Stored human tissue: an ethical perspective on the fate of anonymous, archival material

The furore over the retention of organs at postmortem examination, without adequate consent, has led to a reassessment of the justification for, and circumstances surrounding, the retention of any human material after postmortem examinations and operations. This brings into focus the large amount of human material stored in various archives and museums, much of which is not identifiable and was accumulated many years ago, under unknown circumstances. Such anonymous archival material could be disposed of, used for teaching, used for research, or remain in storage. We argue that there are no ethical grounds for disposing of the material, or for storing it in the absence of a teaching or research rationale. Nevertheless, with stringent safeguards, it can be used even in the absence of consent in research and teaching. Regulations are required to control the storage of all such human material, along the lines of regulations governing anatomy body bequests.     

Spinal cord regeneration: moving tentatively towards new perspectives

The failure of the adult human spinal cord to regenerate following injury is not absolute, but appears to be amenable to therapeutic manipulation. Recent work has shown that the provision of a growth permissive environment by the neutralization of inhibitory influences, or the grafting of fetal tissue, peripheral nerve, Schwann cells, or olfactory ensheathing cells can enhance regeneration in animal models of spinal cord injury. Stem cells are gaining ever-increasing favour as a treatment option for spinal cord injury. The potential of neural stem cells, embryonic stem cells, and bone marrow stromal cells is discussed. Additional treatment options such as pharmacological interventions, functional electrical stimulation and physiotherapy approaches are also explored. Basic science insights are used as a foundation for a discussion of a variety of clinical perspectives including repair of the chronically injured spinal cord, animal models of human spinal cord injuries and clinical trials. A more holistic approach towards spinal cord injury is suggested, one where a hierarchy of needs is recognised and quality of life is paramount. Finally, this review cautions against overly grandiose claims of an imminent miracle cure for human spinal cord injury.     

Parents' perceptions of staff competency in a neonatal intensive care unit

* The aim of this study was to explore and describe parents' perceptions of staff competency in a neonatal intensive care unit (NICU). The study set out to use a grounded theory approach that was modified because of a number of constraints. Eight parents whose babies met a number of inclusion criteria were interviewed using focused conversational interviews. They were then transcribed and thematically analysed. The research approach was modified as the study developed because of practical and ethical access reasons: the sampling strategy and lack of opportunity to exploit fully the constant comparative method. * Four key themes which conceptualize competency as caring emerged from the data: parents are facilitated to integrate into the unit and do not feel a burden; parents feel in control whilst in the unit; parents have a choice to opt out from observing tasks and procedures on their baby; parents and the interprofessional team communicate well and provide appropriate information. These are discussed in the context of available literature. * In conclusion, the results of the study serve to highlight how parents' perceptions of competence in a professional are not based solely on skills and tasks but on many caring behaviours. The grounded theory approach has generated a number of areas for exploration, in particular, ideas about the conceptual basis of caring in an NICU context and its links to competence. The caring behaviours involve learning to share responsibility with families. The findings suggest that when there is 'a handing over' of control to parents and a greater emphasis on parent support, they feel less like 'guests'. These ideas are supported by the available literature. A number of methodological issues are raised.     

Increased activation of lymphocytes infiltrating primary colorectal cancers following immunisation with the anti-idiotypic monoclonal antibody 105AD7

BACKGROUND: The anti-idiotypic monoclonal antibody 105AD7 mimics the tumour associated antigen 791Tgp72, expressed on 70-80% of colorectal cancers. Phase I studies have shown that the vaccine is non-toxic, and a number of patients have been immunised prior to resection of their primary tumours. AIMS: To assess lymphocyte activation at the tumour site by measuring expression of the alpha subunit of the interleukin 2 receptor (CD25). METHODS: Nineteen patients with primary colorectal cancer were immunised with varying doses of 105AD7 prior to resection of their primary tumours. Samples of normal bowel and tumour edge/centre from 16 patients were available for immunohistochemical staining with a monoclonal antibody against CD25. Samples from a matched control group were also stained. Fresh tumours from 14 immunised patients and 31 unimmunised control patients were disaggregated, and the lymphocytes obtained labelled for CD25. Samples were analysed blindly by flow cytometry. RESULTS: Median infiltration of lymphocytes expressing CD25, measured immunohistochemically, was higher in trial patients, as was the ratio of tumour to normal bowel infiltration. Flow cytometric analysis of fresh tumour from immunised patients showed a significantly higher percentage of lymphocytes expressing CD25 tumour infiltrating lymphocytes than their matched and unmatched controls. DISCUSSION: The alpha subunit of the interleukin 2 receptor is increased on tumour infiltrating lymphocytes, in patients immunised with the colorectal cancer vaccine 105AD7. This suggests a population of activated lymphocytes capable of targeting 791Tgp72 expressing tumour cells, such as circulating micrometastases. 105AD7 may have a role as adjuvant therapy in early stage disease.     

Obstructive sleep apnea: diagnosis with ultrafast CT

Patients with sleep-disordered breathing often have physiologic and anatomic abnormalities of the upper airway that are demonstrable while awake. An ultrafast computed tomographic (CT) scanner was used to measure the oropharyngeal and nasopharyngeal cross-sectional areas of 11 patients with obstructive sleep apnea. Twenty-four healthy volunteers served as control subjects. The percentage of change in cross-sectional area during quiet tidal breathing was used as a measure of airway compliance. Compared with weight-matched control subjects, patients with obstructive sleep apnea had smaller oropharyngeal airways (40.4 vs 177.8 mm2) (P less than .001) and smaller nasopharyngeal airways (31.3 vs 134.2 mm2) (P less than .001). In addition, their oropharyngeal airways were significantly more compliant (75% vs 27%) (P less than .001). Patients with obstructive sleep apnea are characterized by a small, collapsible oropharyngeal airway and by nasopharyngeal airway narrowing. These abnormalities can cause sleep-disordered breathing. Ultrafast CT scanning allows rapid, noninvasive assessment of airway variables.     

