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Biomedical subjects

D Snyder

Publications and source records attributed to D Snyder.

At least 19 recordsLinked to original sources
PubMed2007

Multiple vascular anomalies in a regurgitating German shepherd puppy.

Five cardio-thoracic vascular anomalies were detected in a German shepherd puppy. The patent ductus arteriosus (PDA) was detected on physical examination (5/6 continuous murmur) and confirmed by echocardiogram. The persistent right aortic arch (PRAA) was suspected by the signalment and history of the patient, and confirmed by survey thoracic radiographs (leftward deviation of the trachea cranial to the heart on the ventrodorsal projection). The ventrally deviated trachea cranial to the heart on the right lateral thoracic radiograph was suggestive of a persistent retroesophageal left subclavian artery and confirmed at surgery. The persistent left cranial vena cava and the left azygous vein were detected at surgery. This case report gives a thorough description of the clinical signs, diagnostics and treatments required for the detection and successful resolution of PRAA. The report describes the importance of having experienced surgeons who can recognize vascular anomalies associated with PRAA in order to successfully alleviate the arch and the coinciding oesophageal stricture without compromising vital blood supplies.

Animals↗
PubMed2006

Phase I and pharmacokinetic study of halofuginone, an oral quinazolinone derivative in patients with advanced solid tumours.

PURPOSE: Halofuginone (tempostatin) is a synthetic derivative of a quinazolinone alkaloid showing anti-angiogenic, anti-metastatic and anti-proliferative effects in preclinical studies. The objectives of this phase I study were to assess the dose-limiting toxicities (DLTs), to determine the maximum tolerated dose (MTD) and to study the pharmacokinetics (PKs) of halofuginone when administered once or twice daily orally to patients with advanced solid tumours. METHODS: Patients were treated with escalating doses of halofuginone at doses ranging from 0.5 to 3.5 mg/day. For pharmacokinetic analysis plasma sampling was performed during the first and second course and assayed using a validated high-performance liquid chromatographic assay with mass spectrometric detection. RESULTS: Twenty-four patients received a total of 106 courses. The 'acute' MTD was reached at 3.5 mg/day, with nausea, vomiting, and fatigue as DLT. The recommended dose for chronic administration was defined as 0.5mg/day with the requirement of 5HT3 antagonists to control nausea and vomiting considered as DLT. Several patients experienced bleeding complications on treatment with halofuginone in which a causal relationship could not be excluded. The PKs of halofuginone were linear over the dose range studied with a large interpatient variability. CONCLUSIONS: In this study the DLT of halofuginone was nausea, vomiting, and fatigue. The recommended dose for phase II studies of halofuginone is 0.5mg administered orally, once daily.

Administration, Oral↗
PubMed2001

Is arrhythmia detection by automatic external defibrillator accurate for children?: sensitivity and specificity of an automatic external defibrillator algorithm in 696 pediatric arrhythmias.

BACKGROUND: Use of automatic external defibrillators (AEDs) in children aged <8 years is not recommended. The purpose of this study was to develop an ECG database of shockable and nonshockable rhythms from a broad age range of pediatric patients and to test the accuracy of the Agilent Heartstream FR2 Patient Analysis System for sensitivity and specificity. METHODS AND RESULTS: Children aged </=12 years who either developed arrhythmias or were at risk for developing arrhythmias were studied. Two sources were used for the database: children whose rhythms were recorded prospectively via a modified AED and children who had arrhythmias captured on paper and digitized for subsequent analysis. The rhythms were divided into 5-second strips, classified by 3 reviewers, and then assessed by the AED analysis algorithm. A total of 696 five-second rhythm strips from 191 children (81 female and 110 male) aged 1 day to 12 years (median 3.0 years) were analyzed. There was 100% specificity for nonshockable rhythms. Sensitivity for ventricular fibrillation was 96%. CONCLUSIONS: There was excellent AED rhythm analysis sensitivity and specificity in all age groups for ventricular fibrillation and nonshockable rhythms. The high specificity and sensitivity indicate that there is a very low risk of an inappropriate shock and that the AED correctly identifies shockable rhythms, making the algorithm both safe and effective for children.

