Surgical management of chronic, unreduced anterior dislocation of the shoulder

Chronic old unreduced anterior dislocations are extremely rare. We report a case of 75-year-old lady who was seen in policlinic with the symptoms of severe pain and limited shoulder range of motion in which radiographies revealed anteroinferior missed shoulder dislocation. Open reduction with Bankart repair was done, and patient was able to return her daily activities 6 weeks after the operation. To us, if the shoulder was found to be instable after reduction, anteroinferior glenohumeral ligament tear should be looked for, and if it exists should be repaired.     

Pathogenicity Islands PAPI-1 and PAPI-2 Contribute Individually and Synergistically to the Virulence of Pseudomonas aeruginosa Strain PA14

Pseudomonas aeruginosa is a leading cause of hospital-acquired pneumonia and severe chronic lung infections in cystic fibrosis patients. The reference strains PA14 and PAO1 have been studied extensively, revealing that PA14 is more virulent than PAO1 in diverse infection models. Among other factors, this may be due to two pathogenicity islands, PAPI-1 and PAPI-2, both present in PA14 but not in PAO1. We compared the global contributions to virulence of PAPI-1 and PAPI-2, rather than that of individual island-borne genes, using murine models of acute pneumonia and bacteremia. Three isogenic island-minus mutants (PAPI-1-minus, PAPI-2-minus, and PAPI-1-minus, PAPI-2-minus mutants) were compared with the wild-type parent strain PA14 and with PAO1. Our results showed that both islands contributed significantly to the virulence of PA14 in acute pneumonia and bacteremia models. However, in contrast to the results for the bacteremia model, where each island was found to contribute individually, loss of the 108-kb PAPI-1 island alone was insufficient to measurably attenuate the mutant in the acute pneumonia model. Nevertheless, the double mutant was substantially more attenuated, and exhibited a lesser degree of virulence, than even PAO1 in the acute pneumonia model. In particular, its ability to disseminate from the lungs to the bloodstream was markedly inhibited. We conclude that both PAPI-1 and PAPI-2 contribute directly and synergistically in a major way to the virulence of PA14, and we suggest that analysis of island-minus strains may be a more appropriate way than individual gene knockouts to assess the contributions to virulence of large, horizontally acquired segments of DNA.Pseudomonas aeruginosa is an environmentally ubiquitous opportunistic pathogen that causes a wide range of acute life-threatening infections, especially in immunocompromised patients. Hospitalized patients with damaged airways due to mechanical ventilation, injury, or viral infections are at significant risk of acute pneumonia caused by P. aeruginosa (51). Resulting cases of ventilator-associated pneumonia are associated with very high rates of mortality (12). In addition, this bacterium is a common cause of chronic respiratory infection in patients with cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and non-CF bronchiectasis (43, 50). A large variety of extracellular virulence factors, including proteases, hemolysins, pyocyanin, pili, lipopolysaccharide, alginate, and the type III secretion system (T3SS) effector proteins, ExoS, ExoT, ExoU, and ExoY, are associated with P. aeruginosa (52, 62).P. aeruginosa PA14 is a fully sequenced, highly virulent wild-type (WT) reference strain that has been used extensively to study the contribution of putative virulence factors to disease (31). Furthermore, as defined through study of a large panel of strains representative of this species, PA14 was found to belong to the most common P. aeruginosa global lineage (61). Another fully sequenced strain, PAO1, is widely regarded as a laboratory strain of P. aeruginosa. PA14 has been shown to be much more virulent than PAO1 in a number of diverse models of infection, leading to the hypothesis that PA14 is a multihost pathogen capable of infecting invertebrate and vertebrate animal species and plant species (29). The genomes of individual P. aeruginosa strains have a highly mosaic structure made up of conserved cores and variable accessory genomes (36, 61), resulting in composite genomes of 5.2 to 7 Mb (36). The majority of large-scale genomic differences arise from the presence or absence of an expanding list of genomic islands within conserved “hot spots” throughout the genome (36). PA14 carries two well-characterized pathogenicity islands: PAPI-1, a 108-kb island integrated within a lysine tRNA gene (PA4541.1), and PAPI-2, a much smaller, 11-kb island inserted into a sequence-identical but distinct tRNA^Lys gene (PA0976.1) (19). In addition to targeting integration sites bearing identical sequences, these two islands share a limited but recognizable degree of synteny and code for factors that have been implicated in pathogenesis in murine, plant, and nematode models of infection (19, 31, 37, 52). Interestingly, islands with significant homology to PAPI-1 and/or PAPI-2 have been identified in many P. aeruginosa strains and several other bacterial species (5, 6, 19, 23, 27, 30, 61, 63) (see Tables S2 and S3 and Fig. S2 in the supplemental material).PAPI-1 is a member of the increasingly populated pKLC102/PAGI-2 island family (26). PAPI-1 encodes a number of likely virulence factors, including type IVB pili, the cupD1 to cupD5 fimbrial biogenesis gene cluster (39), and PvrR, a two-component response regulator involved in biofilm synthesis and antibiotic resistance (11, 38). However, the large majority of PAPI-1 predicted proteins have no assigned function, and many of these are encoded by homologues on related islands in other P. aeruginosa strains (27, 63). PAGI-5, a hybrid island that shares 79 of 121 predicted open reading frames (ORFs) with PAPI-1, has recently been implicated in acute murine pneumonia (5). Isogenic mutants harboring deletions within NR-I or NR-II, PAGI-5-specific novel regions, were shown to be attenuated in a model of acute murine pneumonia, demonstrating that an island in the pKLC102/PAGI-2 family played a role in this infection.PAPI-2 is a stably integrated island belonging to the ExoU island family (30). This island encodes the cytotoxin ExoU, a potent phospholipase, and its cognate chaperone SpcU. ExoU has been studied extensively and has been shown to be the most potent of the known T3SS effector proteins in P. aeruginosa (54). The introduction of exoU into strains that lacked this gene resulted in marked increases in virulence in a murine acute pneumonia model (1). Recent work has suggested that ExoU impairs host response in the lung through targeted killing of phagocytes, which play a crucial role during the early phase of infection (10). Additionally, the secretion of ExoU by an infecting strain has been shown to be a marker of high virulence and poor clinical outcome in hospital-acquired pneumonia (52).Since genomic islands are widely believed to be acquired and/or lost as whole units, and since PAPI-1-like islands are known to be widespread and possibly highly mobile (46), we investigated the contributions of PAPI-1 and PAPI-2 to virulence as single unitary modules rather than defining the roles of individual island-borne genes (5, 19). We postulated that this en bloc deletion approach would reveal combinatorial and/or synergistic effects that would be missed by single-gene knockout approaches. To pursue this goal, we created three isogenic whole-island deletion mutants that lacked either PAPI-1 (PA14ΔPAPI-1), PAPI-2 (PA14ΔPAPI-2), or both (PA14Δ1Δ2) in a PA14 background and examined these relative to their wild-type parent and the laboratory strain PAO1, which naturally lacks both islands. Our results revealed that both PAPI-1 and PAPI-2 contributed individually and synergistically to the virulence of P. aeruginosa strain PA14 in murine models of acute pneumonia and bacteremia.     

