Isolation and Characterization of Lytic Pseudomonas aeruginosa Bacteriophages Isolated from Sewage Samples from Tunisia

Bacteriophages could be a useful adjunct to antibiotics for the treatment of multidrug-resistant Pseudomonas aeruginosa infections. In this study, lytic P. aeruginosa myoviruses PsCh, PsIn, Ps25, and Ps12on-D were isolated from Tunisian sewage samples. Phage Ps12on-D displayed an adsorption time of ~10 min, a short latency period (~10 min), and a large burst size (~115 PFU per infected cell) under standard growth conditions. All phages were active at broad temperature (4 °C to 50 °C) and pH (3.0 to 11.0) ranges and were able to lyse a wide variety of P. aeruginosa strains isolated from clinical and environmental samples worldwide. Illumina sequencing revealed double-stranded DNA genomes ranging from 87,887 and 92,710 bp with high sequence identity to Pseudomonas phage PAK_P1. All four phages based on sequence analysis were assigned to the Pakpunavirus genus. The presented characterization and preclinical assessment are part of an effort to establish phage therapy treatment as an alternative strategy for the management of multidrug-resistant P. aeruginosa infections in Tunisia.     

Oral manifestations of human immunodeficiency virus infection

It is important that both physicians and dentists recognize the earliest signs of HIV infection in order that a timely diagnosis and patient referral can be made for counseling and treatment. Candidiasis, hairy leukoplakia, and Kaposi's sarcoma are the most common oral manifestations, but there are other important lesions as well. They include severe necrotizing periodontitis, bacterial and viral infections, lymphomas, and carcinomas. The various oral lesions seen in patients with the acquired immunodeficiency syndrome are reviewed and managements are discussed.     

Dosing patterns and treatment costs of erythropoietic agents in elderly patients with pre-dialysis chronic kidney disease in managed care organisations

OBJECTIVES: To investigate dosing patterns and drug costs of erythropoietic agents and assess the frequency of outpatient nephrologist visits in an elderly population with pre-dialysis chronic kidney disease (pCKD) newly initiated on epoetin alfa (EPO) or darbepoetin alfa (DARB). METHODS: An analysis of medical claims from more than 30 healthcare plans covering all census regions of the US in the period July 2002 through February 2005 was conducted. Patients were included if they were > or = 65 years of age, had at least one claim for CKD within 90 days prior to the initiation of any erythropoietic agent, were newly commenced on either EPO or DARB, and had received at least two treatment doses. If a patient received renal dialysis, data were censored 30 days prior to the first date of dialysis. Patients diagnosed with cancer or those who had undergone chemotherapy were excluded from the analysis. The average dosing interval for both EPO and DARB was calculated and classified as once weekly (qw), every 2 weeks (q2w) or every 3 weeks or less frequently (> or = q3w). Weighted average weekly doses were scaled based on treatment duration. The frequency of outpatient nephrologist visits was analysed. Average weekly treatment costs were calculated and presented using the May 2005 Wholesale Acquisition Costs. RESULTS: A total of 293 EPO and 102 DARB patients met the inclusion criteria. The two groups of patients had similar mean age (74.4 years for EPO vs 74.3 years for DARB) and gender distribution (47.4% female for EPO vs 51.0% for DARB). Extended dosing (every 2 weeks or less frequently: > or = q2w) during treatment was observed in both groups (EPO: qw 49.8%, q2w 31.7%, > or = q3w 18.4%; DARB: qw 19.6%, q2w 52.9%, > or = q3w 27.5%). The average dosing interval between injections was 13.6 days for the EPO group and 17.3 days for the DARB group. The weighted average weekly dose was 12,748 units for EPO and 43.5 microg for DARB. The average weekly erythropoietic treatment cost was significantly greater for DARB compared with EPO (190 US dollars vs 155 US dollars per week [2005 values]; p = 0.028). After controlling for covariates, the cost difference between the two groups was more pronounced and remained statistically significant (adjusted cost difference 41 US dollars/week higher for DARB patients; p = 0.013). The frequency of outpatient nephrologist visits during treatment was similar between the two groups (EPO 3.4 vs DARB 3.0 visits). CONCLUSIONS: Based on this analysis of claims data from more than 30 US healthcare plans, extended dosing (> or = q2w) of EPO and DARB was common in elderly pCKD patients treated with erythropoietic agents, with significantly higher weekly drug costs observed in the DARB group compared with the EPO group. The number of outpatient nephrologist visits was not significantly different between EPO and DARB patients. This study was the first to evaluate the dosing patterns of EPO and DARB in elderly pCKD patients in a large managed care population.     

