The effectiveness and safety of oral linezolid for the primary and secondary treatment of osteomyelitis.

The pharmacokinetic profile of oral linezolid makes it an attractive alternative for the treatment of osteomyelitis. Few studies have described the efficacy of linezolid in the treatment of osteomyelitis. A retrospective, observational analysis was conducted at Edward Hines, Jr. VA Hospital. Patients who received oral linezolid from June 2000 to December 2002 were identified from pharmacy records. Forty-two patients who received oral linezolid for osteomyelitis at our institution were identified. Only patients who had received at least six weeks of linezolid therapy were evaluated for clinical effectiveness. Patients were also evaluated for adverse drug reactions due to linezolid. The clinical cure rate was 55% for the 20 patients who received at least six weeks of therapy. Adverse events included gastrointestinal disturbances (15%), thrombocytopenia (10%), anemia (10%), neutropenia (5%) and rash (5%). The authors conclude that oral linezolid is an alterative to intravenous antibiotics for the treatment of osteomyelitis.

Pathogenic relevance of Lactobacillus: a retrospective review of over 200 cases.

Given that Lactobacillus has been reported to be the causative pathogen in many types of infection despite debate regarding the organism's clinical significance, a literature review was conducted to investigate the treatments and outcomes of Lactobacillus infections reported to date. In this article, the characteristics of over 200 reported cases of Lactobacillus-associated infections are summarized. Lactobacillus was found to be frequently associated with endocarditis and bacteremia. Lactobacillus was also associated with a variety of other infections including, but not limited to, peritonitis, abscesses, and meningitis. The species casei and rhamnosus were the most common. The isolates tended to be most sensitive to erythromycin and clindamycin and most resistant to vancomycin. The species that was most sensitive to vancomycin was acidophilus. The overall mortality rate was nearly 30%. There was a significant association between mortality and polymicrobial infection (P=0.004). In the subset of patients with bacteremia, increased mortality was associated with inadequate treatment (P=0.001) and polymicrobial bacteremia (P=0.044).

A prospective and retrospective analysis of the nephrotoxicity and efficacy of lipid-based amphotericin B formulations.

STUDY OBJECTIVE: To determine the usage patterns of the lipid-based amphotericin B formulations at our institution and to compare the observed nephrotoxicity and efficacy of these formulations. DESIGN: Prospective and retrospective observational study SETTING: Urban 350-bed teaching hospital. PATIENTS: Sixty-seven nonhemodialysis patients who were prescribed greater than 3 days of amphotericin B lipid complex (ABLC) or liposomal amphotericin B (L-AmB) from 1996-1999. MEASUREMENTS AND RESULTS: Forty-six patients received ABLC and 21 received L-AmB. Oncology patients accounted for most prescriptions of both formulations. Amphotericin B lipid complex most frequently was prescribed for treatment of documented fungal infections (50%), followed by treatment of neutropenic fever (33%). Liposomal amphotericin B most frequently was prescribed for treatment of neutropenic fever (62%), followed by treatment of documented fungal infections (29%). Seventy-eight percent of patients treated with ABLC and 90% of those who received L-AmB were started on the lipid-based formulation due to being refractory or intolerant to prior antifungal therapy. Two (4.4%) patients receiving ABLC and four (19%) patients receiving L-AmB experienced nephrotoxicity at the end of therapy (NS). Of the patients with a documented fungal infection, 20 out of 23 (87%) of those treated with ABLC and 4 out of 5 (80%) of those treated with L-AmB had a complete or partial response to therapy (NS). One patient with febrile neutropenia had a breakthrough fungal infection while receiving L-AmB. CONCLUSION: No significant differences in nephrotoxicity or efficacy were found between ABLC and L-AmB. Until further studies indicate clinically significant differences in nephrotoxicity between the two liposomal amphotericin B formulations, it is recommended that economics continue to be the major determinant for product selection.

Gene trap screening using negative selection: identification of two tandem, differentially expressed loci with potential hematopoietic function.

A fusion gene between Escherichia coli lacZ and herpes simplex virus thymidine kinase (HSV-tk) was constructed and used in a gene trap screen for hematopoietic loci in mouse embryonic stem (ES) cells. This gene, galtek, allowed both convenient histochemical detection of expression as well as ablation of expressing cells under 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodouracil (FIAU) selection. Individual ES cell clones bearing gene trap insertions were differentiated in the presence of FIAU and scored for erythropoietic activity at day 9 of differentiation. Screening of a total of 235 independent gene trap lines identified one clone, F3, which consistently demonstrated FIAU-sensitive erythropoiesis during in vitro differentiation. Cloning of endogenous transcribed sequences from the F3 insertion site identified two distinct transcription units, F3-1 and F3-2, encoding mRNAs of approximately 1.3 kb and 3.35 kb, respectively. The transcripts were unrelated and did not exhibit similarity to known sequences. Both loci demonstrated similar relative levels of expression in the heart, testis, kidney, and lung as assessed by Northern blot hybridization. Whole-mount in situ hybridization detected F3-2 expression at multiple sites in embryonic day (E) 10.5 embryos, including the genital ridges, the aortic endothelium, and endothelium-associated cell clusters within the aortic lumen. Expression of F3-2 in the aortic endothelium and endothelium-associated clusters overlapped that of gata-2, a gene required for hematopoietic development. The FIAU sensitivity of hematopoiesis in F3 embryoid bodies may result from expression of galtek during the formation of early hematopoietic cells, directed by regulatory signals from one or both of these endogenous loci.

