The use of radiolabeled and fluorescein-labeled antiglobulins in assays to predict platelet transfusion outcome

We used both radiolabeled and fluorescein-labeled antiglobulins in assays to detect antibodies against platelets in multiply transfused patients to determine the value of these tests in predicting the outcome of platelet transfusion in such patients. In 15 allosensitized patients, we studied 68 single-donor platelet transfusions, 43 (63%) of which had a poor outcome, defined as a corrected count increment (CCI), less than 10,000. The results obtained with either test were significantly correlated with the CCI following transfusion (p less than 0.001), but the assay using the radiolabeled antiglobulin had slightly better sensitivity, specificity, and predictive value. When the assays were used in combination, there was again significant correlation with the CCI of the transfusion, p less than 0.001. When both assays predicted failure of the transfusions, 31/31 (100%) such transfusions resulted in a CCI of less than 10,000, and when both assays predicted success of the transfusions, 14/15 (93%) such transfusions resulted in a CCI of greater than 10,000. Both assays are useful in predicting the outcome of the platelet transfusions; when the assay results were concordant, almost total predictive accuracy was obtained.     

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.     

Plateletpheresis in the management of thrombocytosis

Acute thrombotic and hemorrhagic manifestations of thrombocytosis associated with myeloproliferative disorders may be life threatening. Conventional therapy with radioisotopes and/or cytotoxic drugs may require weeks for effective control of platelet counts. In five patients, plateletpheresis by discontinuous-flow (Haemonetics) or continuous-flow (Aminco Celltrifuge) centrifugation was used as a means of reducing platelet counts acutely. With each procedure, approximately 2-9 X 10(12) platelets were removed, resulting in decrements in platelet counts and relief of symptoms. Plateletpheresis is a useful and safe acute means of controlling platelet counts in myeloproliferative disorders.     

Prostaglandin endoperoxide analogues stimulate phospholipase C and protein phosphorylation during platelet shape change

We have studied the effects of two stable prostaglandin endoperoxide analogues on platelet lipid metabolism in relation to specific platelet functional changes. During platelet shape change, the endoperoxide analogues induce the formation of 1,2-diacylglycerol and phosphatidic acid, indicating the activation of a phosphoinositide-specific phospholipase C. In parallel, they stimulate the phosphorylation of a 40-kd and a 20-kd protein. During platelet shape change, arachidonic acid is released, but not metabolized by platelet cyclo-oxygenase or lipoxygenase. Phospholipase C activation and platelet shape change are independent of extracellular Ca++ and Mg++, arachidonate metabolism, and release of adenosine diphosphate (ADP). Activation of phospholipase C during platelet aggregation seems, however, to be mediated partly by release of ADP. We conclude that endoperoxide analogues initially stimulate in platelets the formation of products derived from phospholipase C activation, which might serve as intracellular messengers for phosphorylation of specific proteins related to platelet shape change.     

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.     

Egg sharing and egg donation: attitudes of British egg donors and recipients

The question of payment to egg donors has recently focused the attention of both the Human Fertilisation and Embryology Authority (HFEA) and licensed clinics. An acute shortage of egg donors and the rising costs of assisted conception treatment are matters of grave concern to many patients. To understand the emotional and social effects of egg sharing and egg donation, we conducted a survey of attitudes in a group of women who had some knowledge or experience of egg donation. A total of 750 questionnaires were sent out of which 217 were returned within the specified time limit. From these, 107 respondents had experience of egg donation and 110 had made enquiries about donation. The data from these questionnaires were collated and tabulated by the National Opinion Polls (NOP) Research Group. An analysis of the data produced the following key findings: (i) donating or sharing eggs is a social issue, 94% discuss it with partners/family/friends; (ii) altruistic motives are not the prerogative of non-patient volunteers-egg share donors felt that helping the childless was as important as having a chance of in-vitro fertilization (IVF) for themselves; (iii) the treatment procedure causes the most anxiety for egg donors. The recipients were most concerned about delays, donor characteristics and how the eggs were allocated; (iv) most respondents (65%) with prior experience of egg sharing would do it again - 63% of egg share donors, 72% of egg share recipients; (v) cash rewards to egg donors and outright advertising for donors were rejected by 64 and 62% of the sample respectively; and (vi) counselling was highly valued and there were no instances of 'shattered lives' after treatment. The findings do not support the recently announced intentions of the HFEA to disallow payment to gamete donors on the grounds of devalued consent. There is no precedent in modern medicine for egg sharing. The patients surveyed drew a clear distinction between egg sharing and financial rewards. As long as egg donation is not covered by the National Health Service, it is fairer to offer egg sharing than to refuse treatment to those unable to pay.      

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.