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Biomedical subjects

E Benedetti

Publications and source records attributed to E Benedetti.

At least 127 records · Page 7Linked to original sources

Pancreas graft loss caused by intra-abdominal infection. A risk factor for a subsequent pancreas retransplantation.

OBJECTIVE: To investigate whether previous pancreas graft loss caused by intra-abdominal infection is a risk factor for a subsequent pancreas retransplantation. DESIGN: Retrospective case-series analysis. SETTING: Large university hospital. PATIENTS: Of 97 pancreatic retransplantations (July 1, 1985 to June 30, 1994), 13 (13%) were performed after previous pancreas grafts had been lost because of intra-abdominal infection. MAIN OUTCOME MEASURES: Cause of retransplant graft loss; patient survival. RESULTS: Of 13 cases of pancreatic retransplantations performed after previous grafts had been lost because of intra-abdominal infection, 12 (92%) were again complicated by intra-abdominal infection. Of these 12 retransplantation infections, 10 were caused by the same microbial species that had caused failure of the previous graft 1 to 5 years earlier (8 required graft pancreatectomy [mortality rate, 25%], and 2 were successfully treated) and 2 were caused by different microbial species (both required graft pancreatectomy [mortality rate, 0%]). In 1 of the 13 retransplantations, prophylactic antimicrobial treatment was directed at the microbial species that had caused failure of the previous graft; no recurrent intra-abdominal infection developed. CONCLUSIONS: Intra-abdominal infection after a previous pancreas transplantation is a risk factor for recurrence of infection by the same microbial species after a subsequent retransplantation. For the selected patients who are considered for retransplantation in spite of their previous graft loss caused by intra-abdominal infection, periretransplantation antimicrobial prophylaxis should include a prolonged course of an agent directed against the previously identified microbial species.

Abdomen↗

X-ray crystallography of peptides: the contributions of the Italian laboratories.

The review article summarizes the most relevant solid state structural and conformational results obtained in the laboratories involved in Italy in the studies of synthetic and natural peptides by x-ray diffraction analyses. Some of the topics will include research studies carried out in other European countries, whereas in other cases studies carried out in Italy will be included in other review articles included in this volume. The review deals with peptides containing symmetrically achiral and unsymmetrically chiral C alpha,alpha-dialkylated glycine residues, peptides containing beta-alanine residues, alpha,beta-dehydroamino acid residues, and aminosuccinyl residues, peptides containing the thioamide surrogate, heterochiral peptides and several bioactive peptides systems with the proposed relationships between function and structure.

Amino Acid Sequence↗

Solution and solid state structure of an aib-containing cyclodecapeptide inhibiting the cholate uptake in hepatocytes.

The conformational analysis of synthetic cyclodecapeptide c(Pro-Phe-phe-Aib-Leu)2 related to the cyclolinopeptide A, in the solid state and solution, has been carried out by x-ray diffraction and nmr spectroscopy. The structure of the monoclinic form obtained from methanol [a = 11.351 (5) A, b = 27.455 (2) A, c = 12.716 (8) A, beta = 99.65 (3) degrees; space group P2(1); Z = 2] shows the presence of six intramolecular NH...CO hydrogen bonds, with formation of four turns (three of type I and one of type III) and two C16 ring structures. All peptide units are trans. The solution structure, as found by nmr, indicates that, at room temperature, the peptide is conformationally homogeneous; the structure determined is perfectly symmetrical and topologically similar to that found in the solid state. The cyclodecapeptide exhibits similar biological activity to cyclolinopeptide A.

Animals↗

Determination of the secondary structure of isomeric forms of human serum albumin by a particular frequency deconvolution procedure applied to Fourier transform IR analysis.

