Vitamin supplementation of HIV-infected women improves postnatal child growth

BACKGROUND: Linear growth retardation and wasting are common in children born to HIV-infected women. Inexpensive interventions that could improve the postnatal growth pattern of such children are needed. OBJECTIVE: The objective was to examine the effect of supplementing HIV-infected women with multivitamins or vitamin A and beta-carotene, during and after pregnancy, on the growth of their children during the first 2 y of life. DESIGN: We conducted a randomized placebo-controlled trial in 886 mother-infant pairs in Tanzania. At the first prenatal visit, HIV-infected women were randomly assigned to 1 of 4 daily oral regimens in a 2 x 2 factorial fashion: multivitamins (MV: thiamine, riboflavin, vitamin B-6, niacin, vitamin B-12, vitamin C, vitamin E, and folic acid), preformed vitamin A + beta-carotene (VA/BC), MV including VA/BC, or placebo. Supplementation continued during the first 2 y postpartum and thereafter. Children were weighed and measured monthly, and all received vitamin A supplements after 6 mo of age per the standard of care. RESULTS: Multivitamins had a significant positive effect on attained weight (459 g; 95% CI: 35, 882; P = 0.03) and on weight-for-age (0.42; 95% CI: 0.07, 0.77; P = 0.02) and weight-for-length (0.38; 95% CI: 0.07, 0.68; P = 0.01) z scores at 24 mo. VA/BC seemed to reduce the benefits of MV on these outcomes. No significant effects were observed on length, midupper arm circumference, or head circumference. CONCLUSION: Supplementation of HIV-infected women with multivitamins (vitamin B complex, vitamin C, and vitamin E) during pregnancy and lactation is an effective intervention for improving ponderal growth in children.     

Age dependent assessment of TFPI levels in follicular fluid of women undergoing IVF

BACKGROUND: Tissue factor pathway inhibitor (TFPI) is a multivalent Kunitz-type serine proteinase inhibitor which plays a central role in the extrinsic pathway of blood coagulation. A significant role of TFPI for the follicular development has been discussed in recent studies, and thrombotic complications during IVF procedure are a common problem. To elucidate the pathophysiological mechanisms underlying these problems, we have measured TFPI levels in human follicular fluid (hFF) of women undergoing in vitro fertilisation (IVF). METHODS: Total TFPI concentrations were determined in hFF of 28 women undergoing IVF treatment, 6 of whom developed an ovarian hyperstimulation syndrome (OHSS). RESULTS AND CONCLUSIONS: This is the first study to demonstrate an age-dependance of TFPI concentrations in hFF. Additionally, TFPI levels in hFF of women developing OHSS were determined as 323+/-66.8 ng/mL (mean+/-SD) in comparison with 279+/-137 ng/mL for non-OHSS patients. Our findings demonstrate that, unlike the decreased TFPI levels found in OHSS patients' blood, there is no statistically significant difference in hFF TFPI levels between OHSS and non-OHSS patients. Furthermore, we could show that the outcome of the IVF procedure is not correlated with TFPI levels in hFF.     

Initial experience with oral valganciclovir for pre-emptive cytomegalovirus therapy after lung transplantation

BACKGROUND: The most common opportunistic viral pathogen after lung transplantation is cytomegalovirus (CMV). Oral valganciclovir, a prodrug of ganciclovir, has been introduced as a potential drug for prophylaxis and treatment of CMV infection and disease in lung transplantation. The goal of this study was to describe our initial experience with oral valganciclovir for pre-emptive treatment of CMV infections after lung transplantation. METHODS AND PATIENTS: We summarize our experience with 19 patients who underwent lung transplantation and received pre-emptive oral valganciclovir therapy in the situation of positive CMV polymerase chain reaction (PCR) in either plasma or bronchoalveolar lavage. None of the patients presented with manifest CMV disease. Treatment dosage of valganciclovir was 450 mg to 1800 mg daily, depending on renal function and white blood count. Treatment was continued until the CMV PCR became negative, in any case for a period of at least 14 days. RESULTS: Three patients received two courses of pre-emptive oral valganciclovir; 16 patients were treated once. Eleven patients (57.9%) were treated because of a positive plasma CMV PCR; in eight patients (42.1%) the PCR was positive only in bronchoalveolar lavage. Therapy was initiated 896 +/- 1186 days (range, 108-3911) after transplantation with a mean CMV PCR of 45,536 +/- 149,294 copies (range, 426-706,000). In all cases the PCR fell below detectability (<400 copies) after a period of 22 +/- 10 days of treatment (range, 7-50 days). Mild to moderate leucopenia was observed in seven patients (36.8%) during treatment. None of the patients developed new onset of other potentially drug-related disorders such as neutropenia, anemia, deterioration of renal function or gastrointestinal disorder. CONCLUSIONS: Pre-emptive therapy with oral valganciclovir for CMV infections detected by PCR in either plasma or bronchoalveolar lavage after lung transplantation seems to be efficacious and safe. However, regular blood counts should be performed to detect developing leucopenia.     

