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Biomedical subjects

E Phillips

Publications and source records attributed to E Phillips.

At least 37 records · Page 2Linked to original sources
PubMed1999

Patient-specific mutation databases for oral cancer.

Development of databases, summarising the genetic events associated with oral squamous cell carcinoma (SCC), should increase our understanding of the molecular basis of these lesions. Additionally, databases will help establish whether different cancer subtypes show different growth characteristics, because the multistage carcinogenic process is different in the various tumour subtypes. This new knowledge may also provide new prognostic information, as these aberrations represent fundamental biological characteristics of each tumour. To assess the value of incorporating the results from loss of heterozygosity (LOH) analysis into patient-specific mutation databases, we have carried out microsatellite analysis with 52 polymorphic markers at 13 key chromosomal regions implicated in the pathogenesis of head and neck cancers. Altered expression of the Rb, p53 and DCC tumour suppressor genes has also been studied by immunohistology. Our results shed light on the different pathways that lead to cancer and reveal that a variety of different patterns of allelic imbalance (AI) were detected at all TNM stages, reflecting the different clinical behaviour that tumours classified as being of the same TNM stage may exhibit. Summarising the level of genetic damage as a fractional allelic loss (FAL) score and the presence of AI at 3p22-26, 3p14.3-12.1 and 9p21 was found to be a better predictor of outcome than the TNM system. This finding suggests that molecular data can be incorporated into conventional staging systems to provide more accurate prognostic information for this group of patients.

Adult↗
PubMed1999

Dry powder inhalation as a potential delivery method for vaccines.

Measles vaccine is administered to millions of children annually via a percutaneous injection. There are, however, compelling reasons to search for alternative routes of administration, especially in mass vaccination campaigns. Two key factors are (1) decreased stability of the vaccine upon reconstitution and, (2) the potential risks of contamination associated with needles. Dura has developed a unique inhaler that can deliver a powder dose via the pulmonary route for local or systemic action. The breath-actuated Spiros inhaler uses electromechanical energy to aerosolize and deliver a consistent dose over a wide range of inspiratory flow rates. To achieve alveolar (deep lung) deposition for subsequent systemic absorption, dry-powder vaccine is size reduced to a mass median diameter between 1 and 5 microns. Small vaccine particles are blended with an inert carrier to improve dispersion. Measles vaccine formulated as a powder blend may be more thermostable than existing reconstituted formulations. The Spiros technology is available in three powder storage platforms. Two of these formats are designed specifically for moisture and/or light sensitive compounds and may be particularly suitable for delivery of measles vaccines in mass campaigns because their design (1) eliminates the need for powder reconstitution, and (2) reduces the risk of contamination.

Administration, Inhalation↗
PubMed1999

Electroencephalographic responses to alcohol challenge in Native American Mission Indians.

BACKGROUND: Native Americans have some of the highest rates of alcohol abuse and dependence, yet potential central nervous system risk factors responsible for the problem drinking seen in some tribes remain relatively unknown. METHODS: Background electroencephalographic (EEG) variants and response to alcohol were investigated in 48 Native American Mission Indian men between 18 and 25 years old. RESULTS: Subjects with 50% or greater Native American heritage had a significantly higher proportion of low-voltage EEG variants. Within this sample of Mission Indian men, however, a family history of alcohol dependence was associated with a greater incidence of high voltage alpha EEGs. Mission Indian men also evidenced a "less depressant, more stimulating" response to alcohol as quantified by less alcohol-induced reductions in alpha, greater EEG stability, and increased alcohol-induced beta activity. CONCLUSIONS: These findings demonstrate that certain genetically regulated EEG variants that have been previously associated with risk for alcoholism in Caucasians may also be more common in these Mission Indian men. Additionally, EEG measures of response to alcohol do not provide support for the commonly held idea that Indians are more sensitive to the depressant effects of alcohol.

Adolescent↗
PubMed1999

Immunomagnetic separation for enrichment and sensitive detection of disseminated tumour cells in patients with head and neck SCC.

