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Biomedical subjects

A Humar

Publications and source records attributed to A Humar.

At least 73 records · Page 4Linked to original sources
PubMed1999

Decreased acute rejection in kidney transplant recipients is associated with decreased chronic rejection.

OBJECTIVE: To determine whether a recent decrease in the rate of acute rejection after kidney transplantation was associated with a decrease in the rate of chronic rejection. SUMMARY BACKGROUND DATA: Single-institution and multicenter retrospective analyses have identified acute rejection episodes as the major risk factor for chronic rejection after kidney transplantation. However, to date, no study has shown that a decrease in the rate of acute rejection leads to a decrease in the rate of chronic rejection. METHODS: The authors studied patient populations who underwent transplants at a single center during two eras (1984-1987 and 1991-1994) to determine the rate of biopsy-proven acute rejection, the rate of biopsy-proven chronic rejection, and the graft half-life. RESULTS: Recipients who underwent transplantation in era 2 had a decreased rate of biopsy-proven acute rejection compared with era 1 (p < 0.05). This decrease was associated with a decreased rate of biopsy-proven chronic rejection for both cadaver (p = 0.0001) and living donor (p = 0.08) recipients. A trend was observed toward increased graft half-life in era 2 (p = NS). CONCLUSIONS: Development of immunosuppressive protocols that decrease the rate of acute rejection should lower the rate of chronic rejection and improve long-term graft survival.

Acute Disease↗
PubMed1998

Mycophenolate mofetil in pancreas transplantation.

BACKGROUND: Mycophenolate mofetil (MMF) has been shown to decrease the incidence of acute rejection episodes after kidney transplantation. The use of MMF along with tacrolimus for > or =1 year after pancreas transplantation has not been studied in a large single-center analysis. METHODS: Between July 1, 1995 and June 30, 1997, both MMF and tacrolimus were given to 120 pancreas transplant recipients. By category, 61 underwent simultaneous pancreas-kidney transplantation (SPK); 44 underwent pancreas transplantation after previous kidney transplantation (PAK); and 15 underwent pancreas transplantation alone (PTA). By donor source, 86% of the grafts were from a cadaver, and 14% were from a living-related donor. Induction therapy was with MMF, tacrolimus, prednisone, and antithymocyte globulin (n=109) or OKT3 (n=2). Until oral intake was resumed, recipients initially received intravenous azathioprine. Side effects were as follows: gastrointestinal (GI) toxicity in 53% of recipients receiving combined MMF and tacrolimus therapy; bone marrow toxicity in 24% of recipients receiving MMF alone; nephrotoxicity in 18% and neurotoxicity in 11% of recipients receiving tacrolimus alone. We did a matched-pair analysis to compare outcome in MMF versus azathioprine recipients, using the database of the International Pancreas Transplant Registry. Matching criteria included transplantation category, transplantation number, recipient and donor age, duct management, HLA typing, and transplantation year. RESULTS: One-year patient survival rates were 98% for SPK, 98% for PAK, and 100% for PTA (P=NS). For SPK recipients, 1-year pancreas graft survival rates were 86% with MMF versus 79% with azathioprine (P=NS); kidney graft survival rates were 96% with MMF versus 86% with azathioprine (P=NS). The incidence of first rejection episodes at 1 year was significantly lower for MMF recipients (15% with MMF versus 43% with azathioprine) (P = 0.0003). For recipients of solitary pancreas transplants (PTA and PAK), we found no difference in graft survival rates between MMF and azathioprine. The conversion rate from MMF to azathioprine at 1 year was 14% for SPK recipients, 26% for PAK, and 39% for PTA (P < 0.007). The most common reason for conversion was GI toxicity, in particular for nonuremic (PTA) or posturemic (PAK) recipients. The rates of posttransplant infection and lymphoproliferative disease were low for recipients on MMF and tacrolimus. CONCLUSIONS: The combination of MMF and tacrolimus after pancreas transplantation is highly effective and safe. For SPK recipients, the incidence of acute reversible rejection episodes was significantly lower with MMF than with azathioprine. The conversion rate from MMF to azathioprine because of GI toxicity was lowest for SPK and highest for PTA recipients.

Adult↗
PubMed1998

Venous thromboembolic complications after kidney and kidney-pancreas transplantation: a multivariate analysis.

