Diagnostic and therapeutic quandaries in primary manifestation of Hodgkin's disease in the central nervous system

We report the case of a 23-year-old female with severe neurologic dysfunction without a clear cause at the time of initial presentation. The search for an underlying malignancy revealed a slightly enlarged cervical lymph node with Hodgkin's disease (HD). There was no evidence of a brain tumor despite nonspecific bright changes in proton density in the basal ganglia of the right hemisphere of the cerebellum, right cerebellar tonsil, posterior limb of the internal capsule, and the right side of the medulla spinae as shown by magnetic resonance imaging (MRI) as well as reactive lymphocytosis with slightly elevated protein levels in the cerebrospinal fluid (CSF). The findings suggested a cerebellar disorder, with main differential diagnosis between neurologic paraneoplastic syndrome (NPS) and HD involving the CNS. Based on limited experience with NPS and HD in the CNS, possible diagnostic and therapeutic options are discussed.     

Correlations of selected vaginal cytokine levels with pregnancy-related traits in women with bacterial vaginosis and mycoplasmas

The aim of this study was to examine correlations between vaginal inflammatory cytokines (IL-1alpha, IL-1beta, IL-6 and IL-8) and pregnancy-related traits (gestational age, birth-weight, BMI, weight gain during pregnancy and vaginal pH). Differences in correlation coefficients were examined among bacterial vaginosis (BV) status and the presence or absence of mycoplasmas. A total of 105 women between the 22nd and 34th week of pregnancy were enrolled in this study. There was a strong negative correlation between IL-1alpha and weight gain during pregnancy (r=-0.877, p<0.001) and a strong positive correlation between IL-6 and BMI (r=0.670, p=0.024) in women with normal vaginal flora and mycoplasmas. These correlations were not present in women who had normal flora and no mycoplasmas. In women with BV and no mycoplasmas, there were significant correlations of gestational age with IL-6 (r=0.727, p=0.027) and IL-8 (r=0.689, p=0.040); however, these correlations were not significant in women with mycoplasmas. Our findings support the conclusion that correlations between inflammatory cytokines and pregnancy-related traits are dependent on context, suggesting that expression is labile. In particular, BMI and gestational age correlation differs depending on BV status and the presence or absence of BV-related mycoplasmas such as Mycoplasma hominis and Ureaplasma urealyticum.     

Rifamycin antibiotic resistance by ADP-ribosylation: Structure and diversity of Arr

The rifamycin antibiotic rifampin is important for the treatment of tuberculosis and infections caused by multidrug-resistant Staphylococcus aureus. Recent iterations of the rifampin core structure have resulted in new drugs and drug candidates for the treatment of a much broader range of infectious diseases. This expanded use of rifamycin antibiotics has the potential to select for increased resistance. One poorly characterized mechanism of resistance is through Arr enzymes that catalyze ADP-ribosylation of rifamycins. We find that genes encoding predicted Arr enzymes are widely distributed in the genomes of pathogenic and nonpathogenic bacteria. Biochemical analysis of three representative Arr enzymes from environmental and pathogenic bacterial sources shows that these have equally efficient drug resistance capacity in vitro and in vivo. The 3D structure of one of these orthologues from Mycobacterium smegmatis was determined and reveals structural homology with ADP-ribosyltransferases important in eukaryotic biology, including poly(ADP-ribose) polymerases (PARPs) and bacterial toxins, despite no significant amino acid sequence homology with these proteins. This work highlights the extent of the rifamycin resistome in microbial genera with the potential to negatively impact the expanded use of this class of antibiotic.     

The Comprehensive Antibiotic Resistance Database

The field of antibiotic drug discovery and the monitoring of new antibiotic resistance elements have yet to fully exploit the power of the genome revolution. Despite the fact that the first genomes sequenced of free living organisms were those of bacteria, there have been few specialized bioinformatic tools developed to mine the growing amount of genomic data associated with pathogens. In particular, there are few tools to study the genetics and genomics of antibiotic resistance and how it impacts bacterial populations, ecology, and the clinic. We have initiated development of such tools in the form of the Comprehensive Antibiotic Research Database (CARD; http://arpcard.mcmaster.ca). The CARD integrates disparate molecular and sequence data, provides a unique organizing principle in the form of the Antibiotic Resistance Ontology (ARO), and can quickly identify putative antibiotic resistance genes in new unannotated genome sequences. This unique platform provides an informatic tool that bridges antibiotic resistance concerns in health care, agriculture, and the environment.     

