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Biomedical subjects

S Mitchell

Publications and source records attributed to S Mitchell.

At least 73 records · Page 4Linked to original sources

Assessing medical students' competence in obtaining informed consent.

BACKGROUND: Medical schools increasingly place emphasis on preparing students to perform routine, ethically important clinical activities with sensitivity and acumen. A method for evaluating students' skills in obtaining informed consent that was created at our institution is described. METHODS: Formal assessment of medical students' professional attitudes, values, and ethics skills occurs in the context of three required and developmentally attuned comprehensive examinations. A videotaped station tested senior medical students' ability to obtain informed consent from a standardized patient who expresses concern about undergoing cardiac catheterization. Two checklists were completed by the patient. Videotapes were reviewed by a faculty member, and students' reactions to the assessment experience were documented. RESULTS: Seventy-one senior students participated, and all performed well. Mean scores of 6.3 out of 7 (range 5 to 7, SD = 0.5) on the informed consent checklist and 8.7 out of 9 (range 6 to 9, SD = 0.5) on the communication skills checklist were obtained. Students endorsed the importance of the skills tested. CONCLUSIONS: This method of examining medical students' abilities to obtain informed consent has several positive features and holds promise as an ethics competence assessment tool.

Adult↗

HLA class II haplotypes in primary sclerosing cholangitis patients from five European populations.

The association of primary sclerosing cholangitis (PSC) to HLA class II genes was studied by comparing patients from five different European populations. Deduced HLA-DRB1, DQA1, DQB1 haplotypes of 256 PSC patients from England, Italy, Norway, Spain and Sweden were compared to those observed in 764 ethnically-matched controls. Increased frequencies of the DRB1*03, DQA1*0501, DQB1*02 (RR=3.0, P<0.00001) and the DRB1*13, DQA1*0103, DQB1*0603 haplotypes (RR=2.4, P<0.0001) were observed in all five patient groups. A total of 16% of the PSC patients were homozygous for the DRB1*03, DQA1*0501, DQB1*02 haplotype compared to 1% of the controls (RR=20, P<0.0001). The DRB1*04, DQA1*03, DQB1*0302 haplotype was significantly reduced in frequency(RR=0.4, P<0.00001). Among Norwegian, Swedish and British patients that did not carry neither the DRB1*03, DQA1*0501, DQB1*02 nor the DRB1*13, DQA1*0103, DQB1*0603 haplotype, an increased frequency of the DRB1*15, DQA1*0102, DQB1*0602 haplotype was observed (RR=2.0, P<0.0001). Thus, PSC was found to be positively associated to three different HLA class II haplotypes (i.e. the DRB1*03, DQA1*0501, DQB1*02, the DRB1*15, DQA1*0102, DQB1*0602 and the DRB1*13, DQA1*0103, DQB1*0603 haplotypes) and negatively associated to one HLA class II haplotype (i.e. the DRB1*04, DQB1*0302 haplotype).

Adolescent↗

Trimethylamine and foetor hepaticus.

BACKGROUND: In patients with various degrees of hepatocellular failure and portosystemic shunting of blood, the breath may acquire a sweet, musty, or even slightly faecal aroma, termed foetor hepaticus, which has been attributed mainly to volatile sulphur compounds with contributions from various nitrogenous substances. Not infrequently in such patients, unusual body odours are also encountered and, by analogy with the 'fish-odour syndrome' known to be caused by excessive trimethylamine, the availability of this latter graveolent amine to potentially contribute to odours associated with hepatic disease was investigated. METHODS: Urine (0-24 h) was collected from 63 patients with various liver diseases previously confirmed in hospital by means of various biochemical, immunologic, pathologic, and radiologic investigations. Total trimethylamine and trimethylamine N-oxide levels in urine were measured with head-space gas chromatography. RESULTS: In total, 50% (32 of 63) of the patients (primary liver disease, 25 of 47, or 53.2%; secondary liver disease, 7 of 16, or 43.8%) had urinary trimethylamine levels greater than the upper end of the range considered normal (0.08-1.84 microg/ml). Seventeen patients excreted large amounts of free trimethylamine (more than 10 microg/ml), above the threshold usually associated with the appearance of a 'fish-like' body odour and tainted breath. CONCLUSIONS: Excessive amounts of trimethylamine may well contribute to the overall body odour problems encountered among patients with severe hepatic disease, precipitating in these individuals a secondary form of the 'fish-odour syndrome'.

