PubMed Health⌕ Search

Biomedical subjects

K Watkins

Publications and source records attributed to K Watkins.

At least 19 recordsLinked to original sources
PubMed2006

A DNA prime-modified vaccinia virus ankara boost vaccine encoding thrombospondin-related adhesion protein but not circumsporozoite protein partially protects healthy malaria-naive adults against Plasmodium falciparum sporozoite challenge.

The safety, immunogenicity, and efficacy of DNA and modified vaccinia virus Ankara (MVA) prime-boost regimes were assessed by using either thrombospondin-related adhesion protein (TRAP) with a multiple-epitope string ME (ME-TRAP) or the circumsporozoite protein (CS) of Plasmodium falciparum. Sixteen healthy subjects who never had malaria (malaria-naive subjects) received two priming vaccinations with DNA, followed by one boosting immunization with MVA, with either ME-TRAP or CS as the antigen. Immunogenicity was assessed by ex vivo gamma interferon (IFN-gamma) enzyme-linked immunospot assay (ELISPOT) and antibody assay. Two weeks after the final vaccination, the subjects underwent P. falciparum sporozoite challenge, with six unvaccinated controls. The vaccines were well tolerated and immunogenic, with the DDM-ME TRAP regimen producing stronger ex vivo IFN-gamma ELISPOT responses than DDM-CS. One of eight subjects receiving the DDM-ME TRAP regimen was completely protected against malaria challenge, with this group as a whole showing significant delay to parasitemia compared to controls (P = 0.045). The peak ex vivo IFN-gamma ELISPOT response in this group correlated strongly with the number of days to parasitemia (P = 0.033). No protection was observed in the DDM-CS group. Prime-boost vaccination with DNA and MVA encoding ME-TRAP but not CS resulted in partial protection against P. falciparum sporozoite challenge in the present study.

Adolescent↗
PubMed2003

Inverted spin method for removing RBCs from BM buffy coat products.

BACKGROUND: Inverted spin is a method of removing RBCs that historically has been part of blood banking practice. We investigated the feasibility of using this method for RBC depletion of BM buffy coat products in situations where recipient RBC Abs have been identified to donor RBC Ags. METHODS: The BM buffy coat product was placed in a transfer pack, inverted, centrifuged at 600 g for 10 min, suspended and the RBCs removed slowly into another transfer pack. Nine patients treated between April 1998 and February 2001 received products prepared by our version of the inverted spin procedure. RESULTS: We removed a median value of 81.2% of the RBCs, while still recovering a median of 94.3% of the mononuclear cells (median: 0.35 x 10(8)/kg; range: 0.17-0.9 x 10(8)/kg). The median volume of RBCs remaining in the product was 15.0 mL (range: 7.3-21.9 mL). The CD34(+) cell dose of the final product ranged from 1.0 x 10(6)/kg to 4.8 x 10(6) cells/kg (median: 1.9 x 10 6/kg). Granulocyte recovery (defined as ANC count >or=500/microL for a period of 3 consecutive days) ranged from 18-30 days post-infusion of the allograft (median: 24.0 days). One patient died shortly after his transplant from complications of his disease. No patient had any evidence of an acute hemolytic reaction. DISCUSSION: Advantages of the inverted spin method include no need for additives (e.g. hydroxyethyl starch, HSA, or O negative RBC), and use of equipment readily available in most processing laboratories.

Antigens, CD34↗
PubMed2000

Pitch and timing abilities in inherited speech and language impairment.

Members of the KE family who suffer from an inherited developmental speech-and-language disorder and normal, age-matched, controls were tested on musical abilities, including perception and production of pitch and rhythm. Affected family members were not deficient in either the perception or production of pitch, whether this involved either single notes or familiar melodies. However, they were deficient in both the perception and production of rhythm in both vocal and manual modalities. It is concluded that intonation abilities are not impaired in the affected family members, whereas their timing abilities are impaired. Neither their linguistic nor oral praxic deficits can be at the root of their impairment in timing; rather, the reverse may be true.

