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Biomedical subjects

L B Johnson

Publications and source records attributed to L B Johnson.

At least 73 records · Page 4Linked to original sources

Continuous intravenous infusion of epoprostenol for the treatment of portopulmonary hypertension.

The association of pulmonary hypertension with portal hypertension, also called portopulmonary hypertension (PPHTN), is a known complication of chronic liver disease. Previously, the presence of PPHTN was considered to be a contraindication to orthotopic liver transplantation (OLT). Although there are selected case reports of successful OLT in the setting of PPHTN, an excessive mortality rate is associated with OLT and PPHTN. Heretofore, therapy for chronic management of PPHTN was lacking. Recently, continuous intravenous infusion of epoprostenol has been demonstrated to improve symptomatology and survival in the general population of patients with primary pulmonary hypertension. We now report the use of epoprostenol in the more specific instance of PPHTN. Over a period of 6-14 months, epoprostenol (10-28 ng/kg/min) therapy was associated with a 29-46% decrease in mean pulmonary artery pressure, a 22-71% decrease in pulmonary vascular resistance, and a 25-75% increase in cardiac output in a group of four patients. These results suggest that effective chronic therapy for PPHTN is available. In conjunction with inhaled nitric oxide as acute intraoperative therapy, epoprostenol infusion represents an additional therapeutic option for treatment of PPHTN in the liver transplant candidate.

Adult↗

Simultaneous pancreas/kidney transplantation--a comparison of enteric and bladder drainage of exocrine pancreatic secretions.

Simultaneous pancreas/kidney transplantation (SPK) has evolved to become a therapeutic option for patients with renal failure resulting from type 1 diabetes mellitus. However, the appropriate route for drainage of the exocrine secretions of the pancreas allograft remains unclear. While bladder drainage (BD) is the current state of the art, it is associated with a high frequency of urologic complications, including urinary tract infections, hematuria, metabolic acidosis, dehydration, and reflux pancreatitis. Although enteric drainage (ED) is the more physiologic route, it has been associated in the past with decreased graft survival and increased infectious complications. In addition, BD offered a technique for detection of rejection through measurement of urinary amylase. However, with the advent of improved immunosuppression and antibiotic therapy, percutaneous pancreas biopsy, improved radiologic imaging, and greater understanding of pancreas transplantation, we hypothesized that ED could be performed without increased morbidity or cost. A group of 23 consecutive SPK was performed with ED during the period from July 1995 to November 1995. Another 23 age- and sex-matched recipients of SPK with BD performed from November 1994 to June 1995 served as a historical control group. Because of the differing lengths of follow-up, data were analyzed with respect to the first six months posttransplant. ED and BD were associated with equivalent actuarial one-year patient and graft survival rates: 100% and 88% for ED, and 96% and 91% for BD, respectively. Hospital charges, length of stay, readmissions, rejection, sepsis-related procedures were also equivalent in ED and BD. However, ED was associated with significantly fewer urinary tract infections and urologic complications. In addition, no grafts were lost as the result of sepsis. In the setting of SPK, ED represents a viable alternative to BD for primary drainage of pancreas exocrine secretions. Further studies with extended lengths of follow-up are necessary to confirm our observations.

Actuarial Analysis↗

Prevention of autoimmune islet allograft destruction by engraftment of donor T cells.

