Biomedical subjects

Paul Martin

Publications and source records attributed to Paul Martin.

At least 55 records · Page 3Linked to original sources

PubMed2005

Morbidity in live liver donors: standards-based adverse event reporting further refined.

HYPOTHESIS: The true extent of morbidity among live liver donors remains poorly understood. In this unique and often high-profile area of surgery, the development of standards for defining and reporting complications would foster a better understanding of the incidence and magnitude of such adverse events (AEs). DESIGN: Retrospective review of AEs among live liver donors. SETTING: University-affiliated teaching hospital. PATIENTS AND METHODS: Of 202 individuals undergoing evaluation for live liver donation, 42 (20.8%) proceeded to surgery. Thirty-four underwent a right lobectomy without the middle hepatic vein; 3, a left lateral segmentectomy. Any event causing a deviation from a patient's ideal course was considered an AE and subsequently classified according to a derived framework. Morbidity was defined as 1 or more AEs. MAIN OUTCOME MEASURES: Incidence, timing, type, severity, and impact of AEs. RESULTS: No deaths or significant hepatic dysfunction occurred. In 5 (12%) of the 42 donors, the hepatectomy was aborted for anatomic reasons before parenchymal transection. Eight (22%) of the remaining 37 experienced 11 AEs, of which 10 completely resolved, whereas 1 AE (3%) resulted in a permanent disability (brachial plexopathy). The overall incidence of AEs was 0.30 per case. Ten (91%) of the 11 AEs presented within the first postoperative month. CONCLUSIONS: Most live liver donations are uncomplicated or do not lead to permanent consequence. The adoption of a standards-based classification framework for AEs in live liver donors would allow for an inclusive, consistent, and universally applicable method to collect, analyze, and report donor morbidity.

Adult↗

PubMed2005

Peginterferon alfa-2a for hepatitis C after liver transplantation: two randomized, controlled trials.

There is currently no effective treatment for recurrent hepatitis C after orthotopic liver transplantation (OLT). We therefore performed two randomized, controlled trials--a prophylaxis trial and a treatment trial--to evaluate the safety and efficacy of peginterferon alfa-2a in patients who had undergone OLT. The prophylaxis trial enrolled 54 patients within 3 weeks after OLT, and the treatment trial enrolled 67 patients 6 to 60 months after OLT. In each trial, patients were randomized to treatment with once weekly injections of 180 microg peginterferon alfa-2a or no antiviral treatment for 48 weeks and were followed up for 24 weeks thereafter. Peginterferon alfa-2a treated patients had significantly lower hepatitis C virus RNA levels and more favorable changes in hepatic histological features compared with untreated controls. However, only 2 treated patients in the prophylaxis trial (8%) and 3 in the treatment trial (12%) achieved a sustained virological response. In the prophylaxis trial, 8 patients (31%) in the peginterferon alfa-2a group and 9 (32%) in the untreated group were withdrawn prematurely; whereas in the treatment trial, 10 patients (30%) in the peginterferon alfa-2a group and 6 (19%) in the untreated group were withdrawn prematurely. The incidence of acute rejection was similar in the treated and untreated groups in both the prophylaxis (12% vs. 21%; P = .5) and treatment (12% vs. 0%; P = .1) trials. In conclusion, peginterferon alfa-2a treatment for 48 weeks is safe and tolerable and offers some efficacy in the post-OLT setting. Randomized controlled studies are needed to establish the efficacy of pegylated interferon and ribavirin in patients who have undergone OLT.

Antiviral Agents↗

PubMed2005

Randomized trial of allogeneic related bone marrow transplantation versus peripheral blood stem cell transplantation for chronic myeloid leukemia.

Seventy-two chronic myeloid leukemia patients were enrolled as part of a larger randomized trial at 3 centers between March 1996 and July 2001 to undergo either HLA-matched related allogeneic bone marrow (BM) or filgrastim (granulocyte colony-stimulating factor)-mobilized peripheral blood stem cell (PBSC) transplantation. Forty patients received BM, and 32 patients received PBSCs. There was no statistically significant difference in the incidence of acute or chronic graft-versus-host disease (GVHD), overall survival, disease-free survival, or non-relapse-related mortality between patients receiving BM or PBSC transplants. The cumulative incidence of grade II to IV acute GVHD was 49% in BM and 55% in PBSC recipients ( P = .48). The cumulative incidence of clinical extensive chronic GVHD was 50% in BM and 59% in PBSC recipients ( P = .46). Among 62 chronic phase chronic myeloid leukemia patients, there was no significant difference in overall survival (87% versus 81%; P = .59), disease-free survival (80% versus 81%; P = .61), or non-relapse-related mortality (13% versus 19%; P = .60) by cell source (BM versus PBSCs). Among chronic phase patients, however, there was a trend toward a higher cumulative incidence of relapse at 3 years in BM recipients (7% versus 0%; P = .10) and a higher cumulative incidence of chronic GVHD in PBSC recipients (59% versus 40%; P = .11). The trend toward a higher relapse incidence in BM recipients persisted with a longer follow-up.