Adolescent↗
PubMed1999

Centriacinar remodeling and sustained procollagen gene expression after exposure to ozone and nitrogen dioxide.

Sprague-Dawley rats were exposed to 0.8 ppm ozone (O3), to 14.4 ppm nitrogen dioxide (NO2), or to both gases simultaneously for 6 h per day for up to 90 d. The extent of histopathologic changes within the central acinus of the lungs was compared after 7 or 78 to 90 d of exposure using morphometric analysis by placement of concentric arcs radiating outward from a single reference point at the level of the bronchiole- alveolar duct junction. Lesions in the lungs of rats exposed to the mixture of gases extended approximately twice as far into the acinus as in those exposed to each individual gas. The extent of tissue involvement was the same at 78 to 90 d as noted at 7 d in all exposure groups. At the end of exposure, in situ hybridization for procollagen types I and III demonstrated high levels of messenger RNA within central acini in the lungs of animals exposed to the combination of O3 and NO2. In contrast, animals exposed to each individual gas had a similar pattern of message expression compared with that seen in control animals, although centriacinar histologic changes were still significantly different from control animals. We conclude that the progressive pulmonary fibrosis that occurs in rats exposed to the combination of O3 and NO2 is due to sustained, elevated expression of the genes for procollagen types I and III. This effect at the gene level is correlated with the more severe histologic lesions seen in animals exposed to both O3 and NO2 compared with those exposed to each individual gas. In contrast, the sustained expression of the procollagen genes is not associated with a shift in the distribution of the lesions because the area of change in each group after 7 d of exposure was the same as after 78 to 90 d of exposure.

Animals↗
PubMed1999

Examination of factor structure of the cognitive representations of hypertension scale for ethnic equivalence.

The major purpose of this analysis was to examine the factor structure of separate interpretive dimensions of the Cognitive Representation of Hypertension Scales (CRHTN) for ethnic equivalence. The CRHTN is a theoretically derived measurement of individualized experience of hypertension assessed along three cognitive interpretive dimensions: perceptions, preferences and possibilities. The sample for this study was recruited from a university-based hypertension clinic, a Veterans Administration ambulatory service, and a large urban-based HMO. Analysis of data through confirmatory factor analysis techniques across both samples provided evidence for construct validity of a five-factor model along three dimensions: perceptions, preferences and possibilities. However, multigroup analyses suggest the model may not equally describe cognitive representations of hypertension for different ethnic groups. Differences in fit of the theoretical model to data from two different ethnic groups is discussed. Findings from this study provide a basis for development of culturally sensitive and appropriate cognitive strengthening strategies to influence behavioral outcomes for hypertension management.

Black or African American↗
PubMed1998

Fournier's gangrene with an unusual urologic etiology.

Fournier's gangrene is a necrotizing infection affecting the male genitalia and perineum, caused by synergistic aerobic and anaerobic organisms. We report on a previously undescribed upper urinary tract etiology for this life-threatening infection.

Fournier Gangrene↗
PubMed1998

Supplemental Security Income (SSI), Disability Insurance (DI), and substance abusers.

Federal legislation repealed Supplemental Security Income (SSI) and Disability Insurance (DI) for alcohol and drug abusers as of January 1997. This article outlines the context in which the legislation was passed and summarizes concerns resulting from the legislation. We discuss the effects of the legislation on treatment participation, financing, and availability, and the legislation's impact on individuals with dual mental health and substance abuse problems. We also consider the individual and societal implications of substance abusers' loss of monthly income and health insurance.

Adult↗
PubMed1998

Comparison of progenitor cell content in sequential peripheral blood progenitor collections after mobilization with chemotherapy and granulocyte macrophage colony-stimulating factor.

