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Biomedical subjects

J Edelstein

Publications and source records attributed to J Edelstein.

At least 19 recordsLinked to original sources
PubMed2000

Osteomyocutaneous flap as a preclinical composite tissue allograft: swine model.

Composite tissue allotransplantation (CTA) constitutes one of the last frontiers of microsurgery. Prior to its clinical application, the long-term efficacy of modern immunotherapy must be tested in a pre-clinical CTA model. Based on the concept of osteomyocutaneous forearm flap, we developed a CTA flap model in swine. After identifying the vascular territory of the flaps in six pigs (vascular casting), flaps were transplanted from mismatched donor to recipient pigs (n = 6). Rejection was assessed daily by visual inspection and histopathology of biopsy specimens. Recipient pigs were able to ambulate immediately following surgery. There were no flap failures owing to technical or surgical complications. Rejection occurred over a period of 7 days as manifested by edema, cellular infiltration, epidermalysis, and thrombosis. This pre-clinical flap model is excellent for evaluating the effectiveness of modern immunotherapy because it is anatomically and immunologically relevant and because the minimal morbidity caused to the animal permits long-term studies.

Animals↗
PubMed2000

Swine composite tissue allotransplant model for preclinical hand transplant studies.

Our laboratory previously developed and used an orthotopic radial forelimb osteomyocutaneous flap in the pig as a preclinical composite tissue allograft (CTA) model. To ensure that it mimicked the clinical situation as closely as possible we developed this model taking many immunologic and reconstructive considerations into account. While our original pig CTA model was ideal for studying the methods of preventing skin, muscle, bone, vessel and nerve rejection, and systemic toxicity, it did not include specialized tissues/structures of a joint and digit. Therefore, we were unable to evaluate rejection of these specialized tissues and their functional properties. Recognizing the importance of assessing joint rejection and function in hand transplantation research we developed a new swine forelimb CTA model that included the animal's medial digit. The present study describes the anatomy and the transplantation technique used in this new preclinical CTA model. We transplanted a radial osteomyocutaneous flap that included the medial digit between two size- (17-21 kg) and age- (6-8-week) matched farm pigs. We removed the digit from the recipient pig's forelimb in continuity with a section of the radial bone and replaced it with the same structure transplanted from a donor pig. After transplantation, a full-length cast was placed on the recipient pig's operated limb and changes in flap color, temperature and the presence of edema were monitored continuously for 6 h, and then regularly at predetermined intervals over 4 days. No weight bearing restrictions were placed on the animal's operated limb. After 4 days, the animal was euthanized. Direct visual monitoring of the allograft during 4 days revealed it was viable with no signs of graft failure due to technical complications associated with the transplant procedure. Upon waking from anesthesia, the animal stood and wandered freely about its cage with no apparent difficulty. Based on the animal's high level of activity at this time, we concluded that the procedure caused it minimal morbidity. At 4 days after the operation, early signs of rejection (skin erythema and edema) were observed. By incorporating a digit into our original CTA pig forelimb model we have made it a better model for performing preclinical hand transplant studies. The added advantage of being able to assess methods of preventing rejection in the specialized joint/digital tissues (articular cartilage, digital flexor and extensor systems, the nail complex) and assess long-term function of these structures is important. The fact that the procedure does not cause major morbidity to the animal makes it possible to conduct long-term graft survival and functional studies.

Animals↗
PubMed1999

Scoring of skin rejection in a swine composite tissue allograft model.

BACKGROUND: For the first time, we define and correlate visual and histologic grading systems of composite tissue allograft (CTA) skin rejection in a large-animal model and determine the utility of these grading systems for early diagnosis and monitoring of rejection. MATERIALS AND METHODS: Sixteen pairs of outbred swine underwent transplant of a forelimb osteomyocutaneous free flap. Group I (n = 6) did not receive immunosuppressive therapy. Group II (n = 10) received oral cyclosporin A, mycophenolate mofetil, and prednisone. The flap was visually inspected and protocol skin biopsies were taken at frequent intervals over a 90-day period. Visual Grades 0 (no rejection) to 4 (severe rejection) were assigned based on skin color, bleeding from biopsy site, and blister formation. Histologic Grades 0 to 4 were assigned based on the degree of vasculitis, folliculitis, dermal inflammation, and epidermal degeneration present. RESULTS: All Group I animals progressively rejected their graft by Day 7. Group II grafts survived from 19 and 90 days; 93% of 115 biopsy specimens were read to be within +/-1 histologic score of their assigned flap visual grade. Visual assessment carried an 8% false positive and 39% false negative rate with regard to biopsy-proven rejection. However, 81% of missed rejection specimens were histologic Grade 1. Biopsy, when visually indicated, would detect all rejection episodes when histologically Grade 1 or 2 and still potentially reversible. CONCLUSIONS: Visual scoring of CTA skin serves as a useful tool for initially detecting rejection, but repeated histologic evaluation is necessary for monitoring the subsequent course of the graft.