The German short version of "Profile of Mood States" (POMS): psychometric evaluation in a representative sample

The German short version of "Profile of Mood States" (POMS) was psychometrically tested in a representative sample (1009 subjects in Eastern Germany and 1034 subjects in Western Germany). The 35 items (7 point scale, instruction "How you have been feeling during the past 24 hours?") form the following scales: Depression/Anxiety, Fatigue, Vigor, Hostility. The POMS appears to be an internally consistent instrument (Cronbach's Alpha from 0.89 to 0.95). Replication of the postulated 4 factors was limited. There are hints for convergent validity of POMS-Scales using two questions: "1. Over the past two weeks, have you felt down, depressed, or helpless?" and "2. Over the past two weeks, have you felt little interest or pleasure in doing things?"     

Interaction of nephrocystin-4 and RPGRIP1 is disrupted by nephronophthisis or Leber congenital amaurosis-associated mutations

RPGR-interacting protein 1 (RPGRIP1) is a key component of cone and rod photoreceptor cells, where it interacts with RPGR (retinitis pigmentosa GTPase regulator). Mutations in RPGRIP1 lead to autosomal recessive congenital blindness [Leber congenital amaurosis (LCA)]. Most LCA-associated missense mutations in RPGRIP1 are located in a segment that encodes two C2 domains. Based on the C2 domain of novel protein kinase C epsilon (PKC epsilon), we built a 3D-homology model for the C-terminal C2 domain of RPGRIP1. This model revealed a potential Ca2+-binding site that was predicted to be disrupted by a missense mutation in RPGRIP1, which was previously identified in an LCA patient. Through yeast two-hybrid screening of a retinal cDNA library, we found this C2 domain to specifically bind to nephrocystin-4, encoded by NPHP4. Mutations in NPHP4 are associated with nephronophthisis and a combination of nephronophthisis and retinitis pigmentosa called Senior-L?ken syndrome (SLSN). We show that RPGRIP1 and nephrocystin-4 interact strongly in vitro and in vivo, and that they colocalize in the retina, matching the panretinal localization pattern of specific RPGRIP1 isoforms. Their interaction is disrupted by either mutations in RPGRIP1, found in patients with LCA, or by mutations in NPHP4, found in patients with nephronophthisis or SLSN. Thus, we provide evidence for the involvement of this disrupted interaction in the retinal dystrophy of both SLSN and LCA patients.     

A feasibility study of contrast enhancement of acute myocardial infarction in multislice computed tomography: comparison with magnetic resonance imaging and gross morphology in pigs

INTRODUCTION: Late enhancement magnetic resonance imaging (MRI) of myocardial infarction (MI) is clinically established. There are no reports on MI assessment using state-of-the-art multislice CT technology. For this reason, animal experiments were conducted to examine the applicability of contrast-enhanced ECG-gated multislice computed tomography (MSCT) for the detection of acute MI. The results were correlated with MRI and postmortem tissue staining. MATERIAL AND METHODS: Acute MI was induced in 14 pigs by balloon occlusion of the LAD. In 8 animals, the LAD was reperfused after 45 minutes. In 6 animals, the LAD was permanently blocked. MR imaging was performed 15 minutes after the administration of 0.2 mmol Gd-DTPA/kg/bodyweight. Subsequently, 16-slice MSCT was performed at various timepoints after injecting 120 mL of iodinated contrast medium. 2,3,5-Triphenyltetrazolin-chloride (TTC) staining was acquired for all hearts investigated. Correlation analysis was applied to compare the area of MI derived from MRI, MSCT, and TTC. The reperfused infarcts were compared with the nonreperfused infarcts using an unpaired t test. RESULTS:: Mean infarct area as measured by TTC staining was 18.3% +/- 7.8% of the left ventricular area. Good correlation of the spatial extent of the infarcted area was found for TTC and MRI as well as for TTC and MSCT data obtained 5 minutes postcontrast injection. MSCT imaging demonstrated a significant difference in density (P < 0.001) between nonreperfused (47.0 +/- 6.6 HU) and reperfused (116.4 +/- 19.8 HU) infarction. CONCLUSION: In our pilot study, contrast-enhanced MSCT was feasible to assess myocardial viability in pigs. MSCT also affords differentiation of nonreperfused and reperfused acute MI. MI sizes derived from MSCT imaging correlate well to those obtained with MRI and TTC.