Low baseline antibody level to diphtheria is associated with poor response to conjugated pneumococcal vaccine in adults.

Joining polysaccharide antigens to protein increases immunogenicity in infants. In older adults, using conjugation to protein carriers to improve the immune response to pneumococcal polysaccharide vaccine has thus far proved disappointing. Low immunity to the carrier protein in the elderly may explain the failure of conjugated vaccines to elicit a T-cell-dependent response. We immunized 49 older adults (ages 60-78) and 50 younger adults (ages 18-45) with either 23-valent pneumococcal polysaccharide (PS) vaccine or 5-valent CRM197-conjugated pneumococcal oligosaccharide. Sera obtained before and after vaccination were analyzed for antibody to pneumococcal serotypes 14 and 6B and diphtheria toxin by ELISA. Baseline diphtheria toxin antibody level was lower in older adults than in younger adults (0.31 and 0.88 IU/ml, respectively; p < 0.0001). Adults with higher diphtheria antibody level had a higher antibody level to PS type 6B after vaccination than those with lower diphtheria antibody level (9.9 vs. 3.5 microg/ml, respectively; p = 0.01). Antibody level to PS type 14 was higher, but differed by baseline anti-diphtheria antibody level only when the older group was evaluated alone. Low levels of antibody to diphtheria protein may explain some of the lower responses to conjugate pneumococcal vaccine in older adults.

Safety and efficacy of total dose iron dextran administration in patients on home renal replacement therapies.

OBJECTIVE: To determine the safety and efficacy of intravenous total dose iron (TDI) replacement in patients treated with home renal replacement therapy. DESIGN: Prospective open-label study on end points in the population studied. SETTING: Institutional outpatient home dialysis program. PATIENTS: The study included 20 end-stage renal disease (ESRD) patients, performing chronic peritoneal or home hemodialysis, with iron deficiency defined as ferritin < 100 ng/mL and/or an iron saturation < 20%. INTERVENTION: The total dose of iron dextran was calculated and infused at a rate not exceeding 6 mg/min. Hemoglobin, hematocrit, iron studies, and liver function tests (LFTs) were obtained before and 3 to 4 weeks after TDI infusion. Hematocrit of patients failing to achieve an increase in Hct over this period was re-examined 2 to 4 weeks later looking for a delayed response. MAIN OUTCOME MEASURES: Primary end points for efficacy were changes in Hct, ferritin, and iron saturation. Toxicity was measured as reported immediate and delayed symptoms and elevated transaminases and/or alkaline phosphatase levels. RESULTS: A median iron dose of 1000 mg (range, 325-1500 mg) was administered. The infusions were generally well tolerated. Clinical adverse effects were seen in 2 patients weighing less than 50 kg. No increase in LFT results was seen. Hematocrit increased 2.2% (95% CI, 0.5%-3.9%) from 29.0% to 31.2% (p = 0.01) within 4 weeks of infusion. Significant increases also occurred in iron saturation (from 13% to 22%, p = 0.001) and ferritin (from 234 to 305 ng/mL, p = 0.008). Among the 9 patients who did not respond with a significant increase in Hct, 2 had a delayed response, increasing the overall response from 63% at 4 weeks to 71%, 8 weeks after TDI. Inadequate erythropoietin dosing and low-grade infectious/inflammatory disorders may have contributed to a poor response in several patients. CONCLUSION: Total dose iron is a safe and effective means of restoring iron and erythropoietic response in ESRD patients weighing more than 50 kg who receive their renal replacement therapy at home.

Comparison of pneumococcal polysaccharide and CRM197-conjugated pneumococcal oligosaccharide vaccines in young and elderly adults.

Conjugation of carbohydrate antigens to protein carriers significantly improves the immune response to many carbohydrates. In order to evaluate the potential for this approach to improve the performance of pneumococcal vaccine in the elderly, we evaluated pneumococcal polysaccharide-derived oligosaccharides conjugated to cross-reacting material 197 (CRM197) (CRM-OS) in 49 older adults over 60 years of age (median age, 66 years) and compared the results to those from 50 younger adults under age 45 (median age, 27 years). Subjects were randomly assigned to receive licensed 23-valent polysaccharide vaccine (PS) which contain 25 micrograms of polysaccharide per serotype, or 5-valent CRM-OS, which contains 10 micrograms of oligosaccharide per serotype, in double-blind fashion. Both vaccines were associated with moderate local pain on administration. Antibody responses to type 14 were seen in the majority of both younger and older subjects following administration of both CRM-OS and PS, and there was no significant improvement of responses with CRM-OS in either age group. Antibody responses in young adults to the less immunogenic type 6B were seen in only 36% of subjects receiving PS and in 56% of subjects receiving CRM-OS (P = 0.15), and the geometric mean 6B titer 1 month after vaccination was higher in CRM-OS recipients (10.9 versus 3.7 micrograms/ml; P = 0.04). However, 6B responses were poor following the administration of either vaccine to elderly adults and there was no difference between results with CRM-OS and those with PS in this age group. Relatively few subjects developed measurable mucosal immunoglobulin A responses in nasal secretions following administration of either vaccine. Revaccination of CRM-OS recipients with PS at 2 months did not result in significant additional responses to 6B or 14. Though CRM-OS is possibly more immunogenic in young adults, the formulation of the pneumococcal glycoconjugate vaccine used in this study does not appear to offer an advantage to the elderly for types 6B or 14.