Three-dimensional treatment planning for lung cancer

The experience of four institutions involved in a three-dimensional treatment planning contract (NCI) for lung cancer is described. It was found that three-dimensional treatment planning has a significant potential for optimization of treatment plans for radiotherapy of lung cancer both for tumor coverage and sparing of critical normal tissues within the complex anatomy of the human thorax. Evaluation tools, such as dose-volume histograms, and three-dimensional isodose displays, such as multiple plane views, surface dose displays, etc., were found to be extremely valuable in evaluation and comparison of these complex plans. It is anticipated that with further developments in three-dimensional simulation and treatment delivery systems, major progress towards uncomplicated local regional control of lung cancer may be forthcoming.     

Mammographic screening: how to operate successfully at low cost

To offer mammographic screening to asymptomatic women at low cost requires a different approach than is appropriate for solving the more complex problems presented by symptomatic patients. Since the goal of screening is to detect unsuspected abnormalities, not to characterize them fully, operational procedures can be streamlined to maximize patient throughput and achieve substantial cost savings. Such procedures will be successful only if applied to large numbers of patients, thereby permitting cost reduction by economies of large-scale operation. Computerization of record-keeping and of image interpretation is ideally suited for screening examinations and permits further cost savings. Experience with a prototype low-cost screening program has shown that with only 15 patients per day, operation is feasible at a charge of $50 per patient. The income lost from asymptomatic patients, who will pay lower fees compared with the traditional mammography fees they now pay, is more than offset by the income generated by additional problem-solving mammograms needed to fully characterize screening-detected abnormalities and by the increased use of needle localization procedures to guide biopsy.     

Primary retroperitoneal myxoid/round cell liposarcoma is a nonexisting disease: an immunohistochemical and molecular biological analysis

Almost all primary retroperitoneal liposarcomas can be classified as well-/dedifferentiated liposarcoma. Rarely, however, primary retroperitoneal liposarcoma is classified as myxoid/round cell liposarcoma, based on the presence of myxoid areas and vascular crow's feet pattern, which has resulted in a debate on the classification of liposarcoma in the retroperitoneum. Genetically, myxoid/round cell liposarcoma and well-/dedifferentiated liposarcoma are different diseases. Myxoid/round cell liposarcoma is characterized by a translocation causing FUS-CHOP or EWSR1-CHOP fusion, whereas well-/dedifferentiated liposarcoma is characterized by an amplification of the 12q13-15 region, including MDM2 and CDK4 genes. As myxoid/round cell liposarcoma is highly radio- and chemosensitive, differentiation between subtypes is important to optimize treatment. We studied whether primary retroperitoneal liposarcomas diagnosed as myxoid/round cell liposarcoma represent molecularly true myxoid/round cell liposarcoma or are histopathological mimics and represent well-/dedifferentiated liposarcoma. Primary retroperitoneal myxoid/round cell liposarcoma (n=16) were compared to primary extremity myxoid/round cell liposarcoma (n=20). Histopathological and immunohistochemical features were studied. Amplification status of the 12q13-15 region was studied using a multiplex ligation-dependent probe amplification analysis, and FUS-CHOP or EWS-CHOP translocations were studied using RT-PCR. In primary retroperitoneal myxoid/round cell liposarcoma, MDM2 and CDK4 staining was both positive in 12 of 15 cases. In primary extremity myxoid/round cell liposarcoma, MDM2 was negative in 18/20 and CDK4 was negative in all cases. Multiplex ligation-dependent probe amplification showed the amplification of 12q13-15 region in 16/16 primary retroperitoneal myxoid/round cell liposarcomas and in 1/20 primary extremity myxoid/round cell liposarcomas. Translocation was present in all (18/18) primary extremity myxoid/round cell liposarcomas, but absent in all primary retroperitoneal myxoid/round cell liposarcomas. On the basis of immunohistochemical and molecular characteristics, apparent primary retroperitoneal myxoid/round cell liposarcoma can be recognized as well-/dedifferentiated liposarcoma with morphological features mimicking myxoid/round cell liposarcoma. In these cases, treatment should probably be specifically designed as for well-/dedifferentiated liposarcoma. Moreover, finding of myxoid/round cell liposarcoma translocations in a retroperitoneal localization is highly suggestive of metastasis and should prompt search for a primary localization outside the retroperitoneum.     

Sodium pentosan polysulfate (PPS), an anti-HIV agent also exhibits synergism with AZT, lymphoproliferative activity, and virus enhancement.

Sodium pentosan polysulfate (PPS), a negatively charged polymer of beta-D-xylopyranose units, was evaluated for its anti-HIV effects in normal human peripheral mononuclear cells (PMNC) and its possible synergism with AZT. In the presence of 25 nM AZT, 2.0 micrograms/ml of PPS reduced HIV-1 replication 110-fold, compared with a 3.9- and 7-fold decrease in the presence of either drug individually. Surprisingly, at low (below 1 microgram/ml) concentrations of either PPS or dextran sulfate, an enhancement of virus production was observed. PPS was nontoxic, had a proliferative effect on uninfected and a protective effect on infected PMNC. Virus enhancement at low concentrations of PPS appeared to be linked to its lymphoproliferative effect. These findings suggest that the use of PPS and others such agents as monotherapy for AIDS might have deleterious effects. However, due to its marked synergism with AZT and its lymphoproliferative activities, PPS might prove to be a useful agent in therapeutic trials of AIDS if used in combination with less than the usual dosage of AZT.