Optimal timing of peripheral blood progenitor cell (PBPC) harvest to collect maximal stem cell numbers is unknown. We assessed the progenitor cell content in 128 PBPC harvests from 21 patients primed with chemotherapy and granulocyte macrophage-colony stimulating factor (GM-CSF) in relation to absolute neutrophil count (ANC) at collection time. Samples were obtained by leukapheresis during rebound from chemotherapy-induced neutropenia while receiving GM-CSF, and assayed by flow cytometry for CD34+ and by colony assays for CFU-GM and BFU-E. The CD34+ cell concentrations per sample tended to be greater at an ANC < 1,000 mm3 and decreased with rising ANC (p = 0.001). The CFU-GM and BFU-E concentrations per sample remained relatively constant with rising ANC (p = 0.72, p = 0.90, respectively). Total CD34+ cell number per harvest per kg slightly increased with ANC levels (p = 0.044) whereas the total CFU-GM and the total BFU-E per kilogram increased more modestly with rising ANC (p < 0.001, p < 0.001, respectively). We conclude that after priming with chemotherapy and GM-CSF, PBPC could be collected at different absolute neutrophil counts without greatly affecting total CD34+ cell numbers. The greater concentration of CD34+ progenitor cells at a lower ANC together with the CFU-GM and BFU-E peaking with higher ANC suggest a less mature progenitor cell population at lower ANC levels.

Adult↗
PubMed1997

Original p53 status predicts for pathological response in locally advanced breast cancer patients treated preoperatively with continuous infusion 5-fluorouracil and radiation therapy.

PURPOSE/OBJECTIVE: 1) To test feasibility of preoperative continuous infusion (c.i.) 5-Fluorouracil (5-FU) and radiation (RT) in locally advanced breast cancer. 2) To study clinical and pathological response rates of 5-FU and radiation. 3) To attempt preliminary correlations between biological probes and pathological response. METHODS AND MATERIALS: Previously untreated, locally advanced breast cancer patients were eligible: only patients who presented with T3/T4 tumors that could not be resected with primary wound closure were eligible, while inflammatory breast cancer patients were excluded. The protocol consisted of preoperative c.i. infusion 5-FU, 200 mg/m2/day with radiotherapy, 50 Gy at 2 Gy fractions to the breast and regional nodes. At mastectomy, pathological findings were classified based on persistence of invasive cancer: pathological complete response (pCR) = no residual invasive cells in the breast and axillary contents; pathological partial response (pPR) = presence of microscopic foci of invasive cells in either the breast or nodal specimens; no pathological response (pNR) = pathological persistence of tumor. For each patient pretreatment breast cancer biopsies were analyzed by immunohistochemistry for nuclear grade, ER/PR hormonal receptors, her2/neu and p53 overexpression. RESULTS: Thirty-five women have completed the protocol and are available for analysis. 5-FU was interrupted during radiation in 10 of 35 patients because of oral mucositis in 8 patients, cellulitis in 1, and patient choice in another. Objective clinical response rate before mastectomy was 71% (25 of 35 patients): 4 CR, 21 PR. However, in all 35 patients tumor response was sufficient to make them resectable with primary wound closure. Accordingly, all patients underwent modified radical mastectomy: primary wound closure was achieved in all patients. At mastectomy there were 7 pCR (20%), 5 pPR (14%) and the remaining 23 patients (66%) had pathological persistence of cancer (pNR). Variables analyzed as potential predictors for pathological response (pPR and pCR) were: initial TNM clinical stage, clinical response, nuclear grade, hormonal receptor status, p53 overexpression, and Her2/neu overexpression in the pretreatment tumor biopsy. Only initial p53 status (lack of overexpression at immunohistochemistry) significantly correlated with achievement of a pathological response to this regimen (p = 0.010). CONCLUSION: The combination of c.i. 5-FU and radiation was well tolerated and generated objective clinical responses in 71% of the patients. With the limitation of the small sample size, the complete pathological response achieved (20%) compares favorably with that reported in other series of neoadjuvant therapy for similar stage breast cancer. These preliminary data suggest that initial p53 status predicts for pathological response (pPR and pCR) to the combination of c.i. 5-FU and radiotherapy in locally advanced breast cancer.