BACKGROUND: We reviewed the incidence of and risk factors for venous thromboembolic complications in our population of kidney (KTx) and simultaneous kidney-pancreas transplant (SPK) recipients. METHODS: Information was collected retrospectively from a database on 1833 KTx and 276 SPK recipients who underwent transplant surgery between January 1985 and August 1995. RESULTS: The incidence of deep venous thrombosis (DVT) was 6.2% (n= 132), with significantly higher rates after SPK (18.1%) vs. KTx (4.5%) (P < 0.001). The number of DVT episodes was highest in the first month; 17.5% occurred during this time. For KTx recipients, early thrombotic events were more common on the side of the graft (P=0.03); however, after 1 month, no correlation existed between the side of the graft and the side of DVT. For SPK recipients, DVT tended to be more common on the side of the pancreas (57%) vs. the kidney (43%) (P=0.10). By multivariate analysis, risk factors for DVT were: age > 40 years (odds ratio [OR]=2.2, P < 0.001), diabetes mellitus (DM) (OR=2.0, P=0.002), previous DVT (OR=4.4, P=0.001), and SPK transplant (OR=2.8, P < 0.001). Pulmonary embolus (PE) was identified in 44 recipients (incidence, 2.1%) and was fatal in 13 (30%). The incidence was significantly higher in SPK (4.71%) vs. KTx recipients (1.69%) (P < 0.01). The risk of death from PE was 0.5% in KTx recipients and 1.37% in SPK recipients (P=0.08). Risk factors for PE included DM (OR=2.6, P=0.005) and recent DVT (OR=8.9, P=0.0001). CONCLUSIONS: Based on risk and extrapolating from the general surgical literature, our recommendations for prophylaxis against DVT are use of graduated compression stockings for all recipients and, in addition, low-dose heparin for moderate and high-risk recipients (previous DVT, SPK, age > 40 years, DM).

Adult↗
PubMed1998

Surgical technique for vascularized ear transplantation in mice.

Traditionally, the mouse nonvascularized skin graft has been widely used in organ transplant research. There are, however, several limitations with this model, the main one being the different immune response of vascularized vs. nonvascularized grafts. We have recently developed a vascularized, orthotopic ear transplant model in mice. This model has several advantages that make it a useful tool to study many aspects of transplantation. The donor operation consists of harvesting the ear with intact arterial and venous pedicles. The arterial pedicle is dissected down to the common carotid artery with ligation of all branches except the auricular artery. The venous pedicle is based on the jugular vein with preservation of the auricular veins draining into the posterior facial vein. In the subsequent recipient operation, the graft is transplanted into an orthotopic position using the common carotid artery for arterial inflow and the jugular vein for venous outflow. We performed 16 such transplants (6 isografts, 5 allografts, and 5 xenografts), with a success rate of 94% (15/16). The donor operation time was 1.5 hours and the recipient operation time was 2.5 hours. The total time for anastamosis was 45 +/- 5 minutes. Serial biopsies were obtained on days 3, 5, and 7, and correlated with gross findings. In summary, this study illustrates that it is technically possible to transplant a mouse ear graft. The main advantage of this model is that it is a vascularized graft that can be visibly observed and easily biopsied, thus allowing for good correlation between gross and histological findings after transplantation. We plan to use this model further to study in detail the rejection patterns in an allograft and xenograft setting.

Animals↗
PubMed1998

Effect of cytomegalovirus infection on 1-year mortality rates among recipients of allogeneic bone marrow transplants.

The effect of cytomegalovirus (CMV) infection on 1-year mortality rates among allogeneic bone marrow transplant recipients who are receiving a standard protocol as prophylaxis for CMV infection is unclear. We determined the risk factors for death within 1 year among 103 bone marrow transplant recipients by performing a multivariate analysis. The results of donor and recipient CMV serologies did not predict 1-year mortality, although there was a trend towards higher mortality among CMV-seropositive recipients who received marrow from seronegative donors (P = .077). Multivariate analysis revealed that the factors independently associated with 1-year mortality were the development of CMV antigenemia (relative risk [RR] = 2.74; confidence interval [CI] = 1.28-5.86), bone marrow transplantation (BMT) from unrelated donors (RR = 3.20; CI = 1.30-7.92), and severe acute graft-versus-host disease (RR = 3.50; CI = 1.50-8.17). Although significant on univariate analysis, advanced underlying disease before BMT and the development of active CMV disease after BMT were not independent risk factors. In conclusion, the development of CMV antigenemia after BMT was associated with increased 1-year mortality, while the development of active CMV disease was not. Reactivation of CMV infection may represent a marker of poor immune reconstitution or may contribute to further immunosuppression after BMT.

