Search PubMed⌕ Search

Biomedical subjects

K S Reddy

Publications and source records attributed to K S Reddy.

At least 19 recordsLinked to original sources

Self-assembly of heme A and heme B in a designed four-helix bundle: implications for a cytochrome c oxidase maquette.

Heme A, a prosthetic group of cytochrome c oxidase [EC 1.9.3.1], has been introduced into two de novo designed four helix bundle proteins, [H10A24](2) and [H10H24](2), known to bind 2-4 equiv of heme B, respectively [Robertson, D. E., Farid, R. S., Moser, C. C., Mulholland, S. E., Pidikiti, R., Lear, J. D., Wand, A., J., DeGrado, W. F., and Dutton, P. L. (1994) Nature 368, 425-432]. [H10A24](2), [Ac-CGGGELWKL x HEELLKK x FEELLKL x AEERLKK x L-CONH(2)](2)(2), binds two heme A molecules per four-helix unit via bis-histidine ligation at the 10,10' positions with measured K(d) values of <0.1 and 5 nM, values much lower than those measured for heme B (K(d) values of 50 and 800 nM). The heme A-protein complex, [heme A-H10A24](2), exhibits well-defined absorption spectra in both the ferric and ferrous states, and an electron paramagnetic resonance spectrum characteristic of a low spin heme in the ferric form. A single midpoint redox potential (E(m8)) was determined for [heme A-H10A24](2) at -45 mV (vs SHE), which is significantly higher than that of the protein bound heme B (-130 and -200 mV). The observation of a single midpoint redox potential for [heme A-H10A24](2) and a pair of midpoints for [heme B-H10A24](2) indicates that the di-alpha-helical monomers are oriented in an anti topology (disulfides on opposite sides of bundle) in the former (lacking heme-heme electrostatic interaction) and syn in the latter. A mixture of global topologies was indicated by the potentiometric titration of the related [heme A-H10H24](2) which possess two distinct reduction potentials of +41 (31%) and -65 mV (69%). Self-assembly of the mixed cofactor heme A-heme B-[H10A24](2) was accomplished by addition of a single equivalent of each heme A and heme B to [H10A24](2). The single midpoint redox potential of heme B, E(m8) = -200 mV, together with the split midpoint redox potential of heme A in heme A-heme B-[H10A24](2), E(m8) = +28 mV (33%) and -65 mV (67%), indicated the existence of both syn and anti topologies of the two di-alpha-helical monomers in this four helix bundle. Synthesis of the mixed cofactor [heme A-heme B-H10H24](2) was accomplished by addition of a 2 equiv of each heme A and heme B to [H10H24](2) and potentiometry indicated the pair of hemes B resided in the 10,10' sites and heme A occupied the 24,24' sites. The results indicate that heme peripheral structure controls the orientation of the di-alpha-helical monomers in the four-helix bundle which are interchangeable between syn and anti topologies. In the reduced form, [heme A-H10A24](2), reacts quantitatively to form [carbonmonoxy-heme A-H10A24](2) as evidenced by optical spectroscopy. The synthetic [heme A-H10A24](2) can be enzymatically reduced by NAD(P)H with natural reductases under anaerobic conditions, and reversibly oxidized by dioxygen to the ferric form.

Animals↗

Successful reuse of portal-enteric technique in pancreas retransplantation.

BACKGROUND: The portal venous and enteric drainage (P-E) technique was developed to avoid systemic hyperinsulinemia and bladder related complications. Pancreas retransplantation (Re-Tx) is an important option for patients who have lost their primary grafts. It is unknown whether the P-E technique can be repeated safely in patients who have lost their first pancreas transplant. METHODS: Five patients who lost their pancreas graft after simultaneous kidney-pancreas transplantation with P-E drainage underwent pancreas Re-Tx, again using the P-E technique. RESULTS: P-E Re-Tx was successful in all 5 patients without any technical difficulties or complications. CONCLUSION: The P-E technique can be reused with excellent results in pancreas Re-Tx.

