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Biomedical subjects

E Phillips

Publications and source records attributed to E Phillips.

At least 19 recordsLinked to original sources
PubMed2001

Visual P3 findings in Mission Indian youth: relationship to family history of alcohol dependence and behavioral problems.

Native Americans have some of the highest rates of alcohol abuse and dependence, yet risk factors for problem drinking remain relatively unknown. The amplitude of the P3 component of the event-related potential (ERP) has been suggested to be an index of 'vulnerability to alcoholism', especially when it is elicited by visual tasks in younger individuals. Visual P3 tasks, however, have not been previously investigated in Native American youth. One hundred and four Mission Indian youth between the ages of 7 and 13 years participated in the study. ERPs were collected using two visual target paradigms: a facial discrimination and an estimation of line orientation task. Analyses of covariance revealed that participants with a first degree family history of alcoholism had lower P3 component amplitudes in frontal leads to the facial discrimination task. Lower P3 amplitudes, in posterior areas, were found in the line discrimination task in children who scored above the 75th percentile in delinquent behaviors on the Achenbach Child Behavior Checklist. These findings are consistent with investigations in non-Indian populations demonstrating that the late positive component of the event related potential is sensitive to both familial history of alcohol dependence as well as personal history of externalizing behaviors.

Adolescent↗
PubMed2001

EEG asymmetry: relationship to mood and risk for alcoholism in Mission Indian youth.

BACKGROUND: Left frontal electroencephalogram (EEG) alpha dominance has been hypothesized to be related to depressed mood as well as aversive motivation and emotion. However, few studies have prospectively evaluated electroencephalogram asymmetry during development in high-risk adolescents and children. METHODS: EEG alpha asymmetry was investigated in 134 Mission Indian children who were between 7 and 13 years of age. The relationships between electroencephalogram alpha asymmetry and age, gender, parental history of alcohol dependence, Native American heritage, and mood/ approach behaviors were explored. RESULTS: No significant relationship was found between frontal alpha asymmetry and age, gender, or behavioral measures of depressed mood and/or approach behaviors. However, participants with > or = 50% Native American heritage were significantly more likely to have greater electroencephalogram alpha power in the left frontal cortex than in the right. CONCLUSIONS: The present findings suggest that the hypothesized relationship between EEG alpha asymmetry and measures of depressed mood, aversive motivation, and emotion may not be universal in all age or ethnic groups. Additionally, though the relationship between greater degrees of Native American heritage and alpha asymmetry are not as yet clear, we suggest it may be more related to substance abuse than depression in this population of Mission Indians.

Adolescent↗
PubMed2001

A powder formulation of measles vaccine for aerosol delivery.

Both the mortality rate for measles and the risks associated with injection continue to be high in the developing world. In response to the need for safe, cost-effective vaccine delivery technologies, a powder formulation of measles vaccine has been developed to test the feasibility of administering measles vaccine as an aerosol. The first challenge in aerosol formulation development is to produce fine particles without damaging the activity of the virus or inducing physical changes. In this study, live attenuated measles vaccine is micronized by jet milling to generate particle sizes appropriate for pulmonary delivery (1-5 microm). Milling does not induce detectable physical changes and significant viral potency is maintained. Potency retention of milled vaccine ranges from 31 to 89%, demonstrating that the standard dose of vaccine can easily be achieved. Following size reduction, particles are blended with an inert carrier to improve handling and aerosol dispersion. The measles vaccine formulation is dispersable, as shown by laser light particle size analysis of vaccine aerosols. Thus, evaluation of both the potency retention and the aerosol characteristics of the current formulation clearly demonstrates the feasibility of delivering measles vaccine as a powder aerosol for immunization.

Aerosols↗
PubMed2001

Role of sample adequacy in fine needle aspiration biopsy of palpable breast lesions.

