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Biomedical subjects

M L Jordan

Publications and source records attributed to M L Jordan.

At least 73 records · Page 4Linked to original sources
PubMed1994

FK506 "rescue" for resistant rejection of renal allografts under primary cyclosporine immunosuppression.

Seventy-seven patients with ongoing acute rejection on initial CsA therapy were converted to FK506 to attempt graft salvage. Fifty-nine patients had undergone primary transplantation and 18 had been retransplanted; there were 52 cadaveric and 25 living-donor transplants. The indications for conversion to FK506 were ongoing, biopsy-confirmed rejection in all patients, including vascular rejection in 20. The median interval to rescue was 2 months (range 2 weeks to 36 months) after transplantation. Sixty-one of the 77 patients (79%) had already received one or more courses of an antilymphocyte preparation (OKT3: n = 33; ALG or ATG: n = 1; OKT3+ALG/ATG: n = 27). Of the 77 patients, 57 (74%) have been successfully rescued and still have functioning grafts with a mean follow-up of 14 months, with a mean serum creatinine of 2.35 +/- 0.97 mg/dl. Eighteen patients were already dialysis-dependent at the time of conversion to FK506; of these, 9 (50%) were successfully salvaged and have a mean serum creatinine of 2.3 mg/dl. Of the 61 patients previously treated with antilymphocyte preparations, 48 (79%) were rescued. In those salvaged, prednisone doses have been lowered from 22.2 +/- 7.2 mg/day preconversion to 7.5 +/- 5.6 mg/day postconversion, and 12 patients are on FK506 monotherapy. In nondiabetics, mean serum glucose was 101.4 +/- 20.5 mg/dl preconversion and 93.2 +/- 22 postconversion (P = 0.07), uric acid 7.3 +/- 2.3 and 7.1 +/- 1.5 mg/dl (P = 0.53), and triglycerides 199.2 +/- 101.6 and 167.2 +/- 106.4 mg/dl (P = 0.06). Cholesterol levels were significantly lower following FK conversion (207.7 +/- 46.5 mg/dl pre. vs. 188.3 +/- 39.7 post., P = 0.007). FK506 is capable of salvaging renal allografts with ongoing acute rejection on CsA therapy, even when antilymphocyte preparations have been ineffective.

Adolescent↗
PubMed1994

Comparison of FK-506 and cyclosporine regimens in pediatric renal transplantation.

Clinical aspects of FK-506 or cyclosporine immunosuppression regimens were evaluated in 48 consecutive pediatric renal transplant recipients. Tapering and discontinuation of prednisone was employed only in children receiving FK-506 who experienced minor or no rejection episodes during the 1st posttransplant month. At 1 year follow-up, 17 of 22 (77%) of all children with functioning allografts were receiving no prednisone (n = 13) or a mean dosage of 0.07 mg/kg per day (n = 4). During the 1st month, acute cellular rejection was more common in the FK-506 group (0.58 vs. 0.21 rejections per patient, P < 0.05) but allograft survival (92%) and renal function at 1 year posttransplant were identical in both groups. Compared with the cyclosporine regimen, FK-506 immunosuppression may be associated with a higher incidence of cytomegalovirus or reversible Epstein-Barr virus-induced lymphoproliferative disease. However, the FK-506 group had less hirsutism and gingival hypertrophy and required fewer antihypertensive medications independent of steroid use. Height standard deviation scores and weight-for-height index improved only in pre-adolescents receiving FK-506 but no prednisone (P < 0.02 and P < 0.05, respectively), but did not differ between children on FK-506 plus prednisone and those in the cyclosporine group. We conclude that the major advantages of FK-506 over cyclosporine immunosuppression are a reduced severity of hypertension and an improved cosmetic appearance which may improve long-term medical compliance. When used as monotherapy, FK-506 also shows promise in relieving the growth retardation associated with cyclosporine regimens that include prednisone.

Adolescent↗
PubMed1994

The Substance Abuse Consultation Team. Addressing the problem of hospitalized substance abusers.