Adolescent↗

Mosaic tetrasomy 8q: inverted duplication of 8q23.3qter in an analphoid marker.

We observed an analphoid marker chromosome stable through cell division in a 16-year-old girl with developmental delay, short stature, limb contractures, and ovaries containing multiple cysts. She also developed myasthenia gravis at 15 years. The marker chromosome, present in 75% of metaphases (and in 90% of transformed lymphoblastoid cells), was C-band negative, and had no pan alpha-satellite sequences detectable by fluorescence in situ hybridization (FISH). The 8q origin of the marker was determined by use of subtelomeric probes and was confirmed by chromosome 8 painting probes. The marker was shown to be an inversion duplication of 8q when subtelomeric, telomeric, and c-myc FISH probes hybridized to both ends of the marker. The karyotype was 47,XX,+inv dup(8)(qter--> q23.3::q23.3-->[neocen]-->qter), resulting in tetrasomy for 8q23.3qter. The parents had normal karyotypes. Centromeric proteins CENP-C and CENP-E were present, but alpha associated centromere protein CENP-B was absent at a position defining a neocentromere.

Abnormalities, Multiple↗

A FISH study of variant Philadelphia rearrangements.

A total of 39 variant Philadelphia (Ph) translocations were studied by fluorescence in situ hybridization (FISH) using MBCR/ABL, mBCR/ABL, or DBCR/ABL probes. Seven cases did not have a BCR/ABL fusion signal. Of a total of 32 fusion-positive cases, 5 were simple variants involving chromosome 22 and another chromosome apart from chromosome 9; 23 were complex variants involving chromosomes 22, 9, and a third chromosome (18 cases), or 22, 9, and two other chromosomes (4 cases). Masked Ph rearrangements were detected in 4 cases. One case was a Ph chromosome mimic. Fluorescence in situ hybridization has become a widely used method for studying Ph rearrangements. The latest probe that is being used is the DBCR/ABL (double reciprocal BCR/ABL signals). The expected pattern for this probe is one green ABL signal (1G) on the normal 9, one red BCR signal (1R) on the normal 22, and two fusion signals, BCR/ABL and ABL/BCR (2F), on a derivative 22 and a derivative 9, respectively. Deviant patterns from 1G1R2F, and sometimes 1G1R2F, were indicative of a variant, as long as there was a fusion signal. However, in interphase analysis, it is not possible to visualize a variant rearrangement, and when a deviant pattern involving at least one fusion signal is observed, the following possibilities should be contemplated. The different patterns observed in fifteen Ph variants are described. The patterns observed in variants studied with the DBCR/ABL probe were 2G2R1F (40%), 1G1R2F (20%), 1G1R1F (20%), 1G2R1F (13.3%), and 2G1R1F (6.66%). A single mechanism is involved in the formation of each of these patterns. A 2G2R1F, FISH pattern in 6 cases appears to involve a single concerted event of simultaneous breaks on the participating chromosomes followed by mismatched joining. The three cases with 1G1R2F most probably arose by two sequential rearrangements. The 1G1R1F pattern suggests that either the BCR and ABL breakpoints are different, or there are deletions at the breakpoints, because residual signals are not observed. Two independent events appear to be involved in 1G2R1F with a reverse cryptic 9,22 rearrangement as the first event. In one case of 2G1R1F, the plausible explanation is an insertion of ABL next to BCR and either a simultaneous or a sequential translocation with another chromosome.

Adult↗

FISH analysis of an AML-M5a with segmental rearrangements involving 11q23-MLL region.

A 66-year-old man was diagnosed 10 years ago with thrombocytosis and treated with hydroxyurea. Recently, his condition deteriorated and he was found to have 68% blasts in the blood and AML-M5a. Conventional cytogenetic analysis and fluorescence in situ hybridization studies using 11-painting and MLL probes showed that chromosome 11 had duplications or triplications; the markers were also derived from the chromosome 11-MLL region. Therefore, we have demonstrated segmental rearrangement of chromosome 11 involving the MLL region resulting in multiple copies of the MLL gene.

