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Biomedical subjects

C A King

Publications and source records attributed to C A King.

At least 19 recordsLinked to original sources
PubMed2001

Intervention research with persons at high risk for suicidality: safety and ethical considerations.

There is a critical need for studies designed to reduce suicidality. Individuals at high risk for suicidality deserve safe and effective treatments, just as do other individuals with mental disorders who do not experience suicidality. Points for consideration regarding safety and monitoring procedures are offered to help researchers who conduct treatment trials with individuals who have mental disorders and investigators specifically interested in developing treatments to reduce suicidality. Issues such as study design, increased monitoring and supervision, research clinician competencies, and liability concerns are addressed. Points to consider in planning an intervention trial, a checklist of informed consent issues, and a list of relevant active federal regulations are provided.

Adolescent↗
PubMed2000

Serotonin dysregulation in adolescents with major depression: hormone response to meta-chlorophenylpiperazine (mCPP) infusion.

This study examined central serotonin disturbance, as reflected by neuroendocrine hormones, among adolescents with major depression. Prolactin, cortisol, and growth hormone were measured following the infusion of a serotonin agonist, meta-chlorophenylpiperazine (mCPP). Twelve (M=6, F=6) medication-free adolescents with major depression (MDD) were compared with 12 (M=6, F=6) matched normal control subjects, ranging in age from 13 to 17 years. Baseline evaluations and a battery of laboratory tests were completed. mCPP, 0.1 mg/kg i. v., was administered in a placebo-controlled design. Analyses of the neuroendocrine hormones revealed that the depressed group had a higher baseline prolactin level and an augmented prolactin response to mCPP challenge than did the control group. The depressed group experienced a sharper baseline-cortisol decline between 08.00 and 11.00 h, and compared to control subjects they displayed an augmented response to the challenge. The depressed group reported more side effects than the control group during saline infusion, but not during mCPP infusion. Findings suggest that depressed adolescents have an elevated baseline prolactin level, and also experience enhanced prolactin and cortisol responses to the serotonergic challenge. These preliminary findings will be confirmed during our ongoing study.

Adolescent↗
PubMed2000

Anxiety contributes to suicidality in depressed adolescents.

Several studies have suggested a positive association between anxiety symptoms and suicidality in adults. However, relatively little is known about this topic in adolescents. To investigate this issue, we examined a group of adolescents admitted to our psychiatric inpatient unit. Fifty-six adolescents (mean age = 14.8 +/- 1.4; females = 34, males = 22; race = 95% Caucasians) participated in the study. Diagnoses were made using the DSM-III-R criteria and a diagnostic interview. Anxiety was found to significantly correlate with depression (r = .60; P = < .05) and suicidality (r = .72; P < .05). A multiple regression analysis revealed that anxiety and depression together accounted for more than half (55%) of the variance in suicidal ideation [F(2,46) = 28.4; P < .0001]. In addition, anxiety had an independent ability to predict suicidality (t = 5.01; P < .0001). Self-rated but not clinician-rated suicidality was positively correlated with both anxiety and depression. Clinical and research implications of these findings are discussed.

Adolescent↗
PubMed2000

Major histocompatibility complex phenotypes influence serum testosterone concentration.

