Gas gangrene of the abdominal wall due to underlying GI pathology: seven cases

OBJECTIVE: Gas gangrene of the abdominal wall is a rare clinical occurrence with high rates of morbidity and mortality. The primary source of the infection is often unknown. To analyze the primary underlying intestinal etiologies and diagnostic approaches of gas gangrene of the abdominal wall, and to highlight specific treatment problems, particularly that of constructing a colostomy exteriorized through a massively infected abdominal wall. PATIENTS AND METHODS: Seven cases of abdominal wall gas gangrene due to a gastrointestinal etiology were identified. (Cases arising from proctologic sources or related to recent abdominal surgery were excluded.) During the same period, 39 other patients presenting with abdominal wall gangrene from non-intestinal sources were treated. RESULTS: The etiologies were: perforated sigmoid diverticulitis (n=2), perforated appendicitis (n=1), acute pancreatitis with associated cecal perforation (n=1), and perforated colorectal cancer (n=3). Four of the seven patients died despite treatment (mortality of 57%). CONCLUSION: The clinical presentations of these seven cases demonstrate that a GI source must be suspected whenever a patient presents with abdominal wall gas gangrene, even when there are no specific GI symptoms. Imaging, particularly with CT scan, is essential both to visualize the extent of tissue necrosis and to reveal underlying primary GI pathology. This optimizes the surgical approach both by allowing for complete debridement and drainage of infected tissue, and by focussing the intervention on correction of the underlying primary GI source of infection.     

Limb-girdle muscular dystrophy in the Netherlands: gene defect identified in half the families

Pheno- and genotype correlation is attempted in a Dutch cross-sectional study on limb- girdle muscular dystrophy. Sarcoglycans, caveolin-3, calpain-3, and dysferlin were analyzed on muscle tissue. Mutation analysis of the calpain-3, caveolin-3, and fukutin-related protein gene was executed in successive order for all samples. In 51% of all families a classifying diagnosis was made. Several new mutations in LGMD2A, B, and C patients have been found in this population.     

Impairment of lipid storage by cadmium in the European eel (Anguilla anguilla)

Because European silver eels (Anguilla anguilla) fast during their reproductive migration to the Sargasso Sea, the successful completion of their unusual life cycle depends on quantity of lipids stored beforehand. These lipids are mainly accumulated during the growth phase stage of the animals, called yellow eel, as triglycerides in muscle. They are then catabolized to provide sufficient energy to enable migration, gonad maturation and spawning. In the laboratory, we investigated the possible impact of cadmium on the lipid storage efficiency of yellow eels in order to evaluate the possible contribution of this pollutant to the reported decline of European eel populations. Eels were exposed to dissolved cadmium at nominal concentrations of 0 and 5 microgL(-1) for 1 month. Cd toxicity was then examined by studying the activity and expression level of several enzymes involved in liver lipolysis and lipogenesis and by determining lipid content in muscle. Contaminated eels showed a lower body weight growth with a lower efficiency of lipid storage compared to controls. Using two complementary approaches, genetic and enzymatic, it was possible to conclude that this impairment is mainly explained by an increased utilisation of triglycerides since cadmium contamination did not trigger a reduced fatty acid synthesis. These observations suggest an increased fat consumption in presence of cadmium, which could compromise successful reproduction.     

Granuloma formation and occlusion of an unruptured aneurysm after wrapping

Summary Excessive granulomatous foreign-body reaction is a very rare complication after wrapping of intracranial aneurysms. The pathogenetic mechanisms underlying this process are unknown. We report on a patient who developed a space-occupying granulomatous abscess after wrapping of an unruptured aneurysm of the M2/M3 bifurcation. The patient underwent revision craniotomy for abscess removal. The aneurysm was explored and found to be completely thrombosed and excluded from the circulation. Exuberant granulomatous foreign-body reaction was pathologically confirmed and Candida parapsilosis was isolated from the pus. The patient underwent an antifungal treatment regimen and recovered with no residual neurological deficits. Our findings support the assumption that a low-grade infectious process might trigger excessive inflammatory reaction after wrapping. We suggest that this process may also result in complete thrombosis of cerebral aneurysms, which is otherwise a rarely observed phenomenon.     