Adolescent↗
PubMed1998

Kidney transplantation in children younger than 1 year using cyclosporine immunosuppression.

OBJECTIVE: The optimal age for transplantation in children with end-stage renal disease remains controversial. Supported by national data, many centers recommend dialysis until the child reaches a certain minimum age. The authors' policy, however, has been to encourage living donor (LD) transplants for young children, with no minimum age restriction. METHODS: Between January 1, 1984, and December 31, 1996, the authors performed 248 kidney transplants in children younger than age 13 years, using cyclosporine as the primary immunosuppressive agent. Recipients were analyzed in three age groups: group 1, younger than age 1 year (n = 26); group 2, age 1 through 4 (n = 92); and group 3, age 5 through 13 (n = 130). Almost all recipients in group 1 underwent a primary LD transplant. Therefore, to compare results more meaningfully among the three age groups, only primary LD transplants were analyzed (group 1, n = 25; group 2, n = 59; group 3, n = 58). RESULTS: In primary LD transplants, no significant difference was noted among the age groups in 1-and 5-year patient or graft survival rates. To date, all 25 recipients from group 1 are alive and well; 19 still have a functional original graft. Causes of graft loss in the remaining six recipients were chronic rejection (n = 3), vascular thrombosis (n = 2), and recurrent disease (n = 1). The incidence of acute rejection in group 1 recipients was lower than in the two older groups. However, the incidence of delayed graft function was slightly higher in the youngest group than in the two older groups. For recipients in group 1, growth (as measured by weight) improved significantly posttransplant: the mean standard deviation score rose from -2.8 pretransplant to -0.2 by age 5 and to +1.8 by age 10. The improvement in height was not as dramatic: the mean standard deviation score rose from -3.2 pretransplant to -1.6 by age 5 and to -1.4 by age 10. CONCLUSIONS: Kidney transplantation in young children, including those younger than 1 year old, can achieve results comparable to those in older children. As long as an adult LD is available, the timing of the transplant should be based on renal function rather than age.

Adolescent↗
PubMed1998

The acutely ischemic extremity after kidney transplant: an approach to management.

BACKGROUND: The purpose of this study was to review arterial thromboembolic complications presenting with an acutely ischemic lower extremity after a kidney (KTx) or simultaneous kidney-pancreas transplantation (SPK) and to describe an approach to their management. METHODS: We retrospectively reviewed all such transplantations (a total of 2109) performed between January 1985 and August 1995. We identified 16 recipients (incidence, 0.76%) in whom an acutely ischemic leg developed during the immediate postoperative period (within the first 48 hours). RESULTS: Of the 16 recipients, eight underwent a KTx (incidence, 0.45%) and eight underwent an SPK transplantation (incidence, 2.90%). Median age was 38 years (range, 15 months to 61 years). Thirteen had insulin-dependent diabetes mellitus (IDDM), a significantly higher incidence than in the control group (i.e., transplant recipients without this complication) (p < 0.01). Peripheral vascular disease (PVD) was documented before operation in eight (50%) of the recipients (vs 8.9% in the control group) (p < 0.01). Ten were uremic (on chronic dialysis) before transplantation; six were nonuremic (not on dialysis). Intraoperatively, 14 had moderate to severe atherosclerotic disease affecting the iliac vessels, seven of whom required some manipulation of the artery (either endarterectomy or tacking of the intima) to make it suitable for anastomosis. Heparin was administered systemically during cross clamping to only four. Most of the 16 recipients showed symptoms or signs of arterial occlusion within the first few hours after operation. The most common symptom was pain; the most common physical finding was loss of femoral and distal pulses. Thirteen recipients had moderate to severe ischemia, as judged by physical examination; 15 returned to the operating room for surgical exploration. Eight underwent thrombectomy through an inguinal incision, with successful restoration of flow. Seven underwent exploration through the initial incision because of concern regarding the viability of the transplanted organ; five of them required transplant nephrectomy because of simultaneous thrombosis of the renal artery. No patient needed a bypass procedure to restore flow. Long-term morbidity as a result of the arterial occlusion was related to the severity and length of ischemia. CONCLUSIONS: On the basis of these results, we suggest the following recommendations: (1) all patients should undergo a thorough peripheral vascular examination before and after transplantation; (2) patients at higher risk for arterial thromboembolic complications (e.g., those with significantly diseased vessel at intraoperative examination, nonuremic patients) should receive intraoperative systemic heparin before cross clamping of the artery; and (3) patients with signs or symptoms suggesting arterial occlusion after operation should undergo prompt surgical exploration.