BACKGROUND: The role of fine needle aspiration biopsy (FNAB) in breast lesions remains uncertain because its accuracy has been questioned. We hypothesized that this is related to failure to define standards for adequacy of sample preparation. METHODS: We reviewed cytology and pathology reports from 351 patients undergoing FNAB at a 350-bed community, university-affiliated teaching hospital over a 2-year period. Patients were included if they had an open biopsy within 2 years of an FNAB of the same lesion. Cytology reports were reviewed by a cytopathologist unaware of the clinical setting or subsequent histology; surgeons unaware of the cytology reports reviewed histology reports. Cytological diagnoses were benign, likely benign, probable cancer, and definite cancer. Samples were characterized as satisfactory, less than optimal (few mammary epithelial clusters), or inadequate (no mammary epithelial clusters.) We assessed the proportion of inadequate samples, the accuracy of FNAB, and the influence of sample adequacy upon FNAB sensitivity. RESULTS: Ninety-nine (28%) FNABs were inadequate, 77 (22%) less than optimal, and 175 (50%) satisfactory. Ninety-five patients (27%) had a final diagnosis of malignancy. FNABs classified as satisfactory or less than optimal and characterized as benign (n = 102) had a negative predictive value (NPV) of 0.91; those termed definite cancer (n = 43) had a positive predictive value (PPV) of 0.98. Only 10% of all cancers were identified in the 28% of FNABs that were classified as inadequate (P <0.01). CONCLUSIONS: We concluded that too few FNABs are performed in a fashion that permits definitive cytological interpretation. Inadequate FNABs are less likely to detect malignancy. After excluding inadequate preparations, FNABs interpreted as definite cancer and as benign are highly accurate in identifying patients with and without cancer.

Biopsy, Needle↗
PubMed2001

Pharmacological differences between the human and rat vanilloid receptor 1 (VR1).

Vanilloid receptors (VR1) were cloned from human and rat dorsal root ganglion libraries and expressed in Xenopus oocytes or Chinese Hamster Ovary (CHO) cells. Both rat and human VR1 formed ligand gated channels that were activated by capsaicin with similar EC(50) values. Capsaicin had a lower potency on both channels, when measured electrophysiologically in oocytes compared to CHO cells (oocytes: rat=1.90+/-0.20 microM; human=1.90+/-0.30 microM: CHO cells: rat=0.20+/-0.06 microM; human=0.19+/-0.08 microM). In CHO cell lines co-expressing either rat or human VR1 and the calcium sensitive, luminescent protein, aequorin, the EC(50) values for capsaicin-induced responses were similar in both cell lines (rat=0.35+/-0.06 microM, human=0.53+/-0.03 microM). The threshold for activation by acidic solutions was lower for human VR1 channels than that for rat VR1 (EC(50) pH 5.49+/-0.04 and pH 5.78+/-0.09, respectively). The threshold for heat activation was identical (42 degrees C) for rat and human VR1. PPAHV was an agonist at rat VR1 (EC(50) between 3 and 10 microM) but was virtually inactive at the human VR1 (EC(50)>10 microM). Capsazepine and ruthenium red were both more potent at blocking the capsaicin response of human VR1 than rat VR1. Capsazepine blocked the human but not the rat VR1 response to low pH. Capsazepine was also more effective at inhibiting the noxious heat response of human than of rat VR1.

Amino Acid Sequence↗
PubMed2001

Suppression of the radiation-sensitive phenotype of hamster irs1 and irs2 strains selected for resistance to 3-aminobenzamide.

PURPOSE: The radiosensitive hamster cell lines irs1 and irs2 have phenotypic similarities to cells defective in the early response to DNA-damaging agents as a result of mutations of the genes encoding poly(ADP-ribose)polymerase (PARP) or ataxia-telangiectasia mutated (ATM). Whether modification of PARP activity through selection of strains resistant to 3-aminobenzamide (3-AB) would affect the radiosensitive phenotype of irs1 and irs2 was examined. MATERIALS AND METHODS: 3-AB-resistant strains of irs1, irs2 and their parent line V79 were established and their sensitivity to DNA-damaging agents was measured. In some 3-AB-resistant strains, the radiation resistance of DNA synthesis and the induction of apoptosis were also assayed. Additionally, a number of aspects of PARP function were measured. RESULTS: Independently selected 3-AB-resistant strains of irs2 showed nearly complete suppression of radiation sensitivity, sensitivity to topoisomerase inhibitors, and radioresistant DNA synthesis. 3-AB-resistant strains of irs1 showed partial suppression of phenotype while 3-AB-resistant strains of V79 had no sensitivity changes. The induction of apoptosis in 3-AB-resistant strains of irs2 required substantially higher radiation doses than for irs2 itself. 3-AB-resistant strains had no detectable alteration of PARP level or cleavage following ionizing irradiation and there were no mutations in the PARP gene. CONCLUSIONS: Suppression of radiosensitivity associated with 3-AB resistance has important implications for mechanisms of tolerance to damage because it is able to override responses associated with specific genetic defects.