OBJECTIVES: (a) To confirm our earlier observation that the phenotype HLA-DR4,7 occurs with higher frequency in male patients with rheumatoid arthritis (RA) than in female patients. (b) To test the hypothesis that DR7 is associated with low normal serum testosterone (Te) levels in healthy males; this might explain the increased frequency of DR4,7 in male patients since there appears to be a relationship between low serum Te and RA. (c) To characterize the association between HLA alleles and serum Te concentration in healthy males. METHODS: An additional 82 Newfoundland (NF) RA patients were HLA-DR typed and, combined with our earlier data and data from the 11th International Histocompatibility Workshop, gave HLA-DR and sex information on 373 RA patients. Ninety-four healthy NF males were typed for HLA, the microsatellite marker TNFa (located close to the tumour necrosis factor alpha gene) and complement factor B (BF). An additional 38 males were included, selected partly based on their HLA-B type. RESULTS: We confirmed our earlier finding of a higher frequency of HLA-DR4,7 in male RA patients compared with female RA patients (P<0.01). Contrary to our expectations we found that DR7 was associated with higher than mean values of Te as were B5, B27, DR1, TNFa7 and BF F positivity. Conversely, low Te concentrations were found in men with B15, DR2, DR5, TNFa5 and who were BF F negative. In 28 male 'early-onset' RA patients we did not find an increased frequency of HLA alleles associated with low Te levels as compared with the frequency in 41 'late-onset' patients, suggesting that if low Te level is a risk factor and is present before onset of RA then the level cannot be explained by an association between Te level and major histocompatibility complex (MHC) phenotype. CONCLUSION: This study indicates that a man's MHC phenotype may influence his serum Te concentration, but the relationship of this, if any, to the pathogenesis of RA remains an area of speculation.

Adult↗
PubMed2000

Release of vasoactive cytokines by antibody-enhanced dengue virus infection of a human mast cell/basophil line.

We report here the first demonstration of dengue virus infection and vasoactive cytokine response of a cell of the mast cell/basophil lineage. Infection of KU812 cells was dependent on dengue-specific antibody and gave rise to infectious virions. This antibody-enhanced dengue virus infection triggered a four- to fivefold increase in the release of interleukin-1beta (IL-1beta) and a modest increase for IL-6 but not for an alternate cytokine, granulocyte-macrophage colony-stimulating factor. The results suggest a potential role for mast cells/basophils in the pathogenesis of dengue virus-induced disease.

Animals↗
PubMed1999

Manipulation of pathogen-derived genes to influence antigen presentation via DNA vaccines.

To gain insight into the routes of presentation of pathogen sequences via DNA vaccines, we have compared the abilities of sequences encoding fragment C of tetanus toxin (FrC) and influenza A virus nucleoprotein (NP) to induce antibody or cytotoxic T-cell (CTL) responses in vivo. Strong antibody and CTL responses were induced against FrC targeted to the endoplasmic reticulum (ER) and both were reduced by removal of the leader sequence. In contrast, targeting of NP to the ER generated only a modest antibody response, likely due to misfolding in this site. Removal of the leader sequence led to anti-NP antibodies via cross-priming. For NP, induction of CTLs was not influenced by the leader sequence. Exogenous FrC or NP delivered as proteins were unable to induce CTLs. Routes to induction of optimal immune responses via DNA evidently differ according to the nature of the encoded pathogen sequence. Understanding processing pathways for pathogen sequences should assist rational design of DNA vaccines.

Animals↗
PubMed1999

Factors associated with victimization of personnel in emergency departments.

OBJECTIVE: The purpose of this study was to identify the incidence of ED personnel victimization in Central Florida and examine its relationship to victims' reports of 3 factors: characteristics of the patient/perpetrator, characteristics of the personnel victimized, and characteristics of the ED environment. METHODS: Data were collected anonymously in a mail survey using 37 items from Mahoney's Emergency Department Victimization Questionnaire (EDVQ) and a demographic questionnaire. Chi square, Spearman's rank correlation coefficient, and Pearson's product moment correlation were used to describe frequencies, incidence, and their relationships to the variables studied. A sample of 226 of the 600 direct care personnel (37%) from 18 of the 19 hospital emergency departments in a tri-county area (95%) participated. RESULTS: The incidence of physical assault was reported to be 42% during the past year and 72% during the respondents' careers. Alcohol use was associated with incidence (1-tailed Pearson; P =.001). Verbal abuse was significantly higher on day shift (P =.043). The most desired environmental variable was 24-hour security attendants, available to 51.8% of the respondents. More than a fourth of the subjects reported that they had completed no coursework or had no continuing education in violence prevention. DISCUSSION: Respondents reported avoiding identification on duty, underreporting, postvictimization staff turnover, dissatisfaction with security, and the desire for every security provision listed. The goals of reducing the fears and victimization of ED personnel should become a priority within the health care system.

