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Biomedical subjects

S Porter

Publications and source records attributed to S Porter.

At least 73 records · Page 4Linked to original sources

Gastric and gingival localization of mucosa-associated lymphoid tissue (MALT) lymphoma. An immunohistochemical, virological and clinical case report.

Non-Hodgkin's lymphomas (NHL) of the mucosa-associated lymphoid tissue (MALT) are characterized by their mucosal and glandular tissue localization. The case described here falls into the European-American classification of a low-grade B-cell lymphoma of the MALT type, with a gingival lesion 2 years after a gastric lesion. The pathogenetic mechanisms of NHL in oral MALT and the diagnosis and treatment are discussed.

DNA, Viral↗

DNA studies underestimate the major role of CDKN2A inactivation in oral and oropharyngeal squamous cell carcinomas.

Loss of CDKN2A expression was demonstrated by immunohistochemistry in 87% of oral and oropharyngeal squamous cell carcinoma (OSCC) primary tumor samples. By contrast, DNA studies showed a much lower frequency of loss of the CDKN2A gene. Point mutations and promoter methylation of CDKN2A were seen in 7% and 23%, respectively, of primary tumors. Loss of heterozygosity analysis using a dense set of 9p markers showed allelic imbalance that included CDKN2A in only 31% of samples, but a further 47% showed loss at loci near CDKN2A with apparent retention of CDKN2A. No tumor with any allelic imbalance expressed CDKN2A, whether or not the imbalance appeared to involve the CDKN2A locus. We interpret these data as showing partially overlapping deletions on the two 9p homologues, with homozygous deletion of CDKN2A masked by amplification of contaminating stromal material. Our data show that inactivation of the CDKN2A gene products is a near-universal step in the development of oral and oropharyngeal squamous cell carcinomas, and we suggest that homozygous deletion is the most common mechanism of inactivation. The CDKN2A locus may be particularly prone to deletion because it encodes two unrelated tumor suppressor proteins, CDKN2A (p16INK4a) and p19ARF, and deletion, but not point mutation or methylation, would inactivate both gene products. However, our results also suggest that complex patterns of allelic imbalance in primary squamous carcinomas in general may not provide reliable evidence for the existence of multiple tumor suppressor genes within a single chromosomal region.

5' Untranslated Regions↗

This is my story: a descriptive analysis of a peer education HIV/STD risk reduction program for women living in housing developments.

Descriptive, qualitative data was collected from 30 women who participated in the Centers for Disease Control and Prevention-funded Perinatal HIV Reduction and Education Demonstration Activities (PHREDA) Project. Women were primarily heterosexual, welfare-dependent, African-American mothers. Staff trained women to conduct HIV/STD education as peer volunteers. The theory-based educational components consisted of role model stories developed by women about their experiences with HIV/STDs and discussion groups to build behavioral and communication skills. Women were given role-model stories and safer sex supplies to initiate conversations about women's health and sexual safety in their communities. PHREDA groups allowed women to identify their risk reduction, sexual, and family issues. Role model stories provided a validating medium through which high-risk women explored reproductive health risk and planned steps toward behavioral change. Descriptive data from peer volunteers can provide an important perspective on small group, peer-based community HIV/STD reduction interventions.

Black or African American↗

Development, characterization, and use of monoclonal antibodies made to antigens expressed on the surface of fetal nucleated red blood cells.

BACKGROUND: Current methods for obtaining fetal cells for prenatal diagnosis are invasive and carry a small (0.5-1.0%) but definite risk of miscarriage. An attractive alternative would be isolation of fetal cells from peripheral maternal blood using antibodies with high specificity and avidity. METHODS: To generate antibodies, we purified nucleated red blood cells (NRBCs) from fetal livers and used them as the immunogen to generate monoclonal antibodies (mAbs) directed against surface antigens. RESULTS: The four antibodies recognized at least two conformationally sensitive epitopes of the transferrin receptor. Isolation of NRBCs from 252 maternal blood samples using these antibodies in magnetic activated cell sorting after an initial density gradient centrifugation yielded 0-419 NRBCs per 25 mL of maternal blood. One antibody, 2B7.4, not only isolated the highest number of NRBCs (>10 in 90% of the samples) but also isolated these NRBCs in 78 consecutive maternal samples. CONCLUSION: Antibody 2B7.4 shows promise for the isolation of NRBCs from maternal blood and should allow studies concerning the source of these cells, fetal vs maternal, and the factors controlling their prevalence.

