Reduced recurrence of late hemorrhagic radiation cystitis by WF10 therapy in cervical cancer patients: a multicenter, randomized, two-arm, open-label trial.

BACKGROUND AND PURPOSE: To evaluate the efficacy and the safety of WF10 as adjunct to standard treatment in the management of late hemorrhagic radiation cystitis compared to standard treatment alone. PATIENTS AND METHODS: Cervical cancer patients with Grade 2 or 3 late hemorrhagic radiation cystitis, were randomized and treated with WF10 0.5 ml/kg body weight, diluted in physiological saline or 5% dextrose water 250 ml, intravenous infusions over 2 h on 5 consecutive days, every 3 weeks for 2 cycles plus standard treatment (WF10 group) or standard treatment alone (control group). Fifty patients in each group were evaluated by questioning; urinalysis and cystoscopy during a 1 year follow up. RESULTS: At week 7, 37 patients (74%) in the WF10 group and 32 patients (64%) in the control group showed complete resolution in objective hematuria (P = 0.28). Significantly lower use of antibiotics (P = 0.002) and antispasmodics (P < 0.001) was found in the WF10 group. Among the responders, 24 patients (77%) in the control group experienced recurrent objective hematuria, whereas in the WF10 group only 17 patients (47%) experienced a recurrence (P = 0.01). Recurrence of objective hematuria occurred significantly faster in the control group as evidenced by Kaplan-Meier and log-rank statistics (P = 0.004), suggesting a long-term effect of WF10. Cystoscopy, at the end of the treatment period and after the one year follow up showed overall improvement without significant difference between two groups. No severe toxicity was monitored. CONCLUSIONS: WF10 therapy is a safe, non-invasive and convenient method in the management of late hemorrhagic radiation cystitis. WF10 therapy, as adjunct to standard treatment, has significantly reduced recurrence of objective hematuria, compared to standard treatment alone, during a one year follow up.     

The effect of divalent cations on neuronal nitric oxide synthase activity.

Neuronal nitric oxide synthase (NOS I) is a Ca(2+)/calmodulin-binding enzyme that generates nitric oxide (NO*) and L-citrulline from the oxidation of L-arginine, and superoxide (O(2)*(-)) from the one-electron reduction of oxygen (O(2)). Nitric oxide in particular has been implicated in many physiological processes, including vasodilator tone, hypertension, and the development and properties of neuronal function. Unlike Ca(2+), which is tightly regulated in the cell, many other divalent cations are unfettered and can compete for the four Ca(2+) binding sites on calmodulin. The results presented in this article survey the effects of various divalent metal ions on NOS I-mediated catalysis. As in the case of Ca(2+), we demonstrate that Ni(2+), Ba(2+), and Mn(2+) can activate NOS I to metabolize L-arginine to L-citrulline and NO*, and afford O(2)*(-) in the absence of L-arginine. In contrast, Cd(2+) did not activate NOS I to produce either NO* or O(2)*(-), and the combination of Ca(2+) and either Cd(2+), Ni(2+), or Mn(2+) inhibited enzyme activity. These interactions may initiate cellular toxicity by negatively affecting NOS I activity through production of NO*, O(2)*(-) and products derived from these free radicals.     

Prenatal sonographic diagnosis of Majewski syndrome

Majewski syndrome is an autosomal recessive disorder characterized by short ribs, polydactyly, short limbs, and a cleft lip. A 26-year-old woman with no family history of genetic diseases presented at 31 weeks' menstrual age with preterm labor and underwent prenatal sonography to screen for fetal anomalies. Sonography revealed a small thorax, markedly short ribs, micromelia, polydactyly, a cleft lip, dolichocephaly, and severe oligohydramnios. The other structures appeared normal. The most likely diagnosis was Majewski syndrome. Vaginal breech delivery was allowed to proceed. The 1,850-g male newborn died of respiratory failure shortly after birth. The postnatal appearance and radiographs confirmed the prenatal diagnosis.     

Prenatal sonographic diagnosis of diastrophic dwarfism

A healthy 27-year-old pregnant woman underwent sonographic examination because her uterine size was large for 20 weeks' menstrual age. Sonograms showed short fetal limbs with hitchhiker thumbs and toes, thoracic scoliosis, clubbed feet, and polyhydramnios. The ossification of all bony structures appeared normal, and there was no evidence of fractures. On the basis of these sonographic findings, we diagnosed skeletal dysplasia and short-limbed dwarfism, most likely diastrophic dwarfism. We counseled the parents, and the pregnancy was continued. At 37 weeks menstrual age, the patient vaginally delivered a male infant that weighed 2,560 g. The infant survived with respiratory support during his first few days of life. Postnatal physical and radiologic examinations confirmed the prenatal diagnosis of diastrophic dwarfism. Sonography is the modality of choice for prenatal detection of diastrophic dwarfism.     