The results of clinical islet transplantation have remained poor when compared with the consistent success of pancreas transplantation. Autoimmunity has usually been discounted as a cause of islet transplant failure. Previously, we demonstrated that pancreas transplants from the diabetes resistant BB rat (BB-DR) function indefinitely in autoimmune diabetic hosts, but islets from the same donor are vulnerable to recurrent autoimmunity. Addition of 100 million pancreatic lymph node cells (PLNC) to BB-DR islets restores resistance to autoimmunity and leads to repletion of a T cell subset (RT6.1) in the recipients. Autoimmune (BB-Ac) and streptozocin (BB-Sz) diabetic BB rats were recipients of Wistar Furth (WF) intraportal islet or islets plus PLNC transplants with cyclosporine 5 mg/kg/day recipient treatment. One cohort of Brown Norway (BN) islet transplants to BB-Ac with CsA was performed. At the termination of the experiment, recipient peripheral blood lymphocytes (PBL) were characterized by flow cytometry (FACS) for class I, CD4, CD8, RT6.1, and RT6.2, a T cell maturation marker found in WF but not BB rats. All (14/14) WF and 75% (6/8) BN islet transplants to BB-Ac recipients failed after a mean of 42 and 36 days, respectively, despite CsA immunosuppression. WF islets were successful in 6/8 (75%) transplants to BB-Sz recipients (P<0.001 vs. BB-Ac recipients), confirming that autoimmunity is the major cause of islet failure in BB-Ac rats. Addition of PLNC to WF islets increased the survival in BB-Ac to 82% (9/11) (P<0.0001 vs. WF islets alone). Recipients of islet+PLNC express 19.7% RT6.2 compared with 4.6% and 4.0% for WF islets alone in BB-Ac (P<0.01) and BB-Sz (P<0.01), respectively. Autoimmunity is an important factor leading to islet transplant failure in autoimmune diabetic BB rats. Addition of donor PLNC prevent islet allograft failure and leads to recipient chimerism for a donor T cell subset (RT6.2) associated with resistance to autoimmunity.

Animals↗

Solitary pancreas allografts. The role of percutaneous biopsy and standardized histologic grading of rejection.

OBJECTIVE: To determine the potential impact of ultrasound-guided percutaneous pancreas allograft biopsy and standardized histologic grading on graft and patient survival in a solitary pancreas transplant program. DESIGN: Retrospective case series survey. SETTING: Tertiary care, university teaching hospital. PATIENTS: Thirty-five recipients of solitary pancreas transplants. INTERVENTIONS: Percutaneous pancreas allograft biopsies were performed in solitary pancreas transplant recipients. MAIN OUTCOME MEASURES: Actuarial graft and patient survival, cause of graft loss. RESULTS: Initiation of ultrasound-guided percutaneous pancreas allograft biopsy with standardized histologic grading is associated with a 70% 1-year graft survival and 93% 1-year patient survival in solitary pancreas transplantation. Acute rejection was responsible for only 11% of cases of graft loss. The presence of endotheliitis, vasculitis, or confluent acinar necrosis is associated with decreased pancreas allograft survival, poor response to corticosteroid therapy, and shortened time interval to ultimate graft loss. Clinical criteria for acute rejection such as elevated serum amylase or lipase levels, 50% decrease in urinary amylase levels, unexplained fever, or hyperglycemia are associated with a positive predictive value of only 72%. CONCLUSION: Pancreas allograft biopsy and standardized histologic grading are associated with significantly improved 1-year graft and patient survival in solitary pancreas transplantation.

Actuarial Analysis↗

Methemoglobinemia associated with dapsone treatment in solid organ transplant recipients: a two-case report and review.

Dapsone, a sulfone antibiotic, has been increasingly used in solid-organ transplant recipients for the primary prevention of Pneumocystis carinii pneumonia, especially in patients with documented sulfa allergy. A known side effect of dapsone therapy, however, is methemoglobinemia, a condition leading to impaired tissue oxygen delivery. This report documents two cases of dapsone-induced methemoglobinemia in patients after solid organ transplantation with emphasis on the importance of clinical recognition and benefits of treatment. Further, the pathophysiology and causes of this condition are extensively reviewed.

Aged↗

The evolution of a successful liver transplant program in 1996: the clinical and administrative role of the anesthesiologist.

The establishment of a new liver transplant program requires enormous planning and resources. Extensive negotiations must take place to ensure institutional and departmental commitments to obtain the proper equipment, personnel, and other resources. The formation of a well-trained multidisciplinary team of physicians and nurses becomes the next step. Finally, ample time must be provided to adequately deploy resources, lobby referring physicians, recruit patients, and troubleshoot problems as they arise.