Screening for malignant cells in the blood and bone marrow was introduced as a strategy for the improved detection of tumour spread and may predict the development of distant metastases. The sensitivity of these approaches depends on several factors, including the choice of antibody for immunocytochemistry (ICC) and the number of cells examined. In this study criteria have been defined for scoring cells reactive with a pan-cytokeratin antibody as tumour, by comparing immunostained cells in clinical samples obtained from head and neck cancer patients and a control group without epithelial malignancy. When leucocyte subfractions are prepared by density gradient separation (DGS) from central venous blood obtained from patients with advanced head and neck squamous cell carcinoma (SCC) and screened by ICC, epithelial tumour cells sediment preferentially with the mononuclear cells but may also be detected in the granulocyte (GC) fraction. Some cases were found to have more tumour cells in the GC fraction. Similar results were seen in model experiments. To increase the sensitivity of the ICC approach, the efficiency of positive immunomagnetic selection (IMS) using Dynabeads coated with an antibody recognizing the Ber-EP4 epitope has been compared with negative IMS using anti-CD45 Dynabeads. Tumour cells were recovered from bone marrow aspirates for 2/17 cases using the positive enrichment technique and for 11/17 patients following negative IMS. These findings justify prospective studies incorporating negative IMS to establish the prognostic significance of these disseminated tumour cells for this group of patients.

Antigens, Neoplasm↗
PubMed1999

The prognostic significance of allelic imbalance at key chromosomal loci in oral cancer.

Forty-eight primary oral squamous cell carcinomas (SCC) were screened for allelic imbalance (AI) at 3p24-26, 3p21, 3p13, 8p21-23, 9p21, 9q22 and within the Rb, p53 and DCC tumour suppressor genes. AI was detected at all TNM stages with stage 4 tumours showing significantly more aberrations than stage 1-3. A factional allelic loss (FAL) score was calculated for all tumours and a high score was associated with development of local recurrence (P = 0.033) and reduced survival (P = 0.0006). AI at one or more loci within the 3p24-26, 3p21, 3p13 and 9p21 regions or within the THRB and DCC genes was associated with reduced survival. The hazard ratios for survival analysis revealed that patients with AI at 3p24-26, 3p13 and 9p21 have an approximately 25 times increase in their mortality rate relative to a patient retaining heterozygosity at these loci. AI at specific pairs of loci, D3S686 and D9S171 and involving at least two of D3S1296, DCC and D9S43, was a better predictor of prognosis than the FAL score or TNM stage. These data suggest that it will be possible to develop a molecular staging system which will be a better predict of outcome than conventional clinicopathological features as the molecular events represent fundamental biological characteristics of each tumour.

Adult↗
PubMed1999

Relationship between method of detection of breast cancer and stage of disease, method of treatment, and survival in women aged 40 to 49 years.

The optimal breast cancer screening program for women 40 to 49 years of age remains controversial. To help assess the value of screening mammography for this age group, we studied the relationship between the method of breast cancer detection and stage, therapy, and survival. Cases of breast cancer diagnosed at Sinai Hospital (Detroit, MI) between January 1985 and December 1994 were reviewed. A total of 181 cases involving 40- to 49-year-old women were available for analysis. The distribution of stage of disease significantly differed among the three methods of detection (P<0.0001). Breast-conserving surgery was more commonly performed in cases detected by screening mammography and clinical breast examination than in cases detected by breast self-examination (P = 0.001). Variation in the stage of disease resulted in improved survival for cases detected by screening mammography and clinical breast examination when compared with those detected by breast self-examination (P = 0.019). Women diagnosed with breast cancer between the ages of 40 and 49 years had earlier stage disease, were more likely to be treated with breast-conserving therapy, and had better survival if their disease was first recognized by screening mammography. Screening mammography has an important role for women of this age.

Adult↗
PubMed1999

Is there a risk in being a good Samaritan?

It's Nursing Week and you are at a booth in a busy shopping mall. After spending a couple of hours talking with people, answering questions and taking blood pressure readings, you start to sip a well-earned cup of coffee. You glance down the mall and observe a middle-aged man suddenly clutch at his chest and fall to the floor. You alert your colleagues to call 911 as you run down the mall to do what you can. You reach the man, announce, "I know CPR," and initiate resuscitation. You have just spent an invigorating day on the ski slopes. As you drive home, you are horrified to see a car spin out of control and roll over into the ditch a couple of car lengths ahead of you. Suddenly you face a dilemma. You are an experienced nurse who wants to help and yet, lurking in the back of your mind, there is the nagging fear that you could be sued. You wonder if are you legally obligated to stop and assist. Could you be liable if you fail to do so?

Accidents, Traffic↗
PubMed1998

Determinants of P3 amplitude and response to alcohol in Native American Mission Indians.

