PubMed Health⌕ Search

Biomedical subjects

Richard Miller

Publications and source records attributed to Richard Miller.

31 records · Page 2Linked to original sources

A novel immunohistochemical method to estimate cell-cycle phase distribution in archival tissue: implications for the prediction of outcome in colorectal cancer.

An immunohistochemical method for assessing cell-cycle phase distribution in colorectal resection specimens would enable phase data to be incorporated into diagnostic algorithms for the estimation of prognosis and response to adjuvant chemotherapy in colorectal cancer. In contrast to flow cytometry, an immunohistochemical method would also allow the phase distribution to be examined within morphologically heterogeneous regions of neoplasms. Paraffin sections of normal colon (n = 25), colonic adenoma (n = 15), and colonic adenocarcinoma (n = 30) were analysed by immunohistochemistry using antibodies against markers of cell-cycle entry, Mcm-2 and Ki67, and putative markers of the cell-cycle phase, cyclins D1 and E (putative markers of G1 phase), cyclin A (S phase), cytoplasmic cyclin B1 (G2 phase), and phosphohistone H3 (M phase). The phase specificity of each marker was assessed by examining the degree of co-expression of adjacent phase markers using double-antibody fluorescence confocal microscopy and by comparison with flow cytometric analysis performed on adjacent tissue sections. The S-phase specificity of detectable cyclin A was also assessed in combination with in situ DNA replication using fluorescence confocal microscopy. All cells expressing phase markers co-expressed Mcm-2. Adjacent phase markers were not significantly co-expressed, confirming the relative specificity of these markers in tissue sections of colon. Cell-cycle phase distribution, calculated by immunohistochemistry, compared well with phase analyses obtained by flow cytometry. No cells expressed cyclin A in the absence of active DNA replication. The S-phase labelling index, as defined by detectable cyclin A expression, showed a positive correlation with the Mcm-2 labelling index and increased in the progression from normal colon to adenocarcinoma. In conclusion, a combination of these cell-cycle phase markers can be used to calculate the distribution of cells throughout each phase of the cell cycle in colorectal tissue sections. Detectable cyclin A can be used as a surrogate marker of S phase and may be of value in predicting prognosis and response to adjuvant therapy.

Adenocarcinoma↗

Enlarging pigmented patches on the hand.

This case illustrates the clinical and pathological features of Tinea nigra. Awareness of the characteristic features of this cutaneous infection, especially in areas where the organism is endemic, can ultimately lead clinicians to the appropriate diagnosis. If Tinea nigra should be considered in the differential diagnosis of palmoplantar pigmentation, potassium hydroxide (KOH) preparation may facilitate the diagnosis.

Administration, Topical↗

Topically applied imiquimod inhibits vascular tumor growth in vivo.

Vascular tumors occur in approximately 10% of all infants and may be associated with significant morbidity. Available therapies for vascular tumors, such as systemic corticosteroids, vincristine, and interferon-alpha, may cause toxicity, limiting their use to complicated cases. Using a mouse hemangioendothelioma model, we investigated the efficacy and mechanism of action of imiquimod, a topically applied inducer of cytokines. Application of imiquimod cream, whether initiated at the time of cell inoculation or when tumors became visible, significantly decreased tumor growth and increased animal survival in comparison with control mice. Imiquimod-treated tumors showed decreased tumor cell proliferation, increased tumor apoptosis, and increased expression of tissue inhibitor of matrix metalloproteinase-1 with decreased activity of matrix metalloproteinase-9. The demonstration that local application of imiquimod inhibits vascular tumor enlargement in the mouse vascular tumor model suggests a novel, less toxic means of treating infantile hemangioendotheliomas and perhaps other cutaneous vascular tumors.

Administration, Topical↗

Granulomatous pneumonitis following exposure to the World Trade Center collapse.

We describe a 37-year-old male engineer who presented with cough and dyspnea 3 weeks after exposure to dust resulting from the collapse of the World Trade Center (WTC). Radiographs of the chest and high-resolution CT demonstrated diffuse miliary nodularity. Lung biopsy specimens confirmed the presence of diffuse, noncaseating granulomatous nodules. Scanning electron microscopy and energy-dispersive radiograph analysis revealed large quantities of silicates. Cellular immunologic studies showed normal response to beryllium, and results of Kveim testing were negative. We suspect that exposure to one or more materials resulting from the WTC catastrophe may be implicated in the development of granulomatous pulmonary disease.

