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Biomedical subjects

D L Dunn

Publications and source records attributed to D L Dunn.

At least 163 records · Page 9Linked to original sources
PubMed1992

Antimicrobial therapy of intra-abdominal sepsis.

Intra-abdominal sepsis remains a highly morbid and lethal event despite the availability of potent antimicrobial agents and improvements in surgical management and intensive care. Appropriate management consists of source control, antimicrobial agents directed against both facultative gram-negative and anaerobic organisms, and physiologic and metabolic support. A variety of single and dual agent regimens are appropriate for initial therapy, as long as both aerobes and anaerobes are effectively targeted. Culture, Gram stain, and sensitivity testing may provide valuable information, especially when resistant organisms are encountered. Further studies to determine the relative efficacy of various agents need to be carefully designed both to avoid the pitfalls of previous studies and to provide useful and comparable data.

Abdomen↗
PubMed1992

Intestinal bacterial flora, intestinal pathology, and lipopolysaccharide-induced translocation of intestinal bacteria.

The primary aim of this study was to clarify the mechanism and significance of lipopolysaccharide (LPS)-induced translocation of intestinal bacteria. Female Swiss Webster mice were purchased from two different animal suppliers. Twenty-four hours following parenteral LPS, mice from both suppliers had noticeable morbidity and mortality. However, intestinal pathology, gram-negative bacterial overgrowth, and increased bacterial translocation was noted in mice purchased from one supplier but not the other. Mice with increased translocation also had overgrowth of cecal gram-negative bacilli, i.e., 10(10) per gram of cecum following parenteral LPS; in contrast, mice without LPS-induced bacterial translocation had 1,000- to 10,000-fold fewer cecal gram-negative bacilli. Additional groups of mice with increased bacterial translocation were also sacrificed two and 6 hr after parenteral LPS; morbidity and intestinal pathology were evident without a corresponding increase in bacterial translocation. Separate groups of these mice were also injected with platelet activating factor, resulting in intestinal pathology similar to that noted with parenteral LPS, but no increase in bacterial translocation. Thus parenteral LPS was consistently associated with morbidity and mortality but not with intestinal pathology, enteric bacterial overgrowth, or increased bacterial translocation.

Animals↗
PubMed1991

Appropriate use of antimicrobial agents. Nine principles.

After determining that a patient with an infection would benefit from an antimicrobial agent, several factors must be weighed to arrive at an appropriate choice: seriousness of the infection, the patient's drug allergies, and drug efficacy, toxicity, and cost. Rapid stains, cultures, and sensitivity studies are often helpful in guiding therapy and are critical to appropriate treatment of serious infections. Consideration should also be given to other forms of management, such as control of the source of infection, prophylaxis, and physiologic management.

Anti-Infective Agents↗
PubMed1991

Diagnosis and treatment of cytomegalovirus disease in transplant patients based on gastrointestinal tract manifestations.

Infection due to cytomegalovirus is a substantial cause of morbidity and mortality in immunocompromised patients. In particular, cytomegalovirus infection has been associated with a significant detrimental effect on patient and allograft survival after solid-organ transplantation. We are evaluating a new antiviral agent, ganciclovir 9-[1,3-dihydroxy-2-2 propoxymethyl] guanine (DHPG), used in solid-organ transplant recipients who developed life-threatening cytomegalovirus infections. Between March 1, 1987, and June 30, 1989, we treated 93 solid-organ transplant patients who developed tissue-invasive cytomegalovirus disease. From this group of patients we have identified 14 patients with primary gastrointestinal cytomegalovirus disease who received treatment with DHPG. Tissue diagnosis was made by endoscopy of the upper gastrointestinal tract (11 patients) or colonoscopy (three patients). Invasive cytomegalovirus disease was identified prior to severe complications of the gastrointestinal tract in all but one patient, who suffered colonic perforation prior to treatment with DHPG and subsequently died of bacterial sepsis. While 13 of the 14 patients improved after treatment with DHPG, four patients required additional treatments for recurrent cytomegalovirus disease and recovered. No DHPG toxicity was observed. We believe treatment with DHPG is indicated in this patient population, but that further studies are indicated to fully define the impact of this recommendation on both patient and allograft survival after solid-organ transplantation.

Abdominal Pain↗
PubMed1991

Multiorgan transplantation in the rat: development of a new microsurgical model.

