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Biomedical subjects

J Mayes

Publications and source records attributed to J Mayes.

At least 19 recordsLinked to original sources
PubMed2003

Survival and resource utilization in liver transplant recipients: the impact of admission to the intensive care unit.

The organ allocation system for liver transplantation was recently changed to address criticisms that it was too subjective and relied too heavily on total waiting time. The new system, Model for End-Stage Liver Disease and Pediatric Model for End-Stage Liver Disease (MELD/PELD), stratifies patients based on the risk of 3-month pretransplant mortality, allocating livers thereby. There is concern that such a scheme gives priority to the sickest patients, who may not enjoy good posttransplant outcomes. The aim of the present study was to compare the outcomes of liver transplant recipients who had been admitted to the intensive care unit (ICU) to those who had not. Admission to the ICU is considered here to be another indicator of the severity of illness. Patients who underwent liver transplantation at the Cleveland Clinic between January 1, 1993 and October 31, 1998 and were at least 18 years of age were coded for liver transplantation as status 2, 2A, and 2B (n = 112). These patients fell into three groups: those who had been admitted to an ICU before transplantation (group A, n = 16), those who had been admitted to the hospital but not to an ICU (group B, n = 63), and those who were living at home and had undergone an elective transplant (group C, n = 33). Clinical and demographic information (age, sex, race, disease severity, disease etiology, and cold ischemia time) were associated with patient survival, patient/graft survival, and posttransplant resource utilization (hospital length of stay and hospital charges). Age, sex, race, etiology of disease, and cold ischemia time were similar among the three groups. Patient survival, patient/graft survival, and hospital charges were not statistically different between the three groups. The median length of stay was statistically different only between groups B and C (P =.006). Our data support the idea that if severely ill patients with end-stage liver disease are selected appropriately, liver transplant outcomes are similar to those observed among subjects who are less ill and are transplanted electively from home.

Female↗
PubMed2001

Interferon alpha 2B and ribavirin in severe recurrent cholestatic hepatitis C.

Severe recurrent cholestatic hepatitis C after liver transplantation has a poor prognosis and no standard therapy is currently available. Four cases of severe recurrent cholestatic hepatitis C treated with a combination of interferon alpha 2b and ribavirin are described. All four patients were transplanted for hepatitis C-related cirrhosis. The mean age at transplantation was 45 years (range 41-51 years). Three of the patients were male and one was female. All four patients had hepatitis C virus viremia before and after liver transplantation. At 2 to 23 months after liver transplantation, all four patients developed jaundice, cholestatic elevation of liver enzymes, and histopathology consistent with severe recurrent cholestatic hepatitis C. Combination of interferon and ribavirin was given with prompt virological suppression. Despite this rapid viral suppression, all four patients developed progressive graft failure with three deaths.

Adult↗
PubMed2001

Cryptogenic cirrhosis and posttransplantation nonalcoholic fatty liver disease.

Some patients diagnosed with cryptogenic cirrhosis may have "burned-out" nonalcoholic fatty liver disease (NAFL). To test this hypothesis, we used our liver transplant database (November 1984 to November 1998) to assess the incidence of NAFL in patients with cryptogenic cirrhosis after orthotopic liver transplantation (OLT). We also examined the clinicodemographic features associated with post-OLT NAFL, obtained by chart review and telephone interviews. When available, post-OLT liver biopsy specimens were reviewed blindly by a hepatopathologist according to the NAFL pathology protocol. We identified 51 patients with cryptogenic cirrhosis (mean age, 51 +/- 12 years); 60% were women, 94% were white, and 34% had type 2 diabetes mellitus (DM). Mean pre-OLT body mass index (BMI) was 27.33 +/- 5.54 kg/m(2). Twenty-five patients underwent at least 1 post-OLT liver biopsy. Post-OLT NAFL was identified in 13 patients (25.4%), whereas post-OLT nonalcoholic steatohepatitis (NASH) was seen in 8 patients (15.7%). Features associated with post-OLT NASH were pre- and post-OLT type 2 DM (P < or =.05) and an elevated fasting triglyceride level (P <.05). BMI tended to be greater in patients with post-OLT NAFL or NASH. Those who did not develop post-OLT NAFL showed a decrease in BMI. Patients with cryptogenic cirrhosis undergoing OLT resemble patients with NAFL. Post-OLT NAFL and NASH can be seen in a number of patients with cryptogenic cirrhosis. This supports the notion that some cases of cryptogenic cirrhosis represent burned-out NAFL.

