What does it mean for patients? The expanded Medicare coverage of immunosuppressive medications.
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Biomedical subjects
Publications and source records attributed to C Thomas.
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OBJECTIVE: To recommend practice guidelines for transplant physicians, primary care providers, health care planners, and all those who are concerned about the well-being of the live organ donor. PARTICIPANTS: An executive group representing the National Kidney Foundation, and the American Societies of Transplantation, Transplant Surgeons, and Nephrology formed a steering committee of 12 members to evaluate current practices of living donor transplantation of the kidney, pancreas, liver, intestine, and lung. The steering committee subsequently assembled more than 100 representatives of the transplant community (physicians, nurses, ethicists, psychologists, lawyers, scientists, social workers, transplant recipients, and living donors) at a national conference held June 1-2, 2000, in Kansas City, Mo. CONSENSUS PROCESS: Attendees participated in 7 assigned work groups. Three were organ specific (lung, liver, and kidney) and 4 were focused on social and ethical concerns (informed consent, donor source, psychosocial issues, and live organ donor registry). Work groups' deliberations were structured by a series of questions developed by the steering committee. Each work group presented its deliberations to an open plenary session of all attendees. This information was stored and shaped into a statement circulated electronically to all attendees for their comments, and finally approved by the steering committee for publication. The term consensus is not meant to convey universal agreement of the participants. The statement identifies issues of controversy; however, the wording of the entire statement is a consensus by approval of all attendees. CONCLUSION: The person who gives consent to be a live organ donor should be competent, willing to donate, free from coercion, medically and psychosocially suitable, fully informed of the risks and benefits as a donor, and fully informed of the risks, benefits, and alternative treatment available to the recipient. The benefits to both donor and recipient must outweigh the risks associated with the donation and transplantation of the living donor organ.
Conformationally restricted benzamide bioisosteres were investigated when the aminomethylpyrrolidine derivative 4o proved D3 as well as D4 binding properties which were comparable to those of the atypical neuroleptics sulpiride and clozapine, respectively.
The growth dynamics of indigenous aerobic mesophilic populations (AMP), lactic acid bacteria (LAB) and inoculated (Listeria spp.) microbial populations on cooked and fresh vegetable products, packaged as separate entities and in combination, subjected to temperature fluctuation, were assessed. Microbial proliferation was temperature and product dependent, being most pronounced at 12 degrees C in all products with maximum growth rates of 0.140, 0.175 and 0.126 log10 CFU/g per h being identified for Listeria, aerobic mesophilic and LAB populations, respectively. Listeria spp. and AMP generally demonstrated higher rates of growth within products containing cooked vegetables. Prolonged storage at 3 degrees C resulted in a reduced ability by AMP and Listeria spp. to proliferate upon exposure to growth temperatures; this was not the case with LAB populations. Comparison of Listeria population estimates made using selective (Oxford) and non-selective (nutrient agar) identified reduced recovery on the former. The magnitude of the deviation increased with the duration of exposure of Listeria populations to 3 degrees C with recoveries on selective systems being reduced by 6.3% immediately after inoculation and 82.3% after 168 h at 3 degrees C, respectively. Growth of populations associated with exposure to abuse temperatures was not accompanied by significant changes in product colour (P < 0.05).
OBJECTIVE: To assess the safety and the effect on standardized clinical rating measures of transplanted embryonic porcine ventral mesencephalic (VM) tissue in advanced PD. METHODS: Twelve patients with idiopathic PD underwent unilateral implantation of embryonic porcine VM tissue; six received cyclosporine immunosuppression and six received tissue treated with a monoclonal antibody directed against major histocompatibility complex class I. Patients were followed for 12 months and assessed by clinical examination, MRI, and 18F-levodopa PET. Porcine endogenous retrovirus testing was conducted by PCR-based method on peripheral blood mononuclear cells. RESULTS: Cell implantation occurred without serious adverse events in all patients. Cultures were negative for bacterial and unknown viral contamination. No porcine endogenous retrovirus DNA sequences were found. MRI demonstrated cannula tracts within the putamen and caudate, with minimal or no edema and no mass effect at the transplant sites. In the medication-off state, total Unified Parkinson's Disease Rating Scale scores improved 19% (p = 0.01). Three patients improved over 30%. There were two patients with improved gait. 18F-levodopa PET failed to show changes on the transplanted side. CONCLUSIONS: Unilateral transplantation of porcine embryonic VM cells into PD patients was well tolerated with no evidence of transmission of porcine endogenous retrovirus. Changes in standardized clinical PD rating measures were variable, similar to the results of the first trials of unilateral human embryonic allografts that transplanted small amounts of tissue.
