Preemptive therapy with plasmapheresis/intravenous immunoglobulin allows successful live donor renal transplantation in patients with a positive cross-match.
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Adult↗
Biomedical subjects
R A Montgomery
Publications and source records attributed to R A Montgomery.
Donor horseshoe kidneys for transplantation.
BACKGROUND: Experience with donor horseshoe kidneys for transplantation is very limited. Currently, horseshoe kidneys may be underutilized for transplantation because of the greater incidence of vascular anomalies, associated renal anomalies, and predisposition to renal disease. METHODS: In this report, we review five transplantations using horseshoe kidneys: the largest reported institutional experience. In addition, a review of all published cases in the English literature is performed. RESULTS: All five patients underwent successful renal transplantations with a median follow-up of 35 months. One patient lost his kidney from recurrent disease soon after transplantation. CONCLUSION: With appropriate reconstruction of the vessels, careful division of the isthmus, and avoidance of ureteral obstruction, long-term data revealed good graft survival of donor horseshoe kidneys in renal transplantation.
Adult↗
Should the indications for laparascopic live donor nephrectomy of the right kidney be the same as for the open procedure? Anomalous left renal vasculature is not a contraindiction to laparoscopic left donor nephrectomy.
BACKGROUND: The left kidney is preferred for live donation. In open live donor nephrectomy, the right kidney is selected if the left kidney has multiple renal arteries or anomalous venous drainage. With laparoscopic live donor nephrectomy (LLDN), there is reluctance to procure the right kidney because of the more difficult exposure and further shortening of the right renal vein (RRV) after a stapled transection. An experience with LLDN is reviewed to determine whether the right kidney should be procured laparoscopically. METHODS: From February 1995 to November 1999, 227 patients underwent live donor renal transplants with allografts procured by LLDN. The results of these transplants were analyzed. RESULTS: Of the 227 kidneys transplanted, 17 (7.5%) were right kidneys. In the early experience, three (37.5%) of the eight right renal allografts developed venous thrombosis, two of which had duplicated RRV. Based on these initially unacceptable results, donor evaluation and LLDN techniques were modified. Spiral computerized tomography (CT) replaced conventional angiography to define better the venous anatomy. LLDN was modified in one of three ways: (1) changing the stapler port placement such that the RRV was transected in a plane parallel to the inferior vena cava, (2) relocation of the incision for open division of RRV, or (3) lengthening of the donor RRV with a panel graft constructed of recipient greater saphenous vein. Finally, the recipient operation enjoined complete mobilization of the left iliac vein with transposition lateral to the iliac artery. With these modifications, there were no vascular complications with the subsequent nine right renal allografts (P<0.05). Of the left kidneys transplanted, 31 had multiple renal arteries, 14 had retroaortic or circumaortic veins, 4 had both multiple arteries and venous anomalies, and 1 had a duplicated IVC draining the left renal vein. There were no vascular complications with left renal allografts that had multiple arteries or venous anomalies. CONCLUSIONS: LLDN of the left kidney is technically easier. Left kidneys with multiple arteries or anomalous venous drainage are not problematic. The right kidney can be procured with LLDN; however, a rational approach to preoperative angiographic imaging, donor operation, and recipient operation is crucial.
Blood Vessels↗
Familial Tetralogy of Fallot caused by mutation in the jagged1 gene.
Tetralogy of Fallot (ToF) is the most common form of complex congenital heart disease, occurring in approximately 1 in 3000 live births. Evaluation of candidate loci in a large kindred segregating autosomal dominant ToF with reduced penetrance culminated in identification of a missense mutation (G274D) in JAG1, the gene encoding jagged1, a Notch ligand expressed in the developing right heart. Nine of eleven mutation carriers manifested cardiac disease, including classic ToF, ventricular septal defect with aortic dextroposition and isolated peripheral pulmonic stenosis (PPS). All forms of ToF were represented, including variants with pulmonic stenosis, pulmonic atresia and absent pulmonary valve. No individual within this family met diagnostic criteria for any previously described clinical syndrome, including Alagille syndrome (AGS), caused by haploinsufficiency for jagged1. All mutation carriers had characteristic but variable facial features, including long, narrow and upslanting palpebral fissures, prominent nasal bridge, square dental arch and broad, prominent chin. This appearance was distinct from that of unaffected family members and typical AGS patients. The glycine corresponding to position 274 is highly conserved in other epidermal growth factor-like domains of jagged1 and in those of other proteins. Its substitution in other proteins has been associated with mild or atypical variants of disease. These data support either a relative loss-of-function or a gain-of-function pathogenetic mechanism in this family and suggest that JAG1 mutations may contribute significantly to common variants of right heart obstructive disease.