Adult↗

Early one-stage closure in patients with abdominal compartment syndrome: fascial replacement with human acellular dermis and bipedicle flaps.

Decompressive celiotomy for the treatment of abdominal compartment syndrome (ACS) often results in wounds that are difficult to close. These complicated wounds are frequently managed with a 3-staged surgical approach employing a planned ventral hernia. The authors describe an alternative closure with a single operation using a commercially available human acellular dermis (HACD) as a fascial substitute. Soft tissue coverage is obtained at the same operation by means of bilateral bipedicle flaps. The cohort consisted of 9 patients, ages 19 to 77 years old. On average patients were closed on the ninth postoperative day (range, 3 to 30 days) and were discharged from the trauma center on average 8 days (range, 5 to 29 days) after the abdominal closure. Complications developed in 3 (33%) patients. These complications included a flap hematoma, wound infection, and recurrent hernia. There were no postoperative fistulas. This procedure allows for early, single-staged closure of the abdomen after abdominal compartment syndrome. Once closed, patients were able to be discharged from the hospital early and without need for specialized wound care. Further investigation on the usefulness of this technique is required.

Abdominal Muscles↗

Analysis of minichromosome maintenance proteins as a novel method for detection of colorectal cancer in stool.

Colorectal cancer is a common disease, and more reliable screening methods are needed for early detection. We aim to develop a non-invasive, stool-based assay that can identify colorectal cancer by detection of minichromosome maintenance protein 2 (MCM2) expression in colonocytes retrieved from the faecal surface. We devised a cell line model to investigate methods and conditions for optimum colonocyte retrieval. In our clinical evaluation study, MCM2-positive cells were retrieved from 37 of 40 patients with symptomatic colorectal cancer, but from none of 25 healthy control individuals. These results suggest that immunocytochemical analysis of retrieved colonocytes might enable accurate detection of colorectal cancer in stool.

Adenocarcinoma↗

Full-scale evaluation of mercury control with sorbent injection and COHPAC at Alabama Power E.C. Gaston.

The overall objective of this project was to determine the cost and impacts of Hg control using sorbent injection into a Compact Hybrid Particulate Collector (COHPAC) at Alabama Power's Gaston Unit 3. This test is part of a program funded by the U.S. Department of Energy's National Energy Technology Laboratory (NETL) to obtain the necessary information to assess the costs of controlling Hg from coal-fired utility plants that do not have scrubbers for SO2 control. The economics will be developed based on various levels of Hg control. Gaston Unit 3 was chosen for testing because COHPAC represents a cost-effective retrofit option for utilities with existing electrostatic precipitators (ESPs). COHPAC is an EPRI-patented concept that places a high air-to-cloth ratio baghouse downstream of an existing ESP to improve overall particulate collection efficiency. Activated carbons were injected upstream of COHPAC and downstream of the ESP to obtain performance and operational data. Results were very encouraging, with up to 90% removal of Hg for short operating periods using powdered activated carbon (PAC). During the long-term tests, an average Hg removal efficiency of 78% was measured. The PAC injection rate for the long-term tests was chosen to maintain COHPAC cleaning frequency at less than 1.5 pulses/bag/hr.

Adsorption↗

Plasma versus whole blood perfusion in a bioartificial liver assist device.