RCAS1 decidual immunoreactivity and RCAS1 serum level during cesarean section with respect to the progression of labor

PROBLEM: RCAS1 (a receptor-binding cancer antigen expressed on SiSo cells) is a membrane protein present also in a soluble form that seems to be responsible for the suppression of the cytotoxic immune response during gestation. The present study evaluates the decidual immunoreactivity level of RCAS1 and the serum level of RCAS1 with respect to the progression of labor at the time of cesarean section. METHOD OF STUDY: RCAS1 immunoreactivity was assessed by immunohistochemistry in 47 decidual samples, and the RCAS1 serum level was established in 47 blood serum samples derived from patients on whom cesarean sections were performed. The patients were divided into three groups according to the progression of their labor at the time when the cesarean was performed. RESULTS: The highest RCAS1 serum concentration and the highest RCAS1 decidual immunoreactivity were found in patients on whom cesarean sections were performed during advanced labor and were statistically, significantly higher than in cases where cesarean sections were performed without labor or after the spontaneous beginning of labor. CONCLUSION: Alterations in the RCAS1 serum and decidua levels seem to be associated with immune response changes during the progression of labor.     

Evaluation of the effectiveness of a low-dose aspirin in the treatment of intrauterine growth retardation (IUGR)]

OBJECTIVE: To evaluate the benefits of IUGR treatment by low doses of acetylsalicylic acid (ASA) (1.5 mg/kg) compared to the standard method. The study was based on the reports that aspirin at low doses shifts prostacyclin/tromboxan A2 balance to the dominance of prostacyclin by inhibiting cyclooxygenase activity in platelets, which results in the improvement of the utero-placental circulation. MATERIAL AND METHOD: 31 pregnant women with diagnosed fetal IUGR were randomly assigned to two groups, receiving either low-dose ASA (n = 22) or the standard treatment (Sadamin, Partusisten, glucose i.v., amino acids i.v.) for 10 days. Ultrasound examination of the biometric parameters of the fetus (BPD, AC, FL) was performed and estimated fetal weight (EFW) calculated before and after treatment. The birthweight of infants in the two examined groups was compared. RESULTS: The mean increase in EFW was higher in the aspirin-treated group compared to that receiving standard treatment (478 g vs 246 g, p < 0.05). In all the biometric parameters under study a higher increase was noted in the group with aspirin treatment; however, the difference was not statistically significant. The mean birthweight was found to be higher in the ASA group as well (2856 g vs 2511 g). The frequency of small-for-gestational-age (SGA) infants (birth weight below 10th percentile) was lower in the ASA group than in the controls (27% vs 55%). The low-dose aspirin therapy did not produce any adverse side-effects either among mothers of infants. CONCLUSION: The treatment with low doses of aspirin reduces the proportion of SGA babies and increases birthweight in the case of a diagnosed fetal growth retardation. Since the number of subjects in this study was relatively small, further clinical trials are necessary to evaluate the effectiveness of IUGR treatment by low-dose aspirin.     

Meeting report: atmospheric pollution and human reproduction

BACKGROUND: There is a growing body of epidemiologic literature reporting associations between atmospheric pollutants and reproductive outcomes, particularly birth weight and gestational duration. OBJECTIVES: The objectives of our international workshop were to discuss the current evidence, to identify the strengths and weaknesses of published epidemiologic studies, and to suggest future directions for research. DISCUSSION: Participants identified promising exposure assessment tools, including exposure models with fine spatial and temporal resolution that take into account time-activity patterns. More knowledge on factors correlated with exposure to air pollution, such as other environmental pollutants with similar temporal variations, and assessment of nutritional factors possibly influencing birth outcomes would help evaluate importance of residual confounding. Participants proposed a list of points to report in future publications on this topic to facilitate research syntheses. Nested case-control studies analyzed using two-phase statistical techniques and development of cohorts with extensive information on pregnancy behaviors and biological samples are promising study designs. Issues related to the identification of critical exposure windows and potential biological mechanisms through which air pollutants may lead to intrauterine growth restriction and premature birth were reviewed. CONCLUSIONS: To make progress, this research field needs input from toxicology, exposure assessment, and clinical research, especially to aid in the identification and exposure assessment of feto-toxic agents in ambient air, in the development of early markers of adverse reproductive outcomes, and of relevant biological pathways. In particular, additional research using animal models would help better delineate the biological mechanisms underpinning the associations reported in human studies.