A new deconvolution procedure was applied to the analysis of Fourier transform ir spectra of human serum albumin secondary structure in the native state and in states denatured by heat and acid treatment. The deconvolution method is based on the use of the Conjugate Gradient Minimization Algorithm, with the addition of suitable constraints directly obtained by the application to the measured spectrum of the second derivative operator. This method computes central band frequency, bandwidth, and amplitude of the different spectral components of conformation-sensitive amide bands. In the specific case, it was applied to analysis of the amide I band, and the quantitative determination of the different secondary structures (alpha-helix, beta-sheet, beta-turns, and random) was attempted for all the samples examined. The precision of the quantitative determination depends on the amounts of these structures present in the protein. The coefficient of variation is < 10% for values of amide I component > 15%. The accuracy was tested by comparing, by means of linear regression, the results obtained for human serum albumin, hemoglobin, alpha-chymotrypsin, and cytochrome c, using our method, with those obtained by x-ray crystallography and CD; the results obtained by other vibrational spectroscopic approaches were also compared. The fit standard error between x-ray and ir secondary structure values estimated by our method is 2.5% for alpha-helix, 7.16% for beta structures, and 5.1% for other structures (turns and random coils). Quantitative results are given for the secondary structures (alpha-helix, turns, and beta-strands) present in the native state (turns and beta-strands up to now unknown in aqueous solution), together with the percentages of these structures and additional ones (random coils and beta-sheets) formed during denaturization.

Algorithms↗

Colon vs small bowel rejection after total bowel transplantation in a pig model.

With the advent of FK 506, small bowel transplantation has become clinically feasible. Both clinically and experimentally, jejunal and ileal biopsies are used for early diagnosis of rejection. More recently, the colon, in addition to the small bowel, has been transplanted to decrease the high incidence of diarrhea after small bowel transplantation. A Bishop-Koop ileostomy allows biopsies on a regular basis, but the diagnosis of rejection remains a problem after takedown of the ileostomy. Rejection of the ileum is more frequent and more severe than rejection of the jejunum or the colon. Colon biopsy after ileostomy takedown would not rule out rejection of the ileum.

Animals↗

Combined liver and kidney transplantation.

Patients with end-stage renal and hepatic failure may be treated with combined liver and kidney transplantation (CLKTx). We reviewed the indications and outcomes of 16 CLKTx performed at the University of Minnesota between 1980 and 1994. The majority of the recipients (87.5%) were young patients affected by congenital hepatic anomalies and concomitant end-stage renal failure. Fourteen were treated with cyclosporin-based immunosuppression and had an excellent outcome: with an average of 6 years of follow-up, patient survival was 85.7%, liver graft survival 85.7%, and kidney graft survival 72%. The incidence of rejection episodes was similar to the rate of rejection in our solitary kidney and liver transplants. In conclusion, our experience supports the value of CLKTx in treating patients with simultaneous failure of both organs or with congenital enzymatic hepatic deficits leading to renal failure.

Adolescent↗

The impact of quadruple immunosuppression with OKT3 on kidney transplantation in black recipients.

BACKGROUND: Black recipients of kidney transplants have been shown to have lower graft survival than other racial groups. There is ongoing controversy about the optimal immunosuppressive protocol for blacks after kidney transplantation. PATIENTS AND METHODS: Five hundred-eighty-two recipients of kidney transplants performed between 1985 and 1994 were divided into three groups: (1) nonblacks who received cyclosporine and prednisone (N = 292); (2) blacks who received "quadruple" cyclosporine based immunosuppression with OKT3 induction (N = 98); and (3) blacks who received cyclosporine and prednisone only (N = 192). Patient and graft survival and incidence of acute rejection episodes were compared among the groups. RESULTS: Blacks had lower graft survival when compared with nonblacks. However, in the subgroup of black recipients who received quadruple immunosuppression, graft survival at 1 year was higher and the incidence of acute rejection episodes was significantly decreased compared with blacks without induction. Graft survival and the incidence of acute rejection in blacks on quadruple therapy was comparable with nonblacks. CONCLUSIONS: Our data support the principle that quadruple immunosuppression should be used routinely for black recipients of kidney transplants.

Adult↗

A new method of creating an arteriovenous graft access.

Since the initial description of the radial arteriovenous (AV) shunt, hemodialysis has played a primary role in the survival of patients with chronic renal failure. However, it is not unusual to be confronted with patients on chronic hemodialysis who have exhausted all superficial venous access sites. We describe a technique using the deep veins of the arms the outflow system during AV graft construction. By anastomosing the venous limb of the graft to the larger of the two brachial veins, we have been able to give patients AV access when the superficial veins have been exhausted. We have performed this technique with good success in 12 patients. Further experience and longer follow-up are needed.

Arm↗

Structure and absolute stereochemistry of fusaproliferin, a toxic metabolite from Fusarium proliferatum.

