Bacterial virulence indicates the degree of pathogenicity of a given strain of microbe for a given host. The effect of Escherichia coli virulence on lung microvascular permeability was studied in sheep with chronic pulmonary lymph fistulas following peritoneal contamination. The study was divided into four groups: (1) wild-type E coli (WT group, 2.5 x 10(9) colony-forming units [CFUs]/kg); (2) virulent E coli (PV group, 2.3 x 10(9) CFUs/kg); (3) nonvirulent E coli (PNV group, 2.6 x 10(9) CFUs/kg); (4) high-inoculum wild-type E coli (HIWT group, 6.1 x 10(9) CFUs/kg). In the late period (two to six hours), the increase in lung lymph flow in the PV group was significantly greater than the WT, PNV, and HIWT groups, with no difference noted among groups with respect to the pulmonary artery pressure, pulmonary wedge pressure, or albumin lymph/plasma ratio. It was concluded that (1) increased E coli virulence results in increased lung microvascular damage and (2) increased lung microvascular damage as a function of E coli virulence may not be solely due to increased bacterial numbers as a function of time.

Albumins↗

PubMed1989

Treatment of toxic shock syndrome with endotoxin-neutralizing antibody.

The enhancement of host susceptibility to endotoxin (lipopolysaccharide, LPS) by toxic shock syndrome toxin-1 (TSST-1) is an important mechanism in the pathogenesis of toxic shock syndrome. In these studies, we sought to determine whether an endotoxin-neutralizing monoclonal antibody could be useful in the treatment of toxic shock syndrome. We isolated a murine monoclonal hybridoma (3-H3) which secreted monoclonal antibody (mAb) specific for Escherichia coli 0111:B4 LPS. Spleen cells cocultured with E. coli 0111:B4 LPS demonstrated up to a 60% decrease in mitogenic activity in the presence of 3-H3 mAb, but not control mAb, demonstrating that this antibody neutralized endotoxin in vitro. Rabbits pretreated with 3-H3 mAb or control mAb were injected intradermally with E. coli 0111:B4 LPS. One day later rabbits received E. coli 0111:B4 LPS intravenously to elicit the dermal Shwartzman reaction. Rabbits pretreated with 3-H3 mAb did not develop this reaction (0/6) compared to animals pretreated with control mAb (5/6), demonstrating that this antibody neutralized endotoxin in vivo (P less than 0.05). When this antibody was evaluated in a rabbit model of lethal toxic shock syndrome, rabbits pretreated with antibody demonstrated greater survival (8/14) than saline control animals (1/10) after challenge with TSST-1 and E. coli 0111:B4 LPS (P less than 0.05). Since the suspicion exists that low levels of endogenous LPS may potentiate TSST-1 activity during clinical toxic shock syndrome, we hypothesized that endotoxin-neutralizing antibodies could be useful in the treatment of this lethal disease process.

Animals↗

PubMed1989

A 10-year experience with 290 pancreas transplants at a single institution.

Since our report at the 1984 American Surgical Association meeting of 100 pancreas transplants from 1966 through 1983, another 190 have been performed. The current series, begun in 1978, now numbers 276 cases, and includes 133 nonuremic recipients of pancreas transplants alone (PTA), 46 simultaneous pancreas/kidney transplants (SPK), and 97 pancreas tranplants after a kidney transplant (PAK). Duct management techniques used were free intraperitoneal drainage in 44 cases, duct occlusion in 44, enteric drainage in 89, and bladder drainage in 128. The 1-year patient and graft survival rates in the entire cohort of 276 were 91% and 42%. One-year patient survival rates were 88% in the first 100, 91% in the second 100, and 92% in the last 76 cases; corresponding 1-year graft survival rates were 28%, 47%, and 56% (p less than 0.05). A prospective comparison of bladder drainage (n = 82) versus enteric drainage (n = 46) in PAK/PTA cases since November 1, 1984 favored bladder drainage (1-year graft survival rates of 52% vs. 41%) because of urinary amylase monitoring. The best results were in recipients of primary SPK bladder-drained transplants (n = 39), with a 1-year pancreas graft survival rate of 75%, kidney graft survival rate of 80%, and patient survival rate of 95%. Logistic regression analysis, with 1-year graft function as the independent variable, showed significant (p less than 0.05) predictors of success (odds ratio) to be technique: bladder drainage (5.8) versus enteric drainage (2.5) versus duct injection (1.0); category: SPK (6.0) versus PAK from same donor (3.2) versus PAK from different donor (1.2) versus PTA (1.0); and donor HLA DR mismatch: 0 (5.0) versus 1 (2.5) versus 2 (1.0) antigens. On April 1, 1989, 90 patients had functioning grafts (60 euglycemic and insulin-free for more than 1 year, 10 for 5 to 10 years); these, along with 24 others whose grafts functioned for 1 to 6 years before failing, are part of an expanding cohort in whom the influence of inducing a euglycemic state on pre-existing secondary complications of diabetes is being studied. Only preliminary data is available. In regard to neuropathy, at more than 1 year after transplant in patients with functioning grafts, conduction velocities in some nerves were increased over baseline. In regard to retinopathy, deterioration in grade occurred in approximately 30% of the recipients by 3 years, whether the graft functioned continuously or failed early, but thereafter retinopathy in the patients with functioning grafts remained stable.(ABSTRACT TRUNCATED AT 400 WORDS)

Diabetes Mellitus↗

PubMed1989

Pancreas-transplant outcome in relation to presence or absence of end-stage renal disease, timing of transplant, surgical technique, and donor source.