The ramifications of using whole blood or plasma for perfusion off an hepatocyte containing bioartificial liver bioreactor in which the hepatocytes are separated by a membrane or other physical barrier from the perfusate stream on the rate of change of patient blood concentrations are explored through dynamic modeling of whole blood perfusion as a two compartment system (patient tissue and blood compartments), and plasma perfusion as a three compartment system (patient tissue and blood compartments, and a plasma reservoir). The whole blood perfusion model is described by three dimensionless parameters: the Damkohler number, Da, which represents the ratio of the rate of conversion by the bioreactor to the rate of perfusion; kappa, which represents the ratio of the rate of internal reequilibration between the tissue and blood compartments and the rate of perfusion; and Vtb, the tissue/blood volume ratio. The plasma perfusion model has three additional dimensionless parameters: f, the fraction of plasma withdrawn from the blood in a plasma separator; alpha, the ratio of the plasma perfusion rate in the bioreactor to the blood draw rate; and Vbr, the blood/plasma reservoir volume ratio. Within the physiologic range of parameters, the rate of reduction in blood concentration in both the whole blood-perfused and plasma-perfused systems are sensitive to Damkohler number up to Da approximately 2. Neither system is sensitive to variations in kappa, and the plasma perfusion system has little sensitivity to alpha. Given bioreactors of equivalent activity, a greater rate of blood concentration reduction and lower endpoint blood concentration at equivalent perfusion times will be achieved with whole blood perfusion. There are two physical reasons for this. The first is that the plasma perfused system is only processing a fraction, f, of the blood compared with the whole blood perfusion system. The second reason is that, although the blood-perfused system is limited by overall bioreactor performance, the plasma-perfused system is mass transfer limited to the rate of blood concentration dilution into the plasma reservoir rather than limited by the overall bioreactor performance.

Bioreactors↗

Trends in total knee replacement surgeries and implications for public health, 1990-2000.

OBJECTIVES: Total joint replacements are important surgical interventions for treating severe arthritis of weight-bearing joints. The most common indication for total knee replacement (TKR) is osteoarthritis of the knee joint. The goals of this study were to assess the trend in rate of TKR in Wisconsin and to describe the economic impact of these surgical procedures on the health care system. METHOD: A population-based cross-sectional study of TKR surgeries was conducted among Wisconsin residents aged > or = 45 years. The Wisconsin inpatient hospital discharge data from 1990 through 2000 were used. Rates were age-adjusted to the 2000 U.S. population, and charges for TKR were adjusted for inflation. RESULTS: From 1990 through 2000, the age-adjusted rate for TKR increased by 81.5% (from 162 to 294 per 100,000; p<0.001). The rate increased the most among the youngest age group (45-49 years), rate ratio 5.1 for men, 4.2 for women. The total charges for TKR increased from 69.4 million dollars to 148 million dollars (109.2% inflation-adjusted increase). Medicare received the highest proportion of charges for TKR procedures, but throughout the study period, the proportion of charges covered by private insurance increased by 39%. CONCLUSIONS: The rate and costs of TKR procedures among Wisconsin residents increased substantially from 1990 through 2000, especially among younger age groups. Changes in medical practices probably accounted for some of this increase, but these trends also may reflect an increased prevalence of osteoarthritis, which in turn may be related to dramatic increases in the number of individuals who are overweight.

Age Distribution↗

The impact of a normoglycemic management protocol on clinical outcomes in the trauma intensive care unit.

BACKGROUND: The purpose of this study was to determine if protocol-driven normoglycemic management in trauma patients affected glucose control, ventilator-associated pneumonia, surgical-site infection, and inpatient mortality. METHODS: A prospective, consecutive-series, historically controlled study design evaluated protocol-driven normoglycemic management among trauma patients at Vanderbilt University Medical Center. Those mechanically ventilated > or =24 hours and > or =15 years of age were included. A glycemic-control protocol required insulin infusion therapy for glucose >110 mg/dL. Control patients included those who met criteria, were admitted the year preceding protocol implementation, and had hyperglycemia treated at the physician's discretion. RESULTS: Eight hundred eighteen patients met study criteria; 383 were managed without protocol; 435 underwent protocol. The protocol group had lower glucose levels 7 of 14 days measured. After admission, both groups had mean daily glucose levels <150 mg/dL. No difference in pneumonia (31.6% vs 34.5%; p = .413), surgical infection (5.0% vs 5.7%; p = .645) or mortality (12.3% vs 13.1%; p = .722) occurred between groups. If one episode of blood glucose level was > or =150 mg/dL (n = 638; 78.0%), outcomes were worse: higher daily glucose levels for 14 days after admission (p < .001), pneumonia rates (35.9% vs 23.3%; p = .002), and mortality (14.6% vs 6.1%; p = .002). One or more days of glucose > or =150 mg/dL had a 2- to 3-fold increase in the odds of death. Protocol use in these patients was not associated with outcome improvement. CONCLUSIONS: Protocol-driven management decreased glucose levels 7 of 14 days after admission without outcome change. One or more glucose levels > or =150 mg/dL were associated with worse outcome.

Adult↗