Can "ethical" clinical trials be unethical?
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Biomedical subjects
Publications and source records attributed to M Kaye.
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Vitamin D deficiency may depress bone formation but its effect on bone resorption is not well defined. As an index of bone resorption, the activity of acid phosphatase, a lysosomal enzyme found in osteoclasts, was quantitated in situ from a bone tissue smear preparation. Activity of the enzyme, measured by integrative microdensitometry increased linearly from 25 to 60 min. The distribution of activity in osteoclasts quantitated appeared to follow a normal distribution with a median value of 0.19 integrated optical density units. Animals treated with vitamin D or 1,25 dihydroxycholecalciferol had significantly increased activity of acid phosphatase in osteoclasts compared to animals which were vitamin D deficient. The increase of acid phosphatase activity averaged 63%. Vitamin D or its metabolites may have a permissive effect on the action of parathyroid hormone or act directly to increase bone resorption.
Dialysis patients are at risk for toxicity from formaldehyde used in the reprocessing of dialyzers for reuse; therefore, replacing formaldehyde as a dialyzer sterilant would be advantageous. The potential for RenNew-D as a sterilizing agent was investigated in seven stable in-center hemodialysis patients over 20 consecutive dialyses with cuprammonium cellulose hollow-fiber dialyzers. Treatment with RenNew-D showed no toxicity to patients or dialyzers except for two blood leaks occurring in one patient. The mean number of dialyzer uses was 4.9. In all the dialyzers that passed functional testing small solute clearances were maintained with reuse. The ability of RenNew-D to improve the biocompatibility of reused dialyzers was documented with mean neutrophil counts falling to only 78% of initial values during first reuse of dialyzers processed with RenNew-D compared with a decrease in neutrophil count to 2% of initial values during first use of the same dialyzers. Our results suggest that RenNew-D may be a useful alternative to formaldehyde for the purpose of dialyzer reuse. A reuse procedure that includes processing with RenNew-D is associated with improved biocompatibility, possibly because of maintenance of the blood-derived membrane coating established during prior dialysis.
Should patients be treated when they have specifically refused treatment? Three competent patients are described with end-stage renal disease who, against the advice of their family, friends and care-givers, refused dialysis. Each was treated and subsequently they acknowledged their satisfaction with the outcome. Guidelines for treating patients when consent is refused are discussed and it is suggested that this is permissible in life-saving situations where the patients' refusal is idiosyncratic and irrational.
Several psychiatric facilities have opened their records partially or completely to patients. The authors report the results of a two-part study in which 20 patients on a minimum-security unit of a forensic center were allowed to read their records and later to write in them. Staff and patient attitudes toward granting patients access to their records were measured before and during the study and were compared with staff and patient attitudes on two units where patients were not granted access. Only eight study patients actually read their charts and none wrote in them, but the majority of both study and control patients felt that access had been helpful. No significant differences in patient behaviors were found on any of the units as a result of access. Staff attitudes toward access did not differ significantly before or after the study, and few differences were found in staff charting practices.
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RenNew-D (Alcide), a novel demand-release sporocidal agent, was employed instead of formaldehyde in the reprocessing for reuse of cuprophan hollow fiber dialyzers (Gambro) and the performance of these dialyzers was evaluated over 40 consecutive dialyses in six patients on maintenance hemodialysis. When RenNew-D was part of automated reprocessing performed with 4.3% bleach as specified by the manufacturer (Lixivitron), dialyzer survival was prolonged (16.7 +/- 7.2 uses) and hemodialysis neutropenia was unchanged with reuse. When RenNew-D was part of manual reprocessing conducted in the absence of bleach, marked improvement in dialyzer biocompatibility was observed but with a decreased survival (4.8 +/- 3.0). The majority of dialyzer failures were due to a fall in fiber bundle volume below a 85% set limit. Small solute clearances were maintained with both types of reprocessing. Dialyses were well tolerated throughout. Our data suggest that RenNew-D is a safe and efficacious product which can serve as a valuable alternative to formaldehyde for the purpose of dialyzer reuse.
A dialysis unit's introduction of automated recycling of dialysers is described. The responses of the staff and the patients are outlined, along with the pertinent ethical issues. Suggestions regarding the educational processes necessary with any innovation in long-term medical care are discussed.
