Interdisciplinary approach to abdominal Burkitt’s lymphoma

Burkitt’s lymphoma is a high-grade, rapidly growing B-cell neoplasm. It is recognized by its aggressive course, brief median survival, and low rates of long-term survival. The authors discuss the case of a patient who acutely presented with intraabdominal complications from a new onset of Burkitt’s lymphoma. The clinical and pathological features, staging, treatment options, and survival data are reviewed. In addition, the role of surgical intervention is carefully analyzed.     

Quantifying how location and dose of botulinum toxin injections affect muscle paralysis

Despite the widespread use of botulinum toxin to treat muscle dystonias, no method exists to quantify muscle paralysis in either human or nonhuman models. In this study we examined how the location, dose, and volume of botulinum injection affects paralysis in the rat tibialis anterior muscle. Paralysis was quantified by electrically stimulating the nerve to the tibialis anterior and then staining sections of the muscle for glycogen. The areas of glycogen-containing fibers represented regions of botulinum action. The results showed that the most important injection technique is to inject botulinum directly into the motor endplate region of a muscle. Injections only 0.5 cm from the motor endplate resulted in a 50% decrease in paralysis. Increases in dose increased paralysis, however, some of that increase was simply due to the increased volume of injection. Thus, delivering toxin in small volumes near the MEP band of a muscle should produce the most effectiveparalysis. © 1993 John Wiley & Sons, Inc.     

Nafarelin controlled release injectable: theoretical clinical plasma profiles from multiple dosing and from mixtures of microspheres containing 2 per cent, 4 per cent and 7 per cent nafarelin

Nafarelin controlled release injectable (CRI) releases a decapeptide drug for target one month therapy. Nafarelin, a luteinizing hormone releasing hormone agonistic analogue, is microencapsulated in biodegradable poly(lactide-co-glycolide) microspheres and given by intramuscular injection. Clinical data from a human single dose Phase I clinical study are modelled to develop theoretical multiple dose profiles and theoretical single dose profiles from mixtures of two or three formulations. Single dose injections of nafarelin CRI microspheres (4 mg nafarelin) containing 2, 4, or 7 per cent nafarelin all achieve useful plasma drug levels throughout the target 30 day interval. Therapeutic suppression of testosterone levels was observed in all subjects participating in the phase I clinical study. Highest plasma nafarelin levels are achieved in the 0-10 and 20-35 day post-injection intervals. Theoretical multiple dosing profiles generated from the single dose clinical results show significant oscillations in plasma nafarelin levels depending on the particular dosing interval selected. Thirty or forty day dosing intervals yield significant variability in plasma nafarelin levels at steady state; 15 day dosing intervals show less variability. Therapeutic testosterone suppression was observed in the single dose study, so the nafarelin dose per injection can be reduced in multiple dosing therapies. Theoretical plasma nafarelin profiles from certain mixtures of 2 and 4 per cent nafarelin microspheres or 2 and 7 per cent nafarelin microspheres indicate that a 60 day product could be achieved. In general, all three formulations yield their lowest plasma drug levels during the 10-20 day post-injection interval. Therefore any mixture of these formulations will likewise exhibit low plasma drug levels during this interval.     

Therapeutic Options for Chronic Hepatitis B: Considerations and Controversies

Five agents are currently approved for the treatment of chronic hepatitis B infection. This article will discuss the three agents for which the most extensive data are available; interferon (IFN), lamivudine, and adefovir, while the following article by Dr. Jules Dienstag will discuss the recently marketed agents, entecavir and peginterferon alfa-2a. The advantages of IFN are its finite duration of therapy (4–6 months), lack of emergence of resistance, and durability of response. On the negative side, response to IFN is less durable in patients with HBeAg-negative chronic hepatitis B virus (HBV). Also, use of IFN is limited by adverse effects and the mode of administration (daily to thrice-weekly subcutaneous injection). Lamivudine and adefovir are orally administered and have good tolerability and safety. Even in patients who experience a marked decrease in serum HBV DNA and loss of HBeAg, oral therapy needs to be continued for at least 6 months, to avoid the risk of reappearance of HBeAg and viremia. Rates of HBeAg seroconversion to anti-HBe-positivity increase with duration of lamivudine or adefovir therapy. The likelihood of development of resistance to lamivudine and associated viral breakthrough limits its long-term use. In patients with HBeAg-negative chronic hepatitis B, long-term therapy is usually required, as off-treatment relapse is common. The emergence of resistance to adefovir is delayed and infrequent, hence adefovir may be preferred in patients requiring long-term therapy.     

Usher syndrome: clinical findings and gene localization studies

The issue of genetic heterogeneity is a critical problem in the localization of the gene(s) for Usher syndrome. Based on the data obtained on families studied to date, the differences between type I and type II Usher syndrome appear quite distinct with regard to auditory and vestibular function. Although the majority of families can be confidently diagnosed as typical type I or type II, clinical investigations revealed four families with findings that did not fit into either of the two more common subtypes. These findings emphasize the critical importance of an in-depth clinical analysis concomitant with the linkage investigation to assure accurate subtyping of Usher syndrome. Based on an analysis of only those families with definite type I or type II Usher syndrome, approximately 17% of the genome can be excluded as a potential site of the gene for type I, and 14% can be excluded as the site for the type II gene. This study will continue until the Usher gene(s) is successfully localized.     

Calcaneal fractures

Fractures of the calcaneus generally occur in the event of high-energy trauma, resulting in complex, three-dimensionally oriented fracture patterns. Surgical management is generally indicated for displaced intra-articular fractures, which allows restoration of calcaneal height, width and overall morphology, in addition to the posterior facet articular surface where possible, and allows for a late in situ arthrodesis as a means of salvage in the event of posttraumatic arthritis. What follows is a brief discussion of our preferred methods in the diagnosis and management of calcaneal fractures.