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Biomedical subjects

M B Adams

Publications and source records attributed to M B Adams.

At least 73 records · Page 4Linked to original sources
PubMed1993

Delayed cardiac allograft rejection due to combined cyclosporine and antioxidant therapy.

The effectors of cell death in allograft rejection are poorly understood. Oxygen derived free radicals (ODFR) may participate in graft destruction. We examined the impact of the antioxidants ascorbic acid (AA) and alpha-tocopherol (AT) with low dose CsA on rat cardiac allograft survival. Lewis rats that had undergone heterotopic abdominal cardiac transplantation with Wistar-Furth allografts (day 0) were divided into 6 groups. Group 1 was the control group; groups 2 and 3 received AA (1200 mg/kg), and groups 4 and 5 received AT (800 IU/kg) by gavage daily until rejection. Groups 3, 5, and 6 were given CsA (2.5 mg/kg i.m.) days 1-15. Allograft rejection times (in days) were 7.7 +/- 1, 10.3 +/- 1.5 (P < 0.01 vs. group 1), 37.1 +/- 6.4 (P < 0.01 vs. group 1, P = 0.0004 vs. group 6), 9.0 +/- 1.4, 26.5 +/- 3.6 (P < 0.01 vs. group 1, P < 0.03 vs. group 6), and 20 +/- 4.9 (P < 0.01 vs. group 1) for groups 1, 2, 3, 4, 5, and 6. To assess the impact of AA on ODFR production, chemiluminescence was performed on zymosan-activated Lewis whole blood from control rats and rats administered AA. AA significantly decreased peak chemiluminescence (P < 0.05) as compared with nontreated rats indicating effective ODFR scavenging. To determine whether AA and AT inhibit lymphocyte stimulation, mixed lymphocyte response testing was performed with irradiated Wistar-Furth lymphocytes as stimulator cells for Lew responder cells from rats treated as groups 3, 5, and 6. CsA significantly suppressed (P < .05) proliferation as compared with untreated controls. Neither AA nor AT enhance CsA's immunosuppressive effect by mixed lymphocyte response testing. In summary, prolongation of allograft survival with antioxidants AA and AT does not result from abrogation of lymphocyte responsiveness or alteration in CsA bioavailability. Rather, these data suggest that ODFR are involved in allograft destruction and support a role for effective antioxidant therapy in the treatment of allograft rejection.

Animals↗
PubMed1993

Tulopafant, a PAF receptor antagonist, increases capillary patency and prolongs survival in discordant cardiac xenotransplants.

Hyperacute rejection is a serious complication of xenogeneic organ transplantation. It is believed that platelets play a pivotal role in this phenomenon. In this study, we provide the first known evidence of the efficacy of the PAF receptor antagonist, tulopafant, in improvement in graft function and histology of discordant cardiac xenografts. Transplantation of guinea pig hearts into recipient rats resulted in hyperacute rejection. Pretreatment of recipient animals with tulopafant (but not indomethacin) extended rejection time by 4-5-fold. Histological examination revealed marked diminution of both interstitial hemorrhage and deposition of platelet and granulocytes in capillaries of cardiac xenografts when recipient animals were pretreated with tulopafant.

Animals↗
PubMed1992

Untreated diabetes mellitus promotes intestinal microbial overgrowth.

Gastrointestinal dysfunction is a common secondary complication of insulin-dependent diabetes mellitus, yet its etiology is unclear. Enteric microbial overgrowth may play a role. To quantitate the changes in mucosal-adherent enteric microbial populations in untreated diabetes mellitus and to assess the impact of two forms of insulin replacement therapy upon enteric microbial populations, age-matched male Lewis rats were rendered diabetic by the administration of intravenous streptozotocin (55 mg/kg). After diabetes was confirmed (blood glucose level greater than 250 mg/dL), rats were divided into three groups: no treatment (no insulin), treatment with daily insulin to maintain normoglycemia (3 to 7 units of protamine zinc insulin subcutaneously), or transplantation with a vascularized heterotopic duct-ligated pancreatic isograft. After 1 month, rats were killed, and segments of the proximal, middle, and distal small bowel were obtained. Mucosal samples were rinsed in phosphate-buffered saline to remove nonadherent bacteria prior to aerobic and anaerobic culturing. Microbial recovery was expressed as the log10 colony-forming unit/mg tissue wet weight. Untreated diabetes resulted in an overgrowth of mucosal-associated small bowel aerobic and anaerobic microbial populations compared with populations in normal nondiabetic age-matched control rats. Insulin treatment and pancreatic transplantation prevented microbial overgrowth in the diabetic small intestine. Pancreatic transplantation resulted in strict normoglycemia equivalent to that in nondiabetic control rats, whereas insulin treatment resulted in slightly higher blood glucose levels at sacrifice and wide fluctuations in blood glucose levels compared with nondiabetic control rats. These data suggest that sustained normalization of glucose levels is not required to prevent microbial overgrowth in diabetic rats.