Bone Marrow Transplantation↗

PubMed2005

A phase II multicenter study of visilizumab, humanized anti-CD3 antibody, to treat steroid-refractory acute graft-versus-host disease.

Results of a previous phase I study suggested that a single 3 mg/m2 dose of the humanized non-FcR-binding anti-CD3 monoclonal antibody visilizumab (Nuvion) was well tolerated and had efficacy for the treatment of steroid-refractory acute graft-versus-host disease (GVHD). We now report results of a multicenter phase II study in which visilizumab was given to 44 participants with steroid-refractory acute GVHD. Eighty-two percent of the participants had visceral involvement, and 86% had overall grade III or IV acute GVHD at study entry. The respective complete and overall response rates were 14% and 32% at 42 days. Plasma Epstein-Barr virus DNA increased to more than 1000 copies per milliliter in 19 subjects. Seventeen received rituximab, and no fatal lymphoproliferative disorders were observed. Survival at 180 days was 32% (95% confidence interval, 18%-46%). The administration of visilizumab as used in this study seems to be sufficiently safe and effective to warrant further assessment for treatment or prevention of GVHD.

Acute Disease↗

PubMed2005

Blood and marrow transplant clinical trials network toxicity committee consensus summary: thrombotic microangiopathy after hematopoietic stem cell transplantation.

The syndrome of microangiopathic hemolysis associated with renal failure, neurologic impairment, or both is a recognized complication of hematopoietic stem cell transplantation. This entity is often called hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP), yet it is clear that the pathophysiology of transplant-associated HUS/TTP is different from that of classic HUS or TTP. Furthermore, the incidence of this syndrome varies from 0.5% to 76% in different transplant series, primarily because of the lack of a uniform definition. The toxicity committee of the Blood and Marrow Transplant Clinical Trials Network has reviewed the current literature on transplant-related HUS/TTP and recommends that it be henceforth renamed posttransplantation thrombotic microangiopathy (TMA). An operational definition for TMA based on the presence of microangiopathic hemolysis and renal and/or neurologic dysfunction is proposed. The primary intervention after diagnosis of TMA should be withdrawal of calcineurin inhibitors. Plasma exchange, although frequently used in this condition, has not been proven to be effective. In the absence of definitive trials, plasma exchange cannot be considered a standard of care for TMA. It is hoped that these positions will improve the identification and reporting of this devastating complication after hematopoietic stem cell transplantation and facilitate future clinical studies for its prevention and treatment.

Clinical Trials as Topic↗

PubMed2005

National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report.

This consensus document is intended to serve 3 functions. First, it standardizes the criteria for diagnosis of chronic graft-versus-host disease (GVHD). Second, it proposes a new clinical scoring system (0-3) that describes the extent and severity of chronic GVHD for each organ or site at any given time, taking functional impact into account. Third, it proposes new guidelines for global assessment of chronic GVHD severity that are based on the number of organs or sites involved and the degree of involvement in affected organs (mild, moderate, or severe). Diagnosis of chronic GVHD requires the presence of at least 1 diagnostic clinical sign of chronic GVHD (e.g., poikiloderma or esophageal web) or the presence of at least 1 distinctive manifestation (e.g., keratoconjunctivitis sicca) confirmed by pertinent biopsy or other relevant tests (e.g., Schirmer test) in the same or another organ. Furthermore, other possible diagnoses for clinical symptoms must be excluded. No time limit is set for the diagnosis of chronic GVHD. The Working Group recognized 2 main categories of GVHD, each with 2 subcategories. The acute GVHD category is defined in the absence of diagnostic or distinctive features of chronic GVHD and includes (1) classic acute GVHD occurring within 100 days after transplantation and (2) persistent, recurrent, or late acute GVHD (features of acute GVHD occurring beyond 100 days, often during withdrawal of immune suppression). The broad category of chronic GVHD includes (1) classic chronic GVHD (without features or characteristics of acute GVHD) and (2) an overlap syndrome in which diagnostic or distinctive features of chronic GVHD and acute GVHD appear together. It is currently recommended that systemic therapy be considered for patients who meet criteria for chronic GVHD of moderate to severe global severity.