Animals↗
PubMed2001

Auditory P3 findings in mission Indian youth.

OBJECTIVE: Native Americans have some of the highest rates of alcohol abuse and dependence, yet potential biological risk factors associated with the problem drinking seen in many tribes remain relatively unknown. In this study, the amplitude of the P3 component of the event-related potential (ERP), a measure associated with risk for alcoholism in European-American youth, was investigated in Mission Indians. METHOD: The study participants were Mission Indian children and adolescents (N = 68, 37 male) between the ages of 7 and 13 years. ERPs were collected using two auditory "oddball" paradigms: an easy and a difficult discrimination task. P3 amplitude and latency were statistically evaluated as a function of age, gender, degree of Native American heritage (NAH) and family history (FH) of alcohol dependence. RESULTS: P3 latency was found to vary as a function of age and gender, with girls demonstrating greater decreases in latency with age than boys. suggesting a faster maturation time. Whereas there were no significant relationships between NAH and P3 latency, those participants with at least one alcoholic parent had longer P3 latencies elicited by the difficult auditory task. No significant relationships were found between P3 amplitude generated to the target tones and any of the variables (age, gender, FH, NAH). CONCLUSIONS: Mean P3 amplitudes and latencies obtained from these Mission Indian youth were within the range of those values reported in the literature for samples of children and adolescents of other ethnicities. Although the amplitude of the P3 ERP measure has been associated with FH of alcoholism in studies of predominantly European-American individuals, P3 amplitudes generated in response to these auditory tasks did not robustly differentiate Mission Indian children and adolescents who may be at higher risk for alcoholism from those presumed to be at lower risk.

Adolescent↗
PubMed2001

Effects of age and parental history of alcoholism on EEG findings in mission Indian children and adolescents.

BACKGROUND: Many, but not all, Native American tribes have some of the highest rates of alcohol abuse and dependence. Yet, risk factors for the development of problem drinking in these high risk groups remain largely unknown. In primarily Euroamerican populations, electrophysiological variables have been associated with risk for alcoholism. The EEG has a specific developmental time course that has been described in a diverse set of ethnic groups, but it has not been described in Native American youth. In addition, the relationship between EEG development and risk for alcoholism in Indian youth has not been previously studied. METHODS: Clinical ratings and spectral characteristics of the resting EEG were investigated in 140 Native American Mission Indian children and adolescents between the ages of 7 and 13 years. The specific aims of the study were to (1) investigate the relationship of age and gender with EEG spectral variables to determine if this population conforms to similar trends from previously published data in other ethnic groups and (2) to determine whether children with a parental history of alcoholism differ from those without alcoholic parents on EEG spectral parameters. RESULTS: No excess of abnormal EEG activity was found in this sample of Native American youth. Age, but not gender, was found to have a significant effect on EEG spectral characteristics with younger children (7-11 years old), having significantly more power in slow activity (0.5-7.5 Hz) and in alpha power (8-12 Hz) as well as slower alpha frequencies than older children (12-13 years old). Consistent with other studies of Native American youth, 66% of the children and adolescents participating in this study had at least one parent who had a lifetime diagnosis of alcohol dependence. However, an ANCOVA that covaried for age and gender revealed no significant differences in power or frequency characteristics of the EEG on the basis of parental history of alcoholism. CONCLUSIONS: These studies suggest that this sample of Mission Indian children, despite high levels of parental alcohol dependence and low socioeconomic status, show normal EEG development. As yet, no relationship has been found between any specific EEG phenotype and parental history of alcoholism in this population, however, further EEG maturation may be necessary before any relationships can be fully delineated.