Amino Acid Sequence↗
Laparoscopic live donor nephrectomy. A review of the first 5 years.
Laparoscopic live donor nephrectomy is technically feasible. The operation has evolved over the last 5 years and is greatly improved compared with the procedure originally described. Advantages to the donor when compared with the standard open operation are decreased postoperative pain, shorter hospitalization, a quicker recuperation, an earlier return to driving, and an earlier return to employment. These improvements have resulted in fewer lost wages and a lower financial burden for donors. Live donor nephrectomy also provides improved cosmetic results. It successfully removes many of the disincentives to live kidney donation and has resulted in an increased willingness of individuals to donate their kidneys. The operative risk seems to be equivalent to that of the open donor operation performed through a flank approach. Although there is no financial advantage of the laparoscopic operation in terms of hospital costs, the increase seen in live donor transplantation may result in long-term cost savings overall. Kidneys procured laparoscopically function well in recipents in the short and long term. There is no increased risk for rejection or technical complications, and the recipent's length of hospitalization is unaffected. The laparoscopic donor operation does not have any apparent deleterious effect on the recipient. The procedure is being adopted rapidly by transplant centers around the world and has been performed at more than 100 centers on five continents. The authors believe that laparoscopic live donor nephrectomy will become the standard of care in the not too distant future.
Humans↗
Liver transplantation in patients with severe portopulmonary hypertension treated with preoperative chronic intravenous epoprostenol.
Portopulmonary hypertension (PPHTN) is no longer an absolute contraindication to orthotopic liver transplantation (OLT). The pre-OLT management of patients with PPHTN requires early diagnosis and chronic therapy with intravenous epoprostenol to decrease pulmonary vascular resistance (PVR). Close follow-up is necessary to reassess pulmonary artery pressures (PAPs) and evaluate right ventricular (RV) function. This assists in the optimal timing of OLT. Successful management also necessitates reassessment of pulmonary artery hemodynamics just before OLT, with clearly defined parameters used to determine whether to proceed. Even with the intraoperative and postoperative availability of potent pulmonary vasodilators, clinical management may be suboptimal in reducing PAP. Adequate reduction in PVR and improvement in RV function in response to chronic epoprostenol therapy may facilitate successful OLT. We present a case report and review the limited experience with this treatment.
Adult↗
Plasmapheresis and intravenous immune globulin provides effective rescue therapy for refractory humoral rejection and allows kidneys to be successfully transplanted into cross-match-positive recipients.
BACKGROUND: Hyperacute rejection (HAR) and acute humoral rejection (AHR) remain recalcitrant conditions without effective treatments, and usually result in graft loss. Plasmapheresis (PP) has been shown to remove HLA- specific antibody (Ab) in many different clinical settings. Intravenous gamma globulin (IVIG) has been used to suppress alloantibody and modulate immune responses. Our hypothesis was that a combination of PP and IVIG could effectively and durably remove donor-specific, anti-HLA antibody (Ab), rescuing patients with established AHR and preemptively desensitizing recipients who had positive crossmatches with a potential live donor. METHODS: The study patients consisted of seven live donor kidney transplant recipients who experienced AHR and had donor-specific Ab (DSA) for one or more mismatched donor HLA antigens. The patients segregated into two groups: three patients were treated for established AHR (rescue group) and four cross-match-positive patients received therapy before transplantation (preemptive group). RESULTS: Using PP/IVIG we have successfully reversed established AHR in three patients. Four patients who were cross-match-positive (3 by flow cytometry and 1 by cytotoxic assay) and had DSA before treatment underwent successful renal transplantation utilizing their live donor. The overall mean creatinine for both treatment groups is 1.4+/-0.8 with a mean follow up of 58+/-40 weeks (range 17-116 weeks). CONCLUSIONS: In this study, we present seven patients for whom the combined therapies of PP/IVIG were successful in reversing AHR mediated by Ab specific for donor HLA antigens. Furthermore, this protocol shows promise for eliminating DSA preemptively among patients with low-titer positive antihuman globulin-enhanced, complement-dependent cytotoxicity (AHG-CDC) cross-matches, allowing the successful transplantation of these patients using a live donor without any cases of HAR.
Adult↗
Laparoscopic live donor nephrectomy: the recipient.