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 some tribes remain relatively unknown. The amplitude of the P3 component of the event-related potential (ERP) is perhaps the most studied electrophysiological "marker" of potential vulnerability to alcohol dependence, yet it has not been investigated in Native Americans. Forty-seven, non-alcohol-dependent Native American Mission Indian men between the ages of 18 and 25 years participated in the study. ERPs were collected at 60 minutes following both alcohol (0.56 g/kg) and placebo intake. No relationship was found between P3 amplitude and degree of Native-American heritage (NAH), or family history (FH) of alcohol dependence. The results of this study did, however, replicate previous findings that the P3 component of the ERP is sensitive to the effects of alcohol. A reduction in the P3a component across the scalp was found in these Native American men following alcohol when compared with placebo ingestion. P3 response to alcohol, although not influenced by a subject's NAH or FH, was influenced by the presence of a polymorphism in the alcohol metabolizing enzyme alcohol dehydrogenase (ADH). Men with an ADH2 x 3 allele had significantly higher amplitude P3 components at placebo and also demonstrated more alcohol-induced reductions in P3 amplitude than men with ADH2 x 1 alleles only. In addition, individuals with low P3 amplitude in the placebo condition had less of a reduction or an actual increase in P3a and P3b amplitudes following alcohol intake. Given that a less intense response to alcohol has been associated with greater risk for the development of alcohol-related problems, these data suggest the presence of certain biological variables within this Native American population that may confer both risk and protection for the future development of alcohol dependence.

Acoustic Stimulation↗
PubMed1998

Allelic imbalance at chromosomal loci implicated in the pathogenesis of oral precancer, cumulative loss and its relationship with progression to cancer.

A microsatellite assay was used to screen 31 potentially malignant oral lesions presenting as leukoplakia and erythroplakia, with histological evidence of dysplasia, for genetic abnormalities at loci which frequently show allelic imbalance when oral squamous cell carcinomas (SCC) are examined. The microsatellite and restriction fragment length polymorphism (RFLP) markers selected were at 3p21, 8p21-23, 9p21 and included sequences within the Rb (13q14.2), p53 (17p13.1) and DCC (18q21.1) tumour suppressor genes. 8 patients subsequently developed an invasive tumour at the same site, or within 2 cm of the premalignant lesion. A further 8 patients developed SCC at a distant site. Seventy-seven per cent (24/31) of these potentially malignant lesions showed allelic imbalance (AI) and 55% (17/31) of cases showed microsatellite instability (msi). The probability of developing SCC was much greater for patients with lesions showing AI at two or more relevant loci (P = 0.008 by the logrank test) than the group with AI at fewer loci. The estimated probability of development of SCC in this group by 5 years was 73% (95% Cl: 50-92%). This suggests that determining the number of genetic abnormalities in a potentially malignant lesion can help identify patients with true precancers who should be followed closely to ensure that they receive chemoprevention and appropriate advice to limit risk factors, and to allow the early detection of invasive lesions.

Adult↗
PubMed1998

Spinal neurokinin NK1 receptor down-regulation and antinociception: effects of spinal NK1 receptor antisense oligonucleotides and NK1 receptor occupancy.

To define the effects of antisense oligonucleotides on spinal neurokinin 1 (NK1) receptor function in nociceptive processing, several antisense oligonucleotides directed against the NK1 receptor mRNA were intrathecally injected into rats via an implanted catheter, and their effect on the behavioural response to formalin injected into the paw was assessed. We observed that there was no significant reduction of pain behaviour or immunostaining of spinal NK1 receptors after repeated daily intrathecal treatment with an antisense oligonucleotide. However, spinal application of substance P (SP) in the antisense oligonucleotide-treated animals resulted in a profound and long-lasting reduction in the behavioural response to formalin injection, and a parallel reduction in the NK1 receptor immunoreactivity normally observed in spinal dorsal horn. Intrathecal SP in the control groups, i.e., rats treated with an oligonucleotide containing four mismatched bases, the corresponding sense oligonucleotide, a mixture of the sense and the antisense oligonucleotides, in each case had no effect. The effects of SP were blocked by NK1 receptor antagonists and were not mimicked by NMDA. The mechanism underlying these effects is not clear. It may be due to partial degradation of the internalised receptors, which cannot be replaced by newly synthesised receptors because of the action of the NK1 antisense oligonucleotide.

Animals↗
PubMed1998

A prospective controlled multicentre study of clarithromycin in pregnancy.

