Involvement of the Spinal Cord in Primary Mitochondrial Disorders: A Neuroimaging Mimicker of Inflammation and Ischemia in Children.

BACKGROUND AND PURPOSE: Little is known about imaging features of spinal cord lesions in mitochondrial disorders. The aim of this research was to assess the frequency, imaging features, and pathogenic variants causing primary mitochondrial disease in children with spinal cord lesions. MATERIALS AND METHODS: This retrospective analysis included patients seen at Children's Hospital of Philadelphia between 2000 and 2019 who had a confirmed diagnosis of a primary (genetic-based) mitochondrial disease and available MR imaging of the spine. The MR imaging included at least both sagittal and axial fast spin-echo T2-weighted images. Spine images were independently reviewed by 2 neuroradiologists. Location and imaging features of spinal cord lesions were correlated and tested using the Fisher exact test. RESULTS: Of 119 children with primary mitochondrial disease in whom MR imaging was available, only 33 of 119 (28%) had available spine imaging for reanalysis. Nineteen of these 33 individuals (58%) had evidence of spinal cord lesions. Two main patterns of spinal cord lesions were identified: group A (12/19; 63%) had white ± gray matter involvement, and group B (7/19; 37%) had isolated gray matter involvement. Group A spinal cord lesions were similar to those seen in patients with neuromyelitis optica spectrum disorder, multiple sclerosis, anti-myelin oligodendrocyte glycoprotein-IgG antibody disease, and leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. Group B patients had spinal cord findings similar to those that occur with ischemia and viral infections. Significant associations were seen between the pattern of lesions (group A versus group B) and the location of lesions in cervical versus thoracolumbar segments, respectively (P < .01). CONCLUSIONS: Spinal cord lesions are frequently observed in children with primary mitochondrial disease and may mimic more common causes such as demyelination and ischemia.

Evaluation of Binax NOW RSV as an acute point-of-care screening test in a paediatric accident and emergency unit.

Point-of-care tests (POCTs) for respiratory syncytial virus infections are a useful adjunct to reduce the risk of healthcare-associated infections in paediatric wards. A new test based on immunochromatography, Binax NOW RSV, was introduced in the winter of 2002-03. It has user friendly features making it particularly suitable for non-laboratory personnel in a paediatric accident and emergency unit. A prospective study comparing the POCT with laboratory-based direct immunofluorescence (DIF) showed sensitivity of 87% specificity of 94%, positive predictive value of 89% and negative predictive value 92%. The simplicity of Binax NOW RSV should not detract from training staff and maintaining consistent vigilance on quality control.

The timing of congenital brachial plexus injury: a study of electromyography findings in the newborn piglet.

OBJECTIVE: Permanent congenital brachial plexus palsy is a recognized serious complication associated with shoulder dystocia. The timing and etiology of this injury remains controversial. Previous authorities have used adult-derived, non-brachial plexus data to extrapolate the anticipated timing for electromyographic denervation changes to date such injuries in the newborn. With use of a domestic swine model, this investigation tests the hypothesis that electromyographic evidence of brachial plexus denervation in the newborn is temporally different than that in the adult. STUDY DESIGN: Five healthy 2-day-old and two adult pigs underwent unilateral sharp transection of the brachial plexus. Daily electromyographic studies were performed in brachial plexus innervated muscle groups on the involved and contralateral (control) front limbs. Postmortem measurements of the transected nerve segments were obtained in one piglet and one adult animal. Representative hard copy recordings of individual electromyographic studies were collected. RESULTS: Immediately after surgical transection of the brachial plexus, no electromyographic evidence of denervation was observed. Uniformly in the newborn piglets, at 24 hours after transection, denervation in the form of fibrillation potentials, positive sharp waves, and complex repetitive discharges was seen. Serial testing demonstrated proximal to distal gradients of denervation over the next 24 to 48 hours. A delay in electromyographic evidence of denervation was observed in the two adult pigs until days 5 and 8, respectively. Control limb studies remained normal throughout the study period. Nerve length measurements for individual muscle groups were as follows for the adult and newborn pigs, respectively: deltoid 11.4 cm, 2.5 cm; cleidobrachialis 16.0 cm, 4.0 cm; triceps 15.5 cm, 4.5 cm; forelimb flexors 26.0 cm, 6.5 cm; and extensor carpi radialis 31.0 cm, 9.0 cm. CONCLUSION: Electromyographic evidence of brachial plexus denervation after surgical transection differs between the newborn and the adult pig. Consistent with wallerian degeneration, a correlation exists between length of the distal nerve segment and timing for electromyographic signs of denervation. These findings suggest it would be inappropriate to extrapolate the anticipated timing for electromyographic changes in the newborn on the basis of previously established adult non-brachial plexus data.

