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Biomedical subjects

D Kaufman

Publications and source records attributed to D Kaufman.

At least 73 records · Page 4Linked to original sources
PubMed1996

Toxic effects of immunosuppressive drugs: mechanisms and strategies for controlling them.

Since cyclosporine (CsA) was introduced into clinical practice in late 1983 to prevent rejection in transplant patients, there has been an almost explosive growth in the number and types of transplants and the number of transplant centers, an increase in the life expectancy of the transplanted organ, and substantial decreases in rates of acute rejection and life-threatening infections. Despite these successes, major improvements in immunosuppressive therapy are needed, especially a reduction in toxic side effects and a rigorous definition of the relation between drug concentration and clinical effects. Such improvements may be achievable with the incorporation of new drugs such as tacrolimus and mycophenolate mofetil into immunosuppression protocols and the development of rigorously defined therapeutic drug-monitoring programs.

Cyclosporine↗
PubMed1995

Necrotizing fasciitis originating from pinna perichondritis.

NF is a potentially lethal infectious process usually found in the abdomen, perineum, or extremities. In the head and neck it usually starts from a dental infection but can be initiated from any source. One of the more serious sequelae is extension of the infection down the deep fascial planes of the neck leading to mediastinitis; this is associated with a higher mortality rate. The presence of an associated immunocompromising disease, such as diabetes, has been said to predispose an individual to NF, and the mortality rate has been shown to be higher (although perhaps not significantly so). When first described, NF was thought to be caused only by beta-hemolytic Staphylococcus. Now it known to be a polymicrobial infection with anaerobes and facultative anaerobes found most frequently. Treatment involves broad-spectrum intravenous antibiotics as soon as possible, narrowing the coverage as the results of the gram stain and cultures become available. The importance of aggressive, prompt surgical management cannot be overemphasized in the treatment of NF. Once the diagnosis of NF is strongly suspected, debridement of the affected areas must be accomplished as soon as possible. Despite the advances in the recognition and treatment of NF, there is still significant morbidity and mortality associated with this disease. Continued vigilance must be practiced if the survival rate is to continue to increase.

Aged↗
PubMed1994

Time course of coronary endothelial healing after injury due to ischemia and reperfusion.

BACKGROUND: Although it has been demonstrated in short-term preparations that ischemia with early reperfusion results in coronary vascular injury manifested by abnormal endothelium-dependent relaxation and increased permeability to plasma proteins, it has not been clear whether these abnormalities are permanent or reversible. METHODS AND RESULTS: In a canine model, regional coronary ischemia was accomplished by 1 hour of left anterior descending coronary artery ligation, and follow-up studies were performed after reperfusion for 1 hour, 48 hours, 2 weeks, or 9 weeks. Vasorelaxation was measured in vitro with preconstricted epicardial coronary artery rings subjected to increasing concentrations of the endothelium-dependent vasodilator ADP and the endothelium-independent vasodilator nitroprusside. At 1 and 48 hours of reperfusion, relaxation of rings from the ischemic reperfused artery to ADP was blunted, but relaxation to nitroprusside was normal. At 2 weeks there was a nonsignificant trend toward a blunted response to ADP in the ischemic/reperfused rings, and at 9 weeks a completely normal response to ADP was observed. Coronary microvascular permeability was assessed by measurement of protein leak index (PLI), by using a double-isotope technique with autologous radiolabeled transferrin and erythrocytes. At 1 and 48 hours of reperfusion there were substantial increases in PLI in the previously ischemic regions, indicative of increased extravascular transferrin. There was a small increase in PLI at 2 weeks but a completely normal measurement at 9 weeks. Electron microscopy of ischemic/reperfused vessels demonstrated endothelial cell swelling and other abnormalities in epicardial arteries and the microcirculation at 48 hours of reperfusion but normal endothelium at 2 weeks of reperfusion. CONCLUSIONS: After 1 hour of regional coronary ischemia, coronary endothelial injury occurs early in reperfusion with abnormalities in epicardial coronary artery endothelium-dependent relaxation, coronary microvascular permeability, and both epicardial coronary artery and microvascular histology. This pattern of injury persists for at least 48 hours, but there is partial functional and complete histological recovery within 2 weeks and complete functional recovery within 9 weeks.

