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Biomedical subjects

L B Johnson

Publications and source records attributed to L B Johnson.

At least 55 records · Page 3Linked to original sources

Laparoscopic living donor nephrectomy and multiple renal arteries.

BACKGROUND: Laparoscopic donor nephrectomy (LDN) is a new technique. While the short-term recipient renal function is equivalent to that of the traditional open nephrectomy (ODN), long-term function and potential exclusion criteria, such as the presence of multiple renal arteries, are as yet unknown. METHODS: Retrospective review of 124 consecutive LDN performed from March 1996 to September 1997 with 117 ODN as historical controls. RESULTS: The 1-year actuarial graft and patient survival for LDN kidneys were 94% and 95%, respectively. These were not statistically different from that of the ODN controls. The presence of multiple renal arteries did not alter graft and patient survival or prevalence of immunologic events. The number of recipient ureteral complications in the LDN group was 11.2% compared with 3.4% in ODN (P < 0.01). Following correction for a learning curve with accompanying technical modifications, the prevalence of recipient ureteral complications has decreased to 7% in the last 94 patients (P = nonsignificant versus ODN). CONCLUSIONS: LDN represents a viable alternative to ODN for living renal transplants. Advantages for the donor are matched by equivalent functional results for the recipients.

Adult↗

Reduced transfusion requirements during major hepatic resection with use of intraoperative isovolemic hemodilution.

BACKGROUND: Allogeneic blood transfusion during liver resection for malignancies has been associated with an increased incidence of tumor recurrence and decreased survival in some series. Isovolemic hemodilution (IH) has been utilized in cardiac, orthopedic, and major general surgery procedures to reduce the use of banked blood products. We therefore sought to determine the safety and efficacy of IH during major hepatic resection in an adult population. METHODS: Thirteen consecutive patients undergoing major hepatic resection with IH were compared with 13 age- and disease-matched controls. The diseases included metastatic colorectal adenocarcinoma (8 versus 9), hepatoma (2 in each group) and other (3 versus 2); and the procedures included total (right or left) hepatic lobectomy (8 versus 11), partial lobectomy (3 versus 1) and trisegmentectomy (2 versus 1). RESULTS: There was no significant difference in operating time, estimated blood loss, fresh frozen plasma, platelets, amount of crystalloid or colloid infused between the two groups. There was no perioperative morbidity related to IH. The use of IH resulted in a 60% reduction in mean packed red blood cells transfusion during major hepatic resection. Only 38% of patients undergoing IH required packed red cells transfusion, whereas 77% of historical control patients required allogenic transfusion. CONCLUSION: The use of IH reduces the need for homologous transfusion during major hepatic resection. IH is a safe technique during hepatic resection and is not associated with perioperative morbidity.

Blood Transfusion, Autologous↗

Epstein-Barr virus-related posttransplantation lymphoproliferative disorder involving pancreas allografts: histological differential diagnosis from acute allograft rejection.

The clinical and pathological features of acute pancreas allograft rejection and involvement of the graft by posttransplantation lymphoproliferative disorders (PTLD) overlap. Because the treatment is diametrically opposite in these two types of lesions, an accurate diagnosis is essential. The histological features in pancreas allograft needle biopsy specimens (n=7) and pancreatectomies (n=4) from four patients with Epstein-Barr virus (EBV)-related PTLD were compared with the material from 14 patients who did not develop PTLD after 12 to 58 months of follow-up and whose biopsy specimens (n=10) and pancreatectomies (n=10) showed rejection-related heavy or atypical inflammatory infiltrates. Features typical of rejection included most (>75%) being of mixed small and large, activated-appearing T lymphocytes, a smaller component of mature plasma cells, and variable numbers of eosinophils. Cytologically atypical cells were always a minority (< 10%). The inflammation involved the septal spaces with proportional involvement of the exocrine tissue, veins, ducts, and arteries. The inflammation was particularly targeted against the acini and was associated with acinar cell damage. Features characteristic of PTLD were nodular and expansile infiltrates, composed of a significant proportion of atypical, plasmacytoid B cells (40% to 70% of the infiltrate); Reed-Sternberg-like cells were noted in two patients. The infiltrates involved the parenchyma randomly with no apparent affinity for the acinar tissue. Extensive infiltration of the peripancreatic soft tissues was common. Arterial walls were not involved in PTLD unless there was concurrent acute vascular rejection. Features identified in both conditions were foci of necrosis and infiltration of venous walls with associated endotheliitis. Samples with concurrent PTLD and acute rejection showed combinations of these features. In situ hybridization for EBER (Epstein-Barr-encoded RNAs) was positive only in the samples from patients with PTLD. Based on the assessment of morphological differences and the selective use of relatively simple ancillary techniques, PTLD can be correctly diagnosed even in small tissue samples such as needle biopsy specimens. An early diagnosis will lead to the appropriate treatment.