Comparative proteomic analysis of juvenile and adult liver fluke, Opisthorchis viverrini

We used comparative two-dimensional gel electrophoresis to highlight proteins that are differentially expressed in the maturation stage of the parasite Opisthorchis viverrini (OV). The proteins differentially expressed in the juvenile/adult forms of the parasite are thought to be important for survival and pathogenesis. We used a nonlinear gradient pH ranged 3-10 strips for isoelectric focusing to resolve soluble proteins from four different maturation periods of OV from 1 week juvenile to 4 week adult. Approximately 210-240 protein spots were resolved by 2-DE in two ranges of pI (4.5-5.8 and 6.0-8.0). At least 35 protein spots were differentially expressed in 4 week adult compared to 1 week juvenile fluke. These proteins may involve in sex organ development and egg production. Comparative analysis of the OV proteome of different aged parasites during maturation may help to better understand parasite biology, pathogenesis/carcinogenesis related to this parasite and lead to the identification of new targets of vaccines and drugs.     

Effect of astemizole on psychomotor performance in healthy thais

The absence of CNS-related side effects of astemizole, a new long-acting specific histamine, H₁-antagonist, has been reported by many authors. To investigate the influence of this new antihistamine on psychomotor performance in Thais, oral therapeutic doses of 10 mg once daily were administered for 7 days to 21 healthy Thai volunteers (13 males and eight females). Ages ranged from 22 to 37 years and body weights from 40 to 65 kg. The study used a double-blind crossover design. Subjective assessments were carried out by means of a visual analogue rating scale and a four-point alertness rating scale and objective assessments by means of card sorting, glass bead picking, and recording of reaction times for visual stimuli in a choice situation. Compared to placebo, astemizole caused no change in any of the ratings or performances at either 1 or 2 h subsequent to the first and last (i.e., seventh) dose. It might thus be concluded that astemizole is free of CNS-depressant effects in Thai volunteers.     

Sonographic markers of hemoglobin Bart disease at midpregnancy.

OBJECTIVE: To evaluate the efficacy of various sonographic markers at midpregnancy in predicting fetal hemoglobin Bart disease. METHODS: Four hundred eighty-eight pregnancies at risk of having fetuses with hemoglobin Bart disease were recruited for prenatal diagnosis with cordocentesis at 18 to 21 gestational weeks. Before cordocentesis, the sonographic markers, including cardiothoracic ratio, placental thickness, pericardial effusion, pleural effusion, ascites, subcutaneous edema, cord edema, dilated umbilical vein, and amniotic fluid index, were assessed and recorded. The definite fetal diagnosis was based on blood analysis. The efficacy of each sonographic marker in predicting hemoglobin Bart disease was evaluated by sensitivity and specificity. RESULTS: Among 488 pregnancies undergoing prenatal diagnosis, 100 fetuses were proved to be affected by hemoglobin Bart disease. The cardiothoracic ratio gave the highest sensitivity, 95.0%, with specificity of 96.1%, followed by placental thickness. Signs of hydrops fetalis were observed in 33.0% of cases; they did not increase the sensitivity of the cardiothoracic ratio but strongly reinforced the diagnosis when they appeared. CONCLUSIONS: At midpregnancy, sonographic markers can effectively differentiate normal pregnancies from those with fetal hemoglobin Bart disease. Among couples at risk with no sonographic markers, the risk of having an affected child is nearly eliminated. The most sensitive marker was the cardiothoracic ratio, followed by placental thickness.     

Molecular characterization of VP4, VP6, VP7, NSP4, and NSP5/6 genes identifies an unusual G3P[10] human rotavirus strain

An unusual strain of human rotavirus G3P[10] (CMH079/05) was detected in a stool sample of a 2‐year‐old child admitted to the hospital with severe diarrhea in Chiang Mai, Thailand. Analysis of the VP7 gene sequence revealed highest identities with unusual human rotavirus G3 strain CMH222 at 98.7% on the nucleotide and 99.6% on the amino acid levels. Phylogenetic analysis of the VP7 sequence confirmed that the CMH079/05 strain formed a cluster with G3 rotavirus reference strains and showed the closest lineage with the CMH222 strain. Analysis of partial VP4 gene of CMH079/05 revealed highest degree of sequence identities with P[10] rotavirus prototype strain 69M at nucleotide and amino acid levels of 92.9% and 94.6%, respectively. Phylogenetic analysis of the VP4 sequence revealed that CMH079/05 and 69M clustered closely together in a monophyletic branch separated from other rotavirus genotypes. To our knowledge, this is a novel G–P combination of G3 and P[10] genotypes. In addition, analyses of VP6, NSP4, and NSP5/6 genes revealed these uncommon genetic characteristics: (i) the VP6 gene differed from the four other known subgroups; (ii) the NSP4 gene was identified as NSP4 genetic group C, an uncommon group in humans; and (iii) the NSP5/6 gene was most closely related with T152, a G12P[9] rotavirus previously isolated in Thailand. The finding of uncommon G3P[10] rotavirus in this pediatric patient provided additional evidence of the genetic diversity of human group A rotaviruses in Chiang Mai, Thailand. J. Med. Virol. 81:176–182, 2009. © 2008 Wiley‐Liss, Inc.