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Biomedical subjects

K Smith

Publications and source records attributed to K Smith.

At least 235 records · Page 13Linked to original sources

Comparison of fluorinated polymers against stainless steel, glass and polypropylene in microbial biofilm adherence and removal.

Biofilm formation is a long-standing problem in ultrapure water and bioprocess fluid transport lines. The standard materials used in these applications (316L stainless steel, polypropylene and glass) have long been known to be good surfaces for the attachment of bacteria and other biological materials. To compare the relative tenacity of biofilms grown on materials used in manufacturing processes, a model system for biofilm attachment was constructed that approximates the conditions in industrial process systems. New fluorinated polymers were compared to the above materials by evaluating the surface area coverage of bacterial populations on materials before and after mild chemical treatment. In addition, contact angle studies compared the relative hydrophobicity of surfaces to suspensions of bacteria in growth media, and scanning electron microscopy and atomic force microscopy studies were used to characterize surface smoothness and surface defects. Biofilm adherence to polymer-based substrata was determined to be a function of both surface finish and surface chemistry. Specifically, materials that are less chemically reactive, as indicated by higher contact angle, can have rougher surface finishes and still be amenable to biofilm removal.

Bacterial Adhesion↗

Simple diagnosis of Encephalitozoon sp. microsporidial infections by using a panspecific antiexospore monoclonal antibody.

Microsporidia (phylum Microsproa) have recently become recognized as common opportunistic protozoans in the United States and worldwide, particularly affecting immunodeficient patients. Microsporidian organisms within the genus Encephalitozoon are the cause of nephrologic, ophthalmic, pneumologic, gastroenteric, and systemic infections. However, diagnosis of the small spores by light microscopy is difficult, even with newly developed and improved staining techniques. We have developed an anti-Encephalitozoon species monoclonal antibody-based immunoassay for easy diagnosis. A hybridoma was produced and selected following one main criterion: recognition by immunofluorescence of all known Encephalitozoon spores affecting humans. The selected monoclonal antibody-secreting hybridomas were characterized by enzyme-linked immunosorbent assay, immunofluorescence, Western blot, and immunoelectron microscopy using Encephalitozoon species from fresh and fixed samples from patients and from in vitro cultures. In the immunofluorescence assay, one monoclonal antibody, termed 3B6, strongly recognized Encephalitozoon cuniculi, E. hellem, and E. intestinalis. Monoclonal antibody 3B6 bound to other microsporidia (Nosema and Vairimorpha spp.) without cross-reacting with any other parasite, including Enterocytozoon bieneusi, fungus, or bacterium tested. In immunoelectron microscopy assays, monoclonal antibody 3B6 bound to the exospore of Encephalitozoon species, while in Western blot assays, it recognized three to seven antigens with molecular masses ranging from 34 to 117 kDa. We have developed a sensitive and specific monoclonal antibody-based immunoassay to diagnose common microsporidian infections, particularly with Encephalitozoon species. This is a new tool for identifying spores in bodily fluids and biopsy samples and is an efficient diagnostic test. Additionally, monoclonal antibody 3B6 can serve to assess the prevalence of microsporidial infections in immunodeficient and immunocompetent patients.

AIDS-Related Opportunistic Infections↗

Diagnosis of genitourinary Chlamydia trachomatis infections by using the ligase chain reaction on patient-obtained vaginal swabs.

We compared the ligase chain reaction (LCR) assay to cell culture for diagnosis of genitourinary chlamydial infections in women using swab specimens obtained by clinicians from the endocervix and by patients from their own vaginas. Specimens from 40 (12.9%) of 309 patients were positive for chlamydial infection by culture, while the specimens of 50 (16.2%) patients were positive by LCR. Chlamydia trachomatis infection was verified for 9 of 10 patients whose LCR specimens were positive but whose cultures were negative. Vaginal and cervical swab specimens were positive by LCR for 46 (93.9%) and 44 (89.8%) of 49 chlamydia-infected patients, respectively. These data suggest that LCR testing for chlamydia with vaginal swab specimens obtained by patients themselves is as sensitive as cervical LCR and more sensitive than cell culture.