Adult↗
PubMed1999

Agreement in pathologic interpretation of liver biopsy specimens in posttransplant hepatitis C infection.

Hepatitis C virus-related disease is rapidly becoming the most common indication for orthotopic liver transplant (OLT) in the United States. Although post-OLT hepatitis C viremia is universal, 40% to 60% of patients develop recurrent chronic hepatitis C. Distinguishing recurrent chronic hepatitis C infection from acute rejection may be difficult because of overlapping histopathologic features. To improve our diagnostic accuracy we undertook a study to determine interobserver and intraobserver agreement between pathologists examining post-OLT liver biopsy specimens in patients from our transplant database. Clinical data and microscopic sections from 26 patients with hepatitis C virus-related OLT were reviewed. Biopsy specimens were obtained because of abnormal liver enzymes (21/26) or routine post-OLT follow-up (5/26), representing both early (18+/-11 days) and late (252+/-206 days) post-OLT periods. Unidentified sections were examined by an experienced pathologist in a randomly assigned order and reexamined 6 weeks later in the same fashion by the initial reviewer and a second experienced pathologist. Interobserver and intraobserver agreement was calculated using K statistic. The intraobserver agreement was 81 % with a kappa coefficient of 0.67 (P = .001). The interobserver agreement was 78% with a kappa coefficient of 0.60 (P < .001). The early post-OLT biopsy specimens (18+/-11 days) were the most difficult to interpret.

Adult↗
PubMed1998

Laparoscopic repair of lumbar hernias.

BACKGROUND: Lumbar hernias are rare defects in the posterolateral abdominal wall that may be congenital or acquired. Repairing these defects is difficult by virtue of their location and the inherent weakness of the surrounding tissues. We report a series of seven patients who had their lumbar hernias repaired laparoscopically at two institutions. STUDY DESIGN: We retrospectively reviewed all lumbar hernias repaired laparoscopically in our institutions within the last 16 months (August 1996 to November 1997). Postoperative followup was 1-15 months. RESULTS: Seven patients underwent laparoscopic repair. Five hernias were acquired defects and two were congenital. One to three defects were found per patient. The average size of the hernia defect was 77.8 cm2. We used a polypropylene or a polytetrafluoroethylene mesh in all patients; the average size of the mesh used was 336.4 cm2. The average length of hospital stay was 1.7 days. One patient returned with an abscess over the mesh, which necessitated removal of the graft. Otherwise, there were no complications, and the remaining six patients had no recurrences after followup of 1-14 months. CONCLUSIONS: The laparoscopic approach is safe and effective for repairing lumbar hernias. Advantages of this approach include excellent operative visualization, decreased hospital stay postoperatively, and a solid repair without recurrence during shortterm followup.

Hernia, Ventral↗
PubMed1997

A randomized clinical trial of ursodeoxycholic acid as adjuvant treatment to prevent liver transplant rejection.