Adult↗
PubMed1999

Medication noncompliance in adolescents with psychiatric disorders.

The purpose of the study was to estimate prevalence of medication noncompliance among adolescents, following discharge from hospital. A second purpose was to identify predictors of such noncompliance. Seventy-one adolescents, who had been prescribed a medication during psychiatric hospitalization, were interviewed by telephone, 6-8 months post-hospitalization. Medication noncompliance was defined as discontinuing medication without the recommendation of the treating physician. Twenty-four subjects (33.8%) were noncompliant with medication. Age, race, gender, SES, diagnosis, type and number of medications, severity of depression, and family living arrangement did not predict noncompliance. We concluded that noncompliance with psychotropic medications was relatively common and difficult to predict in adolescents who had been hospitalized to a psychiatric inpatient unit; the majority of them suffered from depression. Clinicians should be aware that medication noncompliance may be common and a relatively unpredictable phenomenon.

Adolescent↗
PubMed1999

Electroconvulsive treatment of a bipolar adolescent postcraniotomy for brain stem astrocytoma.

This is the first reported use of electroconvulsive treatment (ECT) in an adolescent with bipolar mania who had been treated with craniectomy for an intracranial neoplasm. The reported case is of a 16-year-old girl with a history of brain stem glioma (pontomesencephalic astrocytoma) diagnosed at 13 years of age. She presented in a psychiatric emergency room with suicidal ideation, depressed mood, irritability, olfactory hallucinations, early insomnia, grandiosity, and guilt. Her symptoms failed to respond to a trial of an antidepressant, mood stabilizer alone, and mood stabilizer in conjunction with a neuroleptic. The decision to use ECT was based on suicidal ideation, extreme disinhibition, and danger to self and others. Significant improvement in mood and remission in psychosis were noted after the eighth treatment. Comparison of 2-week pre-ECT and 3-month post-ECT cognitive testing revealed no change in IQ. This report highlights rapid response and the ability to tolerate ECT in an adolescent diagnosed with bipolar disorder, who had also been treated with radiation and craniotomy.

Adolescent↗
PubMed1999

Incorporating fun into the business of serious work: the use of humor in group process.

Incorporating formal humor and creative play into group process improves the outcome of serious work. This article discusses the use of humor and play in a traditionally serious setting. On-the-job playfulness improves communication, creativity, problem solving, and team building, thereby increasing productivity and satisfaction.

Burnout, Professional↗
PubMed1999

DNA vaccines against haematological malignancies.

DNA vaccines against cancer have to activate an inadequate or damaged immune system in order to attack residual cancer cells. Although the potential problem of tolerance may be overcome by transplantation, provision of high levels of T-cell help is likely to be an important factor in stimulating effective immune pathways. The fusion gene approach appears to provide the required help, and offers a rational design for raising both antibody and T-cell mediated attack against lymphoma and myeloma, which express idiotypic antigen at the cell surface or as a secreted protein respectively. Intriguingly, preliminary data indicate that the fusion gene approach promotes antibody responses against a different cell surface tumour antigen, CEA. Strategies for using DNA vaccines to induce attack on processed peptides bound to MHC class I molecules are also being developed. We hope and anticipate that all categories of tumour antigen may be susceptible to this powerful new technology. The critical clinical requirement, however, will be to treat the presenting tumour with maintenance or restoration of immune capacity. We await results of the preliminary clinical trials with great interest.

Animals↗
PubMed1998

Sexual dimorphism in the humerus: a comparative analysis of Chinese, Japanese and Thais.