Adult↗
PubMed2000

Effects of allogeneic bone marrow transplantation on recipient bone mineral density: A prospective study.

Allogeneic bone marrow transplant (BMT) recipients have many known risk factors for developing decreased bone mineral density (BMD) after transplantation. We performed a prospective sequential evaluation of BMD in the lumbar spine and nondominant hip using dual-energy x-ray absorptiometry (DEXA) in a cohort of 47 adult patients (median age, 43 years) who were undergoing radiation-based BMT for hematologic malignancies. Baseline DEXA studies were performed before BMT and repeated at 3 to 4 months, 6 to 8 months, and 12 to 14 months after BMT. The majority of patients (60%) had been minimally treated with combination cytotoxic chemotherapy, having received no more than 1 treatment regimen before BMT. Graft-versus-host disease prophylaxis consisted of cyclosporine in combination with either methotrexate or prednisone, or both. Mean lumbar spine and hip BMD were normal before BMT (spine: 1.01 g/cm2, z score = 96%; hip: 0.86 g/cm2, z score = 100%) and gradually decreased (spine: 0.98 g/cm2, z score = 94%; hip: 0.76 g/cm2, z score = 91%) at 12 to 14 months. These declines were statistically significant (P < .006 and < .002 for lumbar spine; P < .001 and < .001 for hip). In addition, the sharpest decline occurred during the first 6 months after BMT and was more marked in the hip than the lumbar spine. These data suggest that BMT adversely affects BMD in this patient population.

Absorptiometry, Photon↗
PubMed2000

Primary peritonitis due to group A streptococcus.

Primary peritonitis is a rare condition occurring, by definition, in patients without underlying causes, such as perforated viscus, pre-existing ascites, or nephrosis. We report a case of primary peritonitis and shock due to group A beta-hemolytic streptococcus, a rare etiology. A review of the world's literature shows a predilection for women to have this condition. The entry site is obscure in most cases. Asymptomatic genital tract colonization may be a portal of entry in some women. Shock or toxic shock syndrome often accompany the abdominal findings. Laparotomy to exclude a perforated viscus may be unavoidable. Despite the significant morbidity, expeditious and appropriate antibiotic therapy is curative.

Adult↗
PubMed1999

Interleukin-2-activated autologous bone marrow and peripheral blood stem cells in the treatment of acute leukemia and lymphoma.

In this pilot trial of interleukin (IL)-2-treated autologous bone marrow (BM) and peripheral stem cell (PSC)-supported high-dose chemoradiotherapy, we report 36 patients with poor-prognosis leukemia and lymphoma who received BM and/or granulocyte colony-stimulating factor (G-CSF)-mobilized autologous PSCs that had been exposed to IL-2 for 24 hours ex vivo. Patients then received IL-2 by low-dose continuous intravenous (i.v.) infusion until hematologic reconstitution and then by intermediate-dose continuous i.v. infusion for six 2-week maintenance cycles given at 1-month intervals. The median Day to neutrophils over 500/microL was 22 with BM and 10 with PSCs (p = 0.01). The median Day to platelets >20,000/microL was 50 for BM and 25 for PSCs, and to platelets >50,000/microL was 138 for BM and 34 for PSCs (p not significant). After the first three patients received IL-2 at 2 mIU x m(-2) x day(-1) and had slow reconstitution, four patients were treated without IL-2 until the maintenance phase following reconstitution. The remaining 29 patients received the initial "post-infusion" IL-2 at 1 mIU x m(-2) x day(-1). Toxicities associated with the infusion of IL-2-activated cells consisted of chills and fever in about one-half of the patients and transient hypotension in 12%. Low-dose IL-2 by continuous i.v. infusion in the early posttransplant period was associated with exacerbation of fever, diarrhea, and altered mental status in a minority of patients. The major dose-limiting toxicities of maintenance IL-2 were fever, fatigue, gastrointestinal symptoms, skin rash, and dyspnea. Among 24 lymphoma patients, nine are in continuous complete remission (CCR) from 18-48 months, and 15 have died (12 due to relapse and three of therapy-related toxicities). Of 12 acute leukemia patients, two with acute lymphoblastic leukemia (ALL) are in CCR at 38 and 43 months, and one patient who was in cytogenetic but not molecular remission of Philadelphia chromosome-positive ALL died of progressive leukemia at Day 108. Three of nine with myeloid leukemia are in CCR at 21, 46, and 53 months; one is in hematologic and cytogenetic remission of acute promyelocytic leukemia at 55 months with multiple new cytogenetic abnormalities; one is alive at 54 months with pancytopenia after incomplete hematologic recovery followed by multiple new cytogenetic abnormalities (myelodysplasia); and one had an unrelated donor transplant after relapsing 4 months following protocol therapy. One myeloid leukemia patient remains without evidence of relapse, but is transfusion-dependent at 15 months following transplant.