Although transplantation of multiple abdominal viscera (MOTx) has been performed in humans, reproducible animal models and extensive laboratory work are needed to explore the physiological and immunological aspects of this new transplant procedure. We therefore developed a microsurgical model that allows en bloc transplantation of three major abdominal viscera. Using isogeneic rat strain combinations, 30% of the liver, pancreas, and duodenum and a segment of small bowel (SB) were heterotopically transplanted. A segment of aorta that included the celiac axis and the superior mesenteric artery provided the blood supply to the graft. Venous outflow occurred via the graft suprahepatic vena cava into the recipient's infrahepatic vena cava. The graft SB was anastomosed to the native SB. After a training period (N = 15), we could achieve a success rate of 83% (N = 23). Mean operation time was 105 minutes. Macroscopic and microscopic appearance of transplanted organs was normal. This study documents the feasibility of MOTx in the rat and provides a microsurgical model that should facilitate preclinical experimental research in this area.

Animals↗
PubMed1991

New approaches to the diagnosis, prevention, and treatment of cytomegalovirus infection after transplantation.

Infection occurring after solid organ transplantation continues to exert a considerable detrimental effect upon patient and allograft survival. While the search for better targeted immunosuppressive regimens continues, we must seek to improve our ability to both diagnose and treat those infections that do occur after transplantation. Viral infections in general, and cytomegalovirus (CMV) infections in particular, represent an area in which substantial progress is being made. Improvement in diagnostic modalities has allowed more rapid and precise identification of CMV infection and disease, and the use of antiviral agents that possess activity against CMV has allowed both prophylaxis and treatment of this frequently life-threatening disease. The prophylactic use of presently available agents in combination and the development of less toxic, more potent anti-CMV agents should serve to further lessen the impact of CMV disease upon the field of solid organ transplantation.

Cytomegalovirus Infections↗
PubMed1991

Graft-versus-host disease after multiorgan transplantation.

A rat model of multiorgan transplantation (MOTx) including the liver, pancreas, duodenum, and variable segments of small bowel (SB) was used to ascertain whether graft-versus-host disease (GVHD) could be produced by this procedure. Rats receiving an isogeneic multiorgan transplant (MOT) survived more than 150 days. MOTx was then performed in the Lewis to (Lewis x Brown Norway) LBNF1 semiallogeneic combination, ensuring unidirectional GVHD. En bloc transplantation of the liver, pancreas, duodenum, and entire jejunum provoked lethal GVHD in all animals, and the mean time to recipient death (MT) was 16.5 +/- 0.43. When only one-half of the jejunum was included in the MOT, lethal GVHD similarly occurred in 100% of animals and the MT was 18 +/- 0.86. Finally, when only liver, pancreas, and duodenum were transplanted, the incidence of lethal GVHD was reduced to 50% (P less than 0.1). In those rats that died of GVHD, MT was 16 +/- 0.33. Fifty percent of the rats in this group, however, recovered from a milder form of GVHD and survived more than 150 days. These results demonstrate that MOTx induces GVHD and that the lethality of this process correlates with the inclusion of the SB in the graft and thus, with the overall amount of transplanted lymphoid tissue.

Animals↗
PubMed1991

Causes of renal allograft loss. Progress in the 1980s, challenges for the 1990s.

A variety of refinements in the care of kidney transplant recipients have been instituted over the past decade. The authors studied the overall impact of these refinements on kidney allograft losses at a single institution. To do this they compared the causes and rates of graft loss for primary kidney transplants in the 1970s (January 1, 1970 to December 31, 1979; n = 1012; 657 nondiabetics, 355 diabetics; 617 living donors, 395 cadaver donors) versus the 1980s (January 1, 1980 to December 31, 1989; n = 1,384; 756 nondiabetics, 628 diabetics; 740 living donors, 644 cadaver donors). Overall patient survival improved significantly, with rates at 1, 5, and 10 years of 94%, 84%, and 68% for the 1980s, compared with 86%, 69%, and 57% for the 1970s (p less than 0.001). Actuarial graft survival also improved significantly, with rates at 1, 5, and 10 years of 86%, 71%, and 52% for the 1980s, compared with 73%, 58%, and 43% for the 1970s (p less than 0.001). This improvement occurred even though there were proportionately more cadaver donors and diabetic recipients in the 1980s. For both decades combined, 24% of the lost grafts were due to chronic rejection, 18% to cardiovascular causes of death with function, 13% to infectious causes of death with function, and 11% to acute rejection. The overall gain in graft survival rates in the 1980s was principally due to fewer cases of acute rejection and fewer infectious deaths. Improvement in graft survival due to the two leading causes--chronic rejection and cardiovascular causes of death--was relatively small, if any. These data indicate that future kidney transplantation research should emphasize prevention of chronic rejection and cardiovascular death.