Aged↗

Fluorescence in situ hybridization identifies inversion 16 masked by t(10;16)(q24;q22), t(7;16)(q21;q22), and t(2;16)(q37;q22) in three cases of AML-M4Eo.

Bone marrow or peripheral blood from three patients had a t(10;16)(q24;q22), t(7;16) (q21;p13.1), and t(2;16)q37;q22), respectively. In all cases, fluorescence in situ hybridization confirmed an inv(16) masked by the translocation. The three patients were diagnosed with acute myelomonocytic leukemia and increased eosinophils. Because inv(16) has a favorable prognosis, identification of masked inv(16) will promote improved management of these cases. Therefore, all cases that have atypical rearrangement of chromosome 16 should be investigated for a possible inversion.

Adult↗

Simultaneous kidney-pancreas transplantation without antilymphocyte induction.

BACKGROUND: The introduction of potent new immunosuppressive agents may allow simultaneous kidney-pancreas transplantation to be performed without antilymphocyte induction. METHODS: We analyzed 30 simultaneous kidney-pancreas transplantations receiving tacrolimus, mycophenolate mofetil, and steroids without without antilymphocyte induction. Eighteen patients underwent pancreas transplantation with portal-enteric (P-E) drainage and the remaining 12 had systemic bladder (S-B) drainage. Target 12 hr trough tacrolimus levels for the first 3 months after simultaneous kidney-pancreas transplantation were 15-20 ng/ml. The oral mycophenolate mofetil dose was 2-3 g/day begun immediately posttransplant in two to four divided doses. Steroids were tapered according to protocol. RESULTS: All patients experienced immediate function of both kidney and pancreas grafts. One-year actuarial patient, kidney, and pancreas graft survival rates are 93, 93, and 90%, respectively. Nine patients (30%) had a total of 13 rejection episodes (12 biopsy proven) including 4 within 2 weeks, 6 between 2 weeks and 3 months, and 3 beyond 3 months after simultaneous kidney-pancreas transplantation. Three rejection episodes were treated with steroids alone and 10 were treated with antilymphocyte therapy (5 OKT3 and 5 ATGAM). A total of seven patients (23%) received antilymphocyte therapy. Three patients (10%) had more than one rejection episode. Two pancreas grafts (7%) and one kidney graft (3%) were lost from rejection. Four patients (13%) developed cytomegalovirus infection, but none had tissue-invasive cytomegalovirus. At present, 22 surviving patients (81%) remain on triple immunosuppression with tacrolimus, mycophenolate mofetil, and prednisone with excellent dual graft function. CONCLUSION: Tacrolimus, mycophenolate mofetil, and prednisone immunosuppression without without antilymphocyte induction is safe and effective after simultaneous kidney-pancreas transplantation.

Adult↗

A child with ALL and ETV6/AML1 fusion on a chromosome 12 due to an insertion of AML1 and loss of ETV6 from the homolog involved in a t(12;15)(p13;q15).

A 4-year-old boy was found to have acute lymphoblastic leukemia characterized by a t(12;15)(p13;q15). FISH investigation using a TEL(ETV6)/AML1 probe detected a fusion signal in 98% of the interphase cells. Sequential FISH on a G-banded slide showed a fusion signal on an apparently normal chromosome 12 and AML1 signals on chromosomes 21. The ETV6 was deleted from the chromosome 12 involved in the t(12;15). These results are best explained as an insertion of AML1 into TEL on one chromosome arm 12p and loss of ETV6 from the chromosome 12 involved in the t(12;15).

Child, Preschool↗

Expression of functional soluble human alpha-globin chains of hemoglobin in bacteria.