Animals↗
PubMed1999

Pharmacokinetics of intra-arterial delivery of tacrolimus to vascularly isolated rabbit forelimb.

A vascularly isolated rabbit forelimb model simulating conditions of composite tissue allografting was used to determine the regional pharmacokinetic advantage achievable in extremity tissue components during i.a. tacrolimus (FK506) administration. FK506 was infused continuously via osmotic minipump into the right brachial artery of New Zealand rabbits at 0.05, 0.1, and 0.2 mg/kg/day. On day 6, FK506 concentrations were measured in aortic whole blood, heart, lung, liver, kidney, spleen, and fat, as well as in skin, muscle, bone, and bone marrow samples from both right and left forelimbs. The relative tissue concentrations of FK506 in descending order were [spleen approximately lung approximately kidney] > [heart approximately skin approximately muscle] > [fat approximately bone marrow] > [liver approximately bone approximately blood]. In marked contrast to previous results with i.a. cyclosporin A infusion, only a minimal regional advantage of local FK506 delivery (mean right/left concentration ratios 1.0-1.4) was obtained in all forearm tissues over the dose range studied. For each limb tissue, left-sided FK506 concentrations significantly correlated with systemic blood levels, and the left-sided tissue-to-whole-blood concentration ratio did not vary significantly with dose. We conclude that FK506 is pharmacokinetically inferior to cyclosporin A for continuous i.a. administration to the vascularly isolated rabbit forelimb, and hypothesize that this difference is the result of differences in the distribution of each drug within whole blood. Our findings suggest that, despite its demonstrated efficacy in experimental and clinical transplantation, FK506 would not be an appropriate immunosuppressant to deliver via the i.a. route for prevention of limb allograft rejection.

Animals↗
PubMed1999

Long-term survival of an extremity composite tissue allograft with FK506-mycophenolate mofetil therapy.

BACKGROUND: High-dose tacrolimus (FK506) monotherapy has significantly prolonged rat hindlimb allograft survival. With an eye toward direct clinical application, we used a large-animal extremity composite tissue allograft model to assess the antirejection efficacy and systemic toxicity of combination FK506-mycophenolate mofetil (MMF) treatment. METHODS: Radial forelimb osteomyocutaneous flap transplants were performed between size-matched outbred pigs assigned to one of two groups: 5 control pigs received no immunosuppression and 9 animals received a once-daily oral FK506-MMF-prednisone regimen. Rejection was assessed by visual inspection of flap skin and was correlated with serial histopathologic examination of skin biopsy specimens. RESULTS: In all control pigs the flap was completely rejected on day 7. Of the 9 pigs receiving treatment, 3 died from pneumonia on days 29, 30, and 83 without signs of rejection and another died from gastric rupture on day 42 with persistent mild rejection. The remaining 5 animals were free of rejection at the end of the 90-day follow-up period (P < 0.005 vs controls). Overall, 5 pigs had pneumonia, 4 septic arthritis, 3 toe abscesses, and 5 diarrhea and decreased weight gain. CONCLUSIONS: Combination oral FK506-MMF treatment provided a superior antirejection effect but more produced more toxicity than that previously demonstrated with cyclosporin A-MMF therapy in our model. Our results suggest that reduction of FK506 or MMF doses might decrease both infectious and drug-specific side effects while still providing adequate prophylaxis against rejection.

Animals↗
PubMed1998

Long-term composite tissue allograft survival in a porcine model with cyclosporine/mycophenolate mofetil therapy.