Acute rejection following orthotopic liver transplantation is a common problem despite current immunosuppressive regimens. Ursodeoxycholic acid (UDCA) has been shown in small, open-labeled studies to prevent rejection episodes, although its effects on complications such as infections, length of hospital stay, and survival have not been evaluated. We conducted a randomized, placebo-controlled, double-blind trial to determine if UDCA (10-15 mg/kg/d) added to a cyclosporine-based immunosuppressive regimen was associated with a decrease in the incidence of at least one episode of acute cellular rejection. Secondary end-points included determining differences in the total number of rejection episodes, the use of muromonab-CD3, the incidence of infections, length of hospital stay, and survival at 90 days and 1 year. Fifty-two patients were randomized, 28 to the treatment group and 24 to the placebo group. During the 3 months of the trial, there was no difference between the placebo and UDCA groups in the number of patients who were rejection-free; however, there were significantly fewer patients in the treatment group who had multiple episodes of acute rejection (0 vs. 6; P = .007). Patients in the treatment group experienced a significantly lower incidence of bacterial infections (4% vs. 29%; P = .02), shorter hospital stay (25 days vs. 34 days; P = .03), and better 90-day survival (100% vs. 83%; P = .04) and 1-year survival (93% vs. 79%). The addition of UDCA to a cyclosporine-based immunosuppressive regimen results in significantly fewer patients experiencing multiple episodes of rejection and improved survival at 90 days and at 1 year. The use of UDCA as adjuvant therapy for patients undergoing liver transplantation who are treated with a cyclosporine-based immunosuppressive regimen should be considered.

Adult↗
PubMed1997

Managed obstetrical care.

The current maternal/newborn care model is outdated and needs to be revised. The health care reform movement has created a window of opportunity to redefine the episode of pregnancy care and develop a more meaningful and more cost-effective model of care. The ultimate satisfaction for physicians will occur when they exert their natural control regarding the manner in which health care dollars are spent by managing the financial risk and the patient care. The optimal management of the health care dollar can only be achieved through initiation of an integrated model in which a coordinated care team supported by the appropriate risk assessment, education, prevention and wellness program, and medically necessary intensive care of the high-risk pregnancy are brought together effectively. An integrated model will give patients what they want: compassionate, convenient, comprehensive care. It will give the payers what they are looking for--appropriate care at an appropriate predicable cost and improved outcomes. Finally, it will give the providers what they want: control over the delivery medical care.

Cost-Benefit Analysis↗
PubMed1996

Transfection of human topoisomerase II alpha into etoposide-resistant cells: transient increase in sensitivity followed by down-regulation of the endogenous gene.

We have investigated the possibility of overcoming the resistance of human brain tumour cells (HBT20) to etoposide by transferring the normal human topoisomerase II alpha (H-topo II) gene into these cells. H-topo II in a mammalian expression vector containing a glucocorticoid-inducible mouse mammary tumour virus (MMTV) promoter was transfected into etoposide-resistant HBT20 cells (HBT20-hTOP2MAM). HBT20 cells transfected with pMAMneo vector alone served as control cells (HBT20-MAM). These were stable transfections. Following a 2 h dexamethasone treatment, H-topo II mRNA expression, protein production, etoposide-induced DNA-protein complex formation and sensitivity to etoposide were increased in HBT20-hTOP2MAM cells compared with control HBT20-MAM cells and with HBT20-hTOP2MAM cells not treated with dexamethasone. However, mRNA and protein levels and cell sensitivity returned to baseline when incubation with dexamethasone was continued for 24 h. This decrease from the 2 h values could not be explained by a loss of the MMTV promoter response to dexamethasone. (H-topo II alpha promoter)-(chloramphenicol acetyltransferase) constructs containing regions -559-0 and -2400-0 were significantly down-regulated in HBT20-hTOP2MAM cells treated for 24 h with dexamethasone compared with dexamethasone-treated control cells. H-topo II mRNA stability after 24 h of dexamethasone treatment was not altered compared with that in control cells. Our data indicate that the exogenously produced H-topo II may have a negative-feedback effect on the endogenous topoisomerase II promoter, causing down-regulation of the endogenous gene.

Animals↗
PubMed1996

Effect of transfection of a Drosophila topoisomerase II gene into a human brain tumour cell line intrinsically resistant to etoposide.