Individual, soluble human alpha-globin chains were expressed in bacteria with exogenous heme and methionine aminopeptidase. The yields of soluble alpha chains in bacteria were comparable to those of recombinant non-alpha chains expressed under the same conditions. Molecular mass and gel-filtration properties of purified recombinant alpha chains were the same as those of authentic human alpha chains. Biochemical and biophysical properties of isolated alpha chains were identical to those of native human alpha chains as assessed by UV/vis, circular dichroism (CD), and nuclear magnetic resonance (NMR) spectroscopy which contrasts with previous results of refolded precipitated alpha chains made in the presence of heme in vitro (M. T. Sanna et al., J. Biol. Chem. 272, 3478-3486, 1997). Mixtures of purified, soluble recombinant alpha-globin and native beta-globin chains formed heterotetramers in vitro, and oxygen- and CO-binding properties as well as the heme environment of the assembled tetramers were experimentally indistinguishable from those of native human Hb A. UV/vis, CD, and NMR spectra of assembled Hb A were also the same as those of human Hb A. These results indicate that individual expressed alpha chains are stable in bacteria and fold properly in vivo and that they then can assemble with free beta chains to form hemoglobin heterotetramers in vivo as well as in vitro.

Globins↗

Fusion of 9 beta-satellite and telomere (TTAGGG)n sequences results in a jumping translocation.

A newborn was found to have an isochromosome for the short arm of chromosome 9, i(9p) and a jumping translocation of the whole long arm. In 94.4% metaphases, 9q was fused to the telomere of chromosome 19p and, in 5.6% of metaphases, 9q was fused to the telomere of chromosome 8p. The net result was trisomy for the short arm of chromosome 9. With the pan telomere probe, fluorescent in situ hybridization (FISH) investigations found an interstitial telomere on the der(19) and der(8). The 9 beta and classical satellite probes gave a signal only on the long arm of chromosome 9 involved in the jumping translocation. The 9 alpha satellite probe hybridized to i(9p) and not to the other derivative chromosomes. A combination of chromosome 9 (red) and chromosome 19 (green) paint probes used to rapidly screen metaphases for the jumping translocation found 88 metaphases had a der(19)t(9;19) and 4metaphases had a der(8)t(8;9). For the first time, the junction of a jumping translocation has been shown to involve the telomere sequence (TTAGGG)n and beta-satellite sequences by FISH. In this paper, we also review the simultaneous occurrence of an isochromosome for the short arm and translocation of the whole long arm and constitutional jumping translocations.

Asian↗

A designed four-alpha-helix bundle that binds the volatile general anesthetic halothane with high affinity.

The structural features of volatile anesthetic binding sites on proteins are being examined with the use of a defined model system consisting of a four-alpha-helix bundle scaffold with a hydrophobic core. Previous work has suggested that introducing a cavity into the hydrophobic core improves anesthetic binding affinity. The more polarizable methionine side chain was substituted for a leucine, in an attempt to enhance the dispersion forces between the ligand and the protein. The resulting bundle variant has an improved affinity (K(d) = 0.20 +/- 0.01 mM) for halothane binding, compared with the leucine-containing bundle (K(d) = 0.69 +/- 0.06 mM). Photoaffinity labeling with (14)C-halothane reveals preferential labeling of the W15 residue in both peptides, supporting the view that fluorescence quenching by bound anesthetic reports both the binding energetics and the location of the ligand in the hydrophobic core. The rates of amide hydrogen exchange were similar for the two bundles, suggesting that differences in binding affinity were not due to changes in protein stability. Binding of halothane to both four-alpha-helix bundle proteins stabilized the native folded conformations. Molecular dynamics simulations of the bundles illustrate the existence of the hydrophobic core, containing both W15 residues. These results suggest that in addition to packing defects, enhanced dispersion forces may be important in providing higher affinity anesthetic binding sites. Alternatively, the effect of the methionine substitution on halothane binding energetics may reflect either improved access to the binding site or allosteric optimization of the dimensions of the binding pocket. Finally, preferential stabilization of folded protein conformations may represent a fundamental mechanism of inhaled anesthetic action.