In vivo marking of spontaneous or vaccine-induced fibrosarcomas in the domestic house cat, using an adenoviral vector containing a bifunctional fusion protein, GAL-TEK.

We evaluated the ability of a replication-deficient, recombinant adenoviral vector to transfer the bifunctional gene GAL-TEK, which expresses a marking/therapeutic gene product, to naturally occurring cat fibrosarcomas in situ. GAL-TEK contains an in-frame fusion of the bacterial LacZ gene for histochemical marking of tumors with beta-galactosidase (beta-Gal) and the HSV tk gene for enzyme-prodrug activation of the prodrug ganciclovir (GCV) to induce selective tumor cell killing. GAL-TEK bifunctional marking and cell killing activities were tested in vitro after adenoviral vector infection of HT1080 human fibrosarcoma cells. The tk activity of GAL-TEK is shown to be almost as potent as HSV tk to catalyze conversion of GCV to GCV nucleotides and promote selective cell killing. Using 8 cats with recurring 2.5-cm2 fibrosarcomas that either arose spontaneously or were induced by vaccine, we determined experimentally the administration routes and times required for optimum GAL-TEK gene transfer by beta-Gal histological staining and reverse transcriptase polymerase chain reaction to the multiple compartments of the growing fibrosarcomas consonant with minimizing collateral infection of neighboring tissues and other unwanted side effects.

The effects of oxalates produced by Salsola tragus on the phosphorus nutrition of Stipa pulchra.

Oxalic acid is produced by some species of plants and mycorrhizal fungi and it may solubilize unavailable soil phosphorus (P) bound by cations (Ca++, Al++, Fe+++). Field and greenhouse experiments were conducted to show whether oxalate produced by the annual Salsola tragus or added oxalic acid would solubilize P from the inorganic-bound soil P pool, making it available for uptake by Stipa pulchra. Oxalate could be leached in the laboratory from the senescent canopy of Salsola, and leaching by rainfall was hypothesized to be a source of potential increased soil P under the Salsola canopy. Both oxalate leached from the canopy of Salsola and added oxalic acid increased the availability of soil P in greenhouse experiments. The source of the increase in available soil P in the greenhouse experiment was shown to be the inorganic-bound P pool, as the total P concentration of the soil decreased with increasing oxalate. There were significant increases in Stipa shoot P in response to Salsola leachates and in response to added oxalate in the greenhouse studies. These results suggest an important role for oxalate in P cycling. On disturbed sites where Salsola invades it may act to facilitate the establishment of later seral species like Stipa by creating a nutrient island of available P.

Intergeneric natural plasmid transformation between E. coli and a marine Vibrio species.

Natural transformation is the mechanism of procaryotic gene transfer that involves the uptake and expression of genetic information encoded in extracellular DNA. This process has been regarded as a mechanism to transfer genes (primarily chromosomal markers) between closely related strains or species. Here we demonstrate the cell-contact-dependent transfer of a non-conjugative plasmid from a laboratory E. coli strain to a marine Vibrio species, the first report of intergeneric natural plasmid transformation involving a marine bacterium. The nucleic acid synthesis inhibitors nalidixic acid and rifampicin inhibited the ability of the E. coli to function as a donor. However, dead cells also served as efficient donors. There was an obligate requirement for cell contact. No transfer occurred in the presence of DNase I, when donors and recipients were separated by a 0.2-micron filter, or when spent medium alone was used as a source of transforming DNA. These results indicate that contact-mediated intergeneric plasmid exchange can occur in the absence of detectable viable donor cells and that small non-conjugative plasmids can be spread through heterogeneous microbial communities by a process previously not recognized, natural plasmid transformation. These findings are important in the assessment of genetic risk to the environment, particularly from wastewater treatment systems and the use of genetically engineered organisms in the environment.

Production of dissolved DNA, RNA, and protein by microbial populations in a Florida reservoir.

Production of dissolved macromolecules by ambient autotrophic and heterotrophic microbial populations was measured in a eutrophic Florida reservoir by in situ labeling with various radioactive substrates. When [3H]thymidine was used as the precursor, production of labeled dissolved DNA, RNA, and protein was observed. The rate of production of labeled dissolved macromolecules was 3.1% the rate of cellular incorporation of [3H]thymidine, and the production of dissolved DNA represented 2.3% the rate of cellular DNA incorporation. Microautotrophic populations labeled with NaH[14C]CO3 produced dissolved RNA and protein at rates of 0.24 and 0.11 micrograms of C/liter per h, respectively, or 1.8% the total rate of carbon fixation, with no measurable dissolved DNA production. In an attempt to specifically label phytoplankton DNA, samples were incubated with [3H]adenine or 32Pi in the presence and absence of the photosynthetic inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU). Although DCMU inhibited 14C fixation by approximately 99%, this antimetabolite had only a slight effect on [3H]adenine incorporation and no effect on 32P incorporation into cellular macromolecules. Significant amounts of dissolved DNA were produced in both [3H]adenine and 32Pi incubations, but again DCMU had no effect on the production rates. These results indicate that actively growing populations of both phytoplankton and bacterioplankton produced dissolved RNA and protein, while only active bacterioplankton produced measurable quantities of dissolved DNA. Dead or senescent phytoplankton may have produced dissolved DNA, but would not be measured in the relatively short incubations used. These findings also indicate that [3H]adenine and 32Pi primarily labeled heterotrophic bacterioplankton and not phytoplankton in this environment.