Adolescent↗

Intracranial neurological injuries associated with orbital fracture.

We attempted to define the central nervous system (CNS) concomitants of various types of orbital fractures in children by reviewing the records of 95 inpatients with admission diagnoses including orbital fracture who presented to the Children's National Medical Center from 1987 through 1994. Patients were divided into three age groups: group I: 0-5 years; group II: 6-12 years; group III: older than 12 years. Orbital fractures were classified by location: roof alone (A); orbital roof plus another orbital wall (B), and orbital fractures sparing the roof (C). Mechanisms of injury included falls (F), motor vehicle accidents (M), and blunt injuries (S). Admission Glasgow Coma Scale (GCS), neurosurgical intervention, nature of associated intracranial injury, and presence of residual neurologic deficit were recorded. Group I included 38 patients, while groups II and III included 28 and 29, respectively. There were 61 boys and 34 girls. Most fractures confined to the roof occurred in group I patients (12 of 16 fractures; 75%). Twenty-four of the 38 group I patients (63%) sustained orbital fractures involving the roof compared to 12 (43%) and 6 (21%) in groups II and III, respectively. Children with orbital fractures involving the roof and another orbital wall, regardless of age, had lower admission GCS. Over half of type B fracture patients (19/26) were involved in motor vehicle accidents. Intracranial injuries were identified in 26 of the 73 patients (36%) whose CT included the brain. Fifteen of 26 patients (58%) with intracranial injuries sustained fractures involving the orbital roof, but only 3 of these had a type A fracture. Seven of the patients with intracranial injury required emergent neurosurgical procedures. Younger children with maxillofacial injury sparing the orbital roof appear more likely to have coexisting intracranial injury, as reflected by CT findings and GCS on admission, than their older cohorts with similar injuries. Fracture of more than one orbital wall greatly increases risk of concurrent intracranial injury in all age groups.

Accidental Falls↗

Ulcerating necrobiosis lipoidica resolving in response to cyclosporine-A.

Necrobiosis lipoidica often fails to respond adequately to therapy with topical and intralesional corticosteroids, or to systemic medications like niacinamide and pentoxifylline (Trental). On the basis of unpublished work which showed a predominance of T helper cells in lesions of necrobiosis lipoidica, and recalling the case of a woman whose necrobiosis lipoidica improved after she was started on cyclosporine for a renal transplant, systemic cyclosporine was successfully used in the cases of two young women who had insulin-dependent diabetes and were disfigured by severe, ulcerating necrobiosis lipoidica on the anterior lower legs. Response to treatment was monitored with photographs. In both cases the ulcers resolved, and remained in remission after cyclosporine was stopped.

Adult↗

Strategies to protect bone mass in the older patient with epilepsy.

The annual incidence of epileptic seizures rises dramatically after the age of 60. Risk factors associated with late-onset epilepsy include cerebrovascular disease, dementia, infection, trauma, and alcoholism. The dominant cause of seizures in older patients is a previous stroke, whereas a significant percentage of cases are attributed to the presence of a tumor. Normal aging is associated with an increased risk for fractures from trauma and osteoporosis. Antiepileptic medications may exacerbate this problem by adversely affecting bone metabolism and increasing the risk of falls related to drug toxicity. The patient work-up, careful prescribing, and monitoring for drug toxicity can help preserve bone integrity in patients receiving antiepileptic drug therapy.

Age Factors↗

Immune reconstitution following T-cell depleted bone marrow transplantation: effect of age and posttransplant graft rejection prophylaxis.

