Risk factors for Clostridium difficile stool cytotoxin b among critically ill patients: role of sucralfate.

To identify risk factors other than antimicrobial exposure for Clostridium difficile stool cytotoxin b, subjects admitted to critical care units over 18 months and who had stool cytotoxin assays were evaluated. Twenty-two cases (cytotoxin b-positive) were compared with 125 controls (cytotoxin b-negative). Cases and controls were similar with respect to age, sex, therapeutic index severity score, duration of hospitalization before cytotoxin b testing, and antimicrobial exposure. Adjusted odds ratios (OR) revealed white blood cell count of > 12,000 on the day of stool sampling (OR, 4.0; 95% confidence interval [CI], 1.3-12.4) and sucralfate exposure (OR, 0.15; 95% CI, 0.05-0.42) as significant independent positive and negative risk factors, respectively. Sucralfate exposure may decrease risk for C. difficile stool cytotoxin b by interfering with its detection, altering toxin production, or inhibiting colonization by the organism. Additional evaluation is needed to elucidate the mechanisms involved.

Novel 3-hydroxy-2(1H)-pyridinones. Synthesis, iron(III)-chelating properties, and biological activity.

The synthesis of a range of novel bidentate and hexadentate ligands containing the chelating moiety 3-hydroxy-2(1H)-pyridinone is described. The pKa values of the ligands and the stability constants of their iron(III) complexes have been determined. The stability constant of the iron(III) complex of one of the hexadentate ligands is comparable to that of desferrioxamine B. The distribution coefficients of the ligands and their iron(III) complexes were also determined. One of the novel hexadentate compounds has been shown to markedly enhance iron(III) excretion from both hepatocytes and iron-overloaded mice.

Predictability of upper lip soft tissue changes with maxillary advancement.

To improve predictability of the esthetic (soft tissue) results after maxillary advancement surgery, a better understanding of the relationships between the dental osseous movement and overlying soft tissue response is essential. Twenty-one adult patients who underwent isolated maxillary advancement via LeFort I osteotomies without adjunctive nasal soft tissue procedures and/or V-Y closure of the vestibular incision were studied. Homogeneity of the patient population was ensured by selecting cases with less than 2 mm vertical change. The mean maxillary advancement and mean change in Sn was calculated for these 21 patients. Additionally, the 21 patients were subdivided into two groups based on lip thickness: group 1 (lips between 10 and 17 mm thick) and group 2 (greater than 17 mm thick). In each patient group a linear regression (LR) was determined on the magnitude of maxillary advancement (MMA) to the change in soft tissue subnasale (Sn) and on the ratio of Sn change to bone move. The results using mean data showed that the relationships produce significantly high standard deviations; thus, a general correlation between change in soft tissue position to bony advancement cannot be made. Individuals with thin lips (12 to 17 mm) had a good correlation between the magnitude of bony move and amount of soft tissue change. However, increased lip thickness (greater than 17 mm) produced a less predictable correlation between soft and hard tissue changes. All lips thinned around 2 mm when compared with preoperative values. Lip thickness stabilized at approximately 6 months postoperatively.

In vivo evaluation of hydroxypyridone iron chelators in a mouse model.

The 59Fe excretion caused by a range of bidentate N-substituted [R group = methyl (CP20), ethyl (CP21), propyl (CP22), isopropyl (CP23), butyl (CP24) or hexyl (CP25)] 3-hydroxypyrid-4-one chelators in iron-overloaded mice is presented. All the compounds cause significant iron excretion when given intraperitoneally, but that the most hydrophobic compounds, CP24 and CP25, were toxic except at low doses. The excretion caused by CP21, CP22 and CP23 were significantly greater than that caused by CP20 and slightly larger than that caused by an equivalent dose of desferrioxamine. These compounds (CP20 through CP24) also caused significant excretion of 59Fe when administered orally. Compounds CP21, CP22 and CP24 were significantly more active than compounds CP20 and CP23. It is concluded that the N-ethyl or N-propyl 3-hydroxypyrid-4-ones are the most promising compounds for clinical application. Preliminary experiments using a hexadentate pyrid-2-one, CP130, show that this causes significant 59Fe excretion both when given intraperitoneally or orally.