Concern about drug abuse in modern populations has led to the development of specific methods for identification of cocaine, opiates and cannabis in human hair. Drug use in prehistory can provide indirect evidence of interpopulational contact and social stratification. This paper reports drug evaluation in nineteen ancient hair samples from archaeological sites in northern Chile. Each sample was tested for the presence of traces of cocaine, opiates and cannabis, in order to establish a standard methodology for studies of drug use among prehistoric groups. Although results are negative, this absence of evidence could be due to two main causes: (1) the individuals evaluated did not use any drugs, which does not mean that other members of their cultural group did, or (2) the wide range of known drugs studied did not consider some group specific drugs, derived from local or imported plants, thus meaning that a greater drug range must be tested. In any case, our study confirms that drug testing in prehistoric samples is viable. However, in order to determine what kind of substances were used in prehistoric times new patterns that incorporate all drugs which are not part of the western pharmacopeia must be created. Finally, a methodology for the study of drug use among prehistoric groups using ancient hair samples is described.
A 43-year-old woman was admitted with progressive leg pains and weakness and was found to have rhabdomyolysis. Prior to this admission the patient had hypercalcemia, but this returned to normal following treatment with calcitonin. During the hospitalization, she developed the syndrome of calciphylaxis consisting of necrotic skin and muscle associated with vascular calcification. This is the first case report of rhabdomyolysis caused by calciphylaxis in a patient without chronic renal failure.
It is not known how the efficiency of intestinal iron absorption is regulated. One hypothesis suggests that an interaction between the transferrin receptor (TfR) and the haemochromatosis protein (HFE) regulates the level of iron loading in crypt cells. The hypothesis goes on to suggest that this determines the amount of transport protein, expressed in villus enterocytes, that is involved in iron absorption. Mice with haploinsufficiency for TfR are iron deficient and this is thought to be caused by reduced iron absorption. This suggests that TfR may play a role in the regulation and/or mechanism of iron absorption. We investigated TfR function and distribution by measuring iron uptake from plasma transferrin and by immunohistochemistry. The uptake of transferrin-bound iron (Tf-Fe2) into mucosal cells subsequently separated along the crypt-villus axis was compared to the presence of TfR, determined by immunohistochemistry using frozen and wax sections. Frozen sections showed TfR staining in crypt and villus epithelial cells. In wax sections TfR was only identified in a supranuclear region commencing in enterocytes at the crypt-villus junction and attaining greatest levels at the villus tip. This indicates that the processing of wax tissue exposes a TfR epitope that otherwise remains undetectable when studied in frozen sections. This appearance in paraffin sections was inversely related to the uptake of Tf-Fe2. Supranuclear TfR was not associated with lysosomes, since there was no difference in the uptake of normal Tf-Fe2 and that of the non-digestible cellobiose Tf-Fe2, and Western blot analysis revealed similar amounts of TfR in crypt and villus cells. Also the uptake of Tf-Fe2 increased linearly with time, albeit less in villus than crypt cells, suggesting that maturation of an efflux system in villus cells is not responsible for this difference. We hypothesise that TfR in the supranuclear region of villus enterocytes may play a role in iron absorption.
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Khoula hospital, one of the major tertiary care hospitals, situated in the capital city, is the national trauma centre of the Sultanate of Oman. The burns-unit at Khoula hospital has developed an unique collaborative service of active participation in the initial management of burns patients admitted to the peripheral hospitals of the country. The description 'Satellite-service' is used in this paper to describe this 'remote-control service' offered by the main burns center, for the management of burned patients admitted the various peripheral hospitals (the 'satellites') throughout the country, during the shock-period of the first 36 hour post-burn. Thereafter the patients are transferred to the main center for further management. This system was instigated with a common protocol for the initial management of burns all over the country in 1981. Central registration of burns patients from peripheral hospitals was started in 1994. Retrospective analysis of the statistics and records of 151 burns patients transferred from 19 peripheral hospitals to Khoula burns center during a 3 year period from September 1994 to August 1997, showed that the satellite service is very effective in the initial management of patients during the shock period, as there was no mortality due to hypovolemia. The advantages of this service include uniform and appropriate 'initial' management of all the burns patients admitted to any of the hospitals of the country. The major disadvantages of the system were the increased work-load of the main center and poor patient-compliance with post-discharge instructions. This paper also describes how the Satellite service works in practice.