Animals↗
PubMed1992

Enisoprost in renal transplantation. The Enisoprost Renal Transplant Study Group.

Prostaglandins of the E-series (PGE) mediate a wide variety of physiologic processes and have been shown to have regulatory roles in cell immunity. Previous animal and human trials have shown lower incidence of acute rejection when prostaglandins are administered in conjunction with standard immunosuppressives. This study evaluated the effects of the PGE analogue, enisoprost (EP), in a multicenter (39 centers) prospective, randomized, double-blind trial in 374 patients undergoing renal transplantation. Groups were placebo, enisoprost 50 micrograms p.o. q.i.d. (EP-50 micrograms), and enisoprost 100 micrograms p.o. q.i.d. (EP-100 micrograms). Patients received cyclosporine, azathioprine, corticosteroids, and Minnesota antilymphocyte globulin or OKT3 according to each center's protocol. Prophylactic antibody therapy (MALG or OKT3) was not randomized. Two hundred fifty-five patients completed the 8-week study period. Of the 119 patients who were withdrawn, 73 did so because of an adverse event. Rejection episodes occurred in 98 of 374 patients (26%). There was no statistically significant difference in the incidence of rejection between placebo- and EP-treated patients (P = 0.782). There was no significant difference in episodes of cyclosporine nephrotoxicity between placebo- and EP-treatment groups (P = 0.883). There was also no difference between incidence of acute tubular necrosis, duration of initial hospitalization, or need for rehospitalization between placebo- and EP-treated groups. Administration of EP was associated with frequent adverse events including elevation of body temperature, dyspepsia, and diarrhea. Antibody-treated patients had a higher percentage of black recipients, higher mean body weight, greater cold ischemic times, fewer living-related donors, and higher panel reactivity. Patients not receiving antibody prophylaxis were better matched immunologically than those receiving either MALG or OKT3. Despite these immunologic differences, there was no significant difference in the incidence of rejection in patients who did or did not receive antibody prophylaxis. Cyclosporine toxicity was more common in MALG-treated patients (P = 0.02). Renal function was worse in antibody-treated patients. There was no detectable effect of enisoprost on the incidence of acute rejection, renal function, or hospitalization in a multicenter prospective, randomized, double-blind trial in 374 patients undergoing renal transplantation.

Adult↗
PubMed1991

Small bowel transplantation promotes bacterial overgrowth and translocation.

Alterations in the symbiotic relationship between immunocompromised hosts and their resident gut microflora may lead to serious complications following small bowel transplantation (SBT). This study examined the effects of SBT and cyclosporine (CsA) immunosuppression on gut bacterial populations and translocation to the mesenteric lymph nodes. Sixty adult male meat-fed Lewis rats were divided into six groups: normal controls, CsA alone (24 mg/kg im qod), CsA carrier vehicle alone, isografts, isografts given CsA, and allografts given CsA. Rats were killed after 3 weeks and segments of small bowel and colon were harvested for quantitative tissue culture. Mesenteric lymph nodes and blood were cultured to identify translocation. Transplantation alone led to an increase in gram-negative aerobes from 2.6 to 4.6 colony forming units/100 mg tissue (P less than 0.05) in the distal ileum (transplanted segment). Eighty-four percent of transplanted animals receiving CsA had bacteria recovered from their mesenteric lymph nodes compared to none in controls (P less than 0.001) and 20% in isografts not receiving CsA (P less than 0.02). Intestinal transplantation alone appears to promote gram-negative overgrowth while the addition of CsA therapy facilitates translocation to the mesenteric lymph nodes and may predispose to gut-associated sepsis following SBT.