Animals↗

Inhibition of hGrb10 binding to the insulin receptor by functional domain-mediated oligomerization.

hGrb10 is a newly identified Src homology 2 (SH2) and pleckstrin homology (PH) domain-containing protein that binds to autophosphorylated receptor tyrosine kinases, including the insulin and insulin-like growth factor receptors. To identify potential downstream proteins that interact with hGrb10, we screened a yeast two-hybrid cDNA library using the full-length hGrb10gamma as bait. A fragment of hGrb10, which included the IPS (insert between the PH and SH2 domain) and the SH2 domains, was found to bind with high affinity to the full-length protein. The interaction between the IPS/SH2 domain and the full-length hGrb10 was further confirmed by in vitro glutathione S-transferase fusion protein binding studies. Gel filtration assays showed that hGrb10 underwent tetramerization in mammalian cells. The interaction involved at least two functional domains, the IPS/SH2 region and the PH domain, both of which interacted with the NH2-terminal amino acid sequence of hGrb10gamma (hGrb10gamma DeltaC, residues 4-414). Competition studies showed that hGrb10gamma DeltaC inhibited the binding of hGrb10 to the tyrosine-phosphorylated insulin receptor, suggesting that this region may play a regulatory role in hGrb10/insulin receptor interaction. We present a model for hGrb10 tetramerization and its potential role in receptor tyrosine kinase signal transduction.

Animals↗

Double-blind randomised controlled trial of monoclonal antibody to human tumour necrosis factor in treatment of septic shock. NORASEPT II Study Group.

BACKGROUND: Despite the availability of potent antibiotics and intensive care, mortality rates from septic shock are 40-70%. We assessed the safety and efficacy of murine monoclonal antibody to human tumour necrosis factor alpha (TNF alpha MAb) in the treatment of septic shock. METHODS: In a randomised, multicentre, double-blind, placebo-controlled clinical trial in 105 hospitals in the USA and Canada, we randomly assigned 1879 patients a single infusion of 7.5 mg/kg TNF alpha MAb (n=949) or placebo (0.25% human serum albumin n=930). Our main outcome measurement was the rate of all-cause mortality at 28 days. FINDINGS: 382 (40.3%) of 948 patients who received TNF alpha MAb and 398 (42.8%) of 930 who received placebo had died at 28 days (95% CI -0.02 to 0.07, p=0.27). We found no association between therapy with TNF alpha MAb and increased rapidity in reversal of initial shock or prevention of subsequent shock. Similarly, baseline plasma interleukin-6 concentrations of more than 1000 pg/mL or detectable circulating TNF concentrations were not associated with improvement in survival after TNF alpha MAb therapy. Coagulopathy but not other organ or system failures, was significantly decreased in the TNF alpha MAb group compared with placebo (day 7, p<0.001; day 28, p=0.005). Serious adverse events were reported in 55.2% of patients given placebo and 54.1% in the TNF alpha MAb group. INTERPRETATION: We did not find an improvement in survival after septic shock with TNF alpha MAb. Therapy not solely dependent on TNF alpha blockade may be required to improve survival.

Adult↗

Magnetic resonance imaging abnormalities and cognitive deficits in systemic lupus erythematosus patients without overt central nervous system disease.

OBJECTIVE: To investigate cerebral magnetic resonance imaging (MRI) abnormalities in relation to cognitive functioning in systemic lupus erythematosus (SLE) patients without a history of central nervous system (CNS) disease. METHODS: Ventricle-to-brain ratios (VBRs) and the total number of white matter hyperintensities (WMHIs) were computed in 20 female patients with non-CNS SLE using established MRI computer-generated quantification procedures. Comprehensive neuropsychological test scores across 8 domains were also obtained. RESULTS: A mean VBR of 2.83% (SD = 0.7) occurred in the non-CNS SLE patients compared with a VBR of 1.36% in a normative sample. The average number of WMHIs was 4.95 (SD = 6.0). Using a combined rating scale (VBR > 2.25%, WMHIs > 5), 7 of 20 MRI scans (35%) were classified as abnormal. Increased VBRs and larger numbers of WMHIs showed a trend association with longer duration of SLE. Thirty-five percent of the non-CNS SLE patients demonstrated neuropsychological deficits. No significant correlations were found between the VBR, total WMHIs, and cognitive scores. Comparisons of cognitively impaired and nonimpaired patients with non-CNS SLE revealed no significant differences across clinical characteristics or MRI values. CONCLUSION: Quantified MRI analyses indicated atypical brain structure and an increased number of WMHIs in a subset of non-CNS SLE patients. However, these MRI abnormalities were not associated with functional abnormalities determined by comprehensive neuropsychological testing. Therefore, MRI analyses are not likely to provide additional clinical information on cognitively impaired SLE patients who have no other evidence of CNS involvement.