INTRODUCTION: Point mutations in N, K and H RAS have been found in adverse haematological malignancies. The background frequency of RAS mutations in the normal population has yet to be determined. Here we report the results of a screen for RAS mutations from normal individuals. MATERIALS AND METHODS: DNA from peripheral blood or bone marrow from 115 haematologically normal individuals was screened for point mutations in N, K and H RAS, at amino acid positions 12, 13 and 61. The screening was done using polymerase chain reaction and oligonucleotide hybridisation and candidate mutations were subsequently confirmed by cloning and sequencing. RESULTS AND CONCLUSION: Point mutations were identified in DNA from two of the 115 individuals. Both mutations resulted in an amino acid substitution at position 12 in H RAS. Both individuals with detectable H RAS mutations remain haematologically normal.
BACKGROUND: Iron stores in the body are thought to be regulated by a mechanism associated with the rate of iron absorption from the diet, with no significant role played by iron excretion. We report the existence of an iron excretory process that results in the loss of significant amounts of liver iron. METHODS AND RESULTS: Rats were fed 3% carbonyl iron for 9 weeks, which resulted in a 20-fold increase in liver non-haem iron. When the rats on this iron-loaded diet were switched to a low iron diet for 2 and 7 days, liver non-haem iron levels fell 30% and 45%, respectively. A similar fall in transferrin-bound plasma iron was also seen. As the liver iron had not redistributed to other body compartments, it was concluded that the iron had been excreted and that the excreted iron represented a loss of 22% and 28% in total body non-haem iron over 2 and 7 days, respectively. Ligation of the common bile duct in iron loaded rats that had been switched to the iron-deficient diet was accompanied by a similar loss of liver iron and also hepatocellular damage. In addition, measurement of enterocyte iron levels showed that only approximately 5% of the total iron excreted was found in these cells. CONCLUSION: Neither bile nor enterocytes play a significant role in iron excretion. The similarity in the degree of fall in transferrin-bound iron levels with a change in diet suggests that iron excretion involves the uptake and excretion of transferrin bound-iron, possibly by goblet cells. The observed hypertrophy of the intestinal mucosa associated with carbonyl iron feeding may facilitate hypersecretion of mucous and the excretion of this iron.
This paper is a report on a procedure to perform open tip rhinoplasty at the time of lip repair in unilateral and bilateral cleft lip and palate deformity. A total of 69 patients who had this operation between 1994 and 1997 have been reviewed. Conventionally there is hesitation to do radical nasal correction for the cleft lip patient because of the fear of possible growth retardation. The present technique, while it achieves excellent postoperative results constantly, does not entail any more trauma to the cartilage complex than any of the conventional closed rhinoplasty techniques. Early results obtained by this method appear to be superior to those by closed rhinoplasty techniques.
BACKGROUND: The more popular the use of different methods for risk adjustment becomes, the more often data are applied without any regard about the primary target and/or about important assumptions. Furthermore, risk adjustment is no longer restricted for quality assurance purposes, but became a "tool" of health policy. Few working groups currently use risk adjustment for the development of new therapeutic concepts. The aim of our study is to clarify possibilities and limitations of popular risk adjustment methods. PATIENTS AND METHODS: 4985 Patients underwent isolated CABG. Statistics was performed by calculating descriptive statistics, Parsonnet, and Higginsscores. Furthermore, the parametric, time-adjusted hazard function by Blackstone was used. RESULTS: Descriptive statistics allows intra-, and interinstitutional comparisons of single items to identify "outlying" results. Risk scores aim to predict preoperatively the risk category of the patient who undergoes cardiac surgery. However, since different scores are based on a score-specific combination of variables, and different definitions of the investigation interval, different results may occur, when different scores are calculated for a single patient. However, the use for example, of scores in patient groups allows description of changing risk structures. Most of the scores derive from univariate analyses and monophasic functions. However, survival curves are predominantly multiphasic and require a consideration of the time-dependency of "risk factors". DISCUSSION: An increasing number of patients with severe comorbidity undergoes cardiac surgery. To evaluate reliably present and futurous therapeutic options, risk adjustment is necessary. Since various tools for risk-adjustment are available, a serious discussion about reliability and application is necessary.