Acute Disease↗

Dopamine transporter mRNA is increased in the CNS of Zucker fatty (fa/fa) rats.

The obese Zucker fa/fa rat is characterized by hyperinsulinemia, obesity, and altered monoamine metabolism in the central nervous system (CNS). It has been proposed that the changes in monoamine metabolism may contribute to the metabolic pathophysiology of these animals. Because it has been reported that insulin may regulate the catecholamine reuptake transporters, which terminate monoaminergic synaptic signaling, in the present study we tested whether messenger ribonucleic acid (mRNA) levels for the noradrenergic (NE) or dopaminergic (DA) transporters were altered in obese fa/fa vs. lean Fa/Fa Zucker rats. We found significantly elevated DA transporter levels in both the ventral tegmental area/substantia nigra pars compacta (VTA/SNc) and zona incerta (ZI) of obese Zucker fa/fa rats (164 +/- 24% of control levels, p = .024; and 316 +/- 61% of control levels, p = .019, respectively). Measurement of mRNA for tyrosine hydroxylase (TH), the rate-limiting enzyme for NE and DA synthesis revealed no effect of the fa gene in either NE or DA neurons. These findings suggest that increased DA clearance, and perhaps decreased DA signaling, may occur in the obese Zucker fa/fa rat.

Animals↗

Acute pancreatitis and fulminant hepatic failure.

BACKGROUND: The association of acute pancreatitis with fulminant hepatic failure (FHF) was first recognized in 1973. Since then, few studies have described the clinical profile of the FHF patient with acute pancreatitis. Identification of the distinguishing attributes of pancreatitis in combination with FHF will provide a more sound basis for clinical management. The purposes of this study were to identify distinguishing clinical characteristics of acute pancreatitis in FHF and to compare outcomes with those of patients with acutely decompensated chronic liver disease and acute pancreatitis (DECOMP). STUDY DESIGN: This was a retrospective survey of 30 patients with FHF and 30 with DECOMP admitted during the period July 1995 to July 1997. RESULTS: The prevalence of acute pancreatitis in FHF and DECOMP was 33% and 23%, respectively. Acute pancreatitis was associated with severe hepatocellular synthetic dysfunction, renal insufficiency, requirement for endotracheal intubation, increased acuity of illness at the time of ICU admission, more rapid decompensation during the disease, and significantly greater mortality in both the FHF and DECOMP groups. CONCLUSIONS: In both FHF and DECOMP, acute pancreatitis increases disease acuity and mortality. Acute pancreatitis does not occur with significantly greater frequency in FHF. Implementation of orthotopic liver transplantation may not be warranted in this setting.

APACHE↗

Insect resistance of transgenic tobacco expressing an insect chitinase gene.