Acute Disease↗
PubMed1998

Why Americans eat what they do: taste, nutrition, cost, convenience, and weight control concerns as influences on food consumption.

OBJECTIVE: To examine the self-reported importance of taste, nutrition, cost, convenience, and weight control on personal dietary choices and whether these factors vary across demographic groups, are associated with lifestyle choices related to health (termed health lifestyle), and actually predict eating behavior. DESIGN: Data are based on responses to 2 self-administered cross-sectional surveys. The main outcomes measured were consumption of fruits and vegetables, fast foods, cheese, and breakfast cereals, which were determined on the basis of responses to questions about usual and recent consumption and a food diary. SUBJECTS/SETTING: Respondents were a national sample of 2,967 adults. Response rates were 71% to the first survey and 77% to the second survey (which was sent to people who completed the first survey). STATISTICAL ANALYSES: Univariate analyses were used to describe importance ratings, bivariate analyses (correlations and t tests) were used to examine demographic and lifestyle differences on importance measures, and multivariate analyses (general linear models) were used to predict lifestyle cluster membership and food consumption. RESULTS: Respondents reported that taste is the most important influence on their food choices, followed by cost. Demographic and health lifestyle differences were evident across all 5 importance measures. The importance of nutrition and the importance of weight control were predicted best by subject's membership in a particular health lifestyle cluster. When eating behaviors were examined, demographic measures and membership in a health lifestyle cluster predicted consumption of fruits and vegetables, fast foods, cheese, and breakfast cereal. The importance placed on taste, nutrition, cost, convenience, and weight control also predicted types of foods consumed. APPLICATIONS: Our results suggest that nutritional concerns, per sc, are of less relevance to most people than taste and cost. One implication is that nutrition education programs should attempt to design and promote nutritious diets as being tasty and inexpensive.

Adult↗
PubMed1998

The age and job satisfaction relationship: does its shape and strength still evade us?

Many investigations have examined the relationship between age and job satisfaction. However, various types of relationships have been reported across studies: positive linear, negative linear, U-shaped, inverted U-shaped or inverted J-shaped, or no significant relations. Such conflicting results have left the true nature of the relationship unresolved. The present study used a large national probability sample of workers (N = 1,095) to investigate the shape and strength of the age--job satisfaction relationship. Results indicated a significant but weak positive linear age--job satisfaction relationship. That is, age failed to explain a substantial proportion of linear variance in our job satisfaction measure. This indicates that age, as a chronological variable, is not a viable predictor of job satisfaction. Future research attempting to explain age differences in job satisfaction should instead focus its attention on other more pertinent psychological variables associated with the underlying aging process.

Adolescent↗
PubMed1997

Regression of tumors in mice vaccinated with professional antigen-presenting cells pulsed with tumor extracts.

