Myoblast transfer in duchenne muscular dystrophy

One biceps muscle of 8 patients with Duchenne muscular dystrophy was injected at 55 sites with a total of 55 million viable, purified, and contamination-free normal myoblasts (myoblast transfer). The other biceps of each patient was injected with a placebo to serve as a control. The procedure was blinded to the patients, parents, and investigators. Myoblasts derived from a biopsy specimen of the fathers were cultured and purified under strict conditions and carefully screened for microbial contamination. All patients received cyclophosphamide for immunosuppression for 6 or 12 months. No serious complications were observed after myoblast transfer, indicating that the procedure is safe. The overall therapeutic efficiency of myoblast transfer was poor as judged by the results in maximal voluntary force generation, dystrophin content of the muscle, magnetic resonance imaging of the muscle, and the lack of donor-derived DNA and dystrophin messenger RNA in the injected muscle. An improved efficiency of the take of myoblasts might be achieved by using younger cells and injecting the myoblasts with a myonecrotic agent (to increase the prevalence of regeneration) and a basal laminal fenestrating agent.     

Improved Assessment of Significant Activation in Functional Magnetic Resonance Imaging (fMRI): Use of a Cluster-Size Threshold

The typical functional magnetic resonance (fMRI) study presents a formidable problem of multiple statistical comparisons (i.e, > 10,000 in a 128 x 128 image). To protect against false positives, investigators have typically relied on decreasing the per pixel false positive probability. This approach incurs an inevitable loss of power to detect statistically significant activity. An alternative approach, which relies on the assumption that areas of true neural activity will tend to stimulate signal changes over contiguous pixels, is presented. If one knows the probability distribution of such cluster sizes as a function of per pixel false positive probability, one can use cluster-size thresholds independently to reject false positives. Both Monte Carlo simulations and fMRI studies of human subjects have been used to verify that this approach can improve statistical power by as much as fivefold over techniques that rely solely on adjusting per pixel false positive probabilities.     

Fatal craniocervical necrotizing fasciitis in an immunocompetent patient: A case report and literature review

Background. Craniocervical necrotizing fasciitis (CCNF) is a rapidly progressive, severe bacterial infection of the superficial fascial planes of the head and neck. Group A beta–hemolytic Streptococcus, staphylococcus aureus, and obligate anaerobic bacteria are common pathogens. The disease usually results from a dental source or facial trauma. Extensive fascial necrosis and severe systemic toxicity are common manifestations of CCNF. Recently the lay press has referred to necrotizing fasciitis in several articles about “flesh eating” bacteria, which have resulted in several deaths. Methods. We report the first case of a fatality in an otherwise immunocompetent patient. The patient was a 66-year-old black man with no identifiable source of infection and no history or evidence of immunocompromising disorders. Results. Despite aggressive surgical debridement and broad-spectrum antibiotic coverage, he died 30 hours after admission from multisystem organ failure secondary to overwhelming sepsis. Conclusion. Treatment consists of early recognition of CCNF combined with aggressive surgical debridement and drainage of the involved necrotic fascia and tissue along with broad-spectrum intravenous antibiotic coverage. Although 11 other fatal cases of CCNF have been previously reported, all had an underlying medical problem which created an immunocompromised state, usually diabetes mellitus or chronic alcoholism. We present a case report and literature review along with a discussion of the related anatomy. © 1995 Jons Wiley & Sons, Inc.     

Borderline findings in fetal cardiac sonography

Borderline or equivocal sonographic findings in the fetal heart are occasionally encountered. Echogenic foci in the ventricles, small pericardial effusions, and mild discrepancy in ventricular size are three such problematic findings. The significance of each of these findings, as currently understood, will be discussed in this article.     

Minor,moderate and severe head injury

Summary The future role of the neurosurgeon in the management of head injury is reviewed in terms of the care of patients with minor, moderate and severe head injuries. In minor head injury it is predicted that there will be increasing pressure on the neurosurgeon to undertake the management and follow-up of all patients who have sustained head injury, and this will place a considerable additional load on each neurosurgical unit. This is based on a survey of 1919 head injuries admitted in one calendar year (1981), consisting of 93 severe injuries (GCS < 8), 210 moderate injuries (GCS 8–12), and 1616 minor injuries (GCS 13/14). In moderate injuries CT will assume a major role in detecting hematoma early and identifying contusions. There may yet be a role for steroids in these cases and there should be a greater use of neurorehabilitation, instead of the current overemphasis on the severely injured. In severe injury future efforts will be to prevent early secondary insults and to find better methods of controlling raised intracranial pressure.     

Collection of blood mononuclear cells by leukapheresis for transplantation in a yucatan miniature swine model

A large animal model is needed to evaluate new apheresis technologies. These technologies include novel methods of harvesting the blood mononuclear cell population which contains the hematopoietic stem cells needed to restore hematopoiesis in recipients of hematopoietically lethal therapy and the use of cytokines to provide a safe and predictable method of manipulating these circulating hematopoietic stem cells. We describe the methods used to collect mononuclear cells by leukapheresis from Yucatan miniature swine. These animals are of sufficient size to tolerate the procedures and have many physiologic and hematologic similarities to man. They are of good temperament and are easily trained. Long-term venous access was obtained using single lumen silicone rubber catheters placed in the inferior vena cava. The animals were apheresed while fully awake using a Haemonetics Model V50 machine and a modified lymphocyte collection protocol. The procedure was highly efficient for the collection of mononuclear cells and a 10 pass procedure yielded a product which contained 19.7 × 10⁹ mononuclear cells, 10.7 × 10⁹ granulocytes, and 17 ml of erythrocytes in a volume of approximately 100 ml. This product can be cryopreserved and used for subsequent transplantation. The content of four apheresis procedures provides hematopoietic reconstitution of lethally irradiated swine on a time scale equivalent to transplantation of optimal numbers of bone marrow cells. © 1992 Wiley-Liss, Inc.