BACKGROUND: Low-dose cyclosporine (CsA)/mycophenolate mofetil (MMF) therapy has significantly reduced the frequency of rejection and drug-induced side effects in rat hindlimb allograft recipients. With an eye toward direct clinical application, we developed a large-animal extremity composite tissue allograft model to assess the antirejection efficacy and systemic toxicity of combination CsA/MMF treatment. METHODS: Radial forelimb osteomyocutaneous flap transplants were performed between size-matched, outbred pigs assigned to one of two groups: 5 control pigs received no immunosuppression, and 10 pigs received a once-daily oral CsA/MMF/prednisone regimen. Rejection was assessed by visual inspection of flap skin and correlated with serial histopathologic examination of skin biopsies. RESULTS: In all control pigs, the flap was completely rejected on day 7. Of the 10 pigs receiving treatment, one died from pneumonia and an another from an anesthetic complication on days 19 and 30, respectively, without signs of rejection. Two flaps were lost on days 25 and 29 from severe rejection. Three pigs were free of rejection at the end of the 90-day follow-up period, and three had stable mild-to-moderate rejection at 90 days (P= 0.0007 vs. controls). White blood cell and platelet counts, serum creatinine values, and liver function tests remained normal in all animals receiving immunosuppressive therapy. CONCLUSIONS: Our results, to our knowledge, demonstrate for the first time that rejection can be significantly delayed in a large-animal composite tissue allograft model including skin using only orally administered agents dosed according to clinically relevant strategies without significant drug-specific systemic side effects.

Animals↗
PubMed1997

Communicating with individuals with Alzheimer's disease: examination of recommended strategies.

Meaningful conversation with individuals in the later stages of Alzheimer's disease (AD) has been considered difficult if not impossible. Limiting communication to simple concrete subjects and closed-ended questions is frequently recommended. Thirty-five 30 minute conversations with individuals with advanced AD (mean Mini-Mental State Examination [MMSE] = 10) were transcribed and the interactions examined. No significant differences in length or relevance of response by type of question was found indicating that subjects were able to respond to open-ended questions. Use of broad opening statements or questions, establishing commonalities, speaking as equals, and sharing of self-facilitated expression of feeling; recognizing themes with salience for the individual helped to maintain the discussion.

Affect↗
PubMed1997

Reliability of physical performance measures in nursing home residents with Alzheimer's disease.

BACKGROUND: Investigation of the effects of exercise on frail, institutionalized individuals with dementia has been impeded by concerns about the reliability of physical performance measures when used in this population. METHODS: The physical performance of 33 institutionalized subjects with Alzheimer's disease was measured during both the morning and afternoon of day 1 by rater 1 and during both the morning and afternoon of day 2, one week later, by rater 1 and rater 2. Intraclass correlation coefficients (ICCs) were calculated to examine the inter- and intrarater reliability of "sit to stand," "25-foot walk," and "the distance walked in 6 minutes" and walking speed over 25 feet and for 6 minutes. An analysis of variance was performed to determine the components of variance for each test. RESULTS: ICCs for "distance walked in 6 minutes" ranged from .80 to .99 with 77% of the variance explained by inter-subject difference. The ICCs for "time to walk 25 feet" ranged from .57 to .97 with 25% of the variance explained by inter-subject differences. In contrast, the "sit to stand" measure produced ICCs ranging from -.07 to .85 with only 7% of the variance explained by inter-subject differences in this impaired population. CONCLUSION: Our results support the contention that some physical performance measures can be used to test individuals in the later stages of Alzheimer's disease given appropriate modification. Although subjects with Alzheimer's disease may have difficulty following commands and/or require physical assistance, this does not prohibit the reliable assessment of physical performance if measurements are made over longer (6-minute walk) rather than shorter periods (25-foot walk).

Aged↗
PubMed1993

Ultrasonic-pathological comparison of the human arterial wall. Verification of intima-media thickness.

Recent intravascular ultrasound experience challenges the accuracy of ultrasonic measurement of arterial wall thickness. We reevaluated the correlation between histological and sonographic measurements of intima-media thickness using standard transcutaneous vascular technology. Carotid and femoral arterial segments were imaged before and after fixation using a 7-MHz linear-array vascular transducer. Log compression and beam orientation were varied. Mean intima, media, and adventitia thicknesses were measured and compared with corresponding histological tunica. Tissue processing caused 2.5% shrinkage. Intraobserver reading error was 0.7% for histology and 5.4% for sonography. Ultrasound overestimated the thickness of the intima and adventitia and underestimated the thickness of the media. For combined intima-media thickness, the differences between histology and imaging were insignificant, averaging 4% for the carotid artery and 9% for the femoral artery in the far-wall projection. In the near-wall projection, sonographic intima-media thickness was 20% less than that determined histologically. We conclude that ultrasonography is limited mainly by axial resolution in quantifying the dimensions of individual arterial tunica but is capable of accurately measuring far-wall intima-media thickness.