Amino Acid Sequence↗

Thymosin-beta(4) changes the conformation and dynamics of actin monomers.

Thymosin-beta(4) (Tbeta(4)) binds actin monomers stoichiometrically and maintains the bulk of the actin monomer pool in metazoan cells. Tbeta(4) binding quenches the fluorescence of N-iodoacetyl-N'-(5-sulfo-1-naphthyl)ethylenediamine (AEDANS) conjugated to Cys(374) of actin monomers. The K(d) of the actin-Tbeta(4) complex depends on the cation and nucleotide bound to actin but is not affected by the AEDANS probe. The different stabilities are determined primarily by the rates of dissociation. At 25 degrees C, the free energy of Tbeta(4) binding MgATP-actin is primarily enthalpic in origin but entropic for CaATP-actin. Binding is coupled to the dissociation of bound water molecules, which is greater for CaATP-actin than MgATP-actin monomers. Proteolysis of MgATP-actin, but not CaATP-actin, at Gly(46) on subdomain 2 is >12 times faster when Tbeta(4) is bound. The C terminus of Tbeta(4) contacts actin near this cleavage site, at His(40). By tritium exchange, Tbeta(4) slows the exchange rate of approximately eight rapidly exchanging amide protons on actin. We conclude that Tbeta(4) changes the conformation and structural dynamics ("breathing") of actin monomers. The conformational change may reflect the unique ability of Tbeta(4) to sequester actin monomers and inhibit nucleotide exchange.

Actins↗

Intrachromosomal triplications: molecular cytogenetic and clinical studies.

A newborn boy had meconium aspiration syndrome, hypospadias, a supernumerary digit on the left hand, hyperbilirubinemia, a fractured right clavicle, osteopenia, liver calcification, and mild pulmonary hyperplasia. Cytogenetic studies showed a chromosome 13 with additional material in 33% of the metaphases. The add(13) was considered to be a probable duplication of 13q12q22. The 13 paint probe hybridized to the add(13) from end to end. Fluorescence in situ hybridization (FISH) studies using retinoblastoma probe (RB)-1 that maps to 13q14 and D13S585 that maps to 13q32-q33 gave one signal for RB and three signals for D13S585. The pattern of the three signals from the 13q32q33 region and the G-banding pattern was best explained as a triplication of 13q22q33, with an inverted middle repeat resulting in tetrasomy for this segment. Mosaicism was confirmed by FISH using a D13S585 probe on a buccal smear. Three triplications detected in our laboratory were compared 13q22q33, 15q11q13, and 2q11.2q21. FISH was critical in identifying triplications 13q22q33 and 15q11q13. The hybridization pattern also indicated an inverted middle repeat. We conclude that intrachromosomal triplications may be more prevalent than previously assumed and they probably share a common mechanism in their formation. When the G-bands do not correspond exactly to a duplication or to a tandem triplication, an important consideration is that the majority of triplications have an inverted middle repeat. Triplications can be mistaken for duplications. Therefore, in assessing duplications, FISH confirmation is recommended.

Abnormalities, Multiple↗

Nonoperative management of bile leaks following liver transplantation.