Comparative serum bactericidal activity of ceftizoxime/metronidazole, ceftizoxime, clindamycin, and imipenem against obligate anaerobic bacteria.

We compared the bactericidal activity of serum obtained from healthy volunteers after single intravenous infusions of the combination of ceftizoxime (1 g) plus metronidazole (1 g) and after infusions of ceftizoxime (2 g), clindamycin (900 mg), and imipenem (1 g) against six obligate anaerobes. All agents were bactericidal but only the combination regimen resulted in bactericidal titres greater than 1:2 at 12 h for all the Bacteroides fragilis group organisms. High titres against Fusobacterium necrophorum and anaerobic Gram-positive cocci were attained with ceftizoxime/metronidazole, ceftizoxime, and imipenem 12 h after the dose. Imipenem and the combination of ceftizoxime/metronidazole had the greatest area under the bactericidal curve (AUBC) against the Bacteroides species. Clindamycin had a significantly smaller AUBC than other regimens for all strains tested except B. thetaiotaomicron. Clinical trials are needed to assess the efficacy and cost-benefit ratio of a 12 h dosing regimen of ceftizoxime in combination with metronidazole for treating mixed aerobic/anaerobic infections.

Effect of peritoneal dialysis fluid and pH on bactericidal activity of ciprofloxacin.

Ciprofloxacin is active in vitro against most bacteria that cause peritonitis associated with peritoneal dialysis. We compared the effects of pH (5.5 and 7.4) and medium (dialysis fluid) on the bactericidal activity of ciprofloxacin, tobramycin, vancomycin plus rifampin, and rifampin against Pseudomonas aeruginosa, Escherichia coli, and three strains of staphylococci. The bactericidal activity of ciprofloxacin was not significantly affected by pH or medium, in contrast to the activity of tobramycin, which was decreased by low pH.

Clindamycin phosphate kinetics in subjects undergoing CAPD.

The kinetics of intraperitoneally administered clindamycin phosphate were studied in 9 volunteer subjects undergoing CAPD. Volunteers were assigned to 2 groups with the first group receiving clindamycin phosphate 300 mg/l in exchanges 1 through 5, and the second group receiving clindamycin phosphate 300 mg/l in exchange 1, and then 30 mg/l in exchanges 2 through 5. Clindamycin serum and dialysate effluent levels were determined by bioassay. When admixed with dialysate fluid and instilled into the peritoneal cavity, clindamycin phosphate is rapidly activated. Serum concentrations of clindamycin were rapidly achieved in both groups during the first exchange. Subjects in groups I and II had peak serum levels of active drug within 3 (3.94 ug/ml) and 5 (7.35 ug/ml) h, respectively. These results support the practice of not only administering intraperitoneal clindamycin phosphate to treat CAPD-related peritonitis, but using this route of administration to treat systemic infections due to susceptible bacteria in patients without intravenous access.

Liquid chromatographic assay of ceftizoxime in sera of normal and uremic patients.

The application of high-pressure liquid chromatography assays for cephalosporin serum concentrations is difficult in uremic patients because of interference from nondialyzable substances. We developed a high-pressure liquid chromatography method for determining the serum concentration of ceftizoxime in normal and uremic patients. The method involves protein precipitation with acetonitrile, followed by removal of the acetonitrile with dichloromethane. Separation was accomplished with a reverse-phase (C-18) column and a mobile phase of 13% acetonitrile and 2.8% acetic acid. UV detection at 310 nm was used to monitor the peaks. This assay produced a linear relationship between peak height ratio and ceftizoxime concentration from 1.5 to 100 micrograms/ml. Samples from 30 patients were assayed by this method and by a bioassay, with a good correlation of results (r = 0.9832). The method was applicable equally to normal and uremic serum samples.