Adolescent↗
PubMed2001

Profiling clonality and progression in multiple premalignant and malignant oral lesions identifies a subgroup of cases with a distinct presentation of squamous cell carcinoma.

A cohort of head and neck cancer patients, without exposure to tobacco and alcohol, presented with multiple preneoplastic and neoplastic lesions, the natural history of which may span several decades. Examination of these cases provides an opportunity to study the relationship between genetic, morphological, and clonal progression in these fields and establish whether they represent a unique presentation of squamous cell carcinoma. The presence of a common novel microsatellite allele, a common breakpoint or concordant allelic imbalance at multiple loci, reveals that a high proportion of these serial lesions arise due to spread of a precursor. The tumors arising in these patients were typically nonaggressive, although metastases developed at a late stage, supporting the notion that the genotype results in a phenotype with a propensity for lateral spread, rather than invasion. Different genetic aberrations were detected in morphologically similar phenotypes such that no consistent early or late events were associated with development of premalignant lesions. Combining information about the clinicopathological features and histological examination of the margins with that derived from clonality analysis reveals that a subgroup of patients, without exposure to the traditional risk factors associated with this disease, developed multiple clonally related oral lesions and represents a unique presentation of head and neck squamous cell carcinoma. We suggest the term clonal cancerization to describe multiple premalignant and malignant lesions when there is conclusive evidence that they arise due to lateral spread from a common precursor.

Adult↗
PubMed2001

Laparoendoscopic approaches to occult gastrointestinal bleeding.

Identification of sites of small bowel hemorrhage remains a difficult problem. Endoscopy performed in association with surgery often proves successful when other attempts have failed. In attempts to minimize morbidity and even increase accuracy, surgeons have explored combining laparoscopic techniques with endoscopy. Although published experiences remain few, expectations remain high.

Endoscopy, Gastrointestinal↗
PubMed2000

(-)-Spiro[1-azabicyclo[2.2.2]octane-3,5'-oxazolidin-2'-one], a conformationally restricted analogue of acetylcholine, is a highly selective full agonist at the alpha 7 nicotinic acetylcholine receptor.

Neuronal nicotinic acetylcholine receptors are members of the ligand-gated ion channel receptor superfamily and may play important roles in modulating neurotransmission, cognition, sensory gating, and anxiety. Because of its distribution and abundance in the CNS, the alpha 7 nicotinic receptor is a strong candidate to be involved in some of these functions. In this paper we describe the synthesis and in vitro profile of AR-R17779, (-)-spiro[1-azabicyclo[2.2. 2]octane-3,5'-oxazolidin-2'-one] (4a), a potent full agonist at the rat alpha 7 nicotinic receptor, which is highly selective for the rat alpha 7 nicotinic receptor over the alpha 4 beta 2 subtype. Preliminary SAR of AR-R17779 presented here indicate that there is little scope for modification of this rigid molecule as even minor changes result in significant loss of the alpha 7 nicotinic receptor affinity.

Acetylcholine↗
PubMed2000

A case-control study confirms that microsatellite assay can identify patients at risk of developing oral squamous cell carcinoma within a field of cancerization.

Distinguishing true precursor lesions on the basis of clinical or histological features alone is unreliable but is important so that appropriate intervention can be instigated. Preliminary studies have shown that a microsatellite assay may provide important new prognostic information. To build on these observations, we have performed a case-control study to establish whether we can be confident about incorporating this new information into clinical practice. We have determined the frequency of allelic imbalance (AI) within key chromosomal regions, by matching 39 cases with dysplastic oral lesions that developed a tumor on the same side of the mouth, for as many variables as possible, with controls presenting with similar lesions that did not progress to malignancy when followed for the same period. Our findings confirm that the group that developed tumor had precursor lesions that harbor AI at more loci (P = 0.002). However, no consistent patterns of AI were associated with the three grades of dysplasia: mild, moderate, and severe. One-third of the tumors developed at the same site as the dysplastic lesion and two-thirds at a different site, which revealed that the presence of these aberrations in a dysplastic lesion provided information about the risk of malignant change within a larger field. This suggests that the process of field cancerization is more widespread than previously recognized. On the basis of these findings, we advocate complete excision of all suspicious areas that show AI at two or more key loci, regardless of the degree of dysplasia. However, because the remaining mucosa is also "at risk," these cases should also be targeted to receive dietary advice and chemoprevention, to minimize their risk of tumor formation at a distant site.