Determination of sex from the skeleton is vital to medicolegal investigations. There is no longer any question that populations differ in size and proportions and these differences affect the metric assessment of sex. The extent of variation in sexual dimorphism among Asian Mongoloids within and between regions has not been quantified by discriminant function analysis, nor have standards for most groups been introduced for the humerus. Therefore, the purpose of this research is to establish metric standards for sex determination from the humerus of Chinese, Japanese and Thais, as well as to compare size and sexual dimorphism in these Asian Mongoloid populations. The database for this study consisted of documented skeletal samples from China (N = 87), Japan (N = 90), and Thailand (N = 104). Six standard dimensions, including maximum length, vertical head diameter, minimum midshaft diameter, maximum midshaft diameter, midshaft circumference, and epicondylar breadth were taken and subjected to stepwise and direct discriminant function analysis. Of dimensions selected by the stepwise function, vertical head diameter and epicondylar breadth were the only elements common to all three groups. Overall, mean accuracies were highest using formulae produced by the stepwise procedure and ranged from 86.8% in the Chinese to 92.4% in the Japanese to 97.1% in the Thais. Group comparisons also revealed that while the Chinese had the largest measurements, they were the least dimorphic. The reverse was true for the Thais and the Japanese were intermediate on both counts. In cross validation tests, classification accuracy decreased in all cases where a formula from one group was applied to another. It was therefore concluded even though all individuals were Asian Mongoloids, these regionally diverse populations exhibited significant metric differences that affect sex determination from the skeleton. These findings confirm those of previous studies that there is a need for group specific metric standards of assessment.

China↗
PubMed1998

DNA vaccines with single-chain Fv fused to fragment C of tetanus toxin induce protective immunity against lymphoma and myeloma.

Vaccination with idiotypic protein protects against B-cell lymphoma, mainly through anti-idiotypic antibody. For use in patients, DNA vaccines containing single-chain Fv derived from tumor provide a convenient alternative vaccine delivery system. However, single-chain Fv sequence alone induces low anti-idiotypic response and poor protection against lymphoma. Fusion of the gene encoding fragment C of tetanus toxin to single-chain Fv substantially promotes the anti-idiotypic response and induces strong protection against B-cell lymphoma. The same fusion design also induces protective immunity against a surface Ig-negative myeloma. These findings indicate that fusion to a pathogen sequence allows a tumor antigen to engage diverse immune mechanisms that suppress growth. This fusion design has the added advantage of overcoming potential tolerance to tumor that may exist in patients.

Animals↗
PubMed1998

Immunoglobulin VH gene sequence analysis of spontaneous murine immunoglobulin-secreting B-cell tumours with clinical features of human disease.

The 5T series of multiple myelomas (MM) and Waldenstrsöm's macroglobulinaemia-like lymphomas (WM), which developed spontaneously in ageing mice of the C57BL/KaLwRij strain, shows clinical and biological features that closely resemble their corresponding human diseases. In order to compare the patterns of somatic mutation in VH genes of mouse tumours with those of human counterparts, we have determined and analysed sequences of immunoglobulin VH genes in five cases of murine MM, two of WM and one of biclonal benign monoclonal gammopathy (BMG). Four of five MM and 2/2 WM cases used VH genes of the large J558 family; one MM used a gene of the VGAM3.8 family, and both clones of the BMG used genes of the 36-60 family. N-region insertions were observed in all cases, but D-segment genes were only identified in 6/9 cases, which were all from the D-SP family and translated in reading frame 3. Compared with human MM, in which the VH genes have been found to be consistently hypermutated (mean% +/- SD = 8.8 +/- 3.2), the degree of somatic mutation in the murine tumours was significantly lower (mean% +/- SD = 2.9 +/- 2.3). There was no significant evidence of clustering of replacement mutations in complementarity determining regions (CDR), a feature considered to be characteristic of antigen-selected sequences. However, one clone of the biclonal BMG case showed intraclonal variation, a feature described in some cases of human BMG. These results indicate that murine VH genes in mature tumours differ from human counterparts in the level and distribution of somatic mutations, but support the concept that BMG may be distinct from MM.