Fusaproliferin is a toxic sesterterpene isolated from Fusarium proliferatum, a widespread pathogen of cereals. Its absolute configuration has been determined by single crystal X-ray diffraction analysis. Fusaproliferin is considered to be a sesterterpene with a new ring skeleton having four C = C double bonds and four chiral atoms. The configurations of the four chiral atoms C10, C14, C15, and C19 are (R), (S), (R), and (S), respectively. In the solid state the macrolide shows a concave hydrophobic surface and hydrophilic convex face. The absolute configuration of C14 and C15 is the same as that observed for retigeranic acid, consistent with fusaproliferin being formed via a sesterterpenic-type biosynthetic pathway.

Animals↗

Vascular graft thrombosis after pancreatic transplantation: univariate and multivariate operative and nonoperative risk factor analysis.

BACKGROUND: Vascular thrombosis is still the leading cause of nonimmunologic, technical pancreatic transplant graft failures. The paucity of published data--coupled with our large institutional experience with pancreatic transplantation in all recipient and transplant categories, using a wide spectrum of surgical techniques--provided the impetus for a retrospective study of graft thrombosis risk factors. STUDY DESIGN: Four hundred thirty-eight patients with pancreatic transplants (45 percent simultaneous pancreas-kidney [SPK], 23 percent pancreas-after-kidney [PAK], and 32 percent pancreatic transplants alone [PTA] and with Type I insulin-dependent diabetes mellitus were studied retrospectively. Of 438 pancreatic transplants, 90 percent were bladder-drained and 10 percent were enteric-drained. Ninety-three percent were from cadaver donors, 90 percent were whole-organ grafts, and 20 percent were retransplantations. Quadruple immunosuppression was given. For bladder-drained, whole-organ transplantations (n=378), we performed Cox regression analyses to study the impact on pancreatic graft thrombosis of donor, recipient, mode of preservation, and surgical variables. RESULTS: The overall thrombosis rate was 12 percent (5 percent arterial, 7 percent venous). For cadaver, bladder-drained, whole-organ pancreatic transplants, the thrombosis incidence was highest in PAK recipients (20 percent). The PAK category was also found to be an independent risk factor for thrombosis by stepwise Cox regression analysis. In separate stepwise Cox regression analyses for each category, other identified risk factors for thrombosis included the following: donor age (PAK, PTA); cardiocerebrovascular cause of donor death (SPK, PAK); the use of an aortic Carrel patch (SPK); arterial pancreatic graft reconstruction using a splenic artery to superior mesenteric artery anastomosis (SPK, PTA) or an interposition graft between the splenic artery and the superior mesenteric artery (PTA); portal vein extension graft (PAK); left-sided implantation into the recipient (PAK); and graft pancreatitis (defined as hyperamylasemia exceeding five days post-transplant [PAK, PTA]). CONCLUSIONS: Older donors or those who died of cardiocerebrovascular disease should not be considered for any recipient category. Preservation time needs to be minimized and strategies need to be developed to decrease graft pancreatitis. Surgically, left-sided implantation and arterial reconstructions other than the Y-graft also increase risk, as do portal vein extensions. Renal transplants alone in prospective PAK recipients with Type I diabetes mellitus should, therefore, always be implanted left-sided to allow for right-sided pancreatic graft placement.

Adult↗

Intra-abdominal fungal infections after pancreatic transplantation: incidence, treatment, and outcome.