Transplantation of T-cell depleted bone marrow has been associated with an increased risk of graft failure, requiring additional immunosuppression to prevent this complication. To determine the effect of graft rejection prophylaxis with posttransplant anti-thymocyte globulin and methylprednisolone on immune reconstitution, the lymphoid phenotype, function, and infectious complications of 170 recipients of a T-cell depleted bone marrow transplantation, 57 of whom received prophylaxis, were analyzed. Neutrophil recovery and normalization of T-cell numbers were more rapid in patients given anti-thymocyte globulin and methylprednisolone. Adults given graft rejection prophylaxis had prolonged inversion of their CD4/CD8 ratio, increased numbers of CD8+ CD11b+, HLA-DR+, CD57+, CD28- T cells, and delayed recovery of T-cell mitogen responses when compared to adults not given ATG and steroids. Even without posttransplant immunosuppression to prevent graft failure, adults experienced delayed recovery of total and CD45RA+ CD4+ cells, prolonged inversion of the CD4/CD8 ratio, and delayed recovery of T-cell mitogen responses when compared to children. During the first posttransplant year, Epstein-Barr Virus-Associated Lymphoproliferative disorders and opportunistic infections were increased in patients given prophylaxis. Patients who developed an opportunistic infection or EBV-LPD had significantly fewer circulating CD4+ T cells than those who did not. This study demonstrates that older age and graft rejection prophylaxis, rather than T-cell depletion alone, are associated with delayed immune reconstitution. In addition, it suggests that CD4 cell counts may be useful in predicting which patients are at increased risk of developing opportunistic infections following successful engraftment.

Adolescent↗

Prediction of developmental patterns through 40 months from 6- and 12-month neurologic examinations in very low birth weight infants.

This study examines whether neurologic examinations at 6 and 12 months of age can predict developmental patterns in very low birth weight infants and fullterm controls through 40 months of age. We performed neurologic examinations at 6 and 12 months; the Bayley Scales of Infant Development at 6, 12, and 24 months; and the Stanford-Binet and the McCarthy Motor scale at 40 months. The very low birth weight infants were categorized on the basis of socioeconomic status and high or low risk for early medical complications. More abnormal neurologic scores predicted greater deceleration of cognitive development for high-risk infants only. The 12-month neurologic examination predicted the degree of deceleration in motor development. Medical risk was an independent predictor of curvature of the psychomotor development curve. We conclude that neurologic examinations during the 1st year of life might be used with other factors in decision concerning referrals to early-intervention programs.

Analysis of Variance↗

Low seroprevalence of Toxoplasma gondii in feral pigs from a remote island lacking cats.

Serum samples from 1,264 feral pigs from Ossabaw Island, Georgia were initially screened for antibodies to Toxoplasma gondii by the modified agglutination test (MAT) using whole-formalinized tachyzoites and mercaptoethanol. Seropositive samples were also tested by the Sabin-Feldman dye test, the latex agglutination test (LAT), and the indirect hemagglutination test (IHAT). Ossabaw Island is a remote, barrier island located southeast of Savannah, Georgia. Antibodies to T. gondii were found in 11 (0.9%) of 1,264 pigs. The antibody titers were 1:20 (1 pig), 1:80 (2 pigs), 1:160 (2 pigs), 1:320 (4 pigs), and 1:640 (2 pigs) by the MAT, and 1:8 (2 pigs), 1:16 (3 pigs), 1:32 (1 pig), 1:64 (2 pigs), 1:128 (1 pig), and > or = 1:256 (2 pigs) by the Sabin-Feldman dye test. By the LAT, 5 pigs had a titer of > or = 1:64 and by the IHAT all 11 pigs had a titer of < 1:64. Antibodies (MAT titer, > or = 1:25) were found in 31 (18.2%) of 170 feral pigs from mainland Georgia. This seroprevalence on the mainland was significantly higher (P < 0.0001) as compared on Ossabaw Island. The markedly low prevalence of T. gondii on Ossabaw Island was attributed to the virtual absence of cats on the Island; only 1 domestic cat was known to be present.

Age Factors↗

Interaction of mouse adenovirus type 1 early region 1A protein with cellular proteins pRb and p107.