Animals↗
PubMed1991

Evaluation of renal transplant dysfunction using color Doppler sonography.

Color Doppler sonography (CDS) detects changes in renal blood flow that may be useful in evaluating renal transplant dysfunction (RTD). To assess the performance of CDS as a clinical test, we reviewed results from 223 CDS measurements in 130 renal transplant recipients during a 26 month period. Spectral wave forms were characterized by pulsatility index (PI) (maximum frequency shift minus minimum frequency shift divided by mean frequency shift). In 27 individuals with stable renal function, mean PI was 1.80 +/- 0.23 (S.D.). Abnormal PI were subsequently defined as greater than two S.D. more than the mean (PI greater than or equal to 2.3). CDS performed during the early post-transplant period (n = 91) could not differentiate acute tubular necrosis (ATN), obstruction and rejection. Abnormal studies were seen in 35 of 46 instances of ATN and in three of obstruction. In 132 studies done after the postoperative period, CDS became abnormal during rejection episodes in only 45 of 71 instances (sensitivity rate of 63 per cent). When abnormal, CDS was highly suggestive of rejection, however (45 of 49, 92 per cent specificity). Cyclosporine toxicity was not associated with abnormal pulsatility (zero of seven). In 68 instances, CDS and conventional 99mTc DTPA renogram flow studies were performed together within 24 hours. CDS was more sensitive in detecting rejection but the difference did not reach statistical significance (25 of 36 versus 17 of 36). The major advantage of CDS over conventional radionuclide imaging relates to its shorter examination time, lower cost and portable capabilities. CDS will probably become the roentgenologic imaging modality of choice in renal transplantation.

Color↗
PubMed1990

Small bowel transplantation in the rat with immediate restoration of intestinal continuity.

Compared with other rat transplant models, small bowel transplantation (SBT) is associated with higher peritransplant morbidity and mortality. We describe a two-stage technique of SBT in the rat that minimizes perioperative complications and also allows immediate restoration of intestinal continuity. Inbred Lewis strain rats were used as donors and recipients. A one-stage technique was originally adopted whereby the distal 50% of the jejunoileum was transplanted followed by near-total resection of the native small intestine and restoration of intestinal continuity. Among 20 rats transplanted with this technique, only one survived longer than 30 days. With the two-stage technique, transplantation of the donor jejunoileum in continuity was performed, followed by native enterectomy 7 days later. With the two-stage technique 17 of 20 rats survived indefinitely (greater than 50 days). Other important technical modifications are described. In the hands of a skilled microvascular surgeon, the two-stage SBT technique results in consistently improved survival and minimal morbidity.

Anastomosis, Surgical↗
PubMed1990

Ozone, acidic rain and soil magnesium effects on growth and foliar pigments of Pinus taeda L.

Height and diameter growth, biomass accumulation and leaf pigment concentrations were measured in loblolly pine (Pinus taeda L.) seedlings grown in soil containing 12 or 35 microg Mg g(-1) and exposed from May to October to subambient, ambient, or twice-ambient ozone (O(3)), and to simulated acidic rain with a pH of either 4.0 or 5.3. At the end of one growing season, height and diameter growth of seedlings exposed to twice-ambient O(3) were not statistically different from those of seedlings exposed to subambient O(3). Biomass of all plant parts was reduced by 7 to 16% in response to increasing O(3) concentration. No statistically significant growth responses to rain chemistry or soil magnesium status were observed, and there were no statistically significant interactive treatment effects. Needle pigment concentrations were not significantly affected by rain chemistry or soil Mg status and there were no visible signs of injury to needles that could be attributed to O(3) stress or Mg deficiency. Concentrations of chlorophyll a and b, and carotenes were 23, 30 and 21% higher (P </= 0.05) respectively, in seedlings exposed to twice-ambient O(3) than in seedlings from the other ozone treatments. There were no interactive treatment effects on needle pigment concentrations.

Journal Article↗