Outcome of unrelated donor bone marrow transplantation in 40 children with Hurler syndrome

Long-term survival and improved neuropsychological function have occurred in selected children with Hurler syndrome (MPS I H) after successful engraftment with genotypically matched sibling bons marrow transplantation (BMT). However, because few children have HLA-identical siblings, the feasibility of unrelated donor (URD) BMT as a vehicle for adoptive enzyme therapy was evaluated in this retrospective study. Forty consecutive children (median, 1.7 years; range, 0.9 to 3.2 years) with MPS I H received high-dose chemotherapy with or without radiation followed by BMT between January 27, 1989 and May 13, 1994. Twenty-five of the 40 patients initially engrafted. An estimated 49% of patients are alive at 2 years, 63% alloengrafted and 37% autoengrafted. The probability of grade II to IV acute graft-versus-host disease (GVHD) was 30%, and the probability of extensive chronic GVHD was 18%. Eleven patients received a second URD BMT because of graft rejection or failure. Of the 20 survivors, 13 children have complete donor engraftment, two children have mixed chimeric grafts, and five children have autologous marrow recovery. The BM cell dose was correlated with both donor engraftment and survival. Thirteen of 27 evaluable patients were engrafted at 1 year following URD BMT. Neither T-lymphocyte depletion (TLD) of the bone marrow nor irradiation appeared to influence the likelihood of engraftment. Ten of 16 patients alive at 1 year who received a BM cell dose greater than or equal to 3.5 x 10(8) cells/kg engrafted, and 62% are estimated to be alive at 3 years. In contrast, only 3 of 11 patients receiving less than 3.5 x 10(8) cells/kg engrafted, and 24% are estimated to be alive at 3 years (P = .05). The mental developmental index (MDI) was assessed before BMT. Both baseline and post-BMT neuropsychological data were available for 11 engrafted survivors. Eight children with a baseline MDI greater than 70 have undergone URD BMT (median age, 1.5 years; range, 1.0 to 2.4 years). Of these, two children have had BMT too recently for developmental follow-up. Of the remaining six, none has shown any decline in age equivalent scores. Four children are acquiring skills at a pace equal to or slightly below their same age peers; two children have shown a plateau in learning or extreme slowing in their learning process. For children with a baseline MDI less than 70 (median age, 2.5 years; range, 0.9 to 2.9 years), post-BMT follow-up indicated that two children have shown deterioration in their developmental skills. The remaining three children are maintaining their skills and are adding to them at a highly variable rate. We conclude that MPS I H patients with a baseline MDI greater than 70 who are engrafted survivors following URD BMT can achieve a favorable long-term outcome and improved cognitive function. Future protocols must address the high risk of graft rejection or failure and the impact of GVHD in this patient population.     

Urethral Venous Malformation: An Unusual Cause of Recurrent Post-Coital Gross Haematuria in Association with Haematospermia

Three cases of recurrent post-coital haematuria are described. Extensive protracted investigations pinpointed urethral varicosities as the likely cause. All patients were successfully treated with diathermy fulguration.     

Public perceptions of quarantine: community-based telephone survey following an infectious disease outbreak

Background  

The use of restrictive measures such as quarantine draws into sharp relief the dynamic interplay between the individual rights of the citizen on the one hand and the collective rights of the community on the other. Concerns regarding infectious disease outbreaks (SARS, pandemic influenza) have intensified the need to understand public perceptions of quarantine and other social distancing measures.     

Knowledge,attitudes and practices about malaria among communities: Comparing epidemic and non-epidemic prone communities of Muleba district,North-western Tanzania

Background  

Muleba district in North-western Tanzania has experienced malaria epidemics in recent years. Community knowledge, attitudes and practices are important in enhancing disease control interventions. This study investigated determinants of malaria epidemics in the study area in relation to household knowledge, attitudes and practice on malaria.     

Taking tissue seriously means taking communities seriously

Background  

Health research is increasingly being conducted on a global scale, particularly in the developing world to address leading causes of morbidity and mortality. While research interest has increased, building scientific capacity in the developing world has not kept pace. This often leads to the export of human tissue (defined broadly) from the developing to the developed world for analysis. These practices raise a number of important ethical issues that require attention.     

Pregnancy following intracytoplasmic sperm injection treatment with dead husband's spermatozoa: ethical and policy considerations

This paper describes the first pregnancy in a childless widow after intracytoplasmic sperm injection (ICSI) treatment with her deceased husband's spermatozoa which had been stored for nearly 3 years before use. Before his death the husband had received treatment for testicular cancer and he had given the appropriate written consent for the future use of his spermatozoa. Of the 10 eggs injected, six resulted in normal embryos. Three embryos were transferred and the remaining three embryos are currently stored for possible future use. The treatment resulted in a continuing singleton pregnancy. The case demonstrated the suitability of ICSI in those difficult cases where the sperm quality is extremely poor. This success is also compared with a widely debated case of another widow who was refused permission to use her deceased husband's spermatozoa. It is concluded that in the case of posthumous use of frozen spermatozoa, the current laws are conveniently applicable in a chronic illness but not so in an acute illness leading to death. In the light of the wide public debate on the issues raised by this legal case, the UK Government has also decided to conduct a review of consent procedures involving the storage and use of genetic material.