We demonstrated functional associations between mouse adenovirus type 1 (MAV-1) early region 1A (E1A) protein and both the mouse retinoblastoma protein (pRb) and the mouse pRb-related protein, p107. Interactions between MAV-1 E1A and mouse pRb or mouse p107 proteins were examined in infected cell lysates using a mouse embryonic fibroblast cell line infected with wild-type and mutant MAV-1 viruses. Using a polyclonal antibody to MAV-1 E1A, exogenously added mouse pRb or mouse p107 was coimmunoprecipitated from wild-type, dIE105 (CR1 delta)-, and dIE106 (CR3 delta)-infected cell lysates. No coimmunoprecipitation was seen with cell lysates from dIE102 (CR2 delta) or pmE109, a mutant virus that produces no detectable E1A protein due to an ATG to TTG point mutation in the initiator methionine. Introduction of mouse pRb into SAOS-2 cells resulted in a flat and enlarged cell phenotype, whereas cotransfection of mouse pRb and MAV-1 E1A resulted in a significant reduction of flat cells, presumably due to E1A binding pRb. CR1 delta and CR2 delta E1A proteins were less effective at reducing the number of flat, enlarged cells induced by pRb expression than were the CR3 delta or wild-type E1A proteins. The reduced ability of these mutants to inactivate pRb relative to wild-type E1A correlated with their reduced ability to bind pRb in the in vitro coimmunoprecipitation experiments. As a measure of p107/MAV-1 E1A complex formation in MAV-1-infected cells, we used mobility shift assays to examine cell extracts for the presence of p107-containing E2F protein-DNA complexes. Mock-, dIE102-, and pmE109-infected cell extracts formed a p107-containing complex, whereas wild-type-infected cell extracts did not. Thus the formation of a p107-E2F complex in wild-type- or these mutant-infected extracts inversely correlated with the presence of E1A-p107 complexes identified in the vitro coimmunoprecipitation experiments. This is consistent with E1A-p107 complexes forming in wild-type MAV-1-infected cells.

Adenovirus E1A Proteins↗

Compartment switching of WNT-2 expression in human breast tumors.

WNT-2 is a secreted polypeptide with mitogenic effects in murine mammary epithelial cells, but its role in human cancer is unknown. Using RNase protection analysis of primary cell preparations and in situ hybridization analysis, we report that WNT-2 is expressed at low levels in normal human breast fibroblasts but not in epithelial cells. WNT-2 was found to be expressed at high levels in both the epithelium and stroma of 5 of 11 infiltrating carcinomas and 2 of 6 fibroadenomas. The high level of WNT-2 expression in tumor epithelium suggests that tumorigenesis may involve the ectopic expression of WNT-2 and the creation of an autocrine Wnt signaling loop.

Breast↗

Ancient single origin for Malagasy primates.

We report new evidence that bears decisively on a long-standing controversy in primate systematics. DNA sequence data for the complete cytochrome b gene, combined with an expanded morphological data set, confirm the results of a previous study and again indicate that all extant Malagasy lemurs originated from a single common ancestor. These results, as well as those from other genetic studies, call for a revision of primate classifications in which the dwarf and mouse lemurs are placed within the Afro-Asian lorisiforms. The phylogenetic results, in agreement with paleocontinental data, indicate an African origin for the common ancestor of lemurs and lorises (the Strepsirrhini). The molecular data further suggest the surprising conclusion that lemurs began evolving independently by the early Eocene at the latest. This indicates that the Malagasy primate lineage is more ancient than generally thought and places the split between the two strepsirrhine lineages well before the appearance of known Eocene fossil primates. We conclude that primate origins were marked by rapid speciation and diversification sometime before the late Paleocene.

Animals↗

Accuracy and precision of a new, portable, handheld blood gas analyzer, the IRMA.