Adult↗
PubMed1996

The impact of the Women, Infants and Children Food Supplement Program on birth outcome.

OBJECTIVE: Our purpose was to compare the birth outcomes of pregnant women in the Women, Infants and Children Food Supplement Program with women not in the program. STUDY DESIGN: The vital records of 4713 women, 2895 enrolled in the Women, Infants and Children Food Supplement Program and 1812 not enrolled in the program, whose infants were delivered at Wishard Memorial Hospital over 18 months were reviewed with respect to age, education, race, substance habits, trimester of entry into prenatal care, maternal weight gain, and status in the program. The primary outcome variables evaluated were low birth weight, as defined by the delivery of an infant < 2500 gm, and infant mortality. The primary predictor was program participation versus nonparticipation. Analysis was by t test, chi2, and logistic regression models. RESULTS: Black women, women with no prenatal care, and women who smoke were more likely to deliver a low-birth-weight infant. The incidence of low birth weight was 13.1% for nonparticipants versus 10.2% for program participants (p < 0.05). Univariate analysis confirmed program participants to be at significantly less risk for a low-birth-weight delivery (odds ratio = 0.75, p < 0.05). This relation, however, was not significant in the multivariate model (odds ratio = 0.88), indicating that the effect of participating in the program is being confounded by race, entry into prenatal care, and smoking. The overall infant mortality rate was 12.4 per 1000 for participants and 16 per 1000 for nonparticipants (p = not significant). CONCLUSION: Nutritional and nonnutritional benefits to participation in the Women, Infants and Children Food Supplement Program were confirmed. Women enrolled in the program were less likely to deliver a low-birth-weight infant. Multiple variables likely contribute to the poorer outcome for nonparticipants.

Birth Weight↗
PubMed1995

Praxic and nonverbal cognitive deficits in a large family with a genetically transmitted speech and language disorder.

A pronounced speech and language disorder affecting half of the 30 members of the four-generational KE family has been attributed by some researchers to a specific defect in the generation of morphosyntactic rules. The reported selectivity of the impairment has led to the view that the affected members suffer from a grammar-specific disorder. Our investigations of the same KE family indicate that the inherited disorder has a broad phenotype which transcends impaired generation of syntactical rules and includes a striking articulatory impairment as well as defects in intellectual, linguistic, and orofacial praxic functions generally. Although the evidence from this family thus provides no support for the existence of "grammar genes," their linguistic difficulties do constitute a prominent part of their phenotype. Investigations of the neural and genetic correlates of their disorder could therefore uncover important clues to some of the bases of the primary human faculties of speech and language.

Cognition Disorders↗
PubMed1995

Increased incidence of central venous catheter-related infections in bone marrow transplant patients.

In view of an apparent increase of central venous catheter-related infections among our bone marrow transplant (BMT) patients, a retrospective study of infectious complications of central venous catheters was conducted. During 1992, 147 central venous catheters were placed in 133 patients. The overall infection rate of all catheters was 3.3 per thousand catheter-days (bacteremia 1.8, site infection 1.5). Patients scheduled for BMT had the highest infection rate of 11.5 (bacteremia 6.7, site infection 4.8). HIV patients had an infection rate of 6.6 per thousand catheter-days (bacteremia 3.8 and site infection 2.8) and patients with other diagnoses had a rate of 2.4 (bacteremia 1.3 and site infection 1.1). The difference of infection risk among the three groups is statistically significant (logrank p < .0001). In analyzing the 11 BMT patients more carefully, 14 catheters were placed. Of these, 9 catheters were removed, 8 (89%) of which were secondary to infection. Multivariate analysis showed that patients under 50 and BMT patients were more likely to develop catheter-related infection. While the cause of this complication is not known at present, the possible association with PBSC harvest is of much concern.

Adult↗