Chronic Disease↗

PubMed2005

Treatment of hepatitis C in potential kidney and heart transplant patients.

Hepatitis C virus (HCV) is common in certain solid organ transplant recipients, most notably in those undergoing liver or kidney transplantation. Infection typically antedates transplantation but may have been acquired at the time of transplantation via infected blood products or organs. A more rapid and aggressive course of HCV-related infection and liver disease is the major concern in organ transplant recipients compared with immunocompetent patients. HCV-related liver disease is an important cause of morbidity and mortality in patients with end-stage renal disease treated by dialysis or transplantation. The outcome of HCV infection in renal and liver transplant recipients has been extensively investigated, whereas literature on HCV-related liver disease among patients with orthotopic heart transplantation is scanty. This article reviews the literature concerning the treatment of HCV-related liver disease in renal and orthotopic heart transplantation.

Antiviral Agents↗

PubMed2005

Tracheal agenesis with unique anatomy.

A premature infant with a unique form of tracheal agenesis is described. The combination of difficulty in intubation, abnormal course of the nasogastric tube on plain x-ray, and gastric perforation raised the suspicion of an upper airway malformation. Tracheal agenesis is an extremely rare, typically fatal, congenital anomaly with scattered case reports of its successful management. On many occasions, the diagnosis is a retrospective one at postmortem examination. The possibility of surgical correction rests on early diagnosis, anatomy, birth weight, and associated anomalies. Early recognition is mandatory, but in our case, the low birth weight precluded consideration for reconstructive surgery.

Fatal Outcome↗

PubMed2005

Treatment of chronic hepatitis C infection in patients with renal failure.

Patients with end-stage renal disease continue to have a high prevalence of hepatitis C virus infection despite screening of blood products and efforts to prevent the transmission of viral hepatitis within dialysis units. Although biochemical dysfunction often is absent in infected patients, an increased rate of mortality from liver disease has been observed in patients on long-term dialysis. In addition, hepatitis C-infected renal transplant recipients have diminished patient and graft survival rates compared with uninfected controls. Antiviral therapy with interferon in renal transplantation candidates has resulted in sustained viral responses that have been durable even after subsequent renal transplantation. Graft dysfunction remains a major concern, limiting the use of interferon after renal transplant. Ribavirin, which accumulates and cannot be removed by dialysis, and may induce hemolysis, generally has been avoided in patients with end-stage renal disease. In pilot studies, cautious use of reduced doses of ribavirin has been possible in this population with close monitoring of hematocrit levels and additional measures to enhance compensatory erythropoiesis.

Antiviral Agents↗

PubMed2005

A comprehensive grassroots model for statewide safety improvement.

BACKGROUND: The Maryland Patient Safety Center (MPSC) a collaboration of the Maryland Hospital Association and Delmarva Foundation for Medical Care, Inc., was designated by the State of Maryland in June 2004. A voluntary, nonregulatory initiative, the MPSC complements the state's regulatory efforts in mandatory reporting and support for performance improvement. PROGRAMS: The MPSC's mission is to bring health care providers together to understand causes of unsafe practices and to put practical, evidence-based improvements in place. Using a multifaceted approach, the MPSC implements its mission through education and training, safety culture collaboratives, adverse-event and near-miss reporting, research, and special projects. Participation in these initiatives is provided at no cost to Maryland providers. Early results show that health care leaders and front-line workers are embracing the MPSC's vision to make Maryland's health care the safest in the nation. More than 2,500 health care providers have participated in the MPSC's programs in its 15 months. Eighty percent of the state's hospitals are taking part in the intensive care unit (ICU) Safety Culture Collaborative, which has already yielded a 36% decrease in catheter-related blood stream infections and a 20% decrease in ventilator-associated pneumonia. A MODEL FOR OTHER STATES: The MPSC's approach can serve as a model for other states to emulate.

Adverse Drug Reaction Reporting Systems↗

PubMed2005

Randomized study comparing banding and propranolol to prevent initial variceal hemorrhage in cirrhotics with high-risk esophageal varices.

