Kidney transplantation in the absence of the infrarenal vena cava.
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Abdomen↗
Biomedical subjects
E Benedetti
Publications and source records attributed to E Benedetti.
Delayed graft function, acute rejection, and outcome after cadaver renal transplantation. The multivariate analysis.
The impact of delayed graft function on outcome after cadaver renal transplantation has been controversial, but most authors fail to control their analyses for the presence or absence of rejection. We studied 457 adult recipients of primary cadaver allografts at a single institution during the cyclosporine era. All patients received sequential immunosuppression. The incidence of delayed graft function (defined as dialysis being required during the first week after transplant) was 23%. There was a significant association between delayed graft function and cold ischemia time > 24 hr (P = 0.0001) and between delayed graft function and the occurrence of at least one biopsy-proven rejection episode (P = 0.004). Actuarial graft survival was not significantly different when comparing delayed graft function versus no delayed graft function for patients without rejection (P = 0.02). However, it was significantly worse for patients with both delayed graft function and rejection versus those with delayed graft function but no rejection (P = 0.005), as well as for grafts preserved > 24 hr versus < or = 24 hr (P = 0.007). By multivariate analysis, delayed graft function per se was not a significant risk factor for decreased graft survival for patients without rejection (P = 0.42). In contrast, rejection significantly decreased graft survival for grafts with immediate function (relative risk = 2.3, P = 0.0002), particularly in combination with delayed graft function (relative risk = 4.2, P < 0.0001). While cold ischemia time > 24 hr was also a significant risk factor (relative risk = 1.9, P = 0.02), other variables (preservation mode, 0 HLA Ag mismatch, age at transplantation, gender, diabetic status, and panel-reactive antibody at transplantation) had no impact on graft survival. Patient survival was significantly affected by the combination of delayed graft function and rejection (relative risk = 3.1, P < 0.0001), age at transplantation > 50 years (relative risk = 2.6, P < 0.0001), and diabetes (relative risk = 1.8, P = 0.006). Further studies are necessary to elucidate the mechanisms linking delayed graft function and rejection, which, in combination, lead to poor allograft outcome.
Adult↗
A percutaneous technique for venous return cannula insertion for veno-venous bypass in hepatic transplantation.
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Adolescent↗
Retransplantation after renal allograft loss due to noncompliance. Indications, outcome, and ethical concerns.
Noncompliance is increasingly recognized as a major cause of renal allograft loss, but the results of retransplantation of such patients have never been described. At our center, 52 of 3525 kidney recipients between June 1, 1963 and December 31, 1993 lost their graft due to overt noncompliance. Of these, 14 (27%) underwent retransplantation after thorough interdisciplinary evaluation. All but 1 patient had returned to dialysis before retransplantation. Of the retransplanted grafts, 2 were lost (1 technical failure, 1 chronic rejection in a compliant patient); both recipients were retransplanted once again. Currently, all retransplanted patients are alive and have a functioning graft. We conclude that for selected patients with graft loss due to noncompliance excellent results can be achieved with retransplantation. However, the issue of retransplanting previously noncompliant patients in the face of a significant donor organ shortage requires public debate.
Adolescent↗
A prospective study of FK506 versus CsA and pig ATG in a porcine model of small bowel transplantation.