Acute Disease↗
PubMed1998

Isolated iliac artery stenosis as a cause of kidney graft dysfunction post-transplant.

We report the case of a kidney transplant recipient who, 1 yr post-transplant, presented with a serum creatinine level elevation secondary to iliac artery stenosis proximal to the graft anastomosis site. Stenosis of the transplant renal artery was initially suspected because of new onset of hypertension in addition to the rising creatinine level. Physical examination, however, revealed a diminished femoral pulse and a significantly lower ankle-brachial index on the right (versus left) lower extremity; these findings suggested a stenosis of the right iliac artery. Angiography confirmed a short stenotic lesion of the external iliac artery just proximal to the graft anastomosis site. The lesion--given its focal nature, its location, and the absence of disease elsewhere in the peripheral vascular system--was most consistent with a vascular clamp injury. The stenosis was managed by placement of an intravascular stent at the time of angiography. This resulted in normalization of the vascular examination findings, return to baseline of the serum creatinine level, and resolution of hypertension. This case demonstrates the value of physical examination in diagnosing this uncommon cause of an increased serum creatinine level post-transplant and the effectiveness of intravascular stents for its management.

Arterial Occlusive Diseases↗
PubMed1998

Thrombotic microangiopathy after liver-small bowel transplant.

We herein report the first case of immunosuppression-associated thrombotic microangiopathy (TMA) in which an extrarenal graft was primarily affected by the characteristic microvascular lesions. Although TMA is a well-known complication of cyclosporine (CSA) or tacrolimus therapy in renal and extrarenal (liver, heart, lung) transplant recipients, the kidney (transplanted or native) is typically the site primarily affected. We describe a combined liver-small bowel transplant recipient who developed tacrolimus-associated TMA that affected both her transplanted small bowel and her native kidneys. Involvement of the bowel, with evidence of microvascular occlusion on biopsy, led to the development of ischemic mucosal ulcers and eventual bowel perforation. Involvement of the kidney manifested with a doubling of the recipient's baseline serum creatinine level. Significant lowering of the tacrolimus dose resulted in healing of the small bowel ulcers and return to her baseline level of renal function. Therefore, it is important to note that, in transplant recipients, TMA with microvascular occlusion may affect extrarenal sites. In small bowel transplant recipients, the result might be ischemic ulcers in the graft and eventual bowel perforation.

Child↗
PubMed1997

Pancreas transplantation: indications, clinical management, and outcomes.

Although many advances have been made, pancreas transplantation still poses several challenges to the surgeon, internist and patient. With success rates now above 80% and improving yearly, diabetic patients must make a major life-style decision when considering a pancreas transplant. The main concerns are will the benefits of insulin-independence off-set the risks of surgery and immunosuppression. For diabetics near dialysis and considering a kidney transplant, the decision may not be as difficult. However, for those patients who are failing insulin therapy (brittle control) and remain with good renal function, the options are limited. As the success of pancreas transplantation improves, the procedure may become routine at more centers and become accepted by more third-party carriers. However, as with other solid organs, the availability of pancreases is limited and the supply soon to be exhausted. Thus, further advances are required for the prevention and treatment of Type 1 diabetes. Hopefully, the new frontiers of the next century will allow physicians to identify and preventively treat those at risk for the development of diabetes. Thus, the population of patients suffering from the consequences of this dreadful disease will be greatly reduced. With new developments in immunosuppression and islet transplantation, diabetic patients of the future may be offered the option of a procedure with reduced risks, less morbidity, and improved long-term cure rates.