Cadaver↗
PubMed1991

Pancreaticoduodenal transplantation with enteric drainage following native total pancreatectomy for chronic pancreatitis: a case report.

Pancreas transplantation is usually performed in patients with denovo type I diabetes, who have advanced secondary complications. We report a case in which whole pancreaticoduodenal transplantation, with enteric drainage, was performed to correct both endocrine and exocrine deficiencies in a patient with hyperlabile diabetes and steatorrhea, unresponsive to oral enzyme replacement therapy, following staged total pancreatectomy for idiopathic or familial chronic pancreatitis. The transplant was performed one year after completion of native pancreatectomy and immediately established an insulin-independent euglycemic state, with normal oral and intravenous glucose tolerance test results and correction of steatorrhea. Beginning one year posttransplant, the patient had intermittent episodes of steatorrhea, associated with mild elevation of blood sugar levels, which were presumed to be due to rejection and, indeed, responded to antirejection treatment with antilymphocyte globulin and temporary increases in steroids dosages. At 20 months posttransplant, steatorrhea did not respond to antirejection treatment and an acute abdomen developed. Laparotomy revealed a perforated graft duodenum, which was resected; pathology showed transmural necrosis secondary to chronic rejection. The pancreas graft itself was left in situ, disconnected from the intestinal tract. The patient remained normoglycemic after graft duodenectomy but resumed oral enzyme replacement therapy in an attempt to combat recurrence of severe steatorrhea. However, his overall situation remained improved compared to pretransplant, since the exocrine deficiency was tolerable in the absence of a diabetic state. Ten months postgraft duodenectomy (38 months posttransplant), elevations in blood sugar levels were treated with another course of antirejection treatment and levels temporarily declined. At 14 months postgraft duodenectomy (42 months posttransplant), graft endocrine function again declined and exogenous insulin was resumed. Six months later, four years after the original transplant, a new enteric-drained pancreaticoduodenal graft was placed, once again resulting in an insulin-independent, steatorrheafree state. With improvements in immunosuppression, pancreas transplantation could be offered to selected patients with hyperlabile diabetes, following total pancreatectomy for benign disease; if the enteric drainage technique is used, in the absence of rejection, exocrine deficiency could be corrected as well.

Adult↗
PubMed1991

Resistance to graft-versus-host disease following small bowel transplantation.

Transplantation of a Lewis rat small bowel allograft (SBTx) into Lewis x Brown Norway F1 (LBNF1) hybrid recipients provokes lethal graft-versus-host disease. GVHD in F1 hybrid rats inoculated with large number of parental lymphocytes may be abrogated by prior treatment of F1 hybrids with a sublethal dose (SLD) of the same parental lymphocytes. Therefore, we sought to determine whether this type of immunomodulation would prevent GVHD after SBTx. We examined whether pretreatment of LBNF1 recipients with a SLD of parental lymphocytes, or with a revascularized segment of parental small bowel, might ameliorate GVHD following transplantation of the entire parental small bowel. Nonpretreated LBNF1 recipients died of GVHD after entire Lew SBTx; 95% of LBNF1 recipients pretreated with SLD of Lew lymphocytes and 84% of LBNF1 recipients first transplanted with a segment of Lew small bowel survived GVHD induced by entire Lew SBTx 10 days later. Of LBNF1 recipients pretreated with SLD of Brown Norway lymphocytes or first transplanted with a segment of BN small bowel, none were protected from GVHD induced by entire Lew SBTx 10 days later. We concluded that pretreatment of LBNF1 recipients either with an SLD of parental lymphocytes or with a segment of parental small bowel provides profound protection from the effects of GVHD following transplantation of an entire small bowel of the same parental strain specificity.

Animals↗