BACKGROUND & AIMS: Standard care for prevention of first esophageal variceal hemorrhage is beta-blockade, but this may be ineffective or unsafe. Our purpose was to compare endoscopic banding with propranolol for prevention of first variceal hemorrhage. METHODS: In a multicenter, prospective trial, 62 patients with cirrhosis with high-risk esophageal varices were randomized to propranolol (titrated to reducing resting pulse by > or =25%) or banding (performed monthly until varices were eradicated) and were followed up on the same schedule for a mean duration of 15 months. The primary end point was treatment failure, defined as the development of endoscopically documented variceal hemorrhage or a severe medical complication requiring discontinuation of therapy. Direct costs were estimated from Medicare reimbursements and fixed or variable charges for services up to treatment failure. RESULTS: Background variables of the treatment groups were similar. The trial was stopped early after an interim analysis showed that the failure rate of propranolol was significantly higher than that of banding (6/31 vs. 0/31; difference, 19.4%; P = .0098; 95% confidence interval for true difference, 6.4%-37.2%). Significantly more propranolol than banding patients had esophageal variceal hemorrhage (4/31 vs. 0/31; difference, 12.9%; P = .0443; 95% confidence interval for true difference, 0.8%-29%), and the cumulative mortality rate was significantly higher in the propranolol than in the banding group (4/31 vs. 0/31; difference, 12.9%; P = .0443; 95% confidence interval for true difference, 0.8%-29%). Direct costs of care were not significantly different. CONCLUSIONS: For patients with cirrhosis with high-risk esophageal varices and no history of variceal hemorrhage, propranolol-treated patients had significantly higher failure rates of failure, first esophageal varix hemorrhage, and cumulative mortality than banding patients. Direct costs of medical care were not significantly different.

Adrenergic beta-Antagonists↗

PubMed2005

Hepatitis C virus antibody status and survival after renal transplantation: meta-analysis of observational studies.

The natural history of hepatitis C virus (HCV) among patients after renal transplantation (RT) remains incompletely defined. We conducted a systematic review of the published medical literature on the impact of hepatitis C antibody status on survival of patients who received RT. We used the random effects model of DerSimonian and Laird to generate a summary estimate of the relative risk (RR) for mortality and graft loss with HCV seropositivity across the published studies. We identified eight clinical trials (6365 unique patients); six (75%) were cohort studies and two (2/8 = 25%) controlled trials, respectively. Pooling of study results demonstrated that presence of anti-HCV antibody was an independent and significant risk factor for death and graft failure after RT; the summary estimate for RR was 1.79 (95% CI, 1.57-2.03; homogeneity test, p = 0.0427) and 1.56 (95% CI, 1.35-1.80; homogeneity test, p = 0.0192), respectively. As a cause of death, hepatocellular carcinoma (HCC) and liver cirrhosis were significantly more frequent among anti-HCV positive than anti-HCV negative RT patients. This meta-analysis demonstrates that RT recipients with anti-HCV antibody have an increased risk of mortality and graft failure compared with HCV antibody negative patients.

Adult↗

PubMed2005

Post-transplant diabetes mellitus and HCV seropositive status after renal transplantation: meta-analysis of clinical studies.

Hepatitis C virus (HCV) infection has a detrimental role on patient and graft survival after renal transplantation (RT). Some studies have also implicated HCV in the development of post-transplant diabetes mellitus (PTDM). We conducted a systematic review of the published medical literature of the relationship between anti-HCV seropositive status and DM after RT. The risk of DM occurrence in anti-HCV-positive and -negative patients after RT was regarded as the most reliable outcome end-point. We used the random effects model of DerSimonian and Laird to generate a summary estimate of the Odds Ratio (OD) of new onset DM in HCV-positive and -negative patients after kidney transplantation. Ten studies involving 2502 unique RT recipients were identified. The incidence of PTDM after RT ranged between 7.9% and 50%. The summary estimate for adjusted OR was 3.97 with a 95% confidence interval (CI) of 1.83-8.61 (p-value for homogeneity <0.0473). Thus, pooling of study results demonstrated the presence of a significant link between anti-HCV seropositive status and DM after RT. This relationship provides one potential explanation for the adverse effects of HCV on patient and graft survival after RT.

Adult↗

PubMed2005

Novel assay using total hepatitis C virus (HCV) core antigen quantification for diagnosis of HCV infection in dialysis patients.