The abuse of alcohol and other drugs represents a significant health care problem that has largely gone unrecognized and undiagnosed by physicians. A Substance Abuse Consultation (SAC) Team was initiated at a tertiary-care teaching hospital to provide expert diagnostic, interventional, and management services for hospitalized substance abusers. This preliminary study represents the first 100 consults received and reviewed. All 100 patients agreed to an interview and evaluation by the SAC Team. It was decided that 91 patients needed alcohol and other drug rehabilitation; 69% of these acknowledged having a substance abuse problem and accepted referral for treatment. The results of this report suggest the usefulness of a SAC Team for identification, evaluation, and intervention with hospitalized substance abusers. This program is easily replicable by other general hospitals and may provide a cost-effective, multidisciplinary approach to the abuse of alcohol and other drugs.

Alcoholism↗
PubMed1994

Macrophage synthesis of nitric oxide in the mouse mixed leucocyte reaction.

The production of nitric oxide (.N = O) in the splenocyte mixed leucocyte reaction (MLR) results in inhibition of allospecific lymphocyte effector function. In order to more clearly define the circumstances which promote .N = O synthesis in the MLR, responder accessory cell depleted spleen cells (ACDSC) were co-cultured with allogeneic macrophage cell lines or peritoneal macrophages. .N = O synthesis and C57BL/6 (H-2b) ACDSC proliferation were concurrently monitored in cultures comparing RAW 264.7 (H-2d, a high .N = O producer), P388D1 (H-2d, a low .N = O and BALB/c (H-2d) peritoneal macrophages as allogeneic antigen presenting cells (APC). A concentration-dependent increase in lymphocyte proliferation was observed in the presence of 1 x 10(4) to 1 x 10(5) P388D1. In contrast, addition of NG-monomethyl-L-arginine (NMA), a competitive inhibitor of .N = O synthase, was necessary in order to observe lymphocyte proliferation in the presence of increasing numbers of RAW 264.7 and BALB/c peritoneal macrophages. The addition of both anti-IL-2 and anti-IFN gamma (interferon-gamma) monoclonal antibodies inhibited .N = O synthesis in alloantigen-stimulated cultures. The IFN gamma induced expression of class II antigen, as well as the constitutive expression of class I antigen, on RAW 264.7 was similar in the presence or absence of NMA, indicating that induction of .N = O synthesis by IFN gamma does not inhibit H-2 antigen expression. Thus, cytokines produced as a result of alloimmune interaction initiate macrophage .N = O synthesis. However, allogeneic APC function, as assessed by H-2 antigen expression and subsequent stimulatory capacity of MLR, is not affected by initiation of the .N = O pathway.

Animals↗
PubMed1994

The role of the urological surgeon in the expansion of the cadaveric donor pool.

The next several years will bring into sharp focus the effects of the increasing demand for cadaveric donor organs in the face of a limited donor pool. Until xenotransplantation becomes a viable option, and unless kidneys can be cloned, we will continue to depend on the cadaveric-donor pool as a source of organs for renal replacement therapy. It is up to us as urological transplant surgeons to not only enhance public awareness of the organ shortage crisis but to continue to provide leadership in improving the techniques of organ recovery and expanding the limits of organs that were once considered to be marginal for transplantation. It is clear that advances in the surgical techniques, preservation solutions, and methods for predicting eventual long-term renal function from marginal donors will be critical in allowing precise selection criteria for kidneys for transplantation, resulting in the optimum use of a scarce and precious resource.

Adult↗
PubMed1993

Endogenous nitric oxide inhibits the synthesis of cyclooxygenase products and interleukin-6 by rat Kupffer cells.