OBJECTIVE: The accuracy and precision of the new IRMA (Immediate Response Mobile Analysis System, Diametrics, Inc., St. Paul, MN) handheld blood gas analyzer was compared with that of two benchtop blood gas analyzers. The IRMA consists of a notebook-sized machine and disposable cartridges, each containing a pH, a CO2 and an O2 electrode, and provides bedside (point-of-care) blood gas analysis. METHODS: A total of 172 samples (arterial and mixed venous) were obtained from 25 informed, consenting patients undergoing cardiopulmonary bypass. The pH, PCO2 and PO2 of each sample was determined on four blood gas analyzers: NOVA Statlabs Profile 5 (NOVA Biomedical, Waltham, MA), the ABL-50 (Radiometer, West Lake, OH), and two IRMA machines. Linear regression and bias +/- precision were determined, comparing each of the analyzers with the NOVA. RESULTS: All three machines showed a similar, high degree of correlation with the NOVA for pH, PCO2, and PO2. The bias and precision of the IRMA machines compared with the NOVA was similar to that of the ABL compared with the NOVA for pH (NOVA:ABL -0.005 +/- 0.011; NOVA:IRMA 1 = 0.0026 +/- 0.025; NOVA:IRMA 2 = 0.0021 +/- 0.025), for PCO2 (NOVA:ABL = -1.4 +/- 1.3 mmHg; NOVA: IRMA 1 = -1.3 +/- 1.9 mmHg; NOVA: IRMA 2 = -1.2 +/- 2.1 mmHg) and PO2 (NOVA:ABL = 3.6 +/- 21.1 mmHg; NOVA:IRMA 1 = 3.4 +/- 19.9 mmHg; NOVA:IRMA 2 = 6.3 +/- 20.9 mmHg). The bias found for pH, PCO2, and PO2 was not affected by extremes of temperature (range 25.5-40 degrees C) or hematocrit (range 11-44%) for any machine. CONCLUSIONS: The new technology incorporated in the IRMA blood gas analyzer provides results with an accuracy that is similar to that of benchtop analyzers, but with all of the advantages of point-of-care analysis.

Blood Gas Analysis↗

Costs of mental illness in Britain.

Cost of illness studies are a growing area of literature without a common methodology and their usefulness has been debated over the years. A short review carried out of the British studies on mental health revealed differences which originate from three main areas: the epidemiological evidence on prevalence, service contact data and the unit costs employed. This paper outlines the differences found in a number of these studies and we develop a worked example using information from the studies to illustrate the issues of concern. We conclude that the area is problematic in two fashions. Firstly, the results are highly sensitive to epidemiological data and assumptions on costs. Secondly, the assumptions on costs and use of services must always be made explicit.

Cost of Illness↗

Delayed diagnosis in a rural trauma center.

BACKGROUND: The rapid and accurate diagnosis of all injuries is critical in trauma surgery. Injuries not diagnosed after the secondary survey are not without serious consequences. Therefore, in an effort to decrease this problem a policy was initiated to perform an ongoing serial exam during the entire course of each patient's involvement with the trauma team at Saint Francis Medical Center. METHODS: Prospective identification and evaluation of patients admitted to a single trauma service with delayed diagnosis was done from July 1, 1993, to October 31, 1995. RESULTS: Sixty-eight delayed diagnoses were identified in 56 patients, for an incidence of 3% of the total 1876 patients evaluated. The vast majority were nonspinal orthopedic injuries (63%). Of seven missed spinal fractures, only one resulted in permanent paralysis. The remaining injuries missed were 11 injuries located in the head and neck area, 3 arterial injuries, 3 pneumothoraces, and 2 small bowel injuries. Thirty-four percent of the patients required surgical intervention for these injuries and one patient died because of the delay. There was a high association of delayed diagnosis in victims with altered mental status, victims intubated in the field, and individuals requiring immediate operation. Twenty percent of our total missed injuries could have been avoided if a thorough evaluation of initial films had been done. CONCLUSIONS: Delayed diagnosis remains a problem in all trauma centers. This study demonstrates that to keep this problem at a reasonable rate, we must: (1) carefully review initial x rays; (2) repeat any study that is not clear; and (3) continue serial examinations of each patient for the entire clinical course. Objective and thoughtful discussion of missed injuries on a routine basis will also keep this problem minimal.

Abdominal Injuries↗