Infantile hypophosphatasia: transplantation therapy trial using bone fragments and cultured osteoblasts.

BACKGROUND: Hypophosphatasia (HPP) is a rare, heritable, metabolic bone disease due to deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase. The infantile form features severe rickets often causing death in the first year of life from respiratory complications. There is no established medical treatment. In 1997, an 8-month-old girl with worsening and life-threatening infantile HPP improved considerably after marrow cell transplantation. OBJECTIVE: Our aim was to better understand and to advance these encouraging transplantation results. DESIGN: In 1999, based on emerging mouse transplantation models involving implanted donor bone fragments as well as osteoblast-like cells cultured from bone, we treated a 9-month-old girl suffering a similar course of infantile HPP. RESULTS: Four months later, radiographs demonstrated improved skeletal mineralization. Twenty months later, PCR analysis of adherent cells cultured from recipient bone suggested the presence of small amounts of paternal (donor) DNA despite the absence of hematopoietic engraftment. This patient, now 8 yr old (7 yr after transplantation), is active and growing, and has the clinical phenotype of the more mild, childhood form of HPP. CONCLUSIONS: Cumulative experience suggests that, after immune tolerance, donor bone fragments and marrow may provide precursor cells for distribution and engraftment in the skeletal microenvironment in HPP patients to form tissue-nonspecific isoenzyme of alkaline phosphatase-replete osteoblasts that can improve mineralization.

Complications associated with bacitracin powder in surgical wounds.

OBJECT: There has been renewed interest in the application of concentrated antibiotic powder to surgical wounds as a method to decrease infection rates. While there is substantial medical literature describing the effectiveness and complications associated with vancomycin and gentamycin powders, very little has been reported regarding the safety and effectiveness of bacitracin powder in surgical wounds. In this paper the authors report their detailed analysis of potential bacitracin powder-related complications in a population of pediatric patients who underwent shunt surgery. METHODS: A detailed retrospective analysis was completed of all CSF shunt surgeries performed by the corresponding author at a large children's hospital between 2001 and 2013. This cohort consisted of many patients who were the subject of a previous report that showed the use of bacitracin powder in shunt wounds potentially decreased infection rates. Data were collected regarding the most common known complications of bacitracin, i.e., anaphylaxis, wound healing difficulties, and renal dysfunction. Data were stratified by typical demographic, medical, and surgical variables, including whether bacitracin powder was applied to wounds prior to closure. RESULTS: A total of 597 patients were reviewed in the analysis: 389 underwent surgery without bacitracin powder and 208 had concentrated bacitracin powder applied to the wounds prior to closure. The application of bacitracin powder was not associated with anaphylaxis (n = 0 both groups) or with an increase in wound breakdown (n = 5 in the control group, n = 0 in the bacitracin powder group) or renal dysfunction (creatinine/estimated glomerular filtration rate) using both comparative and multivariate analyses between the 2 groups. The sample size evaluating renal function was significantly lower (range 6-320) than that of anaphylaxis and wound breakdown analysis because only clinical values acquired during the routine care of these patients were available for analysis. The only significant difference in demographics was the more frequent use of intrathecal vancomycin and gentamycin in patients who received bacitracin powder (n = 1 for controls, n = 21 for bacitracin powder). In the multivariate analysis, only 1 factor, surgery performed on a premature infant within the first 3 months of life, was independently associated with a change in creatinine at 3 months (creatinine decreased by 0.18) compared with the level before surgery (p < 0.0001). Bacitracin powder was not a significant factor. CONCLUSIONS: To the authors' knowledge, this is the first study to systematically analyze the potential complications of concentrated bacitracin powder applied to surgical wounds. The use of topical bacitracin powder in CSF shunt wounds was not associated with anaphylaxis, wound breakdown, or renal dysfunction. Further study using standardized protocols is necessary before widespread use can be recommended.

Attempted bladder reinnervation and creation of a scratch reflex for bladder emptying through a somatic-to-autonomic intradural anastomosis.

An intradural somatic-to-autonomic anastomosis, or Xiao procedure, has been described to create a "skin-CNS-bladder" reflex that improves bladder and bowel function in patients with neurogenic bladder and bowel dysfunction. The authors present their experience with a 10-year-old boy with chronic neurogenic bladder and bowel dysfunction related to spinal cord injury who underwent the Xiao procedure. After undergoing a left L-5 ventral root to left S2-3 intradural anastomosis, the patient reported that his bladder and bowel dysfunction improved between 6 and 12 months. Two years after the procedure, however, he reported that there was no change in his bladder or bowel dysfunction as compared with his condition prior to the procedure. Frequent, systematic multidisciplinary evaluations produced conflicting data. Electrophysiological and histological evaluation of the previously performed anastomosis during surgical reexploration 3 years after the Xiao procedure revealed that the anastomosis was in anatomical continuity but neuroma formation had prevented reinnervation. Nerve action potentials were not demonstrable across the anastomosis, and stimulation of the nerve above and below the anastomosis created no bladder or perineal contractions. This is the first clinical report on the outcome of the Xiao procedure in a child with spinal cord injury outside of China. It is impossible to draw broad conclusions about the efficacy of the procedure based on a single patient with no demonstrable benefit. However, future studies should carefully interpret transient improvements in bladder function, urodynamic findings, and the patient's ability to void in response to scratching after the Xiao procedure. The authors' experience with the featured patient, in whom reinnervation could not be demonstrated, suggests that such changes could be related to factors other than the establishment of a skin-CNS-bladder reflex as a result of a somatic-to-autonomic anastomosis.