Macrophage production of nitric oxide (.N = O) leads to considerable alterations of vital metabolic pathways in various target cells. The present study tested whether .N = O synthesis by Kupffer cells (KCs), the resident macrophages of the liver, interferes with the secretory function of these cells. As in other macrophage-type cells, the combination of lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) was a potent stimulus of .N = O synthesis by KC. Treatment with LPS and IFN-gamma also induced significant production of prostaglandin E2 (PGE2), thromboxane B2 (TBX2), tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), and IL-6. Inhibition of .N = O synthesis by KC. Treatment with LPS and IFN-gamma also induced significant production of prostaglandin E2 (PGE2), thromboxane B2 (TBX2), tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), and IL-6. Inhibition of .N = O synthesis by the L-arginine analogue of NG-monomethyl-L-arginine (NMA) resulted in a further increase of PGE2, TXB2, and IL-6 but not IL-1 and TNF-alpha production, indicating specific inhibitory effects of endogenous .N = O synthesis on the secretory activity of KCs. PGE2 production was most sensitive to the suppressive effect of .N = O and increased 24 h after stimulation with LPS and IFN-gamma from 16.3 +/- 4.9 ng/10(6) KCs without NMA to 94.3 +/- 17.9 ng/10(6) KCs with NMA. This effect of NMA was reversed by a 10-fold increase of the L-arginine concentration. No recovery of PGE2 production was seen when .N = O synthesis was blocked after 24 h. NMA treatment increased cyclooxygenase activity more than threefold, suggesting that .N = O inhibits PGE2 and TXB2 production through diminished PGH2 availability. .N = O synthesis did not significantly affect total protein synthesis or viability of the KCs. These results show that .N = O influences the production of specific inflammatory mediators by KCs.

Animals↗
PubMed1993

The histopathological changes associated with allograft rejection and drug toxicity in renal transplant recipients maintained on FK506. Clinical significance and comparison with cyclosporine.

The histopathological changes in 51 renal allograft biopsies from patients immunosuppressed with FK506 were compared with those seen in 30 needle biopsies obtained from patients on cyclosporine. The frequency and severity of rejection episodes were similar in both groups. Tubular vacuolation and myocyte vacuolation were found to be useful morphological markers to monitor short-term drug toxicity associated with both drugs. Long-term administration of FK506 led to striped interstitial fibrosis and arteriolar hyalinosis, similar to that previously documented for cyclosporine. One case each of hemolytic uremic syndrome and necrotizing arteriopathy was noted in patients receiving FK506. FK506 and cyclosporine are structurally unrelated compounds; hence the parallelism observed in their nephrotoxicity profile suggests that the interactions of these drugs with renal tissue involves the operation of two different initial signal-transducing mechanisms, ultimately activating the same final metabolic pathways.

Adult↗
PubMed1993

Fate of renal allografts transplanted in patients with urinary diversion.

Fifty-five kidneys were transplanted into 50 patients with supravesical urinary diversion at 16 transplant centers between 1970 and 1991. Of the 32 males and 18 females, 40 were adults (> or = 18 years) and 10 were less than 18 years old at the time of first transplant. Mean follow-up was 7.8 years. At last follow-up, 94% of recipients were alive and 73% of the kidneys were functioning. Fifteen kidneys were lost: 9 to rejection, 3 to noncompliance, and 3 patients died with a functioning kidney. Ten (18%) transplants were followed by surgical complications. Twenty-four (44%) were followed by medical complications of which urinary tract infection was most common. Recipients age 18 or younger had more urinary tract infections than older patients. No patient had urinary stones and no patient required medical treatment for metabolic abnormalities. We conclude that drainage of kidney transplants into a supravesical urinary diversion is an effective treatment for end-stage renal disease patients without adequate urinary bladders.

Adult↗
PubMed1993

A dual mechanism of immunosuppression by FK-506. Differential suppression of IL-4 and IL-10 levels in T helper 2 cells.

FK-506 is known to suppress the transcription of several genes encoding cytokines (e.g., IL-2, IFN-gamma) thought to play an important role in the allograft response. This general inhibition of cytokine gene transcription and protein production was previously thought to be the main mechanism by which FK-506 suppressed the immune response. We have studied the pattern of cytokine suppression caused by FK-506 in differentiated murine Th 2 cell lines. Supernatants from Th2 cells treated with FK-506 showed marked suppression of IL-4 but only moderate suppression of IL-10 levels. To determine whether this differential effect on IL-4 and IL-10 could also be seen at the mRNA level, total cellular RNA was isolated from cells treated with (1) media, (2) Con A (2 micrograms/ml), (3) FK-506 (50 ng/ml), or (4) Con A + FK-506. Reverse transcription-polymerase chain reaction and northern blot analysis were used to measure IL-4 and IL-10 mRNA. Similar to results at the protein level, FK-506 suppressed steady state levels of IL-4 mRNA markedly but had a lesser effect on steady state levels of IL-10 mRNA. Furthermore, FK-506 completely abrogated Con A-induced upregulation of IL-4 mRNA, but only slightly suppressed Con A-induced upregulation of IL-10 mRNA. IL-10 (cytokine synthesis inhibitory factor) is a cytokine with immunosuppressive properties that itself inhibits the production of IL-2 and IFN-gamma murine helper cells. IL-10 also downregulates MHC II expression and antigen presentation by monocytes. Therefore, the ability of FK-506 to differentially suppress the mRNA levels of immunostimulatory cytokines such as IL-2, IL-4, and IFN-gamma more than the mRNA levels of the immunosuppressive cytokine IL-10 suggests that the effective immunosuppression seen in vivo with FK-506 may be a combination of these 2 effects.