Rejection remains a major barrier to successful bowel transplantation, and immunosuppressive protocols are far from standardized. In 88 nonrelated outbred pigs, we compared the effects of two immunosuppressive regimens--one with FK506, the other with cyclosporine (CsA) and pig antithymocyte globulin (ATG)--on incidence and severity of rejection in the early, critical posttransplant period. Group A (n = 14) was nonimmunosuppressed (controls). Group B (n = 17) received pig ATG (10 mg/kg/day x 10 days), CsA (3 mg/kg/day), prednisolone (2 mg/kg/day), and azathioprine (2.5 mg/kg/day); prednisolone and azathioprine were each reduced by 50% at 8 and 15 days posttransplant. Trough CsA whole-blood concentrations were > or = 400 ng/ml for the first 7 days, > or = 200 ng/ml thereafter. Group C (n = 13) received FK506 (0.2 mg/kg/day) and prednisolone (2 mg/kg/day); prednisolone was reduced by 50% at 8 and 15 days. FK506 whole-blood concentrations were > or = 20 ng/ml. All immunosuppression in groups B and C was given intravenously. We performed orthotopic small bowel transplants with systemic venous drainage. Recipient bowel was resected distal to the second portion of the duodenum and proximal to the rectum at transplant; bowel continuity was restored by duodenojejunostomy; ileostomy was created distally to allow access for daily biopsies. We graded interstitial and vascular rejection separately, according to a scoring system (no, mild, moderate, and severe rejection). Rejection-free graft survivals at 7, 14, and 21 days posttransplant were 38%, 19%, and 0% in group A; 93%, 93%, and 62% in group B; and 100%, 91%, and 82% in group C (P < 0.001). Comparing rejection in the immunosuppressed groups, group C (FK506) had a stronger tendency toward rejection than group B (CsA-ATG); significant differences between groups B and C were, however, noted only on individual days posttransplant, not over time. The death rate due to irreversible rejection was not significantly different in groups B and C (P = 0.8), but was significantly better in both of these immunosuppressed groups than in group A (P < 0.001). Pig survival was significantly longer in group C than in B (P = 0.001) due to a lower infection rate in group C. Posttransplant serum interleukin 2 and 7 levels did not correlate with rejection grades. Graft-versus-host reaction was noted only in the skin in 29% of group A, 73% of group B, and 77% of group C pigs; liver and native bowel were not involved.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Conformational studies of heterochiral peptides with diastereoisomeric residues: crystal and molecular structures of linear dipeptides derived from leucine, isoleucine, and allo-isoleucine.
The x-ray diffraction analyses of three N- and C-terminally blocked L,D dipeptides, namely t-Boc-D-Leu-L-Leu-OMe (1), t-Boc-L-Ile-D-aIle-OMe (2), and t-Boc-D-aIle-L-Ile-OMe (3) containing enantiomeric or diastereomeric amino acid residues have been carried out. The structures were determined by direct methods and refined anisotropically to final Rf actors of 0.077, 0.058, and 0.072 for (1), (2), and (3), respectively. Peptides 1-3 all assume a similar U-shaped structure with phi and psi torsion angles corresponding to one of the possible calculated minimum energy regions (regions E and G for L residues, and F*, D* and H* for D residues). The peptide backbones of 1-3 are almost superimposable [provided that the appropriate inversion of the chiral centers of (2) is made]. Side-chain conformations of Leu residues in peptide (1) are g- (tg-) for the L-Leu residue and the mirrored g+ (tg+) for the D-Leu residue; however, in peptides (2) and (3) the conformations of the isoconfigurational side chains of the Ile or allo-Ile residues are (g-t) t and (tg+) t for the L-Ile and the D-allo-Ile moieties, respectively. In all cases, these conformations correspond to the more populated conformers of beta-branched residues statistically found in crystal structures of small peptides. The results seem to indicate that, at least in short peptides with enantiomeric or diastereoisomeric residues, the change in chirality in the main-chain atoms perturbs the backbone conformation to a lesser extent and the side chain conformation to a greater extent.
Crystallography, X-Ray↗
Bioactive peptides: conformational studies of [Tyr4] cyclolinopeptide A.
The solid state conformational analysis of [Tyr4] cyclolinopeptide A has been carried out by x-ray diffraction studies. The crystal structure of the monoclinic form, grown from a dioxane-water mixture [alpha = 9.849 (5) A, b = 20.752 (4) A, c = 16.728 (5) A, beta = 98.83 (3) degrees, space group P21, Z = 2], shows the presence of five intramolecular N-H...O = C hydrogen bonds, with formation of one C17 ring structure, one alpha-turn (C13), one inverse gamma-turn (C7), and two beta-turns (C10, one of type III and one of type I). The Pro1-Pro2 peptide unit is cis (omega = 5 degrees), all others are trans. The structure is almost superimposable with that of cyclolinopeptide A. The rms deviation for the atoms of the backbones is on the average 0.33 A.
Amino Acid Sequence↗
Conformational analysis of dolastatin 10: an NMR and theoretical approach.
A solution conformational analysis of dolastatin 10, a powerful antineoplastic agent, has been carried out by means of nmr techniques and theoretical calculations. 1H mono- and bidimensional nmr experiments, as well as 1H-13C heterocorrelated spectra, have been performed on CD2Cl2 solutions. The most interesting nmr data is a huge shielding of the aCH(25) proton of the Dov residue, suggesting the presence of an interaction between the N-terminal and the aromatic C-terminal ends of the molecule. The possibility of a head-to-tail intermolecular association having been discarded, the presence of a series of preferred folded conformation has been hypothesized. Conformational theoretical analysis supports the nmr hypothesis of a folded peptide-like molecule, and a series of possible conformers in good agreement with the experimental data have been analyzed.