Adult↗

A longitudinal study of smoking in year 7 and 8 students speaking English or a language other than English at home in Sydney, Australia.

OBJECTIVE: To compare the rates and predictors of smoking uptake between adolescents speaking English and those speaking a language other than English (LOTE) at home. DESIGN: A cross-sectional survey of year 7 and 8 students (aged 12 and 13 years) was conducted in 1994 and repeated 12 months later. A cohort of students was identified with respondents at baseline matched at follow up. chi 2 and logistic regression were used for analysis. SETTING: 38 schools in southern, east, and northern Sydney, Australia. SUBJECTS: Year 7 and 8 students in the schools were included and examined on two occasions, with complete data for 5947 (80%) students at baseline and 6177 (98%) students at a 12-month follow up. Records were able to be matched perfectly for 3513 respondents (59%). MAIN OUTCOME MEASURES: Smoking rates and predictors of smoking uptake among students speaking English or a LOTE at home. RESULTS: At baseline, 6.1% of students surveyed were smokers. Twelve months later, 15.8% of student surveyed were smokers. There were significantly lower smoking rates among students speaking a LOTE at home compared with those speaking English at home at baseline and at 12 months. Using matched data, for students speaking English at home, five variables were significant predictors of smoking uptake: thinking it acceptable to smoke, perceived benefits of smoking, and having a brother, sister, or close friend who smokes. For students speaking a LOTE, the only predictor was the smoking status of close friends. CONCLUSIONS: Despite the higher smoking prevalence among men with a non-English-speaking background, and the reported strong association between fathers' smoking status and smoking onset of their children, adolescents speaking a LOTE at home were significantly less likely to be smokers than their English-speaking counterparts. Thus, there would seem to be a delay of smoking onset among students speaking a LOTE at home. The smoking rates among respondents speaking a LOTE at home in this study are lower than those obtained from the studies conducted in Europe and the United States. Effective smoking prevention interventions need to be implemented at an early stage of adolescence.

Adolescent↗

Update on oral lichen planus: etiopathogenesis and management.

Lichen planus (LP) is a relatively common disorder of the stratified squamous epithelia, which is, in many ways, an enigma. This paper is the consensus outcome of a workshop held in Switzerland in 1995, involving a selection of clinicians and scientists with an interest in the condition and its management. The oral (OLP) eruptions usually have a distinct clinical morphology and characteristic distribution, but OLP may also present a confusing array of patterns and forms, and other disorders may clinically simulate OLP. Lesions may affect other mucosae and/or skin. Lichen planus is probably of multifactorial origin, sometimes induced by drugs or dental materials, often idiopathic, and with an immunopathogenesis involving T-cells in particular. The etiopathogenesis appears to be complex, with interactions between and among genetic, environmental, and lifestyle factors, but much has now been clarified about the mechanisms involved, and interesting new associations, such as with liver disease, have emerged. The management of lichen planus is still not totally satisfactory, and there is as yet no definitive treatment, but there have been advances in the control of the condition. There is no curative treatment available; immunomodulation, however, can control the condition. Based on the observed increased risk of malignant development, OLP patients should be offered regular follow-up examination from two to four times annually and asked to report any changes in their lesions and/or symptoms. Follow-up may be particularly important in patients with atrophic/ulcerative/erosive affections of the tongue, the gingiva, or the buccal mucosa. Much more research is required into the genetic and environmental aspects of lichen planus, into the premalignant potential, and into the possible associations with chronic liver, and other disorders. More clinical studies are required into the possible efficacy of immunomodulatory drugs such as pentoxifylline and thalidomide.

Adjuvants, Immunologic↗

Exercise-induced bronchospasm in high school athletes via a free running test: incidence and epidemiology.