Adult↗
PubMed2000

Cost-effectiveness analysis of six strategies for cardiovascular surgery prophylaxis in patients labeled penicillin allergic.

The cost-effectiveness of different approaches to antimicrobial prophylaxis for cardiovascular surgery patients labeled penicillin allergic was studied. A decision-analytic model was used to examine the cost-effectiveness of six strategies for antimicrobial prophylaxis in cardiovascular surgery patients at a tertiary care hospital. The strategies consisted of (1) giving vancomycin to all patients labeled penicillin allergic, (2) giving cefazolin to all patients labeled penicillin allergic, (3) giving vancomycin to all patients with a history suggesting an immunoglobulin E (IgE)-mediated reaction to penicillin and cefazolin to patients without such a history, (4) administering a penicillin skin test to patients with a history suggesting an IgE-mediated reaction to penicillin and giving vancomycin to patients with positive results and cefazolin to all others, (5) skin testing all patients labeled penicillin allergic and giving vancomycin to those with positive results and cefazolin to those with negative results, regardless of history, and (6) skin testing all patients and giving vancomycin to those with positive results or a history suggesting an IgE-mediated reaction to penicillin and cefazolin to all others. Giving cefazolin to all patients labeled penicillin allergic was the least expensive strategy but was associated with the highest rate of both anaphylactic and non-life-threatening serious reactions. Selective use of vancomycin in patients with a history suggesting an IgE-mediated reaction to penicillin was associated with an added cost and a slightly lower rate of anaphylaxis. Although skin-testing strategies may decrease both non-life-threatening and anaphylactic reactions, the incremental cost was high. When vancomycin was given to all patients labeled penicillin allergic, the incremental cost was very high. A decision-analytic model indicated that selective use of vancomycin is more cost-effective than indiscriminate use of vancomycin for surgical prophylaxis in cardiovascular surgery patients labeled penicillin allergic.

Anti-Bacterial Agents↗
PubMed2000

Bradyzide, a potent non-peptide B(2) bradykinin receptor antagonist with long-lasting oral activity in animal models of inflammatory hyperalgesia.

Bradyzide is from a novel class of rodent-selective non-peptide B(2) bradykinin antagonists (1-(2-Nitrophenyl)thiosemicarbazides). Bradyzide has high affinity for the rodent B(2) receptor, displacing [(3)H]-bradykinin binding in NG108-15 cells and in Cos-7 cells expressing the rat receptor with K(I) values of 0.51+/-0.18 nM (n=3) and 0.89+/-0.27 nM (n=3), respectively. Bradyzide is a competitive antagonist, inhibiting B(2) receptor-induced (45)Ca efflux from NG108-15 cells with a pK(B) of 8.0+/-0.16 (n=5) and a Schild slope of 1.05. In the rat spinal cord and tail preparation, bradyzide inhibits bradykinin-induced ventral root depolarizations (IC(50) value; 1.6+/-0.05 nM (n=3)). Bradyzide is much less potent at the human than at the rodent B(2) receptor, displacing [(3)H]-bradykinin binding in human fibroblasts and in Cos-7 cells expressing the human B(2) receptor with K(I) values of 393+/-90 nM (n=3) and 772+/-144 nM (n=3), respectively. Bradyzide inhibits bradykinin-induced [(3)H]-inositol trisphosphate (IP(3)) formation with IC(50) values of 11.6+/-1.4 nM (n=3) at the rat and 2.4+/-0.3 microM (n=3) at the human receptor. Bradyzide does not interact with a range of other receptors, including human and rat B(1) bradykinin receptors. Bradyzide is orally available and blocks bradykinin-induced hypotension and plasma extravasation. Bradyzide shows long-lasting oral activity in rodent models of inflammatory hyperalgesia, reversing Freund's complete adjuvant (FCA)-induced mechanical hyperalgesia in the rat knee joint (ED(50), 0.84 micromol kg(-1); duration of action >4 h). It is equipotent with morphine and diclofenac, and 1000 times more potent than paracetamol, its maximal effect exceeding that of the non-steroidal anti-inflammatory drugs (NSAIDs). Bradyzide does not exhibit tolerance when administered over 6 days. In summary, bradyzide is a potent, orally active, antagonist of the B(2) bradykinin receptor, with selectivity for the rodent over the human receptor. British Journal of Pharmacology (2000) 129, 77 - 86

Administration, Oral↗
PubMed2000

Detection of minimal residual cancer to investigate why oral tumors recur despite seemingly adequate treatment.

