Syngeneic bone marrow transplantation reduces the hearing loss associated with murine mucopolysaccharidosis type VII

MPS VII mice are deficient in beta-glucuronidase and share many clinical, biochemical, and pathologic characteristics with human mucopolysaccharidosis type VII (MPS VII). We have shown that syngeneic bone marrow transplantation (BMT) prolongs survival and reduces lysosomal storage in many organs of the MPS VII mouse. In this report, we quantify the hearing loss and determine the impact of syngeneic BMT on the development of deafness and the associated pathology in the MPS VII mouse. Eleven weeks after syngeneic BMT performed at birth, treated MPS VII mice had normal auditory-evoked brainstem responses (ABR), whereas untreated MPS VII mice had ABR thresholds 43 dB higher than normal. Treated MPS VII mice had beta-glucuronidase-positive cells in the temporal bone and in the subepithelial connective tissue of the external auditory canal. There was less thickening of the tympanic membrane and middle ear mucosa and decreased distortion of the ossicles and the cochlear bone. Although transplanted MPS VII mice had increased ABR thresholds by 33 weeks of age, four of the six had thresholds 12 to 32 dB lower than untreated mutants. These data indicate that syngeneic BMT in newborn MPS VII mice prevents early hearing loss and, in some animals, results in long-term improved auditory function.     

Bony inlet stenosis as a cause of nasal airway obstruction

Two cases of congenital bony stenosis of the nasal piriform aperture (anterior nares) are presented. Both patients experienced episodes of respiratory distress and clinical symptoms similar to those seen in patients with posterior choanal atresia. The underlying anatomic abnormalities in congenital bony inlet stenosis are quite different from those in choanal atresia and require different surgical approaches for correction. Computed tomography demonstrates in detail the underlying anatomic abnormality and allows differentiation of bony inlet stenosis from choanal atresia.     

Clinicians' appraisal of sonography

The perceived efficacy of sonography in making diagnostic and management decisions in clinical practice was determined through a questionnaire survey of physicians who had recently referred patients to a university radiology department. Of 2,178 questionnaires sent, 1,611 were returned (74%). Sensitivity and specificity of sonography, corrected for verification bias, were 72% and 84%. Referring physicians considered the studies to be of value in arriving at the final diagnosis and in the clinical management of patients in approximately two-thirds of the cases. Results were considered of no value and misleading in 4% of the cases. Sonography was more accurate and was reported to be valuable by approximately 10% more physicians when a specific indication for an examination could be identified rather than when indications were vague and when sonographic findings were abnormal rather than normal (P less than .005). In general, sonography was of equal value to both specialists and nonspecialists. The results of this study suggest that sonography is, and is perceived by clinicians to be, an accurate and valuable clinical diagnostic modality.     

Exchange transfusion the hard way: massive hemolysis following transplantation of bone marrow with minor ABO incompatibility

BACKGROUND: Bone marrow transplantation using donors with minor ABO incompatibility may result in the rapid production of donor-derived red cell isohemagglutinins, causing hemolysis of recipient red cells. CASE REPORT: The transplant of sibling-donor marrow with minor ABO incompatibility (group O donor marrow to group A recipient), using FK- 506 as an immunosuppressant to prevent graft-versus-host disease, is reported. Following early myeloid engraftment, the recipient developed hemolysis of her entire A red cell population between Day 8 and Day 11. This brisk hemolytic anemia was due to rapid donor lymphoid engraftment that resulted in the explosive production of donor-derived anti-A. CONCLUSION: Patients undergoing the transplantation of marrow from donors with minor ABO incompatibility in which the donor cells can produce isohemagglutinins against the recipient's red cells must be kept under vigilant observation for the possible development of severe hemolysis, particularly in the setting of profound T-cell suppression without B-cell suppression.     

THE DURATION OF ACTION OF INHALED FORMOTEROL DRY POWDER

SUMMARY The duration of action of formoterol inhaled as a dry powder formulation is compared with placebo and a reference treatment of salbutamol dry powder in patients with bronchial asthma. This single-centre, double-blind, cross-over study recruited 23 outpatients with clinically stable asthma. These patients were treated with 12μg formoterol, 400μg salbutamol or placebo in a randomly allocated sequence, with at least 2 days between treatments. Forced expiratory volume in 1s of expiration (FEV₁) was measured at specified time points from 15 min to 15 hours post-treatment. Formoterol produced significantly higher values of FEV₁ at the primary endpoint of 12 hours compared with placebo and salbutamol. No differences between FEV₁ values were seen for the active treatments of formoterol and salbutamol for the first 5 hours post-inhalation. Formoterol was significantly superior to placebo at all time points, whereas salbutamol was significantly superior to placebo for the first 5 hours.This study demonstrates that formoterol, when given as a dry powder inhalation, has a significantly longer duration of acute bronchodilator action than 400μg salbutamol inhaled as a dry powder. The duration of action of formoterol of at least 12 hours seen in this study is at least as long as that reported following administration from a metered dose inhaler (MDI) at the same dose level. The study also demonstrates that 12μg formoterol dry powder is well tolerated by patients.