Animals↗
PubMed1993

Imaging of en bloc renal transplants: normal and abnormal postoperative findings.

OBJECTIVE: Cadaveric kidneys from donors less than 5 years old, previously considered inferior graft material, are now being successfully transplanted en bloc into children and adults. On the basis of our experience with 132 patients, we describe the general principles of the procedure and review the spectrum of normal and abnormal imaging findings in patients who have undergone this promising transplantation procedure. MATERIALS AND METHODS: Paired cadaveric kidneys obtained from donors less than 5 years old (mean age, 24 months) were transplanted en bloc to 132 patients (mean age, 37 years) at our institution between 1981 and 1991. All available medical, surgical, pathologic, and imaging records were retrospectively reviewed to define the surgical technique, 1-year survival rate of the graft, appearance of the transplant on postoperative imaging studies, and the prevalence of and imaging findings caused by vascular, urinary, infectious, and neoplastic complications after transplantation. Complications were confirmed by a definitive imaging study, surgical exploration, or study of a pathologic specimen. RESULTS: Paired donor kidneys were transplanted en bloc extraperitoneally into the recipient's right or left iliac fossa, with intact portions of the donor aorta and inferior vena cava anastomosed to the recipient's external iliac artery and vein. One-year graft survival was 70% during the first 8 years of the study and 78% during the last 2 years. Postoperative imaging, particularly sonography and scintigraphy, clearly depicted the normal individual kidneys, urinary collecting systems, and en bloc vasculature. Postoperative complications were vascular (arterial stenoses and thromboses, venous thromboses, and pseudoaneurysms) in 18%, urinary (obstruction and anastomotic leak) in 11%, infectious (caliceal fungal balls) in 1%, and neoplastic (posttransplant lymphoma) in 1%. The complications involved one kidney in 60% of the patients and both kidneys in 40%. The imaging findings caused by these complications were similar to those caused by complications occurring after transplantation of single cadaveric kidneys; however, their detection was more difficult because of the complexity of the en bloc graft. CONCLUSION: Because of the shortage of available donor organs, en bloc renal transplantation will most likely become increasingly popular. Familiarity with the imaging appearance of the normal transplant and of posttransplantation complications will allow radiologists to perform effective postoperative imaging evaluations.

Adolescent↗
PubMed1993

Randomized trial of FK 506/prednisone vs FK 506/azathioprine/prednisone after renal transplantation: preliminary report.

FK 506 was used as a primary immunosuppressive agent in 125 cases of renal transplantation in a randomized trial comparing FK 506/prednisone with FK 506/azathioprine/prednisone. With a mean follow-up of 5.5 +/- 2.5 months, there has been a 6-month actuarial patient survival of 99% and graft survival of 88%. There is no difference thus far between the two-drug and three-drug groups, although there may be less rejection and diabetes in the three-drug group. These results suggest that FK 506 is a useful immunosuppressive agent in kidney transplantation.

Actuarial Analysis↗
PubMed1993

[Echographic evaluation of kidney transplant "en bloc"].

Kidney transplants from infant donors are associated in the literature with poor results as regards both functionality and the survival of the transplant. Hence the increasing frequency, for kidneys obtained from donors under 5 years of age, of a surgical technique defined as "en bloc", involving the transplant of both kidneys into a single receiver and using the donor aorta and vena cava for vascular anastomosis. This technique seems to provide results comparable with those obtained using adult organs. Ultrasound and Doppler investigations are routinely performed in patients undergoing such a transplant. This study presents ultrasound and Doppler images of "en bloc" transplants, with particular reference to one case of pseudoaneurysm of the donor aorta and one of stenosis of the renal artery, revealed by Echo-Color-Doppler. The importance of ultrasound in this kind of transplant is emphasized, as it enables post-operative monitoring of the physiological growth in volume of the two transplanted infant kidneys.