Chitinase expression in the insect gut normally occurs only during moulting, where the chitin of the peritrophic membrane is presumably degraded. Thus, insects feeding on plants that constitutively express an insect chitinase gene might be adversely affected, owing to an inappropriately timed exposure to chitinase. This hypothesis was tested by introducing a cDNA encoding a tobacco hornworm (Manduca sexta) chitinase (EC 3.2.1.14) into tobacco via Agrobacterium tumefaciens-mediated transformation. A truncated but enzymatically active chitinase was present in plants expressing the gene. Segregating progeny of high-expressing plants were compared for their ability to support growth of tobacco budworm (Heliothis virescens) larvae and for feeding damage. Both parameters were significantly reduced when budworms fed on transgenic tobacco plants expressing high levels of the chitinase gene. In contrast, hornworm larvae showed no significant growth reduction when fed on the chitinase-expressing transgenics. However, both budworm and hornworm larvae, when fed on chitinase-expressing transgenic plants coated with sublethal concentrations of a Bacillus thuringiensis toxin, were significantly stunted relative to larvae fed on toxin-treated non-transgenic controls. Foliar damage was also reduced. Plants expressing an insect chitinase gene may have agronomic potential for insect control.

Animals↗

AvrXa10 contains an acidic transcriptional activation domain in the functionally conserved C terminus.

The avrXa10 gene of Xanthomonas oryzae pv. oryzae, the causal agent of bacterial blight of rice, is a member of the avrBs3 avirulence gene family and directs the elicitation of resistance in a gene-for-gene manner on rice lines carrying the resistance gene Xa10. The carboxyl (C) terminus of AvrXa10 has a previously undescribed domain that is structurally similar to the acidic activation domain of many eukaryotic transcription factors in addition to three nuclear localization signal (NLS) sequences. Removal of the C-terminal 38 codons containing the putative activation domain, but retaining the NLS sequences, was concomitant with the loss of avirulence activity. The C-terminal coding regions of avrBs3 and avrXa7 can be replaced by the corresponding region of avrXa10, and the genes retained specificity for the resistance genes Bs3 in pepper and Xa7 in rice, respectively. The avrBs3 and avrXa7 avirulence activities of the hybrid genes were also lost upon removal of the terminal 38 codons. When fused to the coding sequence of the Gal4 DNA binding domain, AvrXa10 activated transcription in yeast and Arabidopsis thaliana. Removal of the carboxyl region severely reduced transcriptional activation. AvrXa10 would have to be localized to the host cell nucleus to function autonomously in transcriptional activation. Consistent with this requirement, mutations in all three NLS sequences of avrXa10 caused a loss in avirulence activity. The findings demonstrate the requirement of the C terminus for AvrXa10 function and the potential for the members of this family of avirulence gene products to enter the host nucleus and alter host transcription.

Amino Acid Sequence↗

Torsion of intraperitoneal renal transplants: imaging appearances.

OBJECTIVE: Torsion of a renal transplant is a rare complication with nonspecific clinical manifestations. Prompt detection is necessary to allow surgical treatment and to preserve renal function. We describe the radiologic appearances of torsion of intraperitoneal renal transplants in patients who have undergone simultaneous renal and pancreatic transplantation or dual renal transplantation. CONCLUSION: Renal transplant torsion should be suspected when a change in renal axis associated with abnormal perfusion occurs in an intraperitoneal kidney.

Adult↗

Primary hepatic low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) associated with primary biliary cirrhosis.

We describe a case of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) arising in the liver of a patient with early-stage primary biliary cirrhosis (PBC). The patient, a 62-year old woman, presented with abnormal liver function tests, a positive antimitochondrial antibody titer (1:160), and a liver mass. The resected mass, 6.0 x 5.0 x 4.0 cm, had the features of MALT-type lymphoma. The neoplastic cells were small lymphoid cells of B-cell lineage that surrounded reactive lymphoid follicles and infiltrated bile ductules to form lymphoepithelial lesions. The uninvolved liver had histologic evidence of early stage PBC, characterized by segmental duct destruction with granulomata and an inflammatory infiltrate in the portal triads composed of lymphocytes, plasma cells, and occasional eosinophils. A periportal lymph node showed histologic features of the hyaline-vascular type of Castleman's disease, without evidence of malignant lymphoma. Low-grade B-cell lymphomas of the MALT type rarely arise in the liver and, to our knowledge, have not been reported previously in association with PBC. The association in this case suggests that chronic antigenic stimulation as a result of PBC induced the accumulation of acquired MALT, which subsequently transformed to low-grade B-cell lymphoma.