Improvements in surgery and radiotherapy techniques have led to only a modest increase in the 5-year survival rate for patients with head and neck cancer. This is because the pattern of clinical disease is changing, such that locoregional recurrence now accounts for fewer treatment failures, but more patients develop a second primary cancer or distant metastatic disease. In this study, we have used the p53 phage plaque assay, immunocytochemistry, and mutational analysis to assess the contribution of minimal residual cancer and genetic aberrations in clinically normal upper aerodigestive tract mucosa to treatment failure. Eighteen consecutive patients with oral tumors, with conventional clear margins, have been followed for a minimum of 36 months. Molecular assessment identified tumor-positive surgical margins for 6 of 11 assessable patients and additional tumor-positive lymph nodes for three cases. Disseminated malignant cells were detected in the hematopoietic cell compartment for six cases, and one patient had molecular evidence of field cancerization. Locoregional recurrence developed in five patients with tumors harboring a p53 gene mutation; four of these were associated with tumor-positive surgical margins, and one was associated with molecular evidence of field cancerization. Radiotherapy to the primary site did not prevent development of local recurrence when the residual tumor harbored a p53 gene mutation. Three of six cases with a tumor-positive bone marrow aspirate developed distant metastases. These findings reveal that molecular and immunocytochemical detection of minimal residual cancer and field cancerization can help identify patients who may develop locoregional or distant recurrence and justify further studies to evaluate the contribution of these remaining malignant cells to treatment failure.

Adult↗
PubMed1999

Location of candidate tumour suppressor gene loci at chromosomes 3p, 8p and 9p for oral squamous cell carcinomas.

To help define the location of tumour suppressor genes implicated in the pathogenesis of oral squamous cell carcinoma (SCC), we have used microsatellite assay and restriction fragment length polymorphism (RFLP) analysis to screen 48 primary SCC for allelic imbalance (AI) with 32 polymorphic markers at chromosome 3p, and prepared a detailed deletion map. The finding of a high frequency of AI at specific regions, together with the presence of multiple small interstitial deletions involving these loci, identifies 5 areas at this chromosome arm that may harbour tumour suppressor genes. No sequence aberrations affecting the von Hippel Lindau (VHL) and fragile histidine triad (FHIT) genes, which reside within the candidate tumour suppressor gene areas at this chromosome arm, were identified. A more limited analysis of polymorphic sequences at 8p and 9p supports the existence of at least 2 areas that harbour tumour suppressor genes at 8p and evidence that additional targets for deletion reside centromeric and telomeric to the p16 gene at 9p21.

Acid Anhydride Hydrolases↗
PubMed1999

Molecular characterisation of cloned bradykinin B1 receptors from rat and human.

This report describes the characterisation of cloned rat and human bradykinin B1 receptors in African green monkey kidney fibroblast (Cos-7) cells. A ligand binding assay with [3H]des-Arg10-kallidin was used to compare their pharmacology with respect to known bradykinin B1 and B2 receptor ligands. In addition, the pharmacology of T-kinin and its' derivative des-Arg11-T-kinin was investigated. The cloned rat receptor had a similar pharmacology to that of the recently described mouse receptor and differs from that described for the human receptor. The rat receptor had a higher affinity for des-Arg11-T-kinin than the human receptor. These differences in pharmacological properties may relate to the presence of T-kinin, bradykinin and their des-Arg derivatives as the major physiological peptides in rat and the predominance of kallidin and its derivatives in human. We confirm that the rat bradykinin B1 receptor gene is organised in a two exon structure and differs from the human gene which has a three exon structure and we further examine the inducible expression of this gene in a wide range of tissues using Northern blotting.

Amino Acid Sequence↗