Adolescent↗

A gene for autosomal recessive symmetrical spastic cerebral palsy maps to chromosome 2q24-25.

Cerebral palsy has an incidence of approximately 1/500 births, although this varies between different ethnic groups. Genetic forms of the disease account for approximately 1%-2% of cases in most countries but contribute a larger proportion in populations with extensive inbreeding. We have clinically characterized consanguineous families with multiple children affected by symmetrical spastic cerebral palsy, to locate recessive genes responsible for this condition. The eight families studied were identified from databases of patients in different regions of the United Kingdom. After ascertainment and clinical assessment, we performed a genomewide search for linkage, using 290 polymorphic DNA markers. In three families, a region of homozygosity at chromosome 2q24-q25 was identified between the markers D2S124 and D2S148. The largest family gave a maximum LOD score of 3.0, by multipoint analysis (HOMOZ). The maximum combined multipoint LOD score for the three families was 5.75. The minimum region of homozygosity is approximately 5 cM between the markers D2S124 and D2S2284. We have shown that a proportion of autosomal recessive symmetrical spastic cerebral palsy maps to chromosome 2q24-25. The identification of genes involved in the etiology of cerebral palsy may lead to improved management of this clinically intractable condition.

Adolescent↗

A controlled clinical study of the effect of nasal immunization with a Streptococcus mutans antigen alone or incorporated into liposomes on induction of immune responses.

Recent attention to mucosal immunization strategies has been focused on the nasal route for vaccine delivery. This study was designed to determine the effectiveness of a liposome-protein vaccine compared to that of a protein-only vaccine in inducing immune responses in humans. Healthy subjects were randomly assigned to two groups and immunized intranasally with a crude antigen preparation rich in glucosyltransferase (C-GTF) from Streptococcus mutans, alone or in liposomes. Parotid saliva, nasal wash, and serum were collected prior to and at weekly intervals following immunization and were analyzed for anti-C-GTF activity by enzyme-linked immunosorbent assay. The levels of immunoglobulin A (IgA) anti-C-GTF activity in the nasal wash from both groups after immunization increased to a mean peak of fivefold over the baseline level on day 28. Salivary IgA anti-C-GTF responses were induced to a lesser extent. IgG and IgA anti-C-GTF responses in serum were detected on day 14. The IgA responses were predominantly of the IgA1 subclass. These results show that C-GTF vaccines were more effective in inducing a local secretory IgA antibody response than a salivary or serum response when they were given intranasally. The IgA1 anti-C-GTF response in nasal wash samples for liposomal antigen versus antigen only was the only response which was significantly different (P < 0.04). This suggests that the form of the antigen affects the magnitude of the local mucosal response but not that of a disseminated response. These results provide evidence for the effective use of a nasal protein vaccine in humans for the induction of mucosal and systemic responses.

Administration, Intranasal↗

Severe hemolytic disease from rhesus anti-C antibodies in a surrogate pregnancy after oocyte donation. A case report.

BACKGROUND: Maternal sensitization with rhesus anti-C antibodies is comparatively rare and usually benign. In pregnancies conceived using donor oocytes, the mother's blood group may differ from that of both the father and the oocyte donor, making blood group incompatibility more likely. CASE: Twins, the result of a surrogate pregnancy using donor oocytes, were born with severe hemolytic disease due to rhesus anti-C antibodies. Both infants required exchange transfusion for profound anemia at birth. Isoimmunization in the surrogate mother was not detected antenatally. The twins were delivered by emergency cesarean section due to fetal compromise, detected fortuitously when the mother attended for routine fetal assessment at 35 weeks' gestation. CONCLUSION: Isoimmunization with anti-C antibodies is not always benign and may cause significant hemolytic disease. With the success of in vitro fertilization and oocyte donation, more infertile couples may use these methods to conceive, with or without surrogacy arrangements. In such cases, the provision of antenatal care may become a complex matter, involving several parties, and good communication between everyone involved is vital. In pregnancies conceived with donor oocytes, there may be a higher risk of blood group incompatibility, and special vigilance is warranted.