UNLABELLED: The biliary anastomosis has been called 'the Achilles heel' of liver transplantation (RABKIN JM, ORLOFF SL, REED MH. Transplantation 1998: 65 [2]: 193; DAVIDSON BR, RAI R, KURZAWINSKI TR. Br J Surg 1999: 86 [4]: 447). Biliary complications after liver transplantation reportedly occur at an incidence of 20-30%, 10-15% as bile leaks. The management of bile leaks, especially early bile leaks, is controversial. In the present study, we report our experience with the management of bile leaks after liver transplantation. In this retrospective study, we reviewed 85 liver transplants over a 3-yr period. In 79, the biliary anastomosis was choledochocholedochostomy (CDCD) over a small-caliber T-tube, while choledochojejunostomy (CDJ) was used in 7. Over a mean follow up period of 13.5 months (median 10 months), 10 patients (12%) experienced a clinically significant bile leak within the first 3 months after liver transplantation. The early leaks, occurring within 1 month of transplant, were successfully managed by observation (DAVIDSON BR, RAI R, KURZAWINSKI TR. Br J Surg 1999: 86 [4]: 447) or endoscopic retrograde cholangiopancreatography (ERCP) and the placement of a biliary stent for a duration of 6-12 wk (RANDALL HB, WACHS ME, SOMBERG KA. Transplantation 1996: 61 [2]: 258). One of these resulted from accidental dislodgement of the T-tube on postoperative day 1; one resulted from necrosis at the CDCD anastomosis and required CDJ; the remaining four resulted from leaks along the T-tube track. One of the late leaks occurred following the planned removal of the T-tube at 3 months after liver transplantation; the other two were leaks along the T-tube track. All were successfully treated by ERCP and stent placement, though in one case, ERCP was initially unsuccessful because of the inability to advance a guidewire, necessitating a fluoroscopically aided guide wire placement during a mini laparotomy. ERCP was then successfully performed with the placement of a stent. [See table in text] CONCLUSIONS: Our experience indicates that most bile leaks after liver transplantation, including early leaks, can be successfully managed nonoperatively. Most will require intervention, but ERCP and stent placement are usually sufficient.

Adolescent↗

Piggyback technique and selective use of veno-venous bypass in adult orthotopic liver transplantation.

BACKGROUND: The piggyback technique (PT), with preservation of the cava, is being used more frequently in adult orthotopic liver transplantation (OLT). The advantages of PT include hemodynamic stability during the anhepatic phase without a large-volume fluid infusion and obviating the need for veno-venous bypass (VVB). At our center, we changed our practice in July 1997 from the standard technique (ST) of OLT with routine use of VVB to PT and selective use of VVB. The purpose of the present study was to analyze the results with the two different practices, ST-routine VVB versus PT-selective VVB. METHODS: Forty OLTs were performed during the period July 1995 July 1997 using ST-routine VVB (group I) and 36 during August 1997-December 1998 using PT-selective VVB (group II). The etiology of liver disease was similar in the two groups, with hepatitis C and alcoholic liver disease accounting for half of the patients in each group. The UNOS status, age, sex, and percentage of patients with previous upper abdominal surgery were also similar between the two groups. RESULTS: In the PT-selective VVB era (group II), 34/36 patients (94%) underwent OLT with PT and VVB was used for 8 (22%) patients. The decision to use VVB was elective for 3 patients (fulminant hepatic failure, 2; severe portal hypertension, 1) and urgent for 5 patients (hemodynamic instability during hepatectomy). The intraoperative use of packed red blood cells (PRBC) (mean +/- SD) was 15+/-12 units for group I and 9+/-8 units for group II (p = 0.023). Anastomosis time and total operating time (mean +/- SD) were 91 + 30 min and 9.5+/-3.2 h, respectively, for group I patients compared with 52+/-28 min and 7.6+/-1.6 h, respectively, for group II patients (p<0.0001 and 0.002, respectively). Median post-operative stays in the intensive care unit (ICU) and in the hospital were 5 and 17 d, respectively, for group I and 4 and 11 d, respectively, for group II (p = NS). Mean serum creatinine on day 3 was similar in the two groups. Median hospital charges for group I patients were $105439 compared with $91779 for group II patients (p = NS). The 1-year actuarial graft and patient survival rates were 78% and 82%, respectively, for group I, and 92% and 95%, respectively, for group II. CONCLUSIONS: PT is safe and can be performed in the majority of adult patients (>90%) undergoing OLT. With the routine application of the piggyback procedure, the use of VVB has been reduced to 20% of OLTs at our center. The practice of piggyback technique with the selective use of VVB is associated with shorter anhepatic phase and total operating time, lower blood product use, a trend towards shorter hospital length of stay, and reduced hospital charges compared with standard technique of OLT with routine use of VVB.