Discovery of a new family of bis-8-hydroxyquinoline substituted benzylamines with pro-apoptotic activity in cancer cells: synthesis, structure-activity relationship, and action mechanism studies

Bis-8-hydroxyquinoline substituted benzylamines have been synthesized and screened for their antitumor activity on KB3 cell line model. Synthesis of this series of new analogues was accomplished using a one pot specific methodology which allows the synthesis of both bis- and mono-8-hydroxyquinoline substituted benzylamines. Among the synthesized compounds two compounds (4a and 5a), respectively, named JLK 1472 and JLK 1486, were particularly potent on KB3 cell line. Their CC(50) values being, respectively, 2.6 and 1.3 nM. Screened on a panel of cell lines showing various phenotype alterations, both compounds were found inactive on some cell lines such as PC3 (prostate cell line) and SF268 (neuroblastoma cell line) while highly active on other different cell lines. Mechanistic studies reveal that these two analogues did not affect tubulin and microtubules neither they exert a proteasomal inhibition effect. In contrast 4a and 5a activate specifically caspase 3/7 and not caspase 8 and 9, suggesting that their biological target should be located upstream from caspase 3/7. Moreover their cytotoxic effect is potentiated by the pro-apoptotic effects of TRAIL.     

Correlation of Cefoxitin MICs with the Presence of mecA in Staphylococcus spp.