Pancreatic pseudocysts: cause, therapy, and results.

Sixty-nine patients with pancreatic pseudocysts were reviewed. Chronic alcohol abuse was associated with pancreatitis in 78 percent of the patients. Presenting signs and symptoms were nonspecific. Ultrasonographic and computerized axial tomographic scans were most commonly used to established the diagnosis. Twenty patients were managed conservatively and resolution occurred in 11 of these patients. Forty-nine patients underwent operation. Internal drainage was performed on 31 occasions in 29 patients, and external drainage was performed in 11. In addition, pancreatic resection was carried out in 8 patients, and needle aspiration in 2 patients. Infected pseudocysts were present in 11 patients. Complications occurred in 18 patients in the operated group and 2 patients died (4 percent). There was recurrence of pseudocysts in 10 patients. Our results suggest that pseudocysts remain a common complication of pancreatitis, and infected pseudocysts are the major cause of postoperative morbidity. Computerized axial tomography and ultrasonography are the mainstays of diagnosis. Surgical therapy is safe, but continues to be associated with significant rates of morbidity and recurrence. When pseudocysts recur, they are generally anatomically distant from the original lesion and probably represent new disruptions of the pancreatic duct.

Is duodenal ulcer perforation best treated with vagotomy and pyloroplasty?

From 1967 to 1980, 65 patients underwent vagotomy and pyloroplasty for treatment of an acute perforated duodenal ulcer at the University of Oklahoma Health Sciences Center. Their age ranged from 15 to 82 years, with a mean age of 49.6 years. All vagotomies were truncal and pyloroplasties were of the Heineke-Mikulicz variety. The condition of each patient was classified as acute or chronic depending on the duration of symptoms before perforation. The postoperative complication rate and perioperative mortality were higher in the group of patients whose symptoms had been present less than 3 months before perforation. Patients who underwent vagotomy and pyloroplasty more than 24 hours after the onset of symptoms had a higher mortality compared with those who were operated on less than 24 hours from the onset of symptoms. We mainly attributed the perioperative death rate of 11 percent to advanced patient age and associated cardiopulmonary disease. There was no significant difference in the rate of postoperative complications in patients over 60 years of age compared with those under 40 years; hence, age alone does not preclude definitive treatment, such as vagotomy and pyloroplasty. The degree of contamination found at operation did not correlate with a poor postoperative course. There was no significant increase in the mortality in the group with gross contamination. Of the patients available for long-term follow-up, 85 percent remained free of symptoms. These results compare favorably with reports for the elective treatment of duodenal ulcer with vagotomy and pyloroplasty. We conclude that vagotomy and pyloroplasty is acceptable, safe, and ideal for patients with acute perforated duodenal ulcers, except when significant cardiopulmonary disease exists or when the duration of perforation is more than 24 hours.

Colon interposition for benign esophageal disease.

Our experience for the past seven years with colon interposition is reviewed. Colon interposition resulted in all patients being relieved of symptoms and satisfied with their result. Colon interposition for nondilatable benign esophageal stricture was shown to be efficacious. In patients undergoing colon interposition for a failed esophagomyotomy, excellent or good results were obtained in a thirty month follow-up period with no operative failures.

Comparison of Nissen fundoplication and Belsey Mark IV in the management of gastroesophageal reflux.

Our experience for the past four years with antireflux surgery has been reviewed. The Nissen fundoplication resulted in symptomatic improvement in 87.5 per cent of cases as compared with 64 per cent who were improved after the Belsey Mark IV procedure. Objective evaluation as measured by the standard acid reflux test (SART) revealed recurrent reflux in 9 per cent of those who underwent fundoplication and in 47 per cent of those treated with the Belsey repair. Mortality rates were similar. These results indicate that Nissen fundoplication is superior to the Belsey Mark IV procedure in the management of gastroesophageal reflux.

The asymptomatic bruit.

A review of 144 carotid endarterectomies performed in 108 patients at the Oklahoma Health Science Center over the past six years showed an acceptable operative morbidity and mortality in group of patients with an asymptomatic midcervical bruit who underwent prophylactic carotid endarterectomy prior to anticipated elective surgery. Long-term follow-up showed these patients to be free of neurologic symptoms of fatalities in 100 per cent of long-term survivors and suggests that carefully selected patients with an asymptomatic bruit may undergo carotid endarterectomy to prevent future neurologic complication.