Female↗

Apoptosis and hepatic allograft reperfusion injury.

Necrosis and apoptosis are distinct, but nonexclusive mechanisms of cell death. Until recently, investigators have focused upon necrosis as the sine qua non of lethal cell injury. Specifically, within the realm of liver transplantation, preservation strategies dealing with ischemia/reperfusion injury have concentrated upon minimizing the biochemical and histologic correlates associated with necrosis. Little is known of the role of apoptosis in reperfusion injury in human liver transplantation. Post-reperfusion liver biopsies from 35 patients were retrospectively analyzed for histologic evidence of necrosis. Apoptosis was identified histologically and using a chromogenic technique of in situ labeling of fragmented DNA. The number of apoptotic cells increased in parallel with the necrosis reperfusion score in a significant fashion (p = 0.003 by ANOVA). There was not a Zone 1, 2 or 3 predominance to the histologic distribution of apoptotic cells. The recipient peak serum transaminase values were also noted to increase with the reperfusion score (p = 0.001 by ANOVA). These results suggest that: 1) apoptosis occurs in the setting of reperfusion injury during human orthotopic liver transplantation (OLT); and 2) the extent of apoptosis increases in parallel with pathologic and biochemical parameters of reperfusion injury. Given the distinct nature of apoptosis and the highly regulated and conserved pathway for its initiation, inhibition of apoptosis with specific molecular targets, may serve to decrease allograft reperfusion injury.

Adult↗

Reducing the length of stay after kidney transplantation--the intensive outpatient unit.

The need to reduce the costs associated with the initial hospitalization for kidney transplantation has led to the development of outpatient facilities in which patients can be seen on a daily basis. The implementation of a kidney transplant intensive outpatient unit (IOPU) is described. Prior to the opening of the IOPU, the median and mean lengths of stay after kidney transplantation in our program were 14.0 and 18.9 d, respectively. Subsequent to the opening of the IOPU, the median and mean lengths of stay after kidney transplantation have gradually decreased and are currently 5.0 and 7.5 d, respectively. The median inpatient cost of transplantation, excluding organ acquisition charges, has decreased by 54%, from $25516 to $11616. Patient satisfaction has exceeded 80%. The IOPU represents an effective means of reducing the cost associated with transplantation, without sacrificing the quality of care.

Cost Savings↗

A novel approach to the treatment of chronic allograft nephropathy.

BACKGROUND: Progressive deterioration of renal function in kidney transplant recipients is the leading cause of graft failure. Both nonimmunologic and immunologic mechanisms contribute to this deterioration. METHODS: Twenty-eight cyclosporine (CsA)-treated renal transplant recipients (21 cadaveric, 5 living, 2 simultaneous kidney-pancreas) with progressive deterioration of renal function were prospectively enrolled in a clinical trial and had their immunosuppressive regimen changed 24.3+/-7.7 months after transplant. All patients had their CsA dose reduced by 50%, azathioprine was discontinued, and mycophenolate mofetil was added to the medical regimen. The mean creatinine of the patients at the initiation of the change in immunosuppression was 3.5+/-1.2 mg/dl (range 1.9 to 6.2 mg/dl). RESULTS: Before the change in immunosuppression, the mean loss in renal function as indicated by the least-squares slope of the reciprocal of creatinine versus time was -0.006+/-0.002 (mg/dl)-1 per month. The change in immunosuppression significantly decreased the rate of loss in renal function for most patients when compared with their pretreatment values with a mean slope of 0.007+/-0.003 (mg/dl)-1 per month (P=0.003). Renal function improved in 21 of 28 patients. Only one patient had continued deterioration of renal function. In a multivariate analysis adjusting for CsA dose, mean arterial blood pressure, and baseline creatinine, the change in immunosuppression was significantly associated with improved renal function (P=0.02). There were no acute rejections after the immunosuppression change. CONCLUSIONS: We conclude that adding mycophenolate mofetil and reducing CsA in patients with chronic deterioration of graft function is well tolerated and results in a short-term improvement in renal function.

