Pneumothorax in drug abusers. An urban epidemic?

Although intravenous drug abuse is endemic in urban America, only 19 cases of pneumothorax from neck injections have been reported. For this reason, the experience at Detroit Receiving Hospital was reviewed. Data collected included patient demographics, size of pneumothorax, use of antibiotics, and complications related to tube thoracostomy. Of 525 diagnoses of pneumothorax between January 1, 1982 and December 31, 1984, 113 (21.5%) occurred as a result of drug abuse in 84 patients. Average patient age was 32 years (range 20 to 55 years). Thirty-eight (45%) were female. The number of admissions per year has increased, and 11 patients showed multiple admissions over the 3-year study period. Nine patients had bilateral collapse. One hundred six pneumothoraces (94%) were treated with closed thoracostomy with a tube-related hospital stay of 5 days, overall stay averaging 7 days. Only six patients received antibiotics for chest tube prophylaxis, and no in-hospital tube-related infections were identified. Thirteen patients developed residual pneumothorax following tube removal, but only two required a new tube. Pneumothorax in drug abusers is a serious urban problem and one with which physicians need be familiar.     

Host defense mechanisms in the pathogenesis of urinary tract infection

Certain microorganisms have a propensity for causing urinary tract infection, and the route (either ascending or hematogenous) by which microorganisms contaminate the urinary tract from external sources is frequently characteristic of the microorganism. There are local defense mechanisms both in the urine and at each anatomic site in the urinary tract (urethra, bladder, ureter, and kidney). The defense mechanisms at one site may have opposing effects on microbial growth at other sites in the urinary tract. The outcome following entrance of microorganisms into the urinary tract is a result of competing forces, which consist of these local urinary defense mechanisms, the initial numbers of microorganisms contaminating the urinary tract, and microbial virulence factors.     

In Vitro Evaluation of Tobramycin, a New Aminoglycoside Antibiotic

One hundred fifty-two strains of Escherichia coli, Klebsiella-Enterobacter, Pseudomonas aeruginosa, Proteus species, and Staphylococcus aureus were inhibited by 3.1 mug of tobramycin/ml in a broth-dilution method and showed zones of inhibition of 16 mm or more around a 10-mug tobramycin disc in the Kirby-Bauer method. Tobramycin was most active against S. aureus, 100% of strains being inhibited by 0.1 mug/ml. All strains of E. coli, K. pneumoniae, P. aeruginosa, and indole-positive Proteus species, and 80% of Enterobacter species were inhibited by 0.8 mug of tobramycin/ml, whereas only 48% of P. mirabilis strains were inhibited by this concentration. Tobramycin was approximately twice as active as gentamicin against S. aureus, four times as active against P. aeruginosa, slightly more active against E. coli and Enterobacter species, equally active against P. mirabilis, and slightly less active against K. pneumoniae. The minimal bactericidal concentrations of tobramycin and gentamicin were the same as or twice the minimal inhibitory concentrations for all strains except those of P. aeruginosa, against which greater concentrations of both gentamicin and tobramycin were required for bactericidal activity. Tobramycin sterilized cultures of S. aureus, E. coli, and P. aeruginosa, but the rate of bactericidal action was faster with a combination of tobramycin and carbenicillin than with either antibiotic alone in the same concentrations. Tobramycin retained potency in the presence of 200 to 600 mug of carbenicillin/ml for at least 6 hr of incubation at 37 C, but lost potency in the presence of 600 mug of carbenicillin/ml by 24 hr of incubation and in the presence of 800 mug/ml by 2 hr of incubation.     

In vitro susceptibilities of oral pigmented Bacteroides species to trospectomycin and other selected antimicrobial agents.

The in vitro activity of trospectomycin against 97 clinical isolates of oral pigmented Bacteroides species was compared with the activities of five other antimicrobial agents. At 4 micrograms/ml, more than 90% of isolates were inhibited by trospectomycin. Overall, strains that produced beta-lactamase (n = 41) were more resistant to trospectomycin, penicillin G, cefoxitin, piperacillin, and tetracycline but not to clindamycin. In this study, trospectomycin had excellent in vitro activity against oral pigmented Bacteroides species.     