This report describes the results of an 11-laboratory study to determine if a cefoxitin broth microdilution MIC test could predict the presence of mecA in staphylococci. Using breakpoints of ≤4 μg/ml for mecA-negative and ≥6 or 8 μg/ml for mecA-positive isolates, sensitivity and specificity based on mecA or presumed mecA for Staphylococcus aureus at 18 h of incubation were 99.7 to 100% in three cation-adjusted Mueller-Hinton broths tested. For coagulase-negative strains at 24 h of incubation, breakpoints of ≤2 μg/ml for mecA-negative and ≥4 μg/ml for mecA-positive isolates gave sensitivity and specificity of 94 to 99% and 69 to 80%, respectively.The use of a cefoxitin disk test to detect staphylococci that are likely to contain the mecA gene has been widely advocated since the test was first suggested (3, 6) and has been adopted by antimicrobial susceptibility testing organizations worldwide (http://www.bsac.org.uk/_db/_documents/version_6.1.pdf, http://www.srga.org/, http://www.clsi.org/). For laboratories that do not use disk diffusion as their primary testing method, performing disk diffusion requires additional expense and reagents. Consequently, we performed studies to determine if a cefoxitin broth microdilution MIC breakpoint would correlate with the presence of the mecA gene in staphylococci.Cation-adjusted Mueller-Hinton broths (CAMHB) from three manufacturers (BBL, BD Diagnostic Systems, Sparks, MD; Difco, BD Diagnostic Systems, Sparks, MD; and Oxoid, Basingstoke, Hampshire, England) (cation content adjusted if necessary), were used to prepare frozen microdilution panels containing cefoxitin concentrations of 0.5 to 32 μg/ml (including 6 μg/ml) and oxacillin concentrations of 0.06 to 16 μg/ml (in BBL CAMHB only). The frozen panels were shipped to all participants, along with 30-μg cefoxitin disks (BBL). Each laboratory used its current lot of Mueller-Hinton agar for disk diffusion testing. Participating laboratories included the Centers for Disease Control and Prevention (CDC), Atlanta, GA; BD Diagnostic Systems, Sparks, MD; bioMérieux, Inc., Hazelwood, MO; Duke University Hospital, Durham, NC; JMI Labs, North Liberty, IA; Massachusetts General Hospital, Boston, MA; Siemens Healthcare Diagnostics MicroScan, Inc., West Sacramento, CA; University of Rochester, Rochester, NY; Robert Wood Johnson Medical School, New Brunswick, NJ; Statens Serum Institut, Copenhagen, Denmark; and Trek Diagnostic Systems, Cleveland, OH.Each laboratory tested approximately 50 unique clinical isolates from their own collection (30 Staphylococcus aureus isolates and 20 coagulase-negative staphylococci [CoNS]) and quality control strains for each test day (S. aureus ATCC 29213 [tested by MIC only] and S. aureus ATCC 25923 [tested by disk diffusion only]). Additional strains were tested at the CDC, totaling 167 S. aureus isolates and 22 CoNS. The total number of strains tested in all labs was 479 S. aureus isolates and 204 CoNS. All results were read after both 18-h and 24-h incubations. Endpoints were read as the lowest concentration at which no visible growth was observed. At 18 h of incubation, 97.3% of the MIC quality control results (for S. aureus ATCC 29213) and 97.9% of the disk diffusion quality control results (for S. aureus ATCC 25923) were within the range considered acceptable by the Clinical and Laboratory Standards Institute (CLSI).After testing, all strains were shipped to the CDC for further analysis. PCR testing for mecA was performed as previously described (8) on the following strains: (i) any S. aureus strain for which the cefoxitin MIC was <16 μg/ml in any of the three media tested (n = 180); (ii) any S. aureus strain for which the cefoxitin MIC was >8 μg/ml and the oxacillin MIC was <4 μg/ml in any of the three media tested (n = 5); and (iii) a sample of the 304 isolates (n = 16 [5%]) for which the cefoxitin MIC was >8 μg/ml and the oxacillin MIC was >2 μg/ml. All other S. aureus strains for which the cefoxitin MIC was >8 μg/ml and the oxacillin MIC was >2 μg/ml at 24 h of incubation were presumed to be mecA positive. All CoNS were tested by PCR for the presence of mecA and identified to species level by using previously described methods (1). For the purposes of data analysis, mecA or presumed mecA was used as the gold standard.Cefoxitin MIC results for the S. aureus group (which included eight isolates of Staphylococcus lugdunensis) showed a clear separation of mecA-positive and mecA-negative strains between 4 and 6 μg/ml; most isolates with cefoxitin MICs of 6 μg/ml contained the mecA gene (Table ​(Table1).1). Among 13 strains for which the cefoxitin MIC was 6 μg/ml in any medium at either incubation time period, 11 were mecA positive. All the S. lugdunensis strains tested were mecA negative and had cefoxitin MICs of ≤4 μg/ml. Using a cefoxitin breakpoint of ≤4 μg/ml for oxacillin-susceptible or mecA-negative isolates and that of ≥8 μg/ml (rounding 6 μg/ml up to 8 μg/ml) for oxacillin-resistant or mecA-positive isolates, sensitivity and specificity were excellent, 99.7 to 100%. If these breakpoints are applied to the isolate population in this study, there are some category discrepancies between cefoxitin susceptibility testing and oxacillin susceptibility testing. These were limited to isolates for which the cefoxitin MIC was ≥6 μg/ml and oxacillin MIC was <4 μg/ml. The number of isolates varied depending on the medium and time of incubation, with the lowest being three strains at 24 h in BBL CAMHB and the highest being seven strains at 18 h in Difco CAMHB. All were mecA positive except for two isolates. For the mecA-positive isolates, the oxacillin MICs were 1 or 2 μg/ml, and the cefoxitin MICs ranged from 6 to >32 μg/ml.

TABLE 1.