Female↗

Hospital charges following simultaneous kidney--pancreas transplantation: enteric drainage versus bladder drainage.

BACKGROUND: Enteric drainage (ED) is associated with reduced morbidity compared with bladder drainage (BD) after simultaneous kidney-pancreas transplantation (SKPT) and is becoming increasingly common (more than 50% of SKPTs done in the US in 1998 were performed with enteric drainage). Although several studies have reported the morbidity and graft survival of ED compared with BD previously, there are limited data available comparing the length of stay and hospital charges between these two drainage procedures. METHODS: Fourteen SKPTs were performed during the period January 1995 May 1998 using BD and 20 during June 1998-August 1999 using ED. Hospital charges analyzed included the following categories: pharmacy, inpatient room, laboratory, operating room, medical surgical supply, radiology/nuclear medicine, and miscellaneous. Organ acquisition charges and professional fees were not included in this analysis. RESULTS: The mean hospital stay for patients with ED was 7.8+/-2.2 d (range 5-12 d; median 7.5 d) compared with 15.9+/-7 d (range 8-38 d; median 15 d) for patients with BD (p = 0.002). The mean hospital charges during initial hospitalization for the ED group were $36 582+/-11 424 compared with $64 555+/-29 054 for the BD group (p = 0.005). There was a significant decrease in the charges relating to pharmacy, inpatient room, laboratory, radiology/nuclear medicine, and miscellaneous category in the ED group compared with the BD group, while the charges relating to operating room and medical-surgical supply were no different between the two groups. One-year actuarial kidney and pancreas graft survival rates were 83% and 93%, respectively, for the BD group and 90% and 80%, respectively, for the ED group (p = NS). CONCLUSIONS: SKPT patients with ED had a 43% reduction in hospital charges and equivalent pancreas and kidney graft survival rates compared with SKPT patients with BD. A shorter hospital stay and a reduction in pharmacy, radiology/nuclear medicine, and laboratory charges contributed to the decreased hospital charges in SKPT patients with ED.

Adult↗

A prospective comparison of systemic-bladder versus portal-enteric drainage in vascularized pancreas transplantation.

BACKGROUND: Most pancreas transplants are performed with systemic venous delivery of insulin and bladder drainage of the exocrine secretions (systemic-bladder [S-B]). To develop a more physiologic procedure, we performed pancreas transplantations with portal venous delivery of insulin and enteric drainage of the exocrine secretions (portal-enteric [P-E]). METHODS: During an 11-month period, we prospectively alternated 32 consecutive pancreas transplant recipients to either S-B (n = 16) or P-E (n = 16) drainage with standardized immunosuppression. RESULTS: Patient, kidney, and pancreas graft survival rates after simultaneous kidney-pancreas transplantation were 91% S-B versus 92% P-E, 91% S-B versus 92% P-E, and 82% S-B versus 92% P-E, respectively. Pancreas graft survival rates after solitary pancreas transplantation were 80% S-B versus 75% P-E. There were no graft losses either to immunologic or infectious complications in either group, but the incidence of acute rejection was slightly higher in the S-B group (44% S-B vs 31% P-E, P = NS). The cost and length of the initial hospital stay were similar between groups. The incidence of operative complications, major infections, and cytomegalovirus infections were likewise comparable. However, the S-B group was characterized by a slight increase in the number of readmissions, urinary tract infections, and urologic complications. Furthermore, metabolic acidosis and dehydration were more common in the S-B group. CONCLUSIONS: Pancreas transplantation with P-E drainage can be performed with short-term results comparable to those of transplantation with S-B drainage.

Adult↗