Anesthesiology↗

Cytoablative therapy with combined resection and cryosurgery for limited bilobar hepatic colorectal metastases.

BACKGROUND: Cryosurgery can be employed in patients with unresectable hepatic metastases when the tumor size and the number of metastases are limited. However, local recurrence can result from incomplete ablation. We proposed a trial of complete cytoablation with a combined approach of cryosurgery and hepatic resection for patients with bilobar hepatic metastases. METHODS: Seven patients underwent cryosurgery alone (CRYO). Seven additional patients underwent combined resection and cryosurgery (CRYO+RES) for bilobar metastases. RESULTS: In the CRYO group, 5 of 7 patients had at least one centrally located tumor. All 5 of these patients had early recurrence at the site of ablation. In the CRYO+RES group complete ablation was achieved in 7 of 7. Two (28.6%) of these patients developed local recurrence. CONCLUSION: Cytoablation of hepatic metastases can be safely achieved with combined hepatic resection and cryosurgery in selected patients. Long-term survival data are necessary before advocating widespread application of this approach.

Aged↗

Selective bowel decontamination in hospitalized patients awaiting liver transplantation.

BACKGROUND: Infection remains a major contributor to morbidity and mortality following orthotopic liver transplantation (OLT). Selective bowel decontamination (SBD) in hospitalized patients is one strategy for prophylaxis. METHODS: A retrospective case-control study was performed using 18 consecutive hospitalized patients receiving SBD prior to OLT during the period September 1995 to September 1996. Eighteen consecutive hospitalized patients without SBD transplanted during the period March 1995 to September 1995 served as a historical control group. RESULTS: Selective bowel decontamination was associated with a significantly decreased prevalence of positive cultures for gram-negative bacteria and fungi and reduced overall hospital charges. CONCLUSION: In hospitalized patients awaiting OLT, SBD is an effective prophylactic measure against infectious morbidity associated with gram-negative bacteria and fungi.

Adult↗

Increased living donor volunteer rates with a formal recipient family education program.

We have generally encouraged living donation among our kidney recipients. However, an examination of our clinical practice revealed inconsistencies in the depth and content of information transmitted to kidney recipient families regarding living donation. We therefore initiated a structured education program, including an educational video, to ensure that all recipient families would receive a similar exposure to a standard block of information. After the program had been functioning for over a year, we compared the living donor (LD) volunteer rates between the 3-year period before (BEFORE) and the 18 months after (AFTER) initiation of the formal education program. There were 1,363 patients registered on our kidney transplantation waiting list during the 54-month study period (757 white [56%] and 580 black [43%]). We found that 33.4% of the kidney transplant candidates in the period BEFORE the LD education program had at least one potential LD tissue typed, compared with 39.4% in the period AFTER starting the program (P = 0.03). The increase in the proportion of patients with potential donors was greatest among the black (P < 0.05) and elderly (P < 0.01) registrants, which were the groups with the lowest volunteer rates before the program began. Among the registrants with at least one potential donor, the percentage of registrants who ultimately received an LD transplant was highly correlated with the number of donors (R = 0.98). The rate of LD kidney transplantation was significantly higher (P = 0.02) for the patients referred in the period AFTER initiation of the LD education program compared with the period BEFORE the program. The 1- and 3-year graft survival rates for the 170 LD transplants performed in these patients were 96.9% and 93.2%, respectively. These were significantly better than the corresponding 83.9% and 71.4% rates for the 341 kidney transplants from cadaver donors in these registrants (P < 0.001). Black recipients of LD transplants had graft survival rates comparable to whites; the 3-year graft survival rate for LD transplants was 93.9% in whites and 90.6% in blacks (P = NS). We conclude that living kidney donor volunteer rates can be improved by a formal family education program, especially for subgroups of patients with low volunteer rates. A substantial benefit is derived by black patients, who generally experience low graft survival rates with cadaver-donor kidneys. A local formal LD education program is a useful adjunct to national organ donation campaigns.