Cefoxitin MICs for 479 isolates of Staphylococcus aureus tested in three different CAMHB^a

A history of previous childbirths is linked to women's white matter brain age in midlife and older age

Maternal brain adaptations occur in response to pregnancy, but little is known about how parity impacts white matter and white matter ageing trajectories later in life. Utilising global and regional brain age prediction based on multi‐shell diffusion‐weighted imaging data, we investigated the association between previous childbirths and white matter brain age in 8,895 women in the UK Biobank cohort (age range = 54–81 years). The results showed that number of previous childbirths was negatively associated with white matter brain age, potentially indicating a protective effect of parity on white matter later in life. Both global white matter and grey matter brain age estimates showed unique contributions to the association with previous childbirths, suggesting partly independent processes. Corpus callosum contributed uniquely to the global white matter association with previous childbirths, and showed a stronger relationship relative to several other tracts. While our findings demonstrate a link between reproductive history and brain white matter characteristics later in life, longitudinal studies are required to establish causality and determine how parity may influence women''s white matter trajectories across the lifespan.     

The use of metformin for women with PCOS undergoing IVF treatment

BACKGROUND: Metformin appears to improve reproductive function in some women with polycystic ovary syndrome (PCOS). We wished to explore the effect of metformin in women with PCOS undergoing IVF. METHODS: A randomized, placebo-controlled, double-blind study was carried out between 2001 and 2004. Patients with PCOS undergoing IVF/ICSI treatment using a long GnRH agonist protocol were randomized to receive metformin (MET), 850 mg, or placebo (PLA) tablets twice daily from the start of the down-regulation process until the day of oocyte collection. The primary outcome was to be an improvement in the overall fertilization rate. RESULTS: One-hundred and one IVF/ICSI cycles were randomized to receive metformin (52) or to receive placebo (49). There was no difference in the total dose of rFSH required per cycle (median dose: MET = 1200 U, PLA = 1300 U; P = 0.937). The median number of oocytes retrieved per cycle (MET = 17.2, PLA = 16.2; P = 0.459) and the overall fertilization rates (MET = 52.9%, PLA = 54.9%; P = 0.641) did not differ. However, both the clinical pregnancy rates beyond 12 weeks gestation per cycle (MET = 38.5%, PLA = 16.3%; P = 0.023) and per embryo transfer (MET = 44.4%, PLA = 19.1%; P = 0.022) were significantly higher in those treated with metformin. Furthermore, a significant decrease in the incidence of severe ovarian hyperstimulation syndrome (OHSS) was observed (MET = 3.8%, PLA = 20.4%; P = 0.023), and this was still significant after adjustment for BMI, total rFSH dose and age (OR = 0.15; 95% CI: 0.03, 0.76; P = 0.022). CONCLUSION: Short-term co-treatment with metformin for patients with PCOS undergoing IVF/ICSI cycles does not improve the response to stimulation but significantly improves the pregnancy outcome and reduces the risk of OHSS.     

A new method of 3-D cephalometry Part I: the anatomic Cartesian 3-D reference system

The purpose of this study was to present a new innovative three-dimensional (3-D) cephalometric method. Part I deals with the set-up and validation of a voxel-based semi-automatic 3-D cephalometric reference system. The CT data (DICOM 3.0 files) of 20 control patients with normal skeletal relationships were used for this study. To investigate accuracy and reliability of the 3-D cephalometric reference system (Maxilimtrade mark, version 1.3.0) a total of 42 (14 horizontal, 14 vertical and 14 transversal) orthogonal measurements were performed on each patient twice by each of two investigators. The intra-observer measurement error was less then 0.88 mm, 0.76 mm and 0.84 mm for horizontal, vertical and transversal orthogonal measurements, respectively. The inter-observer measurement error was less as 0.78 mm, 0.86 mm and 1.26 mm for horizontal, vertical and transversal orthogonal measurements, respectively. Squared correlation coefficients showed a high intra-observer and inter-observer reliability. The presented 3-D cephalometric reference system proved to be accurate and reliable and can therefore be used for 3-D cephalometric hard and soft tissue analysis.     