BACKGROUND: Intra-abdominal infections account for 15 percent of technical failures after pancreatic transplantation. Although some data are available about intra-abdominal bacterial infections, no study has analyzed the incidence, treatment, and outcome of intra-abdominal fungal infections. STUDY DESIGN: We retrospectively studied 445 consecutive pancreatic transplantations--45 percent were simultaneous pancreatic and renal, 24 percent pancreatic after renal, and 31 percent pancreatic transplantations alone--in patients with Type I diabetes mellitus. Donors were cadavers in 92 percent and living relatives in 8 percent. Primary transplantations were done in 80 percent and retransplantation in 20 percent. Of these 445 pancreatic transplantations, 90 percent were bladder-drained, 9 percent enteric-drained, and 1 percent duct-injected. Only symptomatic patients with documented culture-positive intra-abdominal fungal infections were included. RESULTS: Intra-abdominal fungal infections occurred after pancreatic transplantation in 41 (9.2 percent) of 445 patients. Donor age, but not recipient age, was a significant risk factor. The rate of infections was higher for enteric-drained (21 percent) than for bladder-drained (10 percent) transplantations; for organs donated by living relatives (16 percent) than for those from cadavers (9 percent); and for pancreatic after renal (12 percent) and simultaneous pancreatic-renal (11 percent) than for pancreatic-only (5 percent) recipients. The rate of intra-abdominal fungal infections was 6 percent for recipients who were given antifungal prophylaxis (fluconazole, 400 mg/day for seven days after transplantation) compared with 10 percent for those without prophylaxis. The one-year graft survival rate for recipients with infection was 17 percent compared with 65 percent for those without (p = 0.0001); the survival rate was 70 percent compared with 92 percent for patients with and without infection, respectively (p = 0.0007). In 22 percent of recipients, the infection resolved and graft function persisted; in 58 percent, the infection resolved after transplant pancreatectomy; and in 20 percent, death occurred despite transplant pancreatectomy. Recipients with sole fungal or fungal and bacterial infection (n = 41) were 50 percent less likely to recover with a functioning graft and had a risk of death that was three times higher (p < or = 0.05) than those with sole bacterial infection (n = 48). CONCLUSIONS: Intra-abdominal fungal infections after pancreatic transplants are associated with high morbidity and mortality rates, significantly higher than for sole bacterial infections. In addition to aggressive treatment, including transplant pancreatectomy and reduction of immunosuppression, efforts must be made toward better prevention of intra-abdominal fungal infections.

Adult↗

[Technical options of renal transplant in the absence of a viable ilio-caval venous circuit. Presentation of a case and review of the literature].

Congenital absence of useful ilio-caval venous segment is a very infrequent congenital anomaly and makes unfit grafting of a kidney transplant in iliac fossa. We report the case of a 18 years old male affected by this abnormality who was transplanted in intraabdominal situation. We review technical alternatives offered by the literature.

Adolescent↗

Cystoscopic biopsies in pancreaticoduodenal transplantation. Are duodenal biopsies indicative of pancreas dysfunction?

Tissue diagnosis of pancreas graft dysfunction is desirable. Bladder-drained pancreaticoduodenal transplants allow tissue diagnosis by cytoscopic biopsy procedures of the pancreas and duodenum. To assess the diagnostic utility of duodenal biopsies, we reviewed all cystoscopically obtained pancreas and duodenal biopsy tissues at our institution (July 1, 1989 through September 30, 1993). Adequate tissue for histologic examination was obtained from 75 biopsies in 58 recipients. Indications for cytoscopic biopsies were relative hypoamylasuria in 85%, hematuria in 6%, hyperamylasemia in 3%, and other causes in 6%. Duodenal specimens were available from 52 biopsies (25 with, and 27 without, concurrent pancreas biopsies). Of the 27 duodenal biopsies alone, 3 were diagnostic of rejection, 15 had features consistent with rejection, 6 were normal, 1 showed fibrosis, 1 showed necrosis, and 1 was ulcerated. Thus, two-thirds of the duodenal biopsies alone yielded clinically relevant information resulting in antirejection treatment. In 25 of the duodenal biopsies, pancreas tissue was also available (11 simultaneous pancreas-kidney, 9 pancreas transplant alone, and 5 pancreas after kidney recipients). Findings in both organs completely agreed in 9 (36%) of the biopsies. In 7 (28%), rejection was suggested or diagnosed in both organs, although the organs were discrepant with regard to the presence of vascular rejection (6 pancreas, 1 duodenum). In 2 (11%), minor nonrejection discrepant findings were present. Therefore, in 18 of 25 (72%) pancreas-duodenal biopsies, treatment would not have been different if only one graft had been biopsied. But in the other 7 (28%), treatment would have been different if only the organ with negative findings had been biopsied. In 6 cases (4 duodenal, 2 pancreas), rejection was seen in one organ but not the other. In 1 case, cytomegalovirus (CMV) inclusions were present in the duodenum, but the pancreas was normal. We conclude that (1) the duodenum and pancreas can reject independently of each other, and a negative biopsy does not preclude rejection of the other organ; (2) duodenal biopsies determined therapeutic decisions one-fifth of the time when both tissues were available for examination, and two-thirds of the time when only duodenal tissue was available; and (3) since cystoscopy allows easy access to the duodenum, both the pancreas and duodenum should be biopsied whenever possible; tissue samples of one organ alone are sufficient only with positive findings.

Adult↗