There are many reports of defined culture systems for the propagation of human embryonic stem cells in the absence of feeder cell support, but no previous study has undertaken a multi-laboratory comparison of these diverse methodologies. In this study, five separate laboratories, each with experience in human embryonic stem cell culture, used a panel of ten embryonic stem cell lines (including WA09 as an index cell line common to all laboratories) to assess eight cell culture methods, with propagation in the presence of Knockout Serum Replacer, FGF-2, and mouse embryonic fibroblast feeder cell layers serving as a positive control. The cultures were assessed for up to ten passages for attachment, death, and differentiated morphology by phase contrast microscopy, for growth by serial cell counts, and for maintenance of stem cell surface marker expression by flow cytometry. Of the eight culture systems, only the control and those based on two commercial media, mTeSR1 and STEMPRO, supported maintenance of most cell lines for ten passages. Cultures grown in the remaining media failed before this point due to lack of attachment, cell death, or overt cell differentiation. Possible explanations for relative success of the commercial formulations in this study, and the lack of success with other formulations from academic groups compared to previously published results, include: the complex combination of growth factors present in the commercial preparations; improved development, manufacture, and quality control in the commercial products; differences in epigenetic adaptation to culture in vitro between different ES cell lines grown in different laboratories.

OBJECTIVE: To report the case of a ciprofloxacin-allergic patient who developed a generalized tonic—clonic seizure and toxic epidermal necrolysis (TEN) following a single dose of levofloxacin. CASE SUMMARY: An 87-year-old white woman was admitted to the hospital following a transient episode of unresponsiveness that had been accompanied by flailing of her limbs. Approximately 4 hours earlier, she had developed a pruritic rash on her trunk and limbs, and 3 hours before this had taken a first dose of levofloxacin. The fluoroquinolone had been prescribed for treatment of an upper respiratory tract infection. She had developed a skin rash approximately 3 years earlier following ciprofloxacin prescribed for a urinary tract infection. On admission, the patient had a normal neurologic examination. She was mildly hypomagnesemic (serum magnesium 1.7 mg/dL), with no other electrolyte imbalances present. Skin biopsy confirmed TEN. The lesions progressed to involve 30% of the body surface area and were managed with polymyxin B and gramicidin cream. Levofloxacin was discontinued on admission, and no anticonvulsants were prescribed. The woman remained seizure-free at discharge one week later. DISCUSSION: Generalized tonic—clonic seizures are a rare complication of levofloxacin therapy. TEN following levofloxacin use has, to our knowledge, as of March 28, 2005, been previously reported only once. The seizure and TEN were probably induced by levofloxacin as corroborated by the Naranjo probability scale. We believe that the previous adverse dermatologic reaction to ciprofloxacin sensitized our patient to levofloxacin. CONCLUSIONS: These rare adverse reactions to levofloxacin, involving disparate organ systems, can occur simultaneously. A previous dematologic adverse reaction to a fluoroquinolone can sensitize a patient to more severe adverse reactions (with onset after only a single dose of the subsequent fluoroquinolone). Further fluoroquinolone use should be avoided in such patients.

This study describes the first population Al TK model in a large group of PD patients, which includes a covariate effect. The model confirms the extensive half-life and tissue distribution of Al in a dialysis-dependent population.

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♦ Background: Widespread Al toxicity is unusual today. In 2005, Canadian peritoneal dialysis (PD) centers reported widespread hyperaluminemia in patients using dialysates from one specific manufacturer. Our objectives were to evaluate risk factors related to Al accumulation and to assess its clinical consequences in patients from 2 centers. ♦ Methods: A retrospective closed cohort study was conducted in patients treated with PD in May 2005. A multivariate linear regression model was constructed to identify variables associated with a higher serum Al level in the exposed group at the moment of solution change. Using appropriate statistical methods, anemia and bone metabolism parameters were compared between the exposed and unexposed groups. Time to first peritonitis was estimated by the Kaplan-Meier method. ♦ Results: The study cohort included 87 Al-exposed patients and 95 unexposed patients. In the exposed group, serum Al at the moment of solution change was influenced by the length of exposure to Al-containing dialysates and by PD creatinine clearance; serum Al was inversely correlated with renal creatinine clearance. No consequences of Al accumulation were observed. No difference was observed in the time to first peritonitis between patients who switched manufacturers and those who remained with the original manufacturer. ♦ Conclusions: Our results suggest that hyperaluminemia is directly related to the length and extent of exposure to Alcontaining dialysates; residual renal function is protective against Al accumulation. Because the problem was detected rapidly, no clinical consequences of hyperaluminemia were observed in the study cohort.