Diabetes Complications↗
PubMed1997

Fatal falciparum malaria in Canadian travellers.

The authors report 2 cases of severe falciparum malaria in Canadians that had fatal outcomes. In the first case a man presented to a local hospital shortly after returning from Africa, but a diagnosis of malaria was not considered. He was transferred to a secondary and then to a tertiary care facility, where he subsequently died. Intravenous quinidine therapy, the treatment of choice, was unavailable at all 3 hospitals. In the second case, a woman taking chloroquine prophylaxis while visiting Nigeria developed cerebral malaria and died. These cases illustrate critical management issues: appropriate advice on malaria prevention before departure; consideration of malaria in all febrile people returning from an endemic area; ready access to parenteral therapy for severe malaria in Canadian hospitals; and an increase in awareness of travel medicine among family physicians.

Africa↗
PubMed1997

Living related donor pancreas and pancreas-kidney transplantation.

Our experience with living related donor (LRD) pancreas transplants shows that they can be performed with low morbidity and mortality for both donors and recipients. The recipient survival rate is 90% at both 1 and 5 years post-transplant. Our overall pancreas graft survival rate is comparable to that for cadaver transplants; if only technically successful cases are included, the graft survival rate is significantly better for LRD (versus cadaver) transplants. Advantages for LRD recipients include fewer rejection episodes, less immunosuppression, lower incidence of graft loss from rejection, and elimination of waiting time. Donor mortality in our series was 0%, and the incidence of surgical complications about 10-15%. LRD pancreas transplants are an attractive option for endocrine replacement therapy in certain diabetic patients. Optimal candidates are: (i) patients who are highly sensitized and have a low probability of receiving a cadaver graft; (ii) patients who should avoid high-dose immunosuppression; (iii) patients with nondiabetic identical twins; and (iv) uremic patients who want one operation with no waiting in order to remain or become dialysis free as well as insulin-independent. These transplants can be performed safely in all recipient categories--pancreas transplant alone, pancreas after kidney or simultaneous pancreas-kidney transplant. In all groups, LRD transplants should be done only when the donor, the recipient, and the entire family understands the advantages and disadvantages of LRD versus cadaver transplants.

Decision Making↗
PubMed1997

Parasight F test compared with the polymerase chain reaction and microscopy for the diagnosis of Plasmodium falciparum malaria in travelers.

Imported malaria is an increasing problem worldwide. A rapid and accurate test for Plasmodium falciparum infection would facilitate the diagnosis of malaria in the returned traveler. The ParaSight F antigen capture assay (dipstick test) is a new diagnostic test for P. falciparum based on detection of circulating histidine-rich protein-2 antigen. We performed a blinded evaluation of this assay compared with microscopy and the polymerase chain reaction (PCR) for the detection of P. falciparum infection in 151 febrile travelers. Compared with the PCR, the dipstick test had a sensitivity of 88% and a specificity of 97%. The ability of the dipstick test to detect P. falciparum was similar with that of microscopy (88% versus 83%) since the species of Plasmodium in 14 of 133 malaria-infected patients could not be determined by microscopy due to low parasite numbers. The dipstick test was 40% sensitive for infections with < 50 parasites/microliter, 89% with 50-100 parasites/microliter, and > or = 93% with > 100 parasites/microliter. Circulating antigen was detectable in 68% of the patients seven days after initiation of treatment and in 27% at day 28. The dipstick test represents a simple and accurate test for the diagnosis of P. falciparum infection in the returned traveler.

Adolescent↗
PubMed1997

Effect of early cyclosporine levels on kidney allograft rejection.