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In normal subjects and patients with endstage renal disease, osteoclast cell volumes were constructed using serial 2-micron thick plastic embedded sections from iliac crest bone biopsy specimens. Four cells randomly selected from each of the subjects were analyzed to give both the cell volume from the cumulative areas and thickness of each cell slice and also the cell axes taking the vector along the bone face as width or Y, thickness from the bone surface as breadth or X and vertical dimension length or Z. The mean cell volume was 6,230 microns3 in the control subjects and was significantly larger being 11,730 microns3 and 13,680 microns3 in the two patient groups. The cells showed polarity with the largest axes, Y and Z, being those in apposition to the bone surface. Howship's lacunae were enlarged in the patients and the cross-sectional area of an individual lacuna corresponded to the area of the contiguous osteoclast, r = 0.62, P less than 0.001. All patients had secondary hyperparathyroidism and osteoclast numbers were increased. There was no correlation between osteoclast size and duration of renal failure, previous vitamin D intake, or aluminum exposure. It is suggested that in ESRD, osteoclasts undergo both an increase in number and size and that these cells, being larger, remove more bone than the smaller cells in normal subjects.
It is argued that consent by the patient to reuse dialyzers which have been mechanically cleansed is not required provided adequate standards of practice and safety are utilized. Based on medical benefits, administrative order and cost saving we propose that specific informed consent for such reuse should not be mandatory and that it could at times be unhelpful, both to care givers and recipients.
One procedural protection that has not generally made the transition from the criminal justice system to involuntary civil commitment is the Fifth Amendment protection against self-incrimination. The authors present the results of a study of the implementation of the right to remain silent, which demonstrate that warning patients that anything they say may be used against them in the commitment hearing has little impact on their willingness to talk to staff or to cooperate with treatment. The authors discuss the possible reasons for their findings.
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Studies were performed in patients on maintenance hemodialysis to evaluate the role of prolonged dialyzer reuse in the management of end-stage renal disease. For this purpose the patients were dialyzed without interruption with the same hollow fiber dialyzers (GambroR 120M) reprocessed with the Lixivitron IIR equipment. The data obtained from in vivo clearances in sixteen patients demonstrate that membrane permeability to small solutes (urea, creatinine, phosphate) is maintained up to thirty dialyzer uses. In vitro studies confirmed this observation and established that clearances of larger solutes (vitamin B12) are also maintained over similar extensive dialyzer reuse. Hematological and blood gas studies were performed serially during dialysis in five additional patients. Although circulating leucocyte and neutrophil counts, hemoglobin concentration as well as arterial pH and partial pressures of oxygen and carbon dioxide changed appropriately during dialysis, there was no observable difference from the first to the twentieth use of the same dialyzer. Thus, these results clearly demonstrate that prolonged dialyzer reuse in end-stage renal disease patients constitutes a stable form of renal replacement therapy provided adequate dialyzer reprocessing is applied.
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An animal model was developed to examine the cause of resistance to the calcemic action of PTH in renal failure. Thyroparathyroidectomized (TPTX) rats were repeatedly reinfused with their excreted urine, over a 5-hour period, to produce an acute uremic animal with normal kidneys. Nonuremic controls were infused with equivalent volumes of a simple electrolyte solution. Using this model, we have demonstrated impaired calcemic response to PTH (Lilly Parathyroid Extract, 80 U/100 g) in urine-infused rats compared with electrolyte-infused rats. The final plasma calcium concentrations were 12.0 +/- 0.3 and 14.9 +/- 0.3 mg/dl, respectively (P less than 0.001). The cause of this impaired calcemic response was investigated by reinfusing rats with their own urine that had been pretreated with either activated charcoal or zirconium oxide in two different anionic forms, or urine that had been ultrafiltrated through an Amicon membrane of which the stated molecular-weight cut-off of the smallest pore-size membrane was 500 daltons. It was found that charcoal and ultrafiltration techniques had no effect, whereas the zirconium oxide treatment completely corrected the impaired calcemic response and returned the plasma phosphorus to a concentration similar to that in nonuremic controls. This can be explained by the fact that the principal effect of zirconium oxide on urine is to remove inorganic phosphate. Other groups of TPTX rats given PTH extract were infused with an electrolyte solution containing varying amounts of phosphate up to a maximum similar to the amount that a urine-infused rat would receive. A highly significant inverse relationship was found between the dose of phosphate infused with the electrolyte solution and the measured calcemic response to PTH. This relationship is represented by the following equation: calcium (mg/dl) = 14.84 - 0.139 inorganic phosphate; r = 0.915, P less than 0.001. From these series of studies, we conclude that phosphate retention is the cause of resistance to the calcemic action of PTH extract in this acute uremic model.