Genetic diversity of the Leptospiral immunoglobulin-like (Lig) genes in pathogenic Leptospira spp.

Recent serologic, immunoprotection, and pathogenesis studies identified the Lig proteins as key virulence determinants in interactions of leptospiral pathogens with the mammalian host. We examined the sequence variation and recombination patterns of ligA, ligB, and ligC among 10 pathogenic strains from five Leptospira species. All strains were found to have intact ligB genes and genetic drift accounting for most of the ligB genetic diversity observed. The ligA gene was found exclusively in L. interrogans and L. kirschneri strains, and was created from ligB by a two-step partial gene duplication process. The aminoterminal domain of LigB and the LigA paralog were essentially identical (98.5 ± 0.8% mean identity) in strains with both genes. Like ligB, ligC gene variation also followed phylogenetic patterns, suggesting an early gene duplication event. However, ligC is a pseudogene in several strains, suggesting that LigC is not essential for virulence. Two ligB genes and one ligC gene had mosaic compositions and evidence for recombination events between related Leptospira species was also found for some ligA genes. In conclusion, the results presented here indicate that Lig diversity has important ramifications for the selection of Lig polypeptides for use in diagnosis and as vaccine candidates. This sequence information will aid the identification of highly conserved regions within the Lig proteins and improve upon the performance characteristics of the Lig proteins in diagnostic assays and in subunit vaccine formulations with the potential to confer heterologous protection.     

Tibiotalocalcaneal arthrodesis with retrograde intramedullary nailing

Nineteen patients (20 feet) with severe hindfoot and ankle deformity underwent tibiotalocalcaneal fusion with a retrograde locked intramedullary nail as a limb-salvage procedure. The purpose of this study was to compare the complication rates of this procedure in diabetic versus nondiabetic patients. There were 8 men and 11 women with preoperative diagnoses including Charcot neuroarthropathy, primary osteoarthritis, rheumatoid arthritis, equinocavovarus, posttraumatic osteoarthritis, gouty arthritis, and ankle malunion. Ten of 20 procedures were performed in patients with diabetes. The average patient age was 56 years, and the average postoperative follow-up was 19.8 months. Nineteen of 20 ankles (95%) achieved successful fusion with an average time of 4.1 months. Four patients (21%) required either a fracture brace or an ankle foot orthosis at final follow-up. Five patients (25%) had major complications and 11 patients had minor complications. Major complications included osteomyelitis (n = 2), Charcot arthropathy (n = 2), failure of fixation (n =1), soft-tissue necrosis (n = 1), cardiac arrest (n = 1), cerebral vascular accident (n = 1), and fatal pulmonary embolus (n = 1). All patients with major complications were diabetic, and 14 of 20 combined major and minor complications occurred in patients with diabetes. The complication rate was found to be high in diabetic patients with end-stage deformity undergoing a limb salvage     

Physiological neutrophilia of pregnancy is not associated with a rise in plasma granulocyte colony-stimulating factor (G-CSF)

A patient with neutropenia and life-threatening infections secondary to T-γ lymphoproliferative disease, who did not respond to treatment with recombinant human G-CSF (filgrastim), was treated with filgrastim plus cyclosporine A (CyA). The patient achieved a good response in the absolute neutrophil count and subsequently required a dose reduction in the filgrastim. The patient was eventually discontinued from the CyA but continues on filgrastim alone. While on therapy, the large granular lymphocytes disappeared from the circulation and the beta-TCR rearrangement, which was present prior to beginning therapy, became undetectable. The patient had no significant toxicity to the CyA or the filgrastim and he has not experienced any serious infections or required hospitalization. Filgrastim has proven to be relatively nontoxic and of some benefit to patients with this disease and should probably be utilized first when treatment is necessary. However, if improvement is not observed, these findings suggest that a trial of the combination of CyA plus filgrastim may be beneficial.     

Association of low caregiver health literacy with reported use of nonstandardized dosing instruments and lack of knowledge of weight-based dosing.

OBJECTIVE: Caregivers of young children frequently measure doses of liquid medications incorrectly. Use of nonstandardized dosing instruments and lack of knowledge that dosing is weight-based contribute to dosing errors. We sought to assess whether low caregiver health literacy was associated with these outcomes. METHODS: This was a cross-sectional analysis of caregivers presenting to an urban pediatric emergency room. Dependent variables were caregiver reported use of nonstandardized dosing tools and knowledge of weight-based dosing. The independent variable was caregiver health literacy (Test of Functional Health Literacy in Adults [TOFHLA]). RESULTS: Two hundred ninety-two caregivers were assessed: 23.3% reported use of nonstandardized liquid dosing instruments, and 67.8% were unaware of weight-based dosing. Caregivers who were unaware of weight-based dosing were more likely to use nonstandardized dosing tools (28.3% vs 12.8%; P = .003). In unadjusted analyses, overall health literacy, reading comprehension, and numeracy were all associated with both dependent variables. In analyses adjusting for child age, health care experiences, and caregiver acculturation and education, inadequate/marginal overall health literacy was associated with lack of knowledge of weight-based dosing (adjusted odds ratio [AOR] 2.3; P = .03), whereas lower reading comprehension was associated with both lack of knowledge (AOR 2.0; P = .03) and reported use of nonstandardized instrument (AOR 2.4; P = .007). CONCLUSIONS: Low health literacy, in particular reading comprehension, was associated with reported use of nonstandardized dosing instruments and lack of knowledge regarding weight-based dosing. Both caregiver health literacy and sociodemographic factors should be considered in the design of interventions to prevent medication administration errors.