Management of candiduria is limited by the lack of information about its natural history and lack of data from controlled studies on the efficacy of treating it with antimycotic agents. We compared fungal eradication rates among 316 consecutive candiduric (asymptomatic or minimally symptomatic) hospitalized patients treated with fluconazole (200 mg) or placebo daily for 14 days. In an intent-to-treat analysis, candiduria cleared by day 14 in 79 (50%) of 159 receiving fluconazole and 46 (29%) of 157 receiving placebo (P<.001), with higher eradication rates among patients completing 14 days of therapy (P<.0001), including 33 (52%) of 64 catheterized and 42 (78%) of 54 noncatheterized patients. Pretreatment serum creatinine levels were inversely related to candiduria eradication. Fluconazole initially produced high eradication rates, but cultures at 2 weeks revealed similar candiduria rates among treated and untreated patients. Oral fluconazole was safe and effective for short-term eradication of candiduria, especially following catheter removal. Long-term eradication rates were disappointing and not associated with clinical benefit.
OBJECTIVE: The objective of this work was to identify similarities and differences in primary attending physicians' (generalists' versus oncologists') care practices and outcomes for seriously ill hospitalized patients with malignancy. DESIGN: This was a prospective cohort study (SUPPORT project). SETTING: Subjects were recruited from 5 US teaching hospitals; data were gathered from 1989 to 1994. SUBJECTS: Included in the study was a matched sample of 642 hospitalized patients receiving care for non-small-cell lung cancer, colon cancer metastasized to the liver, or multiorgan system failure associated with malignancy with either a generalist or an oncologist as the primary attending physician. MEASUREMENTS: Care practices and patient outcomes were determined from hospital records. Length of survival was identified with the National Death Index. Physicians' perceptions of patient's prognosis, preference for cardiopulmonary resuscitation (CPR), and length of relationship were assessed by interview. A propensity score for receiving care from an oncologist was constructed. After propensity-based matching of patients, practices and outcomes of oncologists' and generalists' patients were assessed through group comparison techniques. RESULTS: Generalist and oncologist attendings showed comparable care practices, including the number of therapeutic interventions, eg, "rescue care" and chemotherapy, and the number of care topics discussed with patients/ families. Length of stay, discharge to supportive care, readmission, total hospital costs, and survival rates were similar. For both physician groups, perception of patients' wish for CPR was associated with rescue care (P < 0.03), and such care was related to higher hospital costs (P < 0.000). Poorer prognostic estimates predicted aggressiveness-of-care discussions by both types of physicians. Length of the patient-doctor relationship was associated with oncologists' care practices. More documented discussion about aggressiveness of care was related to higher hospital costs and shorter survival for patients in both physician groups (P < 0.001). CONCLUSIONS: Generalists and oncologists showed similar care practices and outcomes for comparable hospitalized late-stage cancer patients. Physicians' perceptions about patients' preferences for CPR and prognosis influenced decision making and outcomes for patients in both physician groups. Length of relationship with patients was associated only with oncologists' care practices. Rescue care increased hospital costs but had no effect on patient survival. Future studies should compare physicians' palliative care as well as acute-care practices in both inpatient and ambulatory care settings. Patients' end-of-life quality and interchange between physician groups should also be documented and compared.
This article is structured in a question/answer format based on interviews with Dr. Carolyn Hope Smeltzer and Salima Manji Lin of PricewaterhouseCoopers, Chicago, and Chuck Thomas of Hinshaw & Culbertson, Rockford. The questions come from CEO's, healthcare executives, and nurse executives at hospitals that are contemplating mergers or that have both succeeded and failed to merge their institutions. The experts share their knowledge.
Xenobiotic resistance in animals, plants, yeast, and bacteria is known to involve ATP binding cassette transporters that efflux invading toxins. We present data from yeast and a higher plant indicating that xenobiotic resistance also involves extracellular ATP degradation. Transgenic upregulation of ecto-ATPase alone confers resistance to organisms that have had no previous exposure to toxins. Similarly, cells that are deficient in extracellular ATPase activity are more sensitive to xenobiotics. On the basis of these and other supporting data, we hypothesize that the hydrolysis of extracellular ATP by phosphatases and ATPases may be necessary for the resistance conferred by P-glycoprotein.