Adult↗

Use of renal allografts from donors positive for hepatitis B core antibody confers minimal risk for subsequent development of clinical hepatitis B virus disease.

BACKGROUND: The risk associated with transplantation of renal allografts from hepatitis B virus core antibody-positive (HBcAb(+)), hepatitis B virus surface antigen-negative (HBsAg(-)) donors is not well defined. METHODS: Over 4 years, we performed 45 kidney transplants from IgG HBcAb(+), IgM HBcAb(-), HBsAg(-) donors into recipients with a history of prior hepatitis B virus (HBV) infection or reported vaccination. We examined HBV-related outcomes in these 45 patients, in comparison with 45 recipients of allografts from HBcAb(-) donors (matched for transplant type, date, and pretransplant HBV antibodies). We sought evidence for HBV transmission by testing posttransplant sera for the presence of HBcAb, hepatitis B virus surface antibody, and HBsAg. Additionally, we analyzed alanine aminotransferase profiles and allograft survival rates for all patients. RESULTS: No patient receiving an allograft from an HBcAb(+) donor developed clinical HBV infection. No patient receiving an allograft from an HBcAb(+) donor had HBsAg detected through retrospective testing of stored sera or through prospective routine clinical evaluation and care. However, among the HBcAb(+) kidney recipients, 27% developed new HBcAb and/or hepatitis B virus surface antibody after transplant; in contrast, only 4% of control patients developed new antibody responses (relative risk=4.94; confidence interval 1.07-22.83). Among the recipients of HBcAb(+) organs, 18% developed elevated transaminases after transplant, in comparison with 36% of the controls. No association was found between "seroconverter" status and elevated alanine aminotransferase profiles in either group. CONCLUSIONS: Transplantation of renal allografts from HBcAb(+), HBsAg(-) donors was not associated with clinically detectable HBV disease or antigenemia. However, recipients had a significantly increased risk of HBV seroconversion, consistent with exposure to HBV antigen. These results suggest that HBcAb(+) kidneys can be safely used if transplanted into appropriate recipients, but highlight the need for effective HBV vaccination and vaccine-response monitoring in potential recipients.

Adult↗

Outcome after splenic vein thrombosis in the pancreas allograft.

The outcome and management of isolated splenic vein thrombosis in the pancreas transplant is unknown. We retrospectively reviewed the records of 76 simultaneous pancreas-kidney transplantations (SPK) and 56 solitary pancreas transplantations (SPT) performed at the University of Maryland from January 1995 to December 1996. A total of 24 patients were identified (9 SPK and 15 SPT recipients). All were systemically anticoagulated for a period of 6-8 weeks after diagnosis. In the SPK thrombosis group, anticoagulation resulted in 1-year graft survival that was equivalent to that of SPK controls (86.1% vs. 95.3%). In contrast, in SPT, thrombosis and subsequent anticoagulation were associated with decreased graft survival compared with SPT controls (26.8% vs. 78.3%; P<0.01). Although the outcome of splenic vein thrombosis in the absence of anticoagulation is unknown, these data suggest that (1) in SPK, anticoagulation for splenic vein thrombosis maintains graft survival, and (2) in SPT, anticoagulation does not alter the ultimate progression of splenic vein thrombosis to complete graft thrombosis.

Adult↗

Evaluation of pancreas transplant needle biopsy: reproducibility and revision of histologic grading system.