Exploratory data analysis: data visualization or torture?

Exploratory Data Analysis offers a set of graphical and statistical tools to find the full meaning from data sets. The user visualizes, analyzes, and transforms data distributions with these tools. Graphs reveal relationships between variables; the residuals left after fitting data show the adequacy of the model. Without this careful examination and understanding of the data, rote data analysis using standard statistical tests can give misleading results. Exploratory Data Analysis has its own set of pitfalls and must be used with confirmatory statistics and studies. Increasing power and resolution in personal computers enables modern statistical software to make these methods widely accessible. By easily moving between data and their graphic representation, analysis can be comprehensive without being tedious. Exploratory Data Analysis can add an exciting and useful tool to the epidemiologist's repertoire. This article illustrates several tools from an evolving list.

Pulmonary mycetoma due to Candida albicans: case report and review.

A pulmonary mycetoma is a round to oval-shaped mass of fungi situated within a cavity in the lung. Most mycetomas are caused by Aspergillus species. Other fungi have occasionally been reported to cause clinically and roentgenographically similar lesions. We report a case of pulmonary mycetoma caused by Candida albicans. Review of the literature suggests that pulmonary mycetoma due to this species is uncommon, and when it has been suspected, specific documentation has been lacking.

Polymicrobial gram-negative bacteremia associated with saline solution flush used with a needleless intravenous system.

BACKGROUND: During a 2-week period, seven cases of nosocomial polymicrobial gram-negative rod bacteremia occurred on a 39-bed medical and cardiac step-down unit. Combinations of Enterobacter cloacae (seven isolates), Klebsiella pneumoniae (five isolates), and Citrobacter freundii (two isolates) were isolated from blood cultures. METHODS: Concurrent and retrospective chart reviews were used to look for further cases and common exposures. Epidemiologic methods were used to refine determination of common exposure. Restriction enzyme DNA analysis was performed on the isolates. RESULTS: Concurrent and retrospective chart reviews revealed four additional possible cases during the same period. All case patients were exposed, through peripheral saline solution locks or central venous catheters, to saline solution "flush" from a central 0.9% saline solution bag and a needleless dispensing pin. Epidemiologic methods implicated probable extrinsic contamination of a single bag and pin used during a 24-48-hour period (Fisher's Exact Test, p < 0.002). There were no other common exposures. Restriction enzyme DNA analysis of the isolates further supported a common source for the outbreak. CONCLUSIONS: The introduction of needleless intravascular systems has been embraced for employee protection. Our report is the first to raise the question of patient safety with such systems. This outbreak highlights the inherent risks in rapid introduction of new technologies and points out the delicate balance among patient health, employee safety, and cost containment.

Zymosan-activated plasma-mediated thromboxane production by the perfused rabbit liver and isolated hepatocytes: involvement of calcium.

The present study investigates the mechanism of zymosan-activated plasma (ZAP)-mediated eicosanoid production by the isolated, perfused rabbit liver and described ZAP-mediated eicosanoid stimulation in cultured hepatocytes. Perfused livers receiving untreated plasma demonstrated no significant changes in portal venous pressure or the rates of release of lactic dehydrogenase or acid phosphatase activity (indicators of cellular injury). The control group livers demonstrated stable rates of release for 6-keto PGF1 alpha and thromboxane B2 (TXB2). In contrast, the infusion of ZAP alone resulted in a rapid but transient release of TXB2 from the livers. No significant changes in perfusion pressure or enzyme release were observed following ZAP administration. Perfusion of livers with a calcium-free buffer decreased the basal rates of both 6-keto PGF1 alpha and TXB2 production and significantly, but not completely, attenuated the ZAP-mediated increase in hepatic TXB2 production. Perfusion of livers with nifedipine (3 microM) had no effect on ZAP-mediated TXB2 production in this model. Isolated hepatocytes responded to ZAP-treatment with significant increases in TXB2 production. These data suggest that activated fluid phase complement components induce thromboxane production by specific cells within the liver and that this stimulation is partially dependent upon the release of intracellular calcium but independent of complement-mediated cellular injury.