Adult↗

Distinctive clinical features of portopulmonary hypertension.

STUDY OBJECTIVE: To differentiate the cardiopulmonary profile of portopulmonary hypertension (PPHTN) from that of primary pulmonary hypertension and chronic liver disease. DESIGN: Retrospective survey. SETTING: Tertiary care center. PATIENTS: Thirty patients with cardiac catheterization-proven PPHTN were compared to 30 randomly selected patients with primary pulmonary hypertension alone and 30 patients with chronic liver disease alone necessitating consideration of liver transplantation (L-CONT). INTERVENTIONS: All patients underwent right heart catheterization, echocardiography, ECG, chest radiography, pulmonary function tests, ventilation-perfusion scanning, and room air arterial blood gas measurements. RESULTS: Patients with PPHTN exhibited elevated pulmonary pressures (mean pulmonary pressure, 48.6+/-2.1 mm Hg) and pulmonary vascular resistance (11.6+/-1.6 mm Hg/L/min/m2) with simultaneous elevation in the cardiac index (3.8+/-0.3 L/min/m2) and depression of systemic vascular resistance (24.9+/-1.7 mm Hg/L/min/m2). Arterial blood gas measurements indicate that PPHTN exhibits a significant accentuation of the chronic respiratory alkalosis (PCO2, 28.7+/-0.5 mm Hg) usually seen with chronic liver disease and pulmonary hypertension. In addition, patients with PPHTN have an increased alveolar-arterial gradient (27.0+/-2.7 mm Hg) when compared to patients with L-CONT, suggesting impaired gas exchange. CONCLUSIONS: PPHTN is associated with a unique clinical profile that possesses characteristics common to and exclusive of liver disease and primary pulmonary hypertension.

Alkalosis, Respiratory↗

Double renal allografts successfully increase utilization of kidneys from older donors within a single organ procurement organization.

BACKGROUND: In 1994, a policy of double renal allografting (DUAL) was used at two centers within our local organ procurement organization to increase utilization of kidneys from older donors that would otherwise be discarded. Both kidneys from an older donor (age > 60 years) were selectively transplanted into a single adult recipient. METHODS: The relative impact of a DUAL policy on the utilization of older donor kidneys is examined for the period of April 1994 to April 1996. Actual utilization is compared with the hypothetical case in which a DUAL policy is not present. RESULTS: In the actual setting, a total of 75 kidneys from older donors (> 60 years) were accepted for transplantation. Thirty-six kidneys were transplanted as singlets, and 16 additional kidneys were transplanted as DUAL renal allografts. Thus, a 44% increase in transplantable kidneys, and a 22% increase in patients transplanted with kidneys from older donors, was realized. In the actual setting, 23 older kidneys were discarded; without the DUAL policy, 39 kidneys would have been deemed untransplantable. When compared with the actual (n = 52) and hypothetical number of kidneys transplanted without a policy of DUAL transplantation (n = 36), the DUAL policy significantly increased the utilization of older donor kidneys (P = 0.01). The actuarial 1-year graft survival rate of the dual kidneys was 100%, with a mean follow-up of 11.1 +/- 2.9 months. Mean 6-month and 1-year serum creatinine level were 1.76 +/- 0.4 and 1.63 +/- 0.6 mg/dl, respectively. CONCLUSIONS: A DUAL policy significantly increased the number of older donor kidneys transplanted in a single organ procurement organization and reduced the rate of discard of older donor kidneys over a 2-year period. Long-term follow-up is necessary to substantiate satisfactory graft function in DUAL from older donors.

Age Factors↗

Late pancreas allograft rejection. Preliminary experience with factors predisposing to rejection.