BACKGROUND: Exercise-induced bronchospasm (EIB) affects up to 35% of athletes and up to 90% of asthmatics. Asthma morbidity and mortality have increased over the past several decades among residents of Philadelphia, PA. It is possible that a simple free running test for EIB may serve as a tool to study the factors contributing to recent trends in asthma, and to screen for asthma in athletes in the urban setting. OBJECTIVES: The purposes of this study were to (1) assess a free running test to screen for EIB, and (2) examine prevalence of and epidemiologic factors associated with EIB in high school athletes. DESIGN: Cross-sectional observational study on the incidence and risk factors for EIB. To validate our method and criteria for the diagnosis of EIB, a repeat test was performed on a portion of the athletes. In a randomized single-blinded fashion, 15 athletes who had demonstrated EIB initially received albuterol or placebo prior to a repeat exercise test. SETTING: Community high school athletic facilities. PARTICIPANTS: We studied 238 male high school varsity football players. INTERVENTION: All athletes underwent an acquaintance session with a questionnaire, followed by a 1-mile outdoor run (6 to 8 mins). MEASUREMENTS: Peak expiratory flow (PEF) measurements were determined prior to and 5, 15, and 30 min after exercise. Heart rates (HRs) and dyspnea scores were measured. EIB was defined as a decrease of 15% in PEF at any time point after exercise. Associations of EIB with demographic factors were assessed by univariate and multivariate analyses. RESULTS: Two hundred thirty-eight athletes participated: 92 European-Americans (EA), 140 African-Americans (AA), 5 Hispanics, and 1 Native American. Mean age was 16+/-1 years. Average HR postexercise was 156+/-24 beats/min. Twenty-four (10%) reported a history of treated asthma. The prevalence of EIB among the remaining 214 athletes was 19 of 214 (9%). The rate of EIB among AA athletes was higher than among EA athletes: (17/126 [13%] AA vs 2/82 [2%] EA, p = 0.01). During the validation portion of the study, the placebo-treated group (n = 7) demonstrated a consistent drop in PEF after exercise on repeat testing, with a 16+/-5% fall in PEF on initial testing and a 14+/-13 drop with placebo. In contrast, the fall in airflow in the albuterol-treated athletes (n = 8) following exercise reversed with albuterol treatment, from a 15+/-6% fall in PEF at initial testing to an increase in PEF of 6+/-9% from baseline following albuterol administration. A history of wheezing (p < 0.001), residence in a poverty area (p < 0.0001), race (p = 0.01), remote history of asthma (p < 0.001), and absolute water content of the air on the day tested (p = 0.04) were significantly associated with EIB. By stepwise regression, EIB was most closely associated with a history of wheezing (p = 0.001) and poverty area residence (p = 0.003). CONCLUSIONS: Our findings indicate a substantial rate of unrecognized EIB exists among urban varsity athletes, and suggest that active screening for EIB, especially for students residing in poverty areas, may be indicated to identify individuals at risk for EIB and asthma.

Albuterol↗

Initial employment experience of 1996 graduates of diagnostic radiology and radiation oncology training programs.

OBJECTIVE: The American College of Radiology sought to detail the initial employment experience of 1996 diagnostic radiology and radiation oncology graduates, the actual effect of factors expected to generate poor employment outcomes, and trends since 1995. MATERIALS AND METHODS: In autumn 1996, questionnaires were mailed to all graduates; 69% responded. The results were compared with a similar survey of 1995 graduates. RESULTS: After graduation, 3-10% of graduates, depending on their field (diagnostic radiology or radiation oncology) and level (residency or fellowship), spent some time working as a locum tenens, working outside their field, or unemployed. However, by a year after graduation, working outside one's field and unemployment had virtually disappeared, even among graduates unable or unwilling to relocate. The Professional Bureau of the American College of Radiology was the most widely used major job search method and drew relatively favorable ratings. At least 15-22% of graduates in posttraining employment had, and disliked, one or more of 11 job characteristics many observers regard unfavorably. Most commonly, the graduates' objection was to having too few patients to remain busy. Relatively poor job outcomes were associated with having a spouse who had to find a job in the same locality as the graduate (only salaries were impaired) but not with other locational constraints, with inadequacy of a major aspect of the training program (as reported by the graduate), and with being female. Changes from 1995 were few, and median salaries were approximately the same as in 1995. CONCLUSION: The employment situation is basically stable, but salaries seem to be lagging behind inflation. Female graduates' poorer employment outcomes are worrisome, especially because studies of women in other professions generally find, unlike our study, that women start their careers even with men.

Adult↗

Orofacial disease: update for the dental clinical team: 2. Ulcers, erosions and other causes of sore mouth. Part I.

