirable, uncontrollable or major events was not different between psoriatic patients and controls. The only stress measure that showed a slight trend towards an association with psoriasis was having experienced four or more stressful events in the preceding year. There was a statistical trend towards an association between alexithymia and psoriasis, whereas there were no significant differences between patients with psoriasis and controls with respect to perceived social support and attachment security. Subgroup analysis suggested that the role of all psychosomatic factors studied might be more important in certain clinical types, such as guttate and diffuse plaque psoriasis. CONCLUSIONS: Our findings provide only limited support for a role of psychosomatic factors in psoriasis. Future studies should investigate chronic and daily stressors in addition to major life events, include measures of stress appraisal and include specifically patients with a recent onset of disease.     

Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936.

In a European BIOMED-2 collaborative study, multiplex PCR assays have successfully been developed and standardized for the detection of clonally rearranged immunoglobulin (Ig) and T-cell receptor (TCR) genes and the chromosome aberrations t(11;14) and t(14;18). This has resulted in 107 different primers in only 18 multiplex PCR tubes: three VH-JH, two DH-JH, two Ig kappa (IGK), one Ig lambda (IGL), three TCR beta (TCRB), two TCR gamma (TCRG), one TCR delta (TCRD), three BCL1-Ig heavy chain (IGH), and one BCL2-IGH. The PCR products of Ig/TCR genes can be analyzed for clonality assessment by heteroduplex analysis or GeneScanning. The detection rate of clonal rearrangements using the BIOMED-2 primer sets is unprecedentedly high. This is mainly based on the complementarity of the various BIOMED-2 tubes. In particular, combined application of IGH (VH-JH and DH-JH) and IGK tubes can detect virtually all clonal B-cell proliferations, even in B-cell malignancies with high levels of somatic mutations. The contribution of IGL gene rearrangements seems limited. Combined usage of the TCRB and TCRG tubes detects virtually all clonal T-cell populations, whereas the TCRD tube has added value in case of TCRgammadelta(+) T-cell proliferations. The BIOMED-2 multiplex tubes can now be used for diagnostic clonality studies as well as for the identification of PCR targets suitable for the detection of minimal residual disease.