A novel case of bisphosphonate-related osteonecrosis of the torus palatinus in a patient with metastatic breast cancer

Bisphosphonates administered orally and intravenously are used for a variety of endocrine and oncologic indications. Long-term intravenous use of bisphosphonates has been shown to cause osteonecrosis of the jaw. We report a case in which a 58-year-old woman with metastatic breast cancer received 18 doses of 4 mg intravenous zoledronic acid over a period of 16 months and developed a region of osteonecrosis on the posterior edge of a large, lobular torus palatinus. Torus palatinus, a type of maxillary exostosis, is common among postmenopausal women, and is vulnerable to blunt trauma that could predispose to osteonecrosis. Sequestrum of dead bone was removed and the site healed within 4 weeks. This case demonstrates that patients with a torus palatinus may be at high risk for osteonecrosis, and reinforces the need for good oral hygiene and frequent dental examination while receiving bisphosphonate therapy.     

High frequency of latent membrane protein-1 30-bp deletion variant with specific single mutations in Epstein-Barr virus-associated nasopharyngeal carcinoma in Moroccan patients

Latent membrane protein 1 (LMP-1) is an Epstein-Barr virus-encoded oncoprotein expressed in approximately 50-70% of nasopharyngeal carcinoma (NPC). Previous studies have shown that NPC-derived LMP-1 variants carrying 30 bp deletion and specific mutations in the 3'C-terminal region confer high oncogenic potential and a weak immunogenicity. Although numerous polymorphism studies of LMP-1 have been carried out so far in the Asian population with NPC, very little is known in this regard on NPC patients from Northern Africa where there is a significantly high occurrence of this tumor. In our study, we examined the frequency of different LMP-1 sequence variants derived from Moroccan NPC patients. As compared to healthy donors, NPC patients showed a high prevalence of the 30bp deletion variant of LMP-1 (i.e. 84% vs. 36%; p<0.0005). Moreover, the del-LMP-1 variant derived from NPC tumors shared identical amino acid substitutions at positions 322, 334, 338, 352 and 366 with the Mediterranean (Med) variant, whereas those derived from peripheral blood mononuclear cells (PBMC) had similar mutation pattern as China1 variant. Additional mutations within the 342-352 regions (identified in LMP-1 variants without deletion derived from NPC tumors) were not found in healthy donors' PBMC. Our results support the assumption that the distribution of LMP-1 variants in NPC tumors co-segregate with geographic regions. Indeed, Med variant is found more frequently in tumors from NPC Moroccan patients, whereas China1 variant is more prevalent in tumors from NPC patients in endemic regions for NPC.     

Results of laparoscopic treatement of common bile duct lithiasis. Report of 30 cases

AIM: The aim of this retrospective study was to report the results of the laparoscopic management of common bile duct stones in an unicentric series of 30 patients. METHODS: From January 2001 to April 2004. 30 patients: 23 women, 7 men (mean age: 54 years). underwent a common bile duct exploration for lithiasis through a laparoscopic approach. The patients were hospitalized for angiocholitis (n = 12), cholecystitis (n= 4), jaundice (n = 4), pancreatitis (n = 3), abnormality of hepatic tests (n = 7). All the patients underwent an intra operative cholangiography. Removal of the stones was tried in 30 cases through a choledochotomy. never through the cystic duct, using Dormia and Fogarty catheters. External biliary drainage with T tube (kehr) and postoperative cholangiography was done systematically. RESULTS: In 21 patients (70 %), removal of the stones was laparoscopically successful. The average diameter of the common bile duct was 10.5 mm (range 6-20 mm). The median number of stones was 5 (E: 1-12). The median operation time was 180mn (range 150-300mn). In 9 patients, a conversion into laparotomy was necessary for several reasons. In 2 patients with residual common bile duct, the stones were treated successfully by endoscopic sphincterotomy. There was no mortality and the morbidity rate was 10 %. The mean postoperative hospital stay was 14.7 days (range 7-18days) and 13.3 days in case of successful laparoscopic management. CONCLUSION: In 70 % of the patients, the treatment of the common bile-duct lithiasis could be achieved laparoscopically, but conventional approach and endoscopic sphincterotomy are still useful in case of failure of the laparoscopic management.