A case series of 31 cadaveric pancreas transplant recipients who were insulin-independent at least for one year was analyzed for the factors predisposing to late acute rejection (> 12 months posttransplant). Sixty-two pancreas transplants were performed in 61 patients, of whom 53 had functioning allografts 3 months posttransplant; 31 of these had a follow-up > 12 months. Twenty had no evidence of late rejection, whereas 11 had evidence of acute rejection after 12 months. All patients received quadruple induction immunosuppression. No demographic or clinical factors-including donor age, organ cold time, HLA mismatch, age, sex, or race-could distinguish the late acute rejection group. The presence of acute rejection in the first year posttransplant was similar in the late rejectors (21 episodes in 9 of 11 patients) compared with patients without late rejection (31 episodes in 16 of 20 patients). Antilymphocyte induction therapy type had no influence, but the amount of immunosuppression with prednisone and cyclosporine (CsA) at 3 months posttransplant was significantly lower in those patients who experienced late rejection. After the first year posttransplant, CsA 12-hr trough levels were significantly lower in late rejection months (121 +/- 7 ng/ml) compared with each patient's own stable months (183 +/- 5 ng/ml, P < 0.0001). Neither prednisone nor azathioprine dosages differed between teh two groups after the first year posttransplant. Our preliminary results suggest that early under immunosuppression with prednisone and CsA in the first year and 12-hr trough CsA levels less than approximately 180 ng/ml after the first year posttransplant predispose to late pancreatic rejection.

Adult↗

The use of bilateral adult renal allografts - a method to optimize function from donor kidneys with suboptimal nephron mass.

Alternatives to traditional organ donor usage has allowed expansion of the organ donor pool to help compensate for the increasing disparity between recipients and donors. The use of bilateral adult renal transplants is a novel idea to salvage older donor kidneys with suboptimal nephron mass that would otherwise be destined for discard. Ten renal transplants were performed utilizing both kidneys from adult cadaver donors with diminished nephron mass determined by calculated glomerular filtration rate or biopsy evidence of significant glomerulosclerosis (>10%). Nine of ten (90%) recipients have satisfactory renal function at a mean follow-up of 7 months. The single case of graft failure was due to documented medical non-compliance. Mean serum creatinine at 6 months was 1.5 mg/dl. Mean measured creatinine clearance was 43.2+/-3.4. These preliminary findings suggest that the use of bilateral renal transplants provide satisfactory early function and allows salvage of older donor kidneys with suboptimal nephron mass.

Adolescent↗

Graft function and outcome of older (> or = 60 years) donor livers.

Livers from donors > or = 60 years of age are often considered inadequate for transplantation by many centers. With waiting times exceeding 1 year in our region, we have aggressively used livers from this donor age group. Between 1990 and 1994, 209 patients received 223 liver grafts at our institution. Of these, 29 (13%) were from donors > or = 60 years of age (group A) and 194 (87%) were from donors < 60 years of age (group B). The two groups were matched for recipient diagnosis and severity of disease. Group A and B donors had similar liver, renal, and hematologic studies prior to donation. Weight, sex, race and vasopressor requirement were also similar. Postoperative alanine aminotransferase, aspartate aminotransferase,and prothrombin time were not significantly different over the first 10 postoperative days. Group A grafts were significantly more cholestatic than group B grafts on postoperative days 6-10. The retransplantation rate for primary graft nonfunction was not significantly different from group A (6.7%) and group B (3.4%; P=0.04). Patient and graft survival rates at 1 year were 58.6 % and 44.8% for group A and 79.2% and 74.5% for group B (P<0.001 for both). Four of 12 deaths in the first year in group A were completely unrelated to graft function. If these are excluded, patient and graft survival rates were 68% and 52%, which are better but still significantly less than in group B. Initial graft function of older donor livers are similar to that of the matched younger group. However, patient and graft survival rates were significantly worse for the older donors, even when corrected for unrelated deaths. Livers should not be discarded based on age alone without inspection and/or biopsy to rule out significant steatosis. Prompt retransplantation for primary graft nonfunction of older donors are generally more cholestatic than those from the younger donor age group; however, many of them function quite well. At the present time, given the inability to identify donor variables associated with decreased recipient survival, we recommend cautious use of older liver grafts in healthier recipients.

Adult↗