The human brain tumour cell line HBT20 is intrinsically resistant to etoposide and does not express mdr-1 mRNA. These studies were conducted to determine whether transfecting a Drosophila (D) topoisomerase II (topo II) gene into HBT20 cells could increase their sensitivity to etoposide. A D-topo II construct in a pMAMneo vector under the control of a mouse mammary tumour virus (MMTV) promoter was transfected into HBT20 cells. The gene is inducible by dexamethasone (Dex). The growth rate of the transfected cells and percentage of the cells in G1, S and G2M was no different than the parental cells. Survival after etoposide exposure (10 microM x 2 h) was measured by colony formation. Parental cells and cells transfected by pMAMneo vector alone showed no enhanced etoposide sensitivity after 24 h of Dex stimulation. By contrast, D-topo II transfected cells were sensitised 3-fold when etoposide treatment was preceded by 24 h Dex stimulation. Northern blotting and Western blotting confirmed that Dex had induced D-topo II expression in the sensitised cells. However, in D-topo II-transfected cells increasing the duration of Dex stimulation to 48 h eliminated the sensitisation to etoposide although increased MMTV promoter activity and expression of the D-topo II gene persisted. Measurement of endogenous human topo-II mRNA and protein revealed a decrease after Dex exposure of greater than 24 h. At these distal times, the total cellular topo II levels (endogenous + exogenous) may be decreased, which may explain why increased sensitivity to etoposide could no longer be demonstrated. This model suggests that D-topo II gene transfection can sensitise de novo resistant HBT20 cells to etoposide but that the time frame of that sensitisation is limited.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Phorbol regulation of topoisomerases I and II in human leukemia cells. Studies in an additional cell pair sensitive or resistant to phorbol-induced differentiation.

We previously reported (Zwelling et al., Cancer Res 50: 7116-7122, 1990) that etoposide-induced DNA cleavage and mRNA coding for topoisomerase II are reduced in HL-60 cells induced to differentiate by phorbol ester. Reduction of etoposide-induced cleavage and topoisomerase II message did not occur in the derived cell line 1E3 (which is resistant to phorbol-induced differentiation), implying that topoisomerase II activity may be related to the state of cell differentiation. We have extended these studies using a new phorbol sensitive/resistant cell pair, S (sensitive) and PET (phorbol ester tolerant). Phorbol ester exposure not only reduced etoposide-induced DNA cleavage and topoisomerase II mRNA in S cells but also decreased the amount of immunoreactive topoisomerase II enzyme in whole S cells. However, immunoreactive topoisomerase II extracted from the nuclei of phorbol-treated S cells was not reduced compared with that from the nuclei of untreated S cells. This suggests that topoisomerase II contained in nuclear extracts is not always representative of the total cellular enzyme. Dramatic decreases in the amount, activity, or gene expression of topoisomerase II were not observed after phorbol treatment of the resistant PET cells; this is consistent with the potential involvement of topoisomerase II in monocytoid differentiation. Levels of topoisomerase I enzyme and mRNA fell in both S and PET cells after phorbol treatment; therefore, the genes for topoisomerases I and II did not appear to be regulated coordinately.

Cell Differentiation↗
PubMed1993

Further characterization of an amsacrine-resistant line of HL-60 human leukemia cells and its topoisomerase II. Effects of ATP concentration, anion concentration, and the three-dimensional structure of the DNA target.

The characterization of type II topoisomerases from amsacrine-sensitive (HL-60) and amsacrine-resistant (HL-60/AMSA) human leukemia cells was extended. The intercalator resistance and etoposide sensitivity of the HL-60/AMSA cells themselves were confirmed, and the stability of this pharmacologic phenotype over many hundreds of cell generations was demonstrated. Prolonging exposure of HL-60/AMSA cells to amsacrine did not alter their sensitivity relative to that of HL-60 cells. Improved methods of immunoblotting allowed clear demonstration that the topoisomerase II within these cells exhibited sensitivity and resistance characteristics that mirrored those of the cells and the isolated enzymes themselves. Additional biochemical characterization of the type II topoisomerases indicated that both enzymes relaxed supercoiled DNA in a distributive fashion and that the ATP concentrations at which optimal catalytic activity of the two enzymes was exhibited were identical. The enzymes differed, however, in their activity optima in buffers of various type and ionic strength. Furthermore, the inability of the HL-60/AMSA enzyme to exhibit enhanced DNA cleavage in the presence of amsacrine could be overcome if the DNA target molecule contained a bend cloned into its polylinker region. By contrast, a bend in a DNA plasmid containing no polylinker was resistant to amsacrine-enhanced cleavage in the presence of HL-60/AMSA topoisomerase II, as was a plasmid containing a polylinker with no bend. This suggests that an unusual DNA conformation (a bend) in a specific DNA context (a polylinker) may be a favored site for topoisomerase II action. It also suggests a mechanism by which the sites and extent of topoisomerase II activity can be controlled in cells.