Dialysis patients remain a high-risk group for hepatitis C virus (HCV) infection. The current diagnosis of HCV infection among dialysis patients includes serological assays and nucleic acid amplification technology (NAT) for assessing serum anti-HCV antibody and HCV viremia, respectively. However, current NAT techniques are expensive and labor-intensive and often lack standardization. An assay prototype designed to detect and quantify total HCV core antigen (total HCV core Ag) protein in serum and plasma in the presence or absence of anti-HCV antibodies has been recently developed. A comparison between a total anti-HCV core Ag enzyme-linked immunosorbent assay (ELISA) and a quantitative HCV RNA assay based on reverse transcription-PCR (RT-PCR) (Amplicor HCV Monitor test) was performed using a large (n = 305) cohort of ELISA HCV 3.0 HCV-negative and -positive patients on maintenance dialysis. The concentrations of HCV core Ag and HCV RNA levels (measured by RT-PCR) were significantly correlated (r = 0.471, P = 0.0001) over a wide range of HCV RNA levels and were maintained among different HCV genotypes (HCV genotype 1, r = 0.862, P = 0.0001; HCV genotype 2, r = 0.691, P = 0.0001). We estimated that 1 pg of total HCV core Ag per ml is equivalent to approximately 19.952 IU of HCV RNA per ml, even if the wide range in the ratio of core Ag to HCV RNA (95% confidence intervals, 2.8 x 10(3) to 1.6 x 10(5) IU/ml) precluded definitive conclusions. In summary, total HCV core Ag proved to be useful for performing HCV RNA measurement among dialysis patients in routine laboratories without the need for special equipment or training. The present study supports the use of the total anti-HCV core Ag ELISA for assessing viral load among dialysis patients with HCV infection.

Aged↗

PubMed2005

Multicenter validation of a multiplex PCR assay for differentiating the major Listeria monocytogenes serovars 1/2a, 1/2b, 1/2c, and 4b: toward an international standard.

The performance of a multiplex PCR assay that separates the four major serovars of the pathogenic Listeria monocytogenes into four distinct PCR groups was evaluated through a multicenter typing study. Identical panels of 90 Listeria isolates were distributed to five participating laboratories that were blind to the nature of the isolates. Isolates were characterized using the previously standardized protocol. Overall concordance was 96.6 to 100%, sufficient for the assay to be used as an alternative to serotyping and confidently applied in laboratories involved in L. monocytogenes typing.

Animals↗

PubMed2005

Imatinib (Gleevec)-induced hepatotoxicity.

Imatinib (Gleevec, Novartis Pharmaceuticals Corp, East Hanover, NJ) is widely used in the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors. To our knowledge, only one case report of histologically proven Imatinib-induced hepatotoxicity has been reported. We describe another case of hepatotoxicity in a 22-year-old woman including the histopathologic changes and the clinical course after the discontinuation of Imatinib.

Adult↗

PubMed2005

Close encounters.

Explore the source record for details and available documents.

Attitude of Health Personnel↗

PubMed2004

Wound healing and inflammation genes revealed by array analysis of 'macrophageless' PU.1 null mice.

BACKGROUND: Wound healing is a complex process requiring the collaborative efforts of different tissues and cell lineages, and involving the coordinated interplay of several phases of proliferation, migration, matrix synthesis and contraction. Tissue damage also triggers a robust influx of inflammatory leukocytes to the wound site that play key roles in clearing the wound of invading microbes but also release signals that may be detrimental to repair and lead to fibrosis. RESULTS: To better define key cellular events pivotal for tissue repair yet independent of inflammation we have used a microarray approach to determine a portfolio of over 1,000 genes expressed across the repair response in a wild-type neonatal mouse versus its PU.1 null sib. The PU.1 null mouse is genetically incapable of raising the standard inflammatory response, because it lacks macrophages and functioning neutrophils, yet repairs skin wounds rapidly and with reduced fibrosis. Conversely, by subtraction, we have determined genes that are either expressed by leukocytes, or upregulated by fibroblasts, endothelial cells, muscle cells and others at the wound site, as a consequence of inflammation. To determine the spatial expression pattern for several genes in each cluster we have also performed in situ hybridization studies. CONCLUSIONS: Cluster analysis of genes expressed after wounding wild-type mice versus PU.1 null sibs distinguishes between tissue repair genes and genes associated with inflammation and its consequences. Our data reveal and classify several pools of genes, giving insight into their likely functions during repair and hinting at potential therapeutic targets.

Animals↗