Acute rejection is the greatest risk factor for development of biopsy-proven chronic rejection and late kidney allograft loss. We previously noted that low cyclosporine (CsA) levels were a risk factor for early acute rejection in pediatric recipients (1). In our current study, we used logistic regression to identify risk factors for acute rejection in 726 adult kidney transplant recipients on triple therapy (prednisone, azathioprine, CsA). Variables considered for logistic regression analysis were donor organ source (cadaver vs. living), degree of HLA mismatch (1 to 6 vs. 0 antigen mismatch), transplant number (primary vs. retransplant), CsA levels (< 125 vs. > or = 125 ng/ml, < 150 ng/ml vs. > or = 150 ng/ml, and < 175 vs. > or = 175 ng/ml), and acute rejection episodes (0 vs. > or = 1). Of 726 recipients, 401 (55%) received cadaver kidneys; 325 (45%), living related. Overall, 572 (79%) had a primary transplant; 154 (21%), a retransplant. The vast majority of acute rejection episodes occurred within the first 2 months posttransplant; 68% of recipients had no acute rejection episodes by 2 months and 58% had none by 60 months posttransplant. Logistic regression analysis revealed that a cadaver donor kidney (vs. living) (p = 0.004), a 1 to 6 antigen mismatch (vs. 0 mismatch) (p = 0.001), and CsA levels < 150 ng/ml (vs. > or = 150 ng/ml) correlated with biopsy-proven acute rejection. The correlation for CsA levels < 150 ng/ml (vs. > or = 150 ng/ml) held true for levels at 1 wk (p < 0.05), 1 month (p = 0.0001), 2 months (p = 0.01), and 3 months (p = 0.02) posttransplant. Similar correlation was found for CsA levels < 125 ng/ml (vs. > or = 125 ng/ml) and < 175 ng/ml (vs. > or = 175 ng/ml). Comparative analyses were made (by Chi-square) of acute and chronic rejection rates when recipients were divided into 3 groups by CsA level (< 125 ng/ml, > or = 125 to < 150 ng/ml, and > or 150 ng/ml). At each time point (1 wk, 2 wk, 1 month, 2 months, 3 months), CsA levels < 125 ng/ml (vs. > or = 125 to < 150 ng/ml and > or = 150 ng/ml) were associated with the greatest increased risk of acute rejection--for both cadaver and living related recipients (all p < 0.05). CsA levels < 125 ng/ml at each time point (1 wk, 2 wk, 1 month, 2 months, 3 months) were also associated with a significantly increased risk of chronic rejection (all p < 0.001). The incidence of both acute and chronic rejection was reduced in the group with CsA levels > or = 125 to < 150 ng/ml and further reduced in the > or = 150 ng/ml group. Our data indicate that maintaining CsA levels > or = 150 ng/ml as part of triple therapy reduces the incidence of both acute and chronic rejection. Because chronic rejection is the leading cause of late allograft loss, maintaining adequate CsA levels should improve long-term graft survival. Based on this analysis, we have modified our own immunosuppressive regimens to achieve higher CsA levels earlier posttransplant.

Adult↗
PubMed1997

Effect of initial slow graft function on renal allograft rejection and survival.

Cadaver renal allografts with immediate excellent function have good long-term outcomes, while grafts with delayed function have been associated with an increased incidence of acute rejection (AR) and subsequent poor long-term graft survival. There is, however, an intermediate group with initial slow function whose outcome is not well defined. This group was examined by reviewing 510 patients that received primary cadaver transplants between 1/85 and 8/95. Recipients were grouped by initial function into: 1) those with immediate graft function (IGF), defined by serum creatinine (Cr) level < 3 mg/dl on post-operative day (POD) 5 (n = 237); 2) those with slow graft function (SGF), defined by serum Cr > 3 mg/dl on POD 5 but no need for dialysis (n = 160); and 3) those with delayed graft function (DGF), defined by the need for dialysis in the first week post-transplant (n = 113). Five-year graft survivals were determined for each group by Kaplan-Meier methods and compared by a generalized Wilcoxon test. The incidence of AR in the first 6 months was significantly higher in those with SGF (40%) vs. those with IGF (30%) (p < 0.05); both groups had a lower incidence than those with DGF (47%) (p < 0.05). In the absence of AR, 5-yr graft survival was similar between the 3 groups, 94%, 97% and 92% for IGF, SGF and DGF respectively. In the presence of AR, 5-yr graft survival was significantly reduced in all groups, but most notably in those with SGF (51%) or DGF (53%), as compared to those with IGF (80%), (p < 0.001). We conclude that recipients with SGF, but no AR, have excellent outcomes, comparable to those with IGF. However, there is an increased incidence of early AR associated with SGF. In recipients with SGF or DGF, AR has a more profound detrimental effect on long-term graft survival than in the IGF group. Thus, recipients with SGF are at increased risk for AR with resultant poor long-term graft survival, and may need modified immunosuppressive protocols.

Adult↗