Cesarean Section↗

The role of type I and type II tumor necrosis factor (TNF) receptors in the ability of TNF-alpha to transduce a proliferative signal in the human megakaryoblastic leukemic cell line Mo7e.

We investigated the effects of tumor necrosis factor (TNF) alpha on the human megakaryocytic leukemic cell lines Mo7e, Meg-01, and Dami/HEL. Our data show that both type I and type II TNF receptors (TNF-RI and TNF-RII) are expressed on all of these cells, and TNF-alpha significantly stimulates the proliferation of growth factor-dependent Mo7e cells but not of Meg-01 or Dami/HEL cells, which grow in a factor-independent manner. TNF-alpha serves predominantly as a mitogen for Mo7e cell proliferation and does not induce Mo7e cell differentiation. Coincubation with both TNF-alpha and anti-TNF-alpha neutralizing antibody completely abolishes the TNF-alpha-induced proliferation of Mo7e cells. In bioassays, there is no detectable level of other stimulatory cytokines in conditioned medium from Mo7e cells previously stimulated by TNF-alpha, implying that the stimulatory effect of TNF-alpha on Mo7e cells is derived from the direct action of TNF-alpha rather than via the induction of secondary cytokines by TNF-alpha. Flow cytometric studies demonstrated that TNF-alpha binds to Mo7e cells that have been pretreated with either anti-TNF-RI or anti-TNF-RII neutralizing antibody, but TNF-alpha does not bind to cells pre-exposed to both receptor antibodies. However, the incubation of Mo7e cells with either TNF-RI or TNF-RII neutralizing antibodies or with either soluble TNF-RI or TNF-RII inhibits TNF-alpha-induced cell proliferation, indicating the requirement of interactions with both TNF receptors for the mitogenic activity of TNF-alpha. Furthermore, our data suggest that an alternative signaling pathway may be involved in TNF-alpha-induced Mo7e cell proliferation, because the common mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription (STAT) signaling pathways activated by other cytokines that induce Mo7e cell proliferation are not activated by TNF-alpha.

Cell Division↗

Increase in endocervical CD4 lymphocytes among women with nonulcerative sexually transmitted diseases.

To assess associations of nonulcerative sexually transmitted diseases (STDs) with human immunodeficiency virus (HIV)-susceptible leukocytes on female genital mucosa, cervicovaginal specimens from 32 HIV-negative STD clinic patients with gonorrhea, chlamydial infection, or trichomoniasis were compared with specimens from 32 clinic patients without these infections. Twenty-eight patients had single infections (15 gonorrhea, 10 chlamydial infection, 3 trichomoniasis), and 4 had dual infections. A saline vaginal wash and saline suspensions of vaginal wall scrapings, ectocervical scrapings, and endocervical brushings were analyzed by flow cytometry. Specimens from the endocervix had the highest proportions of lymphocytes, monocytes, and Langerhans' cells. The median number of endocervical CD4 lymphocytes/10,000 cells was greater among patients with STDs than among those without (476 vs. 245; P < .001). These data suggest that the endocervix may have a particularly important role in heterosexual HIV transmission and that nonulcerative STDs may facilitate HIV transmission by increasing the presence of CD4 lymphocytes at this site.

Adolescent↗

Microleakage of composite restorations bonded with three new dentin bonding agents.