Animals↗
PubMed1993

Cancer therapy and the randomized clinical trial. Good medicine?

True improvements in the treatment of cancer--by the introduction of new drugs or novel drug combinations, new therapeutic modalities, or technologic improvements of old modalities--result in higher response rates and prolonged survival when compared with existing therapies. When a new treatment convincingly meets the test of improving survival rates or, at worst, improving patients' quality of life, it becomes the accepted standard of care if its side effects are acceptable and its cost is not prohibitive. Improved therapeutic results can be demonstrated only by clinical trials with an adequate numbers of patients, appropriate control subjects, and a sufficient duration of follow-up. Therapeutic breakthroughs are revolutionary advances in treatment, usually rapidly and dramatically obvious in comparison with historic controls; demonstration of benefit in these cases does not usually require randomized trials. Much more common, however, are new therapies that represent modest, incremental advances over existing treatment and that usually require randomized comparison trials to demonstrate convincingly statistically significant improvement. A randomized clinical trial should test an important hypothesis. It must be carefully designed to ensure that both groups of patients are comparable in terms of various prognostic variables and to minimize subtle sources of bias. An honest belief that both arms of the trial are a priori equal must be maintained. Meeting these criteria, the randomized clinical trial offers to the individual cancer patient treatment that should be at least equal to the best available nonexperimental therapy. This equates with Good Medicine.

Cost-Benefit Analysis↗
PubMed1993

Taxol in combination with doxorubicin or etoposide. Possible antagonism in vitro.

BACKGROUND: Taxol is a novel chemotherapeutic agent that promotes microtubule assembly and stabilizes tubulin polymer formation. Clinical evaluation of its antineoplastic activity as a single agent and in combination with other chemotherapeutic drugs is in progress. METHODS: To evaluate the effect of combining taxol with other commonly used antineoplastic agents, clonogenic survival of human breast cancer MCF7 cells, human lung adenocarcinoma A549 cells, and human ovarian cancer OVG1 cells were assayed after an initial exposure to taxol for 24 hours (approximately LD90 for taxol), followed by a 1-hour incubation with varying concentrations of doxorubicin or etoposide (total taxol incubation time, 25 hours). RESULTS: When corrected for taxol-induced cytotoxicity, doxorubicin and etoposide caused less cell killing in the presence of taxol compared with control incubations of doxorubicin and etoposide alone. To determine if a different schedule of drug application resulted in a similar finding, MCF7, A549, and OVG1 cells were exposed to doxorubicin for 1 hour, followed by incubation with varying concentrations of taxol for 24 hours. Less-than-additive cytotoxicity for the combination of taxol and doxorubicin was found. Flow cytometry studies in MCF7 cells showed that taxol caused a G2/M cell cycle block. Fewer cells were found to be in S-phase, which is the most doxorubicin-sensitive phase of the cell cycle. The application of doxorubicin or etoposide to MCF7 cells for 1 hour resulted in partial G1 and G2/M cell cycle blocks. Fewer cells were found to be moving through the cell cycle, which is likely required for taxol cytotoxicity. CONCLUSION: Although direct antagonism of the cytotoxicity of doxorubicin or etoposide by taxol has not been proven, there is less-than-additive in vitro cytotoxicity when taxol is combined with these chemotherapeutic agents. The clinical implications of these findings are unknown; however, these findings generate concern about the combination of these agents in clinical trials and suggest that additional studies to determine optimal scheduling are needed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Altitude and time of day effects on EEG spectral parameters.

Electroencephalographic (EEG) recordings were obtained from nine male subjects at sea level and again following rapid ascent to high altitude (4300 meters) at 0900, 1600, and 1830 h. Electroencephalographic data were subjected to Fast Fourier Transformation and analyzed for beta, spindle, alpha, theta, delta, and total amplitudes. Total amplitude increased from baseline to altitude while relative theta (absolute theta/total amplitude) decreased from baseline to altitude. Amplitude for absolute and relative spindle and total amplitude increased across the day. The results indicate that altitude exerts an effect on the waking electroencephalogram which can be quantified via spectral analysis.