Vaccination with tumor extracts circumvents the need to identify specific tumor rejection antigens and extends the use of active immunotherapy to the vast majority of cancers, in which specific tumor antigens have not yet been identified. In this study we examined the efficacy of tumor vaccines comprised of unfractionated tumor material presented by professional antigen-presenting cells (APC): dendritic cells (DC) or macrophages (M phi). To enhance the relevance of these studies for human patients we used 2 poorly immunogenic murine tumor models and evaluated the effectiveness of the vaccination protocols in tumor-bearing animals. APC (in particular DC) pulsed with unfractionated extracts from these "poorly immunogenic" tumors were highly effective in eliciting tumor-specific cytotoxic T lymphocytes. A measurable CTL response could be detected after even a single immunization with tumor extract-pulsed DC. DC or M phi pulsed with tumor extract were also effective vaccines in tumor-bearing animals. In the murine bladder tumor (MBT-2) model a modest extension of survival and 40% cure rate was seen in the animal groups immunized with DC or M phi pulsed with MBT-2 tumor extract. DC or M phi pulsed with B16/F10.9 tumor extract were also remarkably effective in the B16 melanoma lung metastasis model, as shown by the observation that treatment with APC caused a significant reduction in lung metastases. Cumulatively, the CTL and immunotherapy data from the two murine tumor systems suggest that APC (in particular DC) pulsed with unfractionated cell extracts as a source of tumor antigen may be equally or more effective than genetically modified tumor vaccines.

Animals↗
PubMed1997

Antigen-presenting cells pulsed with unfractionated tumor-derived peptides are potent tumor vaccines.

Vaccination with peptides isolated from tumor cells circumvents the need for identifying specific tumor rejection antigens and extends the use of active immunotherapy to the majority of cancers where specific tumor antigens have not yet been identified. In this study, we examined the efficacy of tumor vaccines composed of unfractionated tumor peptides presented by antigen-presenting cells (APC) to induce cytotoxic T lymphocyte (CTL) responses and tumor immunity. RMA-S cells pulsed with peptides isolated from ovalbumin (OVA)-expressing tumor cells were highly effective at inducing primary, OVA-specific CTL responses in vitro and priming CTL responses in vivo. In addition, tumor peptide-pulsed RMA-S cells induced protective immunity in mice when challenged with OVA-expressing tumor cells. To enhance the clinical relevance of these studies, cells pulsed with tumor peptides were evaluated in the poorly immunogenic, B16/F10.9 melanoma post-surgical metastasis model. Treatment of tumor-bearing mice with peptide-pulsed RMA-S cells or with adherent splenocytes (enriched for professional APC) caused a significant reduction in lung metastases. The antimetastatic effect of peptide-pulsed splenocytes could be further enhanced by pretreating the cells with antisense oligonucleotides directed against the TAP-2 gene which was previously shown to increase the density of specific peptide/MHC class I complexes and thereby improve the APC function of the treated cells (Nair et el., J. Immunol. 1996. 156: 1772). This study suggests that APC loaded with unfractionated peptides derived from poorly immunogenic, highly metastatic tumor cells may represent a potent form of tumor vaccine.

Animals↗
PubMed1996

Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo.

Immunization with defined tumor antigens is currently limited to a small number of cancers where candidates for tumor rejection antigens have been identified. In this study we investigated whether pulsing dendritic cells (DC) with tumor-derived RNA is an effective way to induce CTL and tumor immunity. DC pulsed with in vitro synthesized chicken ovalbumin (OVA) RNA were more effective than OVA peptide-pulsed DC in stimulating primary, OVA-specific CTL responses in vitro. DC pulsed with unfractionated RNA (total or polyA+) from OVA-expressing tumor cells were as effective as DC pulsed with OVA peptide at stimulating CTL responses. Induction of OVA-specific CTL was abrogated when polyA+ RNA from OVA-expressing cells was treated with an OVA-specific antisense oligodeoxynucleotide and RNase H, showing that sensitization of DC was indeed mediated by OVA RNA. Mice vaccinated with DC pulsed with RNA from OVA-expressing tumor cells were protected against a challenge with OVA-expressing tumor cells. In the poorly immunogenic, highly metastatic, B16/F10.9 tumor model a dramatic reduction in lung metastases was observed in mice vaccinated with DC pulsed with tumor-derived RNA (total or polyA+, but not polyA- RNA). The finding that RNA transcribed in vitro from cDNA cloned in a bacterial plasmid was highly effective in sensitizing DC shows that amplification of the antigenic content from a small number of tumor cells is feasible, thus expanding the potential use of RNA-pulsed DC-based vaccines for patients bearing very small, possibly microscopic, tumors.