Clarithromycin is a relatively new macrolide antibiotic with an action spectrum similar to that of erythromycin. Its main indications for use are for upper and lower respiratory and skin and soft tissue infections. Little is known about its safety in pregnancy, although animal reproductive studies found an increased rate of cardiovascular anomalies, cleft palate, and embryonic loss. Human data, limited to case reports and one small uncontrolled study, cannot allow evidence based counseling of pregnant women who were exposed to the drug before finding out they were pregnant. Pregnant women who had been counseled on the use of clarithromycin by five centers, were matched for age, smoking, and alcohol use with a control group of pregnant women who were exposed to nonteratogenic antibiotics. A total of 157 women were followed up. Of these, 122 were exposed to the drug in the first trimester. There were no significant differences found between the two groups in the rates of major and minor malformations; 2.3 versus 1.4% for major (p = 0.86) and 5.4 versus 4.9% for minor (p = 0.96). Spontaneous abortion rates in the exposed group was significantly different, higher (14%) than in the control group (7%) (p = 0.04). This first prospective controlled study of exposure to clarithromycin in pregnancy suggests that this agent does not increase the rate of major malformations above the baseline risk of 1-3%. The higher rate of reported spontaneous abortions, although still within the expected baseline rate, may warrant further study.

Anti-Bacterial Agents↗
PubMed1998

Toxoplasmosis.

QUESTION: A 28-year-old patient is 3 months pregnant with her first child. She has heard about toxoplasmosis from her friends and asks if it is safe to keep her cat. How should I reply? ANSWER: Your patient does not have to give up her cat. She should be encouraged to take primary preventive measures. If toxoplasmosis serology is performed, a baseline should be done as early as possible with serial follow up in the second and third trimesters.

Adult↗
PubMed1997

Field cancerisation of the oral cavity: comparison of the spectrum of molecular alterations in cases presenting with both dysplastic and malignant lesions.

Dysplastic lesions and invasive oral squamous cell carcinoma (SCC) from patients with field change were screened by restriction fragment length polymorphism (RFLP) and microsatellite assay. All tumours contained more genetic changes than the matched dysplasia which are likely to represent progression. Four of the 15 dysplastic lesions harboured the same abnormalities detected in the tumour and some paired lesions showed identical novel microsatellite alleles. The finding of identical 'genetic fingerprints' in dysplastic lesions and invasive carcinoma from the same patient provides strong evidence that these dysplasias are precursor lesions and that multiple lesions have probably arisen due to transfer of the progeny of an altered cell. Eight of the 15 dysplastic lesions showed alterations which were not present in the matched cancer, showing that evolution of subclones, or fusion of multiple clones also occurs. A further case showed loss of different alleles in the paired samples. These findings highlight the complexity of the genetic abnormalities present in the mucosa of patients with field change and suggests that the origin of these altered foci may be diverse.

Adult↗
PubMed1997

Negative symptoms in stroke patients and length of hospital stay.

The purpose of this study was to assess whether the presence and severity of psychiatric symptoms in stroke patients correlate with their length of stay (LOS) in a rehabilitation unit, with special emphasis on the role of negative symptoms (NS). Twenty-three stroke patients, consecutively recruited from the inpatient rehabilitation unit, were evaluated on admission with the Mini-Mental State Examination (MMSE), the Positive and Negative Symptom Scale (PANSS), the Hamilton Depression Rating Scale (HDRS), the Scale for Assessment of Negative Symptoms (SANS), and the Functional Independent Measure (FIM). NS scores significantly correlated with LOS, with SANS total score being the most informative, and the attentional impairment subscale the least. The group of patients with pronounced NS stayed in the hospital twice as long as patients with the score on the NS subscale of PANSS below 16. These two groups did not differ in their cognitive performance or in the positive symptom subscale of PANSS scores. Total FIM score on admission was lower and HDRS scores higher in patients with pronounced NS. However, these differences, unlike those of LOS, have not reached statistical significance. The presence and severity of NS in stroke patients are associated with a longer hospital stay. Identification and treatment of NS might lead to a faster discharge from rehabilitation unit.

Aged↗
PubMed1997

Characterization of a recombinant fragment that contains a carbohydrate recognition domain of the filamentous hemagglutinin.

The filamentous hemagglutinin (FHA) of Bordetella pertussis plays an important role in establishing infection by attaching the bacteria to the ciliated respiratory epithelial cells. Expression of DNA encoding residues 1141 to 1279 of FHA in Escherichia coli yields a protein of 18,000 Da that exhibits some of the carbohydrate recognition properties of FHA (S. M. Prasad, Y. Yin, E. Rodzinski, E. I. Tuomanen, and H. R. Masure, Infect. Immun. 61:2780-2785, 1993). We have constructed an E. coli strain that expresses this protein, designated fragment A, in a soluble form at markedly elevated levels. Fragment A could be purified with high purity and yields and was immunogenic in mice. Both fragment A and anti-fragment A sera inhibited the binding of B. pertussis to asialo-GM2 and to rabbit ciliated cells. These observations demonstrate that this fragment of FHA contains a cellular binding domain capable of eliciting functional antibodies.

Adhesins, Bacterial↗