BACKGROUND: Tissue samples for the diagnosis of pancreatic allograft rejection are now obtained routinely through the application of the percutaneous needle biopsy technique. The availability of biopsy material (89% adequate for diagnosis in our setting) presents a challenge for pathologists who are asked to provide a fast and accurate diagnosis of rejection and its severity, while at the same time being able to differentiate rejection from other causes of graft dysfunction. METHODS: To differentiate rejection from other pathologic processes, 26 histologic features were assessed in 92 biopsies performed for confirmation of clinical diagnosis of rejection and the results were compared with 31 protocol biopsies, 12 allograft pancreatectomies with non-rejection pathology, and 30 native pancreas resections with various disease processes. RESULTS: Based on these comparisons, a constellation of findings relating to the vascular, septal, and acinar inflammation was identified for the diagnosis of rejection. Application of these features led us to revise our scheme for grading rejection (ranging from 0-normal to V-severe rejection) to include the categories of "inflammation of undetermined significance" and "minimal rejection." The scheme was used by five pathologist to grade 20 biopsies independently of any clinical data and the interobserver level of agreement was highly significant (kappa=0.83, P<0.0001). This grading scheme was applied blindly to all (183) biopsies from 77 patients with 6-52 months of follow-up. The correlation of the highest degree of rejection on each patient and ultimate graft loss (0% for grades 0-I, 11.5% for grade II, 17.3% for grade III, 37.5% for grade IV, and 100% for grade V) was highly statistically significant (P<0.002). The fraction of grafts lost due to pure immunologic causes increased proportionally to the grade of rejection (0, 50, 66, and 100% for grades II, III, IV, and V, respectively). CONCLUSIONS: This study provides strong support for the proposed pancreas rejection grading scheme and confirms its potential for practical use.

Adult↗

Safe pancreas transplantation in patients with coronary artery disease.

BACKGROUND: This study was conducted to determine the risk of clinically significant posttransplant cardiac events (PCEs) in a cohort of diabetic patients referred for pancreas transplantation. METHODS: Between April 1991 and December 1995, 316 insulin-dependent diabetics were evaluated for pancreas transplantation. Patients were assessed for risk factors for coronary artery disease (CAD), and underwent screening for significant CAD by a standardized algorithm that included selective coronary angiography. For the 3-year period following transplantation, PCEs were identified, and related to pretransplant cardiac risk factors. RESULTS: Only four patients (1.3%) were turned down for cardiac contraindications. Coronary angiography was done in 74 patients (27% of the active transplant candidates) during the evaluation period because of the patient's history or a positive stress test. Significant coronary artery stenoses were found in 54% of the patients catheterized. Twenty-five of these 40 patients (63%) underwent revascularization with percutaneous transluminal coronary angioplasty and/or coronary artery bypass grafting. A total of 359 organs were subsequently transplanted into 194 of these patients. No deaths occurred within 30 days of any of the transplants; four percent of transplant recipients died of cardiac causes within the follow-up period (median 23 months). Those with no pretransplant evidence of CAD had significantly lower rates of PCE (2% and 8% at 1 and 3 years, respectively) than those with pretransplant evidence of CAD (11% and 29% at 1 and 3 years, P<0.01; relative risk, 4.3). CONCLUSIONS: Routine cardiac screening of pancreas recipients with selective angiography and revascularization allows patients with significant CAD to safely undergo pancreas transplantation. Patients should rarely be excluded from pancreas transplantation for cardiac causes.

Adolescent↗

Successful emergency transplantation of a liver allograft from a donor maintained on extracorporeal membrane oxygenation.

The critical shortage of cadaveric donors for organ transplantation has led many transplant centers to accept life-saving organs from donors who would have previously been refused for transplantation. We report a novel case of the use of a liver allograft from a donor whose oxygen delivery was maintained by extracorporeal membrane oxygenation (ECMO) for 29 days before suffering an anoxic brain injury from ECMO dysfunction. Liver transplantation was successfully performed in a patient with fulminant hepatic failure. Immediate graft function was obtained in the recipient, with full neurologic recovery and return to gainful employment 4 months after transplantation. ECMO may provide an intriguing option for the maintenance of organ function in the critically unstable brain-dead organ donor to salvage organs for transplantation. Further studies are currently underway.

Adult↗