Animals↗
PubMed1996

Induction of antitumor immunity using bone marrow-generated dendritic cells.

We have previously shown that bone marrow-generated dendritic cells (DC) pulsed with a class I-restricted peptide are potent inducers of CD8+ CTL. In the present study we have investigated whether bone marrow-generated DC are capable of inducing antitumor immunity. We show that a single immunization with DC pulsed with OVA peptide was highly effective in eliciting a protective immune response against a challenge with tumor cells expressing the OVA gene (E.G7-OVA), more so than immunization with irradiated E.G7-OVA cells, OVA peptide-pulsed RMA-S cells, or free OVA peptide mixed with adjuvant. The addition of free OVA protein to day 4 or day 7 bone marrow cultures, but not to day 9 mature DC, was also effective in eliciting CTL and engendering antitumor immunity, but was less effective than peptide-pulsed DC. Induction of CTL and antitumor immunity by bone marrow-generated DC pulsed with the class I-restricted OVA peptide correlated with the expression of syngeneic MHC class II molecules on the DC. This and the fact that induction of tumor immunity was dependent on CD4+ T cells suggest that in vivo priming of CTL and induction of antitumor immunity by bone marrow-generated DC also require the presentation of MHC class II-restricted epitopes and activation of CD4+ T cells. This observation has potentially important implications to the use of peptide-pulsed DC in clinical immunotherapy.

Animals↗
PubMed1996

Cells treated with TAP-2 antisense oligonucleotides are potent antigen-presenting cells in vitro and in vivo.

Treatment of RMA and EL4 cells or freshly isolated splenocytes with antisense (AS) oligonucleotides directed against the TAP-2 gene recreates the phenotype seen in cells that are genetically deficient in TAP function. Cells incubated with AS oligonucleotides exhibit reduced MHC class I expression on the cell surface, which can be increased by incubating the oligonucleotide-treated cells at 28 degrees C or by adding MHC haplotype-matched peptides to the culture medium. RMA cells or splenocytes treated with AS oligonucleotides and incubated with peptide were highly effective in generating primary CTL responses in vitro. The bulk of the AS oligonucleotide-responsive and CTL-inducing cells resided in the adherent fraction of splenocytes. Moreover, TAP-2 AS oligonucleotide-treated adherent splenocytes pulsed with OVA peptide elicited potent OVA-specific CTL responses in vivo and provided effective protection from challenge with tumor cells expressing the corresponding Ag. AS oligonucleotide technology provides a simple approach to develop broadly applicable methods for generating potent APC to study TAP function in normal cells and to identify other gene products involved in MHC class I presentation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Frontal brain asymmetry predicts affective style in men.

Recent research suggests that a significant relationship between frontal brain asymmetry (FBA) and affective style can be documented in women with 1-measurement occasion. The purpose of this study was to determine whether this finding is generalizable to men. Resting electroencephalogram (EEG) activity was recorded from male adults during 5 60-s baselines on 1 measurement occasion. Mean alpha power asymmetry was extracted in midfrontal and lateral-frontal sites. For the lateral-frontal site, but not the midfrontal site, there was a significant relationship between relative left anterior activation and positive affective style. These results suggest that lateral FBA is a robust and state-independent measure of affective style in men.

Adolescent↗