BACKGROUND: Laparoscopic live donor nephrectomy offers advantages to the donor in terms of decreased pain and shorter recuperation. Heretofore no detailed analysis of the recipient of laparoscopically procured kidneys has been performed. The purpose of this study was to determine whether laparoscopic donor nephrectomy had any deleterious effect on the recipient. METHODS: A retrospective review was conducted of all live donor renal transplantations performed from January 1995 through April 1998. The control group received kidneys procured via a standard flank approach (Open). Rejection was diagnosed histologically. Creatinine clearance was calculated using the Cockroft-Gault formula. RESULTS: A total of 110 patients received kidneys from laparoscopic (Lap) and 48 from open donors. One-year recipient (100% vs. 97.0%) and graft (93.5% vs. 91.1%) survival rates were similar for the Open and Lap groups, respectively. A similar incidence of vascular thrombosis (3.4% vs. 2.1%, P=NS) and ureteral complications (9.1% vs. 6.3%, P=NS) were seen in the Lap and Open groups, respectively. The incidence of acute rejection for the first month was 30.1% for the Lap group and 31.9% for the Open group (P=NS). The rate of decline of serum creatinine level in the early posttransplantation period was initially greater in the Open group, but by postoperative day 4 no significant difference existed. No difference was observed in allograft function long-term. The median length of hospital stay was 7.0 days for both groups. CONCLUSIONS: Laparoscopic live donor nephrectomy does not adversely effect recipient outcome. The previously demonstrated benefits to the donor, and the increased willingness of individuals to undergo live kidney donation, coupled with the acceptable outcomes experienced by recipients of laparoscopically procured kidneys justifies the continued development and adoption of this operation.
Acute Disease↗
Enzymatic mutation detection (EMD) of novel mutations (R565X and R1523X) in the FBN1 gene of patients with Marfan syndrome using T4 endonuclease VII.
The Enzymatic Mutation Detection (EMDtrade mark) method is a streamlined and improved version of the original Enzymatic Cleavage of Mismatch (EMC) method. EMD is a fully homogeneous, rapid four step procedure that allows for detection and localization of mismatched or unmatched nucleotides within heteroduplex DNA. To test the utility of EMD for use in the screening of large and complex genes, the fibrillin 1 (FBN1) gene was scanned in a cohort of six patients diagnosed with connective tissue disorders. Four of the six patients were diagnosed with classic Marfan syndrome (MFS). The results were compared with a previous MDEtrade mark scanning of the same patient cohort. Two causative mutations, R565X and R1523X, were detected by EMD that were not detected by MDE. In both cases, the mutation resulted in premature termination of translation. In addition, several polymorphisms were detected by the enzymatic approach that failed detection by heteroduplex analysis. We propose that the EMD method is a sensitive and rapid approach to mutation detection in large genes such as FBN1.
Adult↗
Laparoscopic live donor nephrectomy: pre-operative assessment of technical difficulty.
Laparoscopic live donor nephrectomy decreases disincentives to live kidney donation. Thus, many centers are interested in adopting this procedure. However, the high stakes involved for both the donor and the recipient, and the technical difficulties of the operation, have tempered the enthusiasm of some surgeons. Ideally, if early in their series, surgeons could select patients that would be the least challenging technically, it would facilitate the dissemination of this operation. The purpose of this study is to determine if anatomic or radiologic parameters can accurately assess pre-operatively the degree of technical difficulty of laparoscopic live donor nephrectomy for any individual patient. Abdominal spiral three-dimensional CT scanning was performed prior to laparoscopic donor nephrectomy. CT scans were reviewed for six radiographic anatomic parameters. Seven clinical anatomic measurements relating to body habitus were recorded upon induction anesthesia at the time of surgery. Demographic data for gender, age, race, weight, height, and smoking history were collected. Following laparoscopic live donor nephrectomy, the following six component parts of the operation were graded on a scale of 1-4 (1 = easy, 4 = very difficult) for technical difficulty: a) mobilization of the colon; b) mobilization of the upper pole; c) dissection of the renal vein; d) dissection of the renal artery; e) division of the adrenal vein; and f) dissection of the ureter. Also, operative time, estimated blood loss, and intra-operative fluid requirements were recorded as surrogate markers of operative difficulty. Forty-one patients were included in the study. Laparoscopic donor nephrectomy was successfully completed in all cases. The sum of the difficulty scores was 9.9+/-3.1 (mean) (range, 6-18). No anatomic, demographic, or radiologic parameters were predictive of the total operative difficulty score. Of the surrogate markers, only operative time correlated with total difficulty score (R = 0.47, p = 0.003). Donor weight and abdominal girth correlated with operative time (R = 0.50, p = 0.002; R = 0.38, p = 0.019) but not with total difficulty score (R = 0.10, p = 0.51; R = -0.02, p = 0.90, respectively). When the easiest cases and the hardest cases (< or = 25th percentile and > or =75th percentile total difficulty score, respectively) were segregated out, again no anatomic, demographic, or radiologic parameters were predictive of operative technical difficulty. In conclusion, laparoscopic live donor nephrectomy technical difficulty could not be predicted by body habitus from the variables examined in this study. Hence, it was equally likely that performing laparoscopic live donor nephrectomy using a heavy donor would be technically easy, as using a thin donor would be difficult. Although, in general, operative time increased with donor size and weight, it appears that laparoscopic live donor nephrectomy operative technical difficulty is dependent upon such factors as amount of laparoscopic working space, quality of tissue planes, and retractability of the colon and mesocolon; factors that, to date, are not quantifiable.