Mouth ulcers are one of the most common oral complaints. The term ulcer is used usually where there is damage to both epithelium and lamina propria, and a crater, sometimes made more obvious clinically by swelling caused by oedema or proliferation in the surrounding tissue. The term erosion is usually used where the damage is somewhat more superficial. Most ulcers/erosions are due to local causes such as trauma or burns. Some are caused by aphthae or malignant neoplasms, and a few have aetiology in obvious systemic disease. Ulcers of local cause, drugs, aphthous ulcers, Behcet's syndrome and malignant ulcers are discussed in this article. The next two articles discuss the ulcers due to systemic disease including disorders of the blood, gastrointestinal disorders, skin diseases, connective tissue disease and infective diseases.

Behcet Syndrome↗

Determination of Ro 48-3656 in rat plasma by reversed-phase high-performance liquid chromatography. Comparison of 1.5-microm nonporous silica to 3.5-microm porous silica analytical columns.

We describe a method for measuring Ro 48-3656 in EDTA rat plasma by neutral pH, reversed-phase high-performance liquid chromatography using a 1.5-microm nonporous silica, C18 analytical column and UV absorbance detection to support pharmacokinetic studies. We also describe a comparison of the 1.5-microm nonporous silica C18 column versus 3.5-microm porous silica C18 columns. The final method using the 1.5-microm nonporous silica column demonstrated good precision (of both quantification and retention time), accuracy and recovery, linearity of dilution and limit of quantification (40 ng/ml Ro 48-3656 using a 20 microl injection). Samples of neat EDTA rat plasma were prepared by ultrafiltration followed by direct injection onto the HPLC column.

Animals↗

Deletion mapping defines three discrete areas of allelic imbalance on chromosome arm 8p in oral and oropharyngeal squamous cell carcinomas.

Deletions on chromosome arm 8p, as defined by allelic imbalance, are a frequent event in many different types of malignant tumors, including those of the head and neck. These regions are thought to harbor tumor suppressor genes. In order to define a high-density deletion map of this chromosomal arm in oral and oropharyngeal squamous cell carcinomas, we have tested for allelic imbalance in 35 such tumors with 22 short tandem-repeat polymorphisms. Overall, 21 (60%) of the 35 tumors showed allelic imbalance at one or more loci on chromosome arm 8p. Interstitial deletions defined three discrete areas of deletion: at 8p23, 8p22, and 8p12-p21. Tumors of TNM stages II-IV showed a significantly higher frequency of allelic imbalance on 8p than did TNM stage I tumors. Our data suggest that there are least three tumor suppressor loci on chromosome arm 8p that may be implicated in oral carcinogenesis. Furthermore, inactivation of such genes may be associated with high-grade tumors.

Carcinoma, Squamous Cell↗

Cardiac troponin I in pediatrics: normal values and potential use in the assessment of cardiac injury.

OBJECTIVE: To establish normal values and determine the impact of congenital or acquired heart disease on serum cardiac troponin I (cTnI). METHODS: Concentrations of cTnI were measured in two groups of children. Group A represented ambulatory pediatric patients with no apparent cardiac disease (n = 120) and patients in stable condition with known congenital or acquired cardiac abnormalities (n = 96); group B was composed of patients admitted to intensive care units with normal echocardiograms (n = 16), with abnormal echocardiograms (n = 36), and those with blunt chest trauma who were thought to have cardiac contusions (n = 7). RESULTS: The cTnI concentrations were generally less than 2.0 ng/ml in group A and frequently below the level of detection for the assay (1.5 ng/ml). There was no statistical difference between the two outpatient subgroups (p = 0.66). Nine intensive care patients had cTnI values greater than 2.0 ng/ml. Six of these patients, all with abnormal echocardiograms, had values less than 7.7 ng/ml. All improved and had subsequent normal cTnI concentrations. None of the three remaining patients (two with systemic illness (trauma and sepsis) and one with severe pulmonary hypertension), all with values greater than 8.0 ng/ml, survived. Three of the four patients with high likelihood of cardiac contusion had cTnI concentrations greater than 2.0 ng/ml (including one patient who died). CONCLUSIONS: Cardiac troponin-I values are generally not elevated in children with stable cardiac disease or general pediatric conditions. In the context of severe acute illness, significant elevation of cTnI may be an indicator of poor outcome. Elevation of cTnI may also have diagnostic value in cases when cardiac contusion is suspected.

Adolescent↗