Adenosine Triphosphate↗
PubMed1993

Activity of two novel anthracene-9,10-diones against human leukemia cells containing intercalator-sensitive or -resistant forms of topoisomerase II.

We have examined the activities of two novel aza-anthracene-9,10-diones (aza), 1-aza and 2-aza, in HL-60 human leukemia cell lines containing type II topoisomerases with different sensitivities to inhibition by other intercalating agents. The sensitive line, HL-60, was sensitive to 2-aza but not to 1-aza, whereas the resistant HL-60/AMSA was sensitive to neither agent. Measurements of 1- and 2-aza-induced, topoisomerase II-mediated DNA cross-linking in the cells revealed patterns of resistance and sensitivity that paralleled the results in the cytotoxicity assays. However, measurements of drug-induced topoisomerase II-mediated DNA cross-linking using purified HL-60 and HL-60/AMSA topoisomerase II indicated that both agents could stabilize a covalent complex between DNA and the HL-60 enzyme. HL-60/AMSA topoisomerase II resisted stabilization by either agent. This suggests that the resistance of HL-60 cells to 1-aza is not due to the inability of this drug to inhibit topoisomerase II but rather to another, undefined mechanism.

Anthraquinones↗
PubMed1993

Circumvention of resistance by doxorubicin, but not by idarubicin, in a human leukemia cell line containing an intercalator-resistant form of topoisomerase II: evidence for a non-topoisomerase II-mediated mechanism of doxorubicin cytotoxicity.

The novel, topoisomerase II-reactive anthracycline intercalator idarubicin (IDA) was demonstrated to produce protein-associated DNA cleavage in HL-60 human leukemia cells. Like a host of other antineoplastic intercalating agents, IDA produced this effect to a much lesser extent in HL-60/AMSA cells, a line that is primarily resistant to the intercalator amsacrine, but is cross-resistant to a variety of topoisomerase II-reactive DNA intercalating agents including IDA. This resistance is thought to be secondary to the resistance of the topoisomerase II within HL-60/AMSA cells. Surprisingly, HL-60/AMSA cells were minimally resistant to the cytotoxic and DNA cleaving actions of another anthracycline, doxorubicin (ADR). Comparing other effects of the two anthracyclines revealed that IDA, but not ADR, produced endonucleolytic cleavage, a marker of apoptosis. These results suggest that DNA intercalating anthracyclines can have different effects in human leukemia cells. In the case of IDA, drug actions were similar to those produced by the majority of intercalating agents examined in this cellular system. In the case of ADR, the ability to circumvent the resistance of HL-60/AMSA suggests additional, non-topoisomerase II-mediated mechanisms of cytolysis that may also explain the broad spectrum of clinical activity of ADR.

Binding Sites↗
PubMed1993

A retrospective view of factors that affect catheter healing: four years of experience.

To determine factors that lead to successful healing, the results of catheter placement were collected by retrospective chart review in 103 peritoneal dialysis patients between January 1988 and March 1992. There were a total of 112 catheter insertions. A healing time of less than 2 weeks was defined as an optimal outcome. Data were analyzed using contingency tables. Strong predictors of early and effective healing were the following: exit site size less than 0.7 cm, the use of a tunneler to create the exit site, the use of Swan neck catheters, immobilization using Viasorb dressings, and postoperative prophylaxis with intravenous vancomycin. Dialysate leak and the development of hematomas significantly delayed healing. Leaking was associated with early use of the catheter for peritoneal dialysis. Hematoma formation was associated with the use of a tunneler. Uremic or nutritional status, diabetes, immunosuppressive agents, or HIV-positive did not affect catheter healing. Careful attention to intraoperative and postoperative factors optimizes healing independent of complications of primary disease processes in peritoneal dialysis patients.

Adolescent↗