This report evaluates the impact of two dentin bonding techniques on microleakage of Class V restorations bonded with three new dentin bonding systems. Forty-eight extracted human premolar and molar teeth were randomly assigned to four groups for bonding with EBS Bonding System (ESPE, Seefeld, Germany); Syntac Single-Component (Ivoclar-Vivadent, Schaan, Liechtenstein); Scotchbond 1 (3M Dental Products, St. Paul, Minnesota); and a control, Prime and Bond 2.1 (Dentsply, DeTrey, Konstanz, Germany). Cavities were cut in both the buccal and lingual surfaces. The coronal half of each preparation was in enamel, and the gingival half was in cementum or dentin. The cavities were restored with composite after the application of dentin bonding agents, using two different drying techniques for each material. The teeth were stored in distilled water for 6 days at 37 degrees C and then thermocycled. The restorations were examined microscopically for leakage, using Procion brilliant red as a marker. All groups showed microleakage at both the enamel and dentin margins. At the gingival margin, there was no significant difference between any of the experimental materials and the control for either wet bonding (Kruskal-Wallis: p = .8920) or dry bonding (Kruskal-Wallis: p .9973); or between the two techniques for each material (Mann-Whitney U in all cases p > .05). Scanning electron microscopic examination confirmed that the zones of microleakage, as indicated by dye penetration, were principally resincohesive failures within the collagen-rich hybrid layer. Three water-based bonding agents were unable to prevent microleakage at either the enamel or dentin margins of Class V cavities regardless of which bonding technique was employed. All systems behaved equally.

Analysis of Variance↗

A scanning electron microscopic study of the effect of Gluma CPS bonding system on dentinal smear layers produced by different bur types and rotational speeds and on the resin-dentin interface.

OBJECTIVE: The purpose of this study was to investigate the effect of conditioners on smear layers produced by different bur types and rotational speeds and to study the interaction of subsequently applied primer and sealer with these conditioned surfaces. METHOD AND MATERIALS: Smear layers were produced on human teeth immediately after extraction by burs rotating at approximately 6,000 rpm without water spray and 400,000 rpm with water spray. Gluma CPS etchant was applied for 15, 30, and 60 seconds, and a 20% phosphoric acid liquid (control) was applied for 30 seconds to smear layers. The specimens were prepared by critical point drying for scanning electron microscopic imaging within 24 hours. Additional specimens were prepared and treated with Gluma CPS primer and sealer, according to the manufacturer's instructions. RESULTS: There were only small variations in the smear layer thicknesses with different bur types or speeds of rotation. Gluma CPS conditioner, applied for the recommended times, did not completely remove the smear layer. An altered smear layer, composed of a reaction product, remained on the dentinal surface. A zone of demineralization did occur, however, beneath the partially removed smear layer in both the 15- and 30-second specimens but was only partly filled by primer and sealer. Smear layers were completely removed by the 20% phosphoric acid liquid to expose a delicate collagen network. CONCLUSION: An understanding of the appropriate treatment for smear layers is crucial to the development of improved dentin bonding systems.

Acid Etching, Dental↗

Effect of wet and dry bonding techniques on marginal leakage.

PURPOSE: To evaluate the effect of wet and dry bonding on microleakage of Class V restorations bonded with three bonding agents. MATERIALS AND METHODS: 60 extracted human premolars and molars were randomly assigned to three groups for bonding with Gluma CPS, EBS (ESPE) and Prime & Bond 2.1. Cavities were cut in both the buccal and lingual surfaces. Half of each preparation was in enamel and the other was in cementum/dentin. The cavities were restored with composite after the application of dentin bonding agents using a wet and dry technique for each material. The teeth were stored in distilled water for 6 days at 37 degrees C, thermocycled, and the restorations examined microscopically for leakage using Procion Brilliant Red as a marker. RESULTS: All groups showed microleakage at both the enamel and dentin margins. At the gingival margin, there was a significant difference between the groups for both wet-bonding (P = 0.039) and dry-bonding (P = 0.024). There was no significant difference between the groups at the enamel margin (wet bonding: P = 0.179, dry-bonding: P = 0.357). The wet-bonding technique was compared with the dry-bonding technique for each material at both the gingival and enamel margins and no significant differences were observed (in all cases P > 0.47). SEM showed that in dye-labeled areas debonding occurred mostly, but not always, near the resin-hybrid interface.

Analysis of Variance↗