The differences in pancreas-transplant outcome according to recipient status, surgical approach, and donor source are illustrated by an analysis of results at one institution with experience in several categories. From July 1978 to January 1988, 210 pancreas transplants were performed, and 67 grafts are still functioning, the longest for 9.7 yr. Since October 1984, a uniform immunosuppressive protocol has been used, antilymphocyte globulin, cyclosporin, azathioprine, and prednisone for induction and the last three drugs for maintaining antirejection therapy. During this period, 110 pancreas transplants were performed, 62 in nonuremic non-kidney transplants, 28 in recipients of a previous kidney, and 20 simultaneous with a kidney; 64 with bladder and 43 with enteric drainage; and 25 from related and 85 from cadaver donors. The overall patient survival rate at 1 yr was 91%, and there were no significant differences between the various categories. Graft survival rates, however, differed between the various categories created by combinations of the above variables. With bladder drainage, 1-yr function rates were 58% (n = 30), 47% (n = 15), and 77% (n = 19) in recipients of a pancreas transplant alone, a pancreas after a kidney, or a simultaneous pancreas-kidney transplant; with enteric drainage, 1-yr function rates were 33% (n = 32) and 36% (n = 11) in the pancreas transplant alone and pancreas after kidney categories (enteric drainage was not done in double-transplant patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

PubMed1989

Transplant renal artery stenosis.

A group of 31 patients with transplant renal artery stenoses was identified among 2002 patients undergoing renal transplantation at the University of Minnesota; 29 of the stenoses were at the anastomosis. A total of 43 procedures were performed to correct the stenosis. Angioplasty was performed 25 times, with 3 patients cured and 2 patients improved; 20 procedures resulted in a poor result (3) or a failure (17). The failures were usually due to recurrent stenosis (7 patients) or to arterial injury that resulted in graft loss (4 patients) or successful emergency surgery to save the transplant (3 cases). Surgical repair of the stenosis was performed 18 times. No grafts were lost and 13 patients were cured or improved. These data suggest that angioplasty for anastomotic stenosis yields poor results and that a surgical repair is probably warranted. All 7 patients who had a poor results or failed a technically successful intervention did not have a rise in creatinine secondary to captopril or had a systolic pressure gradient of less than 60 mmHg across the anastomosis. These data also suggest that patients without physiological evidence of renal artery stenosis may not have improvement in their hypertension following repair.

Angioplasty, Balloon↗

PubMed1989

Long-term outcome of renal transplantation in patients with systemic lupus erythematosus.

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Adult↗

PubMed1989

Use of the circular stapler in construction of the duodenoneocystostomy for drainage into the bladder in transplants involving the whole pancreas.

The use of a circular stapler to construct a duodenoneocystostomy for exocrine drainage of transplants of whole pancreas is described herein. All but one of 15 grafts were technically successful, and the one failure was not related to the anastomosis. This method is easier than the handsewn technique we had been using, and the complication rate may be lower.

Anastomosis, Surgical↗

PubMed1989

Treatment of experimental gram-negative bacterial sepsis with murine monoclonal antibodies directed against lipopolysaccharide.

Monoclonal antibodies (MAbs) directed against gram-negative bacterial lipopolysaccharide (endotoxin, LPS) are currently being evaluated as an adjunctive form of therapy for lethal gram-negative bacterial sepsis and shock. The exact binding site within the LPS molecule against which antibody should be directed in order to maximize both cross-reactivity among bacterial strains and protective capacity has not been established. By developing a panel of MAbs that bound to various regions of the LPS molecule (O saccharide; outer, intermediate, and inner core; lipid A), we were able to determine that some epitopes in the inner core/lipid A region of LPS were broadly shared among different genera of gram-negative microorganisms, on the basis of immunoblot analysis of MAb binding to LPS. Pretreatment with lower doses of O saccharide-specific MAbs (2 micrograms per animal) provided protection against a lethal intraperitoneal challenge of viable Salmonella minnesota bacteria, compared with core LPS-specific MAbs, which required at least 1.0 mg of MAb per mouse to provide a similar degree of immunoprotection. Although inner core LPS-specific MAbs are less protective than O saccharide-specific MAbs, these MAbs will probably be more useful in the treatment of gram-negative sepsis because of their ability to bind to many types of LPS and enhance survival during infection, which is caused by a wide variety of gram-negative bacteria.

Animals↗

PubMed1989

New approaches to living donor renal transplantation [corrected].

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ABO Blood-Group System↗

PubMed1989

Noninvasive temporary pacing: experience in a community hospital.

During a 1-year period 37 patients who underwent treatment with a noninvasive temporary pacemaker were followed to evaluate effectiveness and outcome of therapy. The device was most frequently used in the emergency department and coronary care unit and was applied by a nurse in 51% of cases. Pacing thresholds ranged from 20 to 110 mA (mean 43 mA) with 91% obtaining capture. Pacing was continuous in 11 patients for 5 to 180 minutes (mean 32 minutes) and intermittent in 16 patients for up to 72 hours. Pacing did not take place in 10 patients because of failure to capture or because a satisfactory intrinsic rate was maintained. After external pacing, six patients received permanent pacemakers, 14 required temporary transvenous pacemakers, 10 required no further pacing, and seven (19%) died. Few problems were encountered, although eight of the 20 responsive patients had severe discomfort related to pacing, with two of these requiring discontinuation of pacing. The number of temporary transvenous pacemaker insertions in the coronary care unit decreased 32% over a 6-month period after introduction of the noninvasive temporary pacemaker. We conclude that the noninvasive temporary pacemaker is safe and effective although discomfort may limit its use in some patients.

Adult↗