Amino Acid Sequence↗
Conformational studies of retro-inverso peptides: the crystal and molecular structure of the hydantoin from H-Ala-g-Ala-mGly-OBzl.
The crystal structure of the hydantoin 1-[(S)-1'-aminoethylmalonyl benzyl ester]-(S)-4-methylimidazolidin-2,5-dione (1) derived from the peptide H-Ala-gAla-mGly-OBzl, having the retro-inverso modification of the Ala-Gly bond, has been determined by x-ray diffraction analysis. The crystals are orthorhombic, space group P2(1)2(1)2(1) with a = 6.539, b = 14.721, c = 17.101 A, z = 4. The structure was solved by direct methods and refined with anisotropic thermal factors to a final R value of 0.067 for the 947 observed reflections. Reversal of the Ala-Gly amide bond perturbs the folding tendency of the backbone shown by the parent peptide t-BuCO-Ala-Gly-NHiPr. The gem-diamino residue, gAla, and the malonyl moieties are found in the helical and the extended conformations, respectively. Intramolecular hydrogen bonding is not observed. The molecules in the crystal are held together by the formation of two intermolecular hydrogen bonds of the N-H ... O=C type with N ... O distances of 2.86 and 3.17 A, respectively.
Amides↗
Human leptospirosis in Italy, 1986-1993.
In the eight-year period 1986-1993, the Italian National Center for Leptospirosis and the Regional Leptospira Laboratories confirmed 312 cases of clinical leptospirosis by using the microscopic agglutination (MA) assay. The majority of cases was observed in Northern regions of the Country. Cases were reported in all age groups, but were most common in the working-age population. Of 312 cases, 291 (93.3%) occurred among males. The largest number of infections was ascribed to occupational activities (45.8%). The typical leptospiral seasonal course, with a peak during the summer, was observed. Involvement of the liver was the most frequent manifestation. Influenza-like symptoms were the only signs of illness in 11.1% of cases. Anti-leptospira antibodies, cross-reacting with two or more serovars, were found in 28.2% of sera. The most frequent serovar-specific antibodies were those against poi, icterohaemorrhagiae, bratislava, copenhageni and sejroe.
Adolescent↗
The polypeptide 3(10)-helix as a template for molecular recognition studies. Structural characterization of a side-chain functionalized octapeptide.
A N alpha-blocked, Aib-rich octapeptide methylamide containing two N omega-benzoylated L-Lys residues at positions 3 and 6 was synthesized by solution methods and fully characterized. A solution and crystal-state conformational analysis, performed by using FT-IR, 1H NMR, CD, and X-ray diffraction techniques, showed that the peptide is folded into a regular, right-handed 3(10)-helix stabilized by seven consecutive N-H...O=C intramolecular H-bonds of the beta-turn III type. The two benzamidobutyl L-Lys side chains, located on the same side of the helix after one complete turn, generate a cleft the minimal width of which was found to be 3.47 A.
Amino Acid Sequence↗
Laparoscopic drainage of lymphoceles after kidney transplantation: indications and limitations.
BACKGROUND: Symptomatic lymphoceles are not uncommon after kidney transplantations. Surgical marsupialization with internal drainage is the treatment of choice. However, laparoscopic drainage is reportedly as effective, with only minimal trauma. METHODS: We attempted 14 laparoscopic lymphocele drainages during a 3-year period and studied the indications and limitations, using intraoperative ultrasonography in all cases. RESULTS: Laparoscopic drainage was successful in only 9 (64%) of 14 patients. A conversion to open laparotomy was necessary in five patients; their lymphoceles were lateral and either posterior or inferior to the kidney. Two patients with initially successful laparoscopic drainage required conversion to open laparotomy 21 and 83 days later; their lymphoceles were inferior to the kidney. Laparoscopic drainage shortened the median hospital stay by 4 days versus open surgical drainage and by 7 days versus conversion. Hospital costs for laparoscopic drainage averaged $7400 less versus open drainage and $10,300 less versus conversion. CONCLUSIONS: In patients with symptomatic lymphoceles medial and either superior or anterior to the kidney, laparoscopic drainage under intraoperative ultrasonographic guidance is easy, safe, and effective. It decreases hospitalization, convalescence, and costs. In patients with symptomatic lymphoceles lateral and either posterior or inferior to the kidney, laparoscopic drainage may fail because of anatomic inaccessibility and technical impracticability.
