Biomedical subjects

Merril Dayton

Publications and source records attributed to Merril Dayton.

4 recordsLinked to original sources

PubMed2005

Randomized prospective trial of early steroid withdrawal compared with low-dose steroids in renal transplant recipients using serial protocol biopsies to assess efficacy and safety.

BACKGROUND: Corticosteroid therapy after renal transplantation is associated with many adverse effects. Newer immunosuppressive agents may allow for safe and effective reductions in dose or early steroid withdrawal. METHODS: In this prospective, single-center clinical trial, 60 patients were randomized into 2 groups: control patients (n = 28), who received low doses of prednisone throughout, and study patients (n = 32), who were withdrawn from steroids 7 days posttransplant. Patients received a limited course of rabbit antilymphocyte globulin (rALG) induction therapy, tacrolimus (TAC), and mycophenolate mofetil (MMF). Patients were followed for clinical outcomes and renal function. Protocol biopsies were performed at 1, 6, and 12 months. RESULTS: Clinical rejections occurred in 11% of controls and 13% of study patients. Renal function was well maintained and equivalent in both groups. In all, 111 protocol biopsies were performed without complications. Subclinical rejection was noted in only 2 protocol biopsies, and borderline changes were seen in 12 biopsies, all of which were distributed equally between both groups. Unsuspected acute TAC toxicity was seen in 8 biopsies. Protocol biopsies led to changes in therapy in 10% of patients. In both groups, serial protocol biopsies demonstrated increased allograft fibrosis over time, which was significant at 1 year in the steroid withdrawal group. CONCLUSION: The immunosuppressive combination of rALG, TAC, and MMF prevents subclinical rejection and the need for high doses of steroids after transplantation. However, continual low-dose steroid therapy may aid in preventing chronic allograft fibrosis. Protocol biopsies help define the short-term and long-term risks of steroid withdrawal therapy.

Adult↗

PubMedDate not supplied

Impact of journal articles and grand rounds on practice: CT scanning in appendicitis.

The purpose of this study was to determine whether a report in a high-impact journal published in January 1998 changed practice patterns and to further explore the impact of a review of the subject in a department of surgery grand rounds (January 2000). Charts from all patients undergoing appendectomy at our institution during three time periods (January to December 1997, January to December 1999, and January to June 2000) were reviewed. Rates of CT scanning, negative appendectomy, and perforated/gangrenous appendicitis were compared for the three periods to determine the impact of the journal article and the subject review during grand rounds on practice patterns and outcomes. Charts from 230 (88%) of 262 patients who underwent appendectomy during the time periods were available for review. Age, percentage of male patients, temperature on admission, and white blood cell count did not differ among the groups. The rate of CT scanning increased significantly from 1997 to 1999 and again in 2000 (6.7%, 43%, and 70%, respectively; P < 0.001), whereas the proportion of perforated/gangrenous appendicitis decreased significantly from 33% in 1997 and 31% in 1999 to 13% in 2000 (P = 0.012). The use of CT scanning in appendicitis increased both after publication of a report in a high-impact journal and after review during grand rounds. A rate of CT scanning above 45% appeared to affect outcomes as well.

Adult↗

PubMedDate not supplied

Tissue eosinophilic infiltration: a useful marker for assessing stromal invasion, survival and locoregional recurrence in head and neck squamous neoplasia.

UNLABELLED: The assessment of stromal invasion in aerodigestive neoplastic squamous proliferation often poses diagnostic and therapeutic challenges. Eosinophilic infiltration is thought to be an adjunctive histologic criterion in determining tumor aggressiveness and invasion. We investigated whether an eosinophilic infiltration in head and neck squamous cell carcinoma measured in biopsies would aid in predicting tumor invasion, response to treatment, locoregional recurrence, and survival. METHODS: Eighty-seven patients with in situ and invasive squamous cell carcinoma of the head and neck region were evaluated and treated according to their staging. The number of eosinophils per high-power field (eosinophil/HPF), and per 10 high-power fields (eosinophil/10 HPF) at the tumor interface and in tumor tissue, was counted and classified as focally or diffusely present. Each sample was assigned an eosinophilic index of 1-4 based on the number of eosinophils/HPF or 10 HPF. Of 87 patients, 20 patients were followed up after appropriate treatment for locoregional recurrence, distant metastasis, and disease-free survival. RESULTS: Eosinophilic counts were elevated focally and/or diffusely more frequently in invasive squamous cell carcinoma than in noninvasive tumors. The increased eosinophilic counts, specifically > 10/HPF and > 20/10 HPF, were both significantly associated with stromal invasion. Greater than 10 eosinophils/HPF and/or > 20 eosinophils/10 HPF had the highest predictive power for invasion, with sensitivity, specificity, and positive predictive values of 66%, 94%, 96% and 61%, 100%, and 100%, respectively. Eosinophilic counts greater than 20 eosinophils/10 HPF and eosinophilic indices > 2 were virtually diagnostic for tumor invasion. Patients' biopsies with eosinophilic indices < 2 had a better survival (P = 0.0156). Using Cox regression analysis, we found that most patients' biopsies that had eosinophilic indices > 2 recurred locally or regionally. CONCLUSIONS: The elevated eosinophilic counts in biopsies and eosinophilic indices in specimens of squamous cell carcinoma of the aerodigestive tract are a histopathologic marker associated with tumor invasion and a clinical predictor for aggressive tumor biology. Similarly, the presence of eosinophils meeting these thresholds in an excisional specimen should indicate the need for additional therapeutic measures and close surveillance to detect earlier locoregional recurrence and possible distant metastasis.

Adult↗

PubMedDate not supplied

Aberrant crypt foci.

Colon cancer evolves through epithelial cell deregulation and inappropriate proliferation. These histopathological characteristics are exemplified in the biochemical, immunohistochemical, genetic and epigenetic elements detected within colonic mucosa. Early detection is paramount for the prevention of colon cancer deaths. Aberrant crypt foci (ACF) are thought to be the earliest identifiable neoplastic lesions in the colon carcinogenetic model. The progression of ACF to polyp and, subsequently, to cancer parallels the accumulation of several biochemical alterations and mutations whereby a small fraction of ACF evolve to colon cancer. Recent data indicate that, not uncommonly, some ACF bypass the polyp stage in their carcinogenesis thus reinforcing the importance of their early detection and our understanding of their pathogenesis. Since ACF were first detected in carcinogen-treated mice, research efforts have focused on these microscopically visible lesions both in animal and human models. ACF show variable histological features, characterized by Kudo (20) and, therefore, can be grouped into differing categories by in vivo examination with high-magnification-chromoscopic-colonoscopy (HMCC). As expected, ACF are more frequently detected in distal animal and human colons coinciding with the geographic distribution of colorectal cancer (CRC). Various proteomic (Prot) markers may be altered within ACF suggesting possible prospective pathological changes. These markers include Calreticulin, Transgelin, Serotransferrin, Triphosphate isomerase and Carbonic anhydrase II. Other markers of importance include carcinoembryonic antigen (CEA), B-catenin, placental cadherin (P-cadherin), epithelial cadherin (E-cadherin), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2) and P16INK4a. Genetic mutations of K-ras, B-Raf APC and p53 have been demonstrated in ACF as well as the epigenetic alterations of CpG island methylation. Genomic instabilities (GI), illustrated by a higher GI Index (GII), microsatellite instability (MSI), loss of heterozygosity (LOH) and defects in mismatch repair (MMR) systems, are also expressed. These transformations may lead to the identification of the earliest pathological features initiating colon tumorigenesis. In this review, the advances in ACF research as precursors of CRCs are highlighted.

Animals↗