Adult↗
PubMed1993

Incorporation of dietary n-3 fatty acids into molecular species of phosphatidyl choline and cholesteryl ester in normal human plasma.

To understand the differences in the antiatherogenic actions of eicosapentaenoic acid (EPA, 20:5) and docosahexaenoic acid (DHA, 22:6), we determined their incorporation into molecular species of phosphatidylcholine (PC) and cholesteryl ester (CE) after feeding 12 g marine lipid concentrate/d to six normolipidemic males for 28 d. The time course of incorporation of EPA into plasma PC and CE showed a precursor-product relationship. In contrast, the DHA concentration of CE was markedly lower than that in PC, and the EPA-DHA ratio was 2-6-fold higher in CE than in PC at all time intervals. Three PC species--16:0-20:5, 16:0-22:6, and 18:0-20:5--increased, whereas 18:1-18:2, 18:0-18:2, and 16:0-20:3 decreased. In vitro formation of CE species in plasma by lecithin-cholesterol acyltransferase (LCAT) showed an increased formation of 20:5 CE but not 22:6 CE, indicating that DHA is a poor substrate for LCAT. These results demonstrate a differential incorporation of EPA and DHA into plasma lipids, which may be related to the differences in their biological effects.

Adult↗
PubMed1993

Prediction of early symptomatic recurrence after intestinal resection in Crohn's disease.

OBJECTIVE: This study was performed to identify clinical criteria that may help recognize patients with Crohn's disease who are at high risk for early symptomatic postoperative recurrence. SUMMARY BACKGROUND DATA: Currently, no reliable criteria are available to help recognize patients who are prone to experience early symptomatic recurrence. METHODS: One hundred sixty-four patients undergoing intestinal resection for Crohn's disease at the Mount Sinai Hospital between 1976 and 1989 were studied prospectively. Patients with symptomatic recurrent disease within 36 months were defined as having an early recurrence. RESULTS: Multivariate analysis revealed that the number of anastomoses was the most important prognostic indicator (p = 0.001), followed by inflammation at the resection margins (p < 0.05). Patients requiring an ileostomy had a significantly lower early recurrence rate than those having single or multiple anastomoses. There was no significant correlation between inflammation at the margins and early recurrence in patients requiring an ileostomy (n = 38), or a single anastomosis (n = 98). When the margins were examined in the 28 patients with 2 or more anastomoses, 10 of 11 patients (91%) with inflammation at either margin experienced early recurrence. Patients having multiple anastomoses with normal margins had the same recurrence rate as patients with single anastomosis (42%). CONCLUSIONS: Patients with extensive Crohn's disease requiring multiple resections with anastomosis, especially when microscopic inflammation is present at the margins, are at very high risk for symptomatic early recurrence. Ileostomy seems to be associated with a significantly lower early recurrence potential than anastomosis. Further study is needed to determine whether avoidance of multiple anastomosis and adjuvant medical treatment can alter the course of the disease after intestinal resection in patients at high risk for early symptomatic recurrence.

Adolescent↗
PubMed1993

Effective corneal retrieval in a general hospital. The Royal Melbourne Hospital Eye Bank.

An active program of corneal transplantation depends upon a constant supply of high quality donor tissue. We describe an effective and inexpensive system of corneal donor retrieval in a major teaching hospital, and present an analysis of its donor population. During the five-month period studied in detail (May to October 1991), 365 deaths occurred in the hospital. The relatives of the decreased were contacted and consent for donation was requested after 323 (88.5%) of these deaths. Consent was given in 212 cases (65.5% of requests), with a mean age of the donor population of 69 years. After screening donor tissue for quality, 110 pairs of corneal buttons and 10 globes of sclera were dispatched for surgery during the study period, giving an overall procurement rate of over 30%. Further, the efficient notification and 'on-call' retrieval system led to very rapid corneal retrieval, resulting in an average death to storage medium time of less than two hours.

Adolescent↗