Assessment of DNA damage in postmenopausal women under osteoporosis therapy

OBJECTIVE: The following study was designed to examine possible DNA damage levels in peripheral blood leukocytes, using the alkaline Comet assay, isolated from postmenopausal women undergoing osteoporosis treatment. STUDY DESIGN: Thirty-two postmenopausal women were randomized into two groups of 16. A dosage of 2.5 mg/day of tibolone (Livial) and 10mg/day of alendronate sodium (Fosamax) were administered to Group 1 over a 12-month period while Group 2 took 10 mg/day of alendronate alone over the same period. The control group consisted of 16 postmenopausal women who did not receive any treatment. Genotoxicity was assessed by the standard method of alkaline Comet assay. RESULTS: When the results of the study groups were compared with those of the control group, significant differences in terms of DNA damage levels were found (p<0.05). However, no difference was detected between Groups 1 and 2 (p>0.05). CONCLUSION: Although, no statistical difference in terms of DNA damage levels between tibolone plus alendronate as opposed to alendronate alone was found, an increase in DNA damage levels was observed in Groups 1 and 2 compared with the control group. Consequently, it can be asserted that the frequency of DNA damage in postmenopausal women with osteoporosis increases under alendronate treatment with or without tibolone.     

Chromosomal anomalies and additional sonographic findings in fetuses with open neural tube defects

Objective

To evaluate the results and the necessity of chromosome analysis in fetuses prenatally detected with a neural tube defect and to determine the significance of ultrasonographic evaluation for the identification of underlying or accompanying chromosomal anomalies.

Methods

Ninety fetuses that underwent prenatal and/or postnatal chromosome analysis after being diagnosed with open neural tube defects (NTD) between the years 2006 and 2010 in the Department of Obstetrics and Gynecology at Ondokuz Mayis University School of Medicine were included in this study. Detailed fetal ultrasonography was performed in all cases in order to investigate any additional anomalies. Karyotype was determined in the prenatal period by amniocentesis in 72 (80?%) of the 90 fetuses, and by cordocentesis in 5 (5.5?%). In 13 (13.3?%) fetuses, karyotype was determined in the postnatal period by blood sampling.

Results

Fourteen (15.5?%) of the 90 fetuses were diagnosed with acrania/anencephaly, 14 (15.5?%) with encephalocele, 2 (2.2?%) with iniencephaly, 60 (66.6?%) with open spina bifida. None of the 90 fetuses with open NTD who had undergone chromosome analysis was diagnosed with chromosomal anomalies. None of the 19 (21.1?%) fetuses diagnosed with additional ultrasound findings had a chromosomal abnormality, either. Seventy-one (78.9?%) fetuses having sonograhically isolated NTD were also isolated in postmortem examination.

Conclusion

In fetuses with open NTD, we could not find the chromosomal anomaly rate as high as reported in previous literature. The necessity of fetal karyotyping should be questioned especially in isolated cases.     

Sustained seroconversion of chronic hepatitis B infection after stem cell transplantation

Serap A, Funda O, Bengu K, Mehmet K, Nazan C, Rasit Y, Savas K. Sustained seroconversion of chronic hepatitis B infection after stem cell transplantation.
Pediatr Transplantation 2011: 15: E92–E95. © 2010 John Wiley & Sons A/S. Abstract: We present an 18‐yr‐old adolescent with acute lymphocytic leukemia, who underwent peripheral blood SCT with serologically and histologically documented chronic hepatitis B infection. Prior and during the transplant process, lamivudine was administered orally and he underwent SCT with a twofold decrease in viral load at the time of transplant from his HLA full matched, HBV natural immune (anti‐HBs and anti‐HBc positive) donor. Successful engraftment was achieved and three months after SCT, HBV seroconversion was documented accompanied with an ALT flare. Chronic graft‐versus‐host disease coincided after the transplantation, and he has been on immunosuppressive treatment for 25 months with sustained HBV seroconversion. We assume that adoptive immunity transfer combined with antiviral treatment might also constitute sustained seroconversion in chronic HBV, besides the reported risk of reactivation.