Amino Acid Sequence↗
PubMed1998

Metric and comparative analysis of sexual dimorphism in the Thai femur.

Identification of sex from the skeleton is an important demographic assessment in medicolegal investigations. Studies have demonstrated that populations differ from each other in size and proportions and that these differences can affect the metric assessment of sex. It is therefore vital to determine if population differences are great enough to necessitate group-specific standards. To date, there have been no attempts to create standards of assessment for modern Thais. Therefore the purpose of this research is to establish standards from which to determine sex from the femur using a new skeletal collection housed at the Chiang Mai University Department of Anatomy. The sample is composed of 104 individuals (70 males, 34 females). Six standard osteometric dimensions including maximum length, maximum head diameter, midshaft circumference, midshaft anterior-posterior and transverse diameters, and bicondylar breadth were measured and analyzed by stepwise discriminant function statistics. To understand population differences, formulas derived from Chinese, South African whites and American whites and blacks using the same method and variables were tested on the Thai sample. Results indicated that maximum head diameter and bicondylar breadth are the optimal combination for sex diagnosis and yielded 94.2% accuracy. Direct analysis using predetermined single or multiple variables also revealed bicondylar breadth as the best single dimension (93.3%). In cross-tests on the Thais, the Chinese formula gave the most favorable outcome with unsatisfactory results for all other groups. The present research confirms that sexual dimorphism is better reflected in breadth dimensions than in bone length. Comparisons showed that Thais are very different metrically from whites and blacks, and although they most resemble the Chinese, these two groups are not identical. These findings underscore the need for population-specific formulas for identification of sex from the skeleton.

Adolescent↗
PubMed1998

Suicide across the life span: pathways to prevention.

As reflected in a recent series of highly visible suicide awareness and prevention activities, the call for a comprehensive suicide prevention strategy has never been stronger, nor more unified. Using the framework provided by the transactional model of human development, the author illustrates the central implications that a developmental perspective has for suicide prevention, emphasizing the need to consider multiple pathways to prevention, to place renewed emphasis on prevention strategies that have their impact earlier in the life course and earlier in the course of mental disorder, and to collaborate with prevention specialists and advocates in related fields.

Comorbidity↗
PubMed1997

DNA vaccines against lymphoma: promotion of anti-idiotypic antibody responses induced by single chain Fv genes by fusion to tetanus toxin fragment C.

Idiotypic determinants can act as tumor-associated Ags for B cell lymphoma. Vaccination with idiotypic protein and adjuvant is known to induce specific protection against lymphoma challenge in mice, largely mediated by anti-idiotypic Ab. For facilitating the approach for patients, the V(H) and V(L) genes used to encode the individual idiotypic determinants of each tumor can be obtained by PCR and assembled as single chain Fv (scFv). DNA vaccines containing scFv sequences alone induce low and poorly reproducible levels of anti-idiotypic Ab, likely to be insufficient to suppress tumor in patients. In addition, it may be necessary to break tolerance to Id in tumor bearers. By fusing the gene for fragment C of tetanus toxin to the C terminus of human scFv, we have promoted the anti-scFv Ab response in mice by >50-fold in three of three cases. The induced Abs are mainly against idiotypic determinants, and react specifically with patients' tumor cells, indicating optimal folding of the scFv molecule in the fusion protein. For both antigenic components of the DNA vaccine, the IgG subclass distribution showed a relative increase in IgG2a as compared with vaccination with IgM protein in adjuvant. In patients, the fusion gene should both promote anti-idiotypic Ab and induce Abs against fragment C of tetanus toxin. The latter response would provide a potentially useful comparative measure of the ability of patients to respond to conventional Ag delivered via DNA.

Amino Acid Sequence↗