Adolescent↗
Correlation between cystoscopic biopsy results and hypoamylasuria in bladder-drained pancreas transplants.
BACKGROUND: Urinary amylase (UA) remains the most common biochemical parameter to detect rejection in bladder-drained pancreas allografts. With the development of the cystoscopic transduodenal pancreas transplant biopsy technique, tissue samples of the pancreas graft are now frequently obtained. A definitive correlative analysis between UA activity and biopsy results has not been done in the three different pancreas transplant categories (simultaneous pancreas-kidney, pancreas transplant alone, and pancreas after kidney). METHODS: We studied 66 pancreaticoduodenal biopsy specimens obtained for hypoamylasuria. Rejection was defined as a greater than 25% decrease from stable posttransplantation baseline on two consecutive measurements at least 12 hours apart. To perform biopsies we used our newly developed 14- and 16-gauge core-cut needles (50 cm long). Biopsy specimens were considered positive if either pancreatic or duodenal rejection was found. To assess the quality of UA activity we studied 13 biopsy specimens from patients with stable UA levels; these 13 specimens were negative for rejection. RESULTS: Acute rejection was diagnosed in 36 biopsy specimens (55%). The mean decrease in UA levels was 67% +/- 8% (range, 28% to 99%) for the positive biopsy results, and 57% +/- 16% (range, 22% to 92%) for the negative biopsy results (p = 0.147). Within 1 month, UA levels returned to baseline in 19% of our patients with positive biopsy results versus 97% with negative results; postbiopsy 1-year graft survival was 64% versus 97% (p < or = 0.05). In assessing the test quality of our biopsy specimens (including 13 obtained for reasons other than hypoamylasuria), we found a sensitivity of 100% (stable UA levels mean no rejection) and a specificity of 30%. The predictive value of a positive test was 53%; of a negative test it was 100%. By performing biopsies we avoided antirejection treatment in 47% of the patients studied. We found no biopsy-related complications. CONCLUSIONS: Stable UA levels reliably rule out rejection; a decrease is a marker for acute rejection but is unspecific. Performing biopsy is currently the only way to reliably diagnose rejection in solitary pancreas recipients (pancreas transplant alone and pancreas after kidney) and in simultaneous pancreas-kidney recipients with isolated hypoamylasuria. The procedure is safe and should always be attempted to avoid unnecessary rejection treatment.
Adult↗
Renal transplantation.
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Graft Rejection↗
Short- and long-term outcomes of kidney transplants with multiple renal arteries.
OBJECTIVE: The authors determined whether the use of kidney allografts with multiple renal arteries adversely effects post-transplant graft and patient outcome or increases the incidence of vascular and urologic complications. BACKGROUND: Kidney grafts with multiple renal arteries have been associated with an increased incidence of early vascular and urologic complications. Kidney transplants with single versus multiple renal arteries have not been compared in regard to long-term graft and patient outcome or post-transplant incidence of hypertension, acute tubular necrosis, rejection, and late vascular and urologic complications. METHODS: We analyzed 998 adult kidney transplants done from December 1, 1985 through June 30, 1993, in which only the recipient's external or internal iliac artery was used for anastomosis. We divided the study population into 3 groups: Group A-1 renal artery, 1 arterial anastomosis (n = 835), Group B-->1 renal artery, 1 arterial anastomosis (n = 112), Group C-->1 renal artery, > 1 arterial anastomosis (n = 51). We compared the incidence of post-transplant hypertension, acute tubular necrosis, acute rejection, and vascular and urologic complications; mean creatinine levels at 1, 3, and 5 years post-transplant; and patient and graft survival. Univariate and multivariate analyses were done to identify risk factors for vascular complications. RESULTS: We found no significant differences among the three groups for the following variables: post-transplant hypertension, acute tubular necrosis, acute rejection, creatinine levels, early vascular and urologic complications, and graft and patient survival. In kidneys with single arteries, the presence (vs. absence) of an aortic patch and the type of the arterial anastomosis (end-to-end to the hypogastric vs. end-to-side to the external iliac artery) did not have an impact on the incidence of early or late vascular complications. In kidneys with multiple arteries, only the rate of late renal artery stenosis was higher, the rate of early vascular and urologic complications was not different. Our multivariate analysis identified acute tubular necrosis as a risk factor for renal artery and vein thrombosis; graft placement on the left side for arterial thrombosis; and preservation time > or = 24 hours and multiple renal arteries for renal artery stenosis. CONCLUSIONS: Results of kidney transplants using allografts with multiple versus single arteries are similar.