Multicenter Study To Determine Disk Diffusion and Broth Microdilution Criteria for Prediction of High- and Low-Level Mupirocin Resistance in Staphylococcus aureus

Mupirocin susceptibility testing of Staphylococcus aureus has become more important as mupirocin is used more widely to suppress or eliminate S. aureus colonization and prevent subsequent health care- and community-associated infections. The present multicenter study evaluated two susceptibility testing screening methods to detect mupirocin high-level resistance (HLR), broth microdilution (BMD) MICs of ≥512 μg/ml, and a 6-mm zone diameter for a disk diffusion (DD) test with a 200-μg disk. Initial testing indicated that with Clinical and Laboratory Standards Institute methods for BMD and DD testing, the optimal conditions for the detection of mupirocin HLR were 24 h of incubation and reading of the DD zone diameters with transmitted light. Using the presence or absence of mupA as the “gold standard” for HLR, the sensitivity and specificity of a single-well 256 μg/ml BMD test were 97 and 99%, respectively, and those for the 200-μg disk test were 98 and 99%, respectively. Testing with two disks, 200 μg and 5 μg, was evaluated for its ability to distinguish HLR isolates (MICs ≥ 512 μg/ml), low-level-resistant (LLR) isolates (MICs = 8 to 256 μg/ml), and susceptible isolates (MICs ≤ 4 μg/ml). Using no zone with both disks as an indication of HLR and no zone with the 5-μg disk plus any zone with the 200-μg disk as LLR, only 3 of the 340 isolates were misclassified, with 3 susceptible isolates being classified as LLR. Use of standardized MIC or disk tests could enable the detection of emerging high- and low-level mupirocin resistance in S. aureus.Mupirocin is a topical antibacterial agent that is used both for the treatment of skin infections and for the suppression or elimination of nasal carriage of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) (8). The recommendations of the Healthcare Infection Control Practices Advisory Committee suggest the use of a tiered approach to the prevention and control of infections with multidrug-resistant organisms, including MRSA, in acute-care settings (20). In their recommendations, decolonization is presented as one intervention that may be considered when intensified MRSA control measures are needed; if decolonization is used, susceptibility testing and monitoring for the emergence of resistance to the decolonization agent are recommended in one study (21).There are two levels of resistance to mupirocin: low-level resistance (LLR), for which the MICs are 8 to 256 μg/ml, and high-level resistance (HLR), for which the MICs are ≥512 μg/ml (11). The mupirocin MICs of strains susceptible to mupirocin are MICs ≤4 μg/ml. HLR is associated with the presence of the plasmid-mediated mupA gene, which encodes a mupirocin-resistant isoleucyl-tRNA synthetase, although S. aureus strains with HLR that lack mupA have occurred (this study) and can also be created in the laboratory (23). LLR results from mutation of the native, chromosomal isoleucyl-tRNA synthetase ileS gene (1). Studies suggest that S. aureus strains with HLR to mupirocin cannot be successfully eliminated with mupirocin and that the occurrence of HLR is increasing (22). It has been suggested that S. aureus strains demonstrating LLR could be eliminated by topical application of mupirocin because of the high concentrations achieved locally, but this has not been demonstrated definitively (11, 21).Until recently, methods for testing topical agents have not been included in susceptibility testing documents published by the Clinical and Laboratory Standards Institute (CLSI; formerly NCCLS), although guidelines for testing by various methods have been suggested by others (9, 10, 12, 13, 16, 17). The British Society for Antimicrobial Chemotherapy has formal recommendations for the testing of mupirocin (www.bsac.org.uk) that include testing of a 5-μg and a 20-μg mupirocin disk. Their recommendations require MIC testing to determine the level of resistance if a 5-μg disk is used alone. An initial investigation at the Centers for Disease Control and Prevention (CDC), Atlanta, GA, showed that a 200-μg mupirocin disk was able to differentiate isolates with LLR from those with HLR (15). We undertook the study described here to determine the MIC and disk diffusion criteria for the detection of S. aureus strains with high- or low-level mupirocin resistance and to validate quality control tests. Using data from this study, a screen test for prediction of high-level mupirocin resistance is now included in CLSI susceptibility testing documents (3, 6, 7).