Adult↗
PubMed1992

FK-506 inhibits proliferation and IL-4 messenger RNA production by a T-helper 2 cell line.

FK-506 is a potent immunosuppressant which is known to decrease the generation of allospecific cytotoxic T cells, possibly through its effect on cytokine production. FK-506 has been reported to have a suppressive effect on cytokine synthesis and secretion by pooled lymphocytes; its action on more selective subsets of lymphocytes is unknown. We currently report the effect of FK-506 on proliferation and IL-4 messenger RNA production by the differentiated mouse T-helper 2 cell line Ly1+2-/9. Ly1+2-/9 cells were grown in culture and treated with (1) media alone, (2) Con A, (3) FK-506, and (4) Con A + FK-506. Proliferation to Con A was determined by treating cells with 10 micrograms/ml Con A +/- FK-506 and measuring [3H]TdR uptake. Reverse transcriptase-polymerase chain reaction amplification was used to quantitate the level of IL-4 mRNA expression. FK-506 markedly inhibits Con A-induced proliferation and IL-4 mRNA production by the T-helper 2 cell line Ly1+2-/9. The ability of FK-506 to block the proliferation and IL-4 production by this helper cell subset suggests that this effect may contribute to its observed marked immunosuppressive properties in vitro and in vivo.

Cell Division↗
PubMed1992

Therapeutic use of ganciclovir for invasive cytomegalovirus infection in cadaveric renal allograft recipients.

Between November 1987 and September 1989, 419 cadaveric renal transplants were performed at our university. Of the patients 36 (8.6%) had invasive cytomegalovirus infection documented by gastric or duodenal mucosal biopsy in 23 (64%), bronchoalveolar lavage in 12 (33%), allograft biopsy or nephrectomy specimen in 5 (14%) and/or liver biopsy in 1 (3%). Cytomegalovirus severity was defined as mild in 27 patients, moderate in 6 and severe in 3. Ganciclovir [9-(1,3-dihydroxy-2-propoxymethyl)-guanine] was begun once the diagnosis was confirmed by histology or culture at a median of 56 days from transplantation (range 28 to 133 days). Duration of ganciclovir therapy was a minimum of 7 days or until fever was absent for 5 consecutive days (mean 12.2 +/- 3.5 days, range 4 to 21). Ganciclovir was well tolerated and side effects were limited to de novo neutropenia (7 patients), thrombocytopenia (2) and rash (1). Initial clinical improvement was observed in all patients. Two patients had recurrent cytomegalovirus infections that responded to a second course of ganciclovir. The 1-year actuarial patient survival was 100%. At a mean followup of 12.7 +/- 6.2 months 19 patients retained allograft function with a mean serum creatinine of 2.5 mg./dl. (range 1.2 to 4.6). Ganciclovir appears to be a safe and effective drug for the treatment of tissue invasive cytomegalovirus infection in cadaver renal transplant recipients. Prompt institution of this drug at diagnosis of invasive cytomegalovirus may lower the mortality rate formerly associated with this disease.

Adolescent↗
PubMed1992

Renal transplantation in patients 65 years old or older.

Between January 1982 and August 1989, cadaveric renal transplantation was performed in 22 patients 65 years old or older. Mean recipient age was 68 years (range 65 to 73 years). There were 17 men and 5 women. Additional risk factors included retransplantation (3 patients), high (greater than 30%) panel reactive antibody (4) and diabetes (1). All patients received cyclosporine as part of the immunosuppressive regimen. The 3-year actuarial patient and allograft survival rates were 89% and 71%, respectively. There were 6 graft losses due to chronic rejection (2 patients), renal vein thrombosis (1), myocardial infarction (1), withdrawal of immunosuppression because of sepsis (1) and primary nonfunction (1). Of the 16 patients with a functioning graft 12 currently have a serum creatinine of less than 2.0 mg./dl. These results suggest that cadaveric renal transplantation is an acceptable form of treatment for patients older than 65 years with end stage renal disease.

Age Factors↗