Aged↗
PubMed1992

The wedge punctoplasty for treatment of punctal stenosis.

We describe a new instrument, the Reiss punctal punch, which is specifically designed to performa "wedge" punctoplasty. The Reiss punctal punch was used alone to treat three eyelids of three patients, and in conjunction with horizontal tightening of the eyelid to treat 35 eyelids of 18 patients with symptomatic epiphora related to punctal ectropion with secondary punctal stenosis. After a mean follow up of 12 months, 36/38 (95%) of the eyelids demonstrated a patent punctum, and symptomatic relief was achieved in 35/38 (92%) of the eyes.

Dacryocystorhinostomy↗
PubMed1991

Acitretin plus UVB therapy for psoriasis. Comparisons with placebo plus UVB and acitretin alone.

UVB radiation is beneficial for the treatment of psoriasis vulgaris. Patients with recalcitrant disease, however, are slow to respond to UVB phototherapy with and without the use of coal tars or emollients. Etretinate and, more recently, acitretin have proved useful, but clinical improvement is slow when they are used as monotherapy in plaque psoriasis. Each drug also produces side effects, some of which are dose related. This study was designed to compare results of treatment with UVB combined with either acitretin (50 mg/day) or placebo to determine if psoriasis would respond faster and to less cumulative exposure to UVB and acitretin. The psoriatic disease cleared to a greater degree in patients treated with acitretin-UVB with fewer treatments and smaller amounts of UVB radiation than in patients treated with either placebo-UVB or acitretin alone.

Acitretin↗
PubMed1991

Dermatoglyphics and acute lymphocytic leukemia in children.

Cellular features of acute lymphocytic leukemia (ALL) in children suggest that it originates in abnormal embryogenesis. Because palmar flexion creases develop in the embryo at the same time as the blood-forming cells, and because both arise from mesodermal tissue, insults to the embryo that may lead to leukemic changes in the blood-forming cells may also result in aberrant palmar crease patterns. This study investigated the relationship between aberrant palmar creases and ALL in children who developed leukemia at age 6 years or younger. Odds ratios and chi squares demonstrated significant differences in bilateral aberrant palmar creases between ALL children and relatives (P less than .025). Differences were not explained by familial clustering of aberrant creases. These results support the theory that the insult occurred during pregnancy, probably in the first trimester. There were no significant differences in either bilateral or unilateral aberrant palmar creases between ALL children and their siblings. All children with bilateral aberrant creases had a higher incidence of central nervous system involvement (50%) than those without bilateral aberrant creases (6%). This may reflect a preleukemic change in utero before the time the blood-brain barrier has been established.

California↗
PubMed1989

Elderly patients' satisfaction with care under HMO versus private systems.

In one community, 100 elderly persons (25 HMO and 75 private patients) completed a 20-item scale that measured satisfaction with medical care. Data on demographics, health care utilization, and self-assessed health status also were collected to determine whether these variables would relate to HMO membership. Satisfaction scores were compared between HMO and private care groups by multivariate analysis of variance. Satisfaction with the doctor-patient relationship and convenience of care was higher in the private care group, whereas satisfaction with cost was higher in the HMO group. Interestingly, the HMO group evaluated private care and HMO care similarly. The private group rated HMO care less favorably. Additional comments reveal specific areas of satisfaction/dissatisfaction.

Aged↗
PubMed1985

The influence of the family on control of diabetes.

The aim of this paper was to determine if the adult diabetic's perception of his family environment influenced control of his diabetes. Diabetic men (N = 97) living with their families completed a 10-factor Family Environment Scale. Family scores at baseline were then used to predict metabolic control 6 months later using stepwise multiple regression analysis. Diabetic control was derived from weighted scales for hemoglobin A1, fasting blood glucose, triglyceride and cholesterol. Three of the family factors were significant statistically. Those patients in better control of their disease perceived their families to be low in conflict and organization and oriented toward achievement. The high achievement environment activates responsibility towards success, which apparently carries into physical management of the disease. Lower conflict among family members as well as less organization creates a more relaxed atmosphere which perhaps encourages flexibility, less anxiety, less pressure and greater support associated with better metabolic control.

Blood Glucose↗