Replication and meta-analysis of 13,000 cases defines the risk for interleukin-23 receptor and autophagy-related 16-like 1 variants in Crohn��s disease

BACKGROUND/OBJECTIVE:

Variants in the interleukin-23 receptor (IL23R) and the autophagy-related 16-like 1 (ATG16L1) genes have been associated with an increased risk of Crohn’s disease (CD). Both genes were identified through genome-wide association scans and subsequent studies have validated these associations. To assess the effect size of these variants, an independent case-control association study and meta-analysis were performed.

METHODS:

British Caucasian subjects with inflammatory bowel disease (n=500) and 877 ethnically matched controls were genotyped for the disease-associated variants in IL23R and ATG16L1. In addition, meta-analyses of 12,991 patients and 14,598 controls, and 11,909 patients and 15,798 controls, were conducted on independently published data for the associations between IL23R and ATG16L1 variants and CD, respectively.

RESULTS:

In the present cohort, both susceptibility variants showed highly significant associations, including IL23R (rs11209026, P=0.0006; OR 0.37; 95% CI 0.21 to 0.67) and ATG16L1 (rs2241880, P=0.0017; OR 1.36; 95% CI 1.12 to 1.66). The meta-analysis based on the random effects model showed similar combined effects for rs11209026 (n=26, OR 0.41; 95% CI 0.37 to 0.46) and rs2241880 (n=25, OR 1.33; 95% CI 1.28 to 1.39). There was no statistically significant gene-gene interaction between caspase recruitment domain (CARD15) variants and the IL23R or ATG16L1 polymorphisms (P=0.44 and P=0.24, respectively).

CONCLUSION:

The present cohort and meta-analysis provides strong evidence that, in addition to CARD15, polymorphisms in both IL23R and ATG16L1 alter susceptibility to CD and that these effects are consistent across all populations of European ancestry; however, only ATG16L1 is relevant to inflammatory bowel disease in the Asian population.     

Perinatal hypoxic/ischemic brain injury induces persistent production of striatal neurons from subventricular zone progenitors

Ischemia-induced production of new striatal neurons in young and adult rodents has been studied. However, it is unclear whether neonatal hypoxic/ischemic (H/I) brain injury-induced neuronogenesis in the striatum is transient or sustained, nor has it been established whether these new neurons arise from progenitors within the striatum or from precursors residing in the adjacent subventricular zone. Here, we report that from 2 weeks to 5 months after H/I there are more doublecortin-positive (Dcx+) cells and Dcx+/NeuN+ cells in the damaged striatum compared to the contralateral striatum. After the S-phase marker 5-bromo-2'-deoxyuridine (BrdU) was injected at both short and long intervals (2 days and 2 months) after H/I to label newly born cells, more BrdU+/Dcx+ and BrdU+/NeuN+ cells were observed in the ipsilateral striatum compared to the contralateral striatum. Retroviral fate-mapping studies demonstrated that these newly born striatal neurons are generated from precursors within the subventricular zone. Altogether, these observations indicate the neonatal brain initiates a prolonged regenerative response from the precursors of the subventricular zone (SVZ) that results in persistent production of new striatal neurons.     

Ciliary neurotrophic factor and interleukin-6 differentially activate microglia

Studies have shown that cytokines released following CNS injury can affect the supportive or cytotoxic functions of microglia. Interleukin-6 (IL-6)-family cytokines are among the injury factors released. To understand how microglia respond to IL-6 family cytokines, we examined the effects of ciliary neurotrophic factor (CNTF) and IL-6 on primary cultures of rat microglia. To assess the functional state of the cells, we assayed the expression of tumor necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1beta), and cyclooxygenase 2 (COX-2) following stimulation. We show that CNTF reduces COX-2 levels, whereas IL-6 increases the expression of IL-1beta, TNFalpha, and Cox-2. We also examined trophic factor expression and found that CNTF enhances glial cell-line derived neurotrophic factor (GDNF) mRNA and protein secretion, whereas IL-6 has no effect. Correspondingly, conditioned media from CNTF-stimulated microglia promote motor neuron survival threefold beyond controls, whereas IL-6-stimulated microglia decrease neuronal survival twofold. To understand better the signaling mechanisms responsible for the opposite responses of these IL-6-family cytokines, we examined STAT-3 and ERK phosphorylation in CNTF- and IL-6-stimulated microglia. IL-6 markedly increases STAT-3 and ERK phosphorylation after 20 min of treatment, whereas these signal transducers are weakly stimulated by CNTF across a range of doses. We conclude that CNTF modifies microglial activation to support neuronal survival and that IL-6 enhances their capacity to do harm, as a result of different modes of intracellular signaling.