Adolescent↗
Conformation and structure of linear peptides with regularly alternating L- and D-residues: structure of the blocked hexapeptide tert-butyloxycarbonyl-(D-alloisoleucyl-L-isoleucyl)3 methyl ester monohydrate.
Peptides with a regular sequence of enantiomeric residues (L and D) along the chain have received considerable attention because of their accessibility to unique conformations and because they are model compounds for the naturally occurring peptide gramicidin A, which shows monovalent cation selective transmembrane transport. The solid-state structure of the linear hexapeptide t-Boc-(D-alle-L-Ile)3-OMe has been determined by X-ray diffraction techniques and refined to a final R factor of 0.068. The molecule shows a bent U-shaped conformation stabilized by three intramolecular H-bonds of the N-H...O = C type: a type II beta-bend (4-->1 bend or C10 ring structure) with L-Ile2 and D-aIle3 at positions 2 and 3 of the bend, an alpha-turn (5-->1 bend or C13 ring structure) and a 1-->5 bend or C17 ring structure. The first two 10-membered and 13-membered bends are enclosed in the latter 17-membered hydrogen-bonded ring structure. This structural motif is common to hepta- and octa-peptide cyclic molecules, showing that ring closure is not required to achieve a particular topology in the molecular design of specific bended conformations.
Amino Acid Sequence↗
Incidence, complications, treatment, and outcome of ulcers of the upper gastrointestinal tract after renal transplantation during the cyclosporine era.
BACKGROUND: Ulcers of the upper gastrointestinal tract after renal transplantation have been reported as a frequent and often lethal complication. Considering the continuous expansion of renal recipient criteria, we reviewed our experience with post-transplant ulcers after 1,034 renal transplants performed during the cyclosporine era. STUDY DESIGN: Our retrospective study analyzed only endoscopy-proven ulcers of the esophagus, stomach, and duodenum in 439 (42 percent) living related adult recipients and 595 (58 percent) cadaver or living unrelated adult recipients. For ulcer prophylaxis, only oral antacids were routinely given post-transplant. RESULTS: There were 41 ulcers in 33 patients (esophageal: n = 5, 12 percent; gastric: n = 17, 42 percent; duodenal: n = 19, 46 percent). Significant complications (n = 16) included 15 bleeding episodes and one perforation. The pathogenesis was viral in seven cases (gastric: n = 6, 15 percent; duodenal: n = 1, 2 percent). The ulcers occurred significantly earlier post-transplant in cadaver or living unrelated compared with living related recipients (median, 53 compared with 508 days, p = 0.02). Nonoperative treatment was successful for 96 percent of all ulcers. We found no ulcer-related mortality or graft loss. For living related recipients, the actuarial graft survival rate at three years was 69 percent for patients with ulcers compared with 86 percent for those without ulcers (p = 0.02); for cadaver or living unrelated recipients, it was 48 percent for patients with ulcers compared with 77 percent for those without ulcers (p = 0.9). For living related recipients, the actuarial patient survival rate at three years was 92 percent for patients with ulcers compared with 93 percent for those without ulcers (p = 0.8); for cadaver or living unrelated recipients, it was 59 percent for patients with ulcers compared with 88 percent for those without ulcers (p = 0.002). CONCLUSIONS: With more specific immunosuppression and more effective antiviral therapy, the incidence of post-transplant ulcers is low. Considering the excellent results of nonoperative ulcer therapy and a zero percent ulcer-related mortality rate, renal transplantation is safe for patients with specific (e.g., ulcer history) as well as nonspecific (e.g., chronic obstructive pulmonary disease) ulcer risk factors.
Adolescent↗
A technique of removal of the Tenckhoff peritoneal dialysis catheter.
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Anesthesia, Local↗