Adult↗
Laparoscopic live donor nephrectomy.
Live donor renal transplantation has many advantages including greater graft and patient survival, shorter waiting periods, improved human leukocyte antigen matching, and less cold ischemia. Until recently, disincentives from the operation, such as prolonged hospitalization, postoperative pain, and significant convalescence, have deterred live donor renal transplantation. This article describes the technique of laparoscopic live donor nephrectomy and briefly reports the results. The procedure has resulted in improved postoperative recovery and shorter convalescence, with no effect on recipient renal function.
Humans↗
Technical considerations in the delivery of the kidney during laparoscopic live-donor nephrectomy.
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Humans↗
Laparoscopic live donor nephrectomy: the four year Johns Hopkins University experience.
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Humans↗
Laparoscopic live donor nephrectomy: debating the benefits. Pro: similar costs to traditional surgery and procedure wins donors.
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Costs and Cost Analysis↗
Living-donor nephrectomies: laparoscopy and open techniques.
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Humans↗
Multiple molecular mechanisms underlying subdiagnostic variants of Marfan syndrome.
Mutations in the FBN1 gene, which encodes fibrillin-1, cause Marfan syndrome (MFS) and have been associated with a wide range of milder, overlap phenotypes. The factors that modulate phenotypic severity, both between and within families, remain to be determined. This study examines the relationship between the FBN1 genotype and phenotype in families with extremely mild phenotypes and in those that show striking clinical variation among apparently affected individuals. In one family, clinically similar but etiologically distinct disorders are segregating independently. In another, somatic mosaicism for a mutant FBN1 allele is associated with subdiagnostic manifestations, whereas germ-line transmission of the identical mutation causes severe and rapidly progressive disease. A third family cosegregates mild mitral valve prolapse syndrome with a mutation in FBN1 that can be functionally distinguished from those associated with the classic MFS phenotype. These data have immediate relevance for the diagnostic and prognostic counseling of patients and their family members.
Adult↗
Semi-quantitative polymerase chain reaction analysis of cytokine and cytokine receptor gene expression during thymic ontogeny.
Semi-quantitative, polymerase chain reaction (PCR) is used to uncover the patterns of cytokine transcription in the mouse thymus from day 14 to day 20 of gestation, a time period which includes many of the important events in thymic ontogeny. Interleukin 4 (IL-4), IL-7 and interferon gamma (IFN-gamma) mRNA is abundant from fetal day (Fd) 14-16, corresponding with the period of rapid proliferation of immature thymocytes in vivo. As the level of mRNA for these cytokines diminishes, the induction and increased expression of IL-3 and IL-2 occurs. The transcription of these cytokines correlates temporally with the period of proliferation-dependent phenotypic differentiation between Fd 16 and 20. The thymic epithelium (TE)-derived cytokines including IL-1alpha, IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) begin to be transcribed between Fd 14-15 and show peak mRNA abundance from Fd 16-20. IL-5, tumour necrosis factor alpha (TNF-alpha) and LT (lymphotoxin or TNF-beta) constitute a fourth group of cytokines, along with the IL-4 receptor (IL-4R), which are transcribed at an even level throughout the fetal period. The IL-2 receptor beta chain (IL-2Rbeta) and IL-10 show abundant mRNA from Fd 14-20 and have a peak level of mRNA content on Fd 16. Taken together, these studies uncover complex, overlapping patterns of cytokine gene expression. The mRNA abundance and pattern of expression of each cytokine or cytokine receptor may indicate the relative contribution that it makes to different stages of fetal thymic ontogeny.
Animals↗