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Biomedical subjects

C Black

Publications and source records attributed to C Black.

At least 145 records · Page 8Linked to original sources
PubMed1992

Reliability of skin involvement measures in scleroderma. The UK Scleroderma Study Group.

Two methods have been proposed to quantify the extent of skin involvement in scleroderma. These are (1) a scoring system which quantifies and summates this severity rating in 17 areas of skin surface and (2) a method estimating the percentage of skin involvement using a shaded manikin. We report on a study comparing the inter-observer reliability of these two approaches using the ratings of six clinicians on 12 patients. Systematic bias between observers was noted with both methods, but inter-observer agreement, as-assessed by the intraclass correlation coefficient (ICC), was higher with the score method. The manikin method resulted in a greater degree of disagreement between the observers, as well as a higher amount of random error, reflecting the difficulty of defining the bounds of abnormal skin. Despite the presence of bias, the score method is the preferred method for assessing the level of skin involvement.

Analysis of Variance↗
PubMed1992

The immunogenetic background of scleroderma--an overview.

Currently it may be stated that the MHC associations in scleroderma support the classification of disease subsets, but in no ethnic group is the overall association strong enough for clinical use. In different ethnic groups, the distribution of MHC alleles varies, as does the degree of linkage disequilibrium between alleles of the linked loci. This concept is even relevant to relatively close populations. Thus Whiteside noticed that, if those patients referred from more than 100 miles from the study centre were excluded, then the strength of the DR1 association increased. The environmental contribution to scleroderma is unknown, except in the case of toxin or solvent associated disease. Different causal environmental agents found in different global regions might result in separate MHC associations and hence explain the discrepancies noted above. There are indications that associations between specific subsets of SSc patients and genetic markers will assume greater importance both diagnostically and prognostically. The lung fibrosis group look prime candidates, for example. Genetic markers are also a useful means of relating chemically-induced SSc-like disorders to the classical disease. Vinyl chloride disease provides an example. There is much heterogeneity within the disease, in terms of extent of skin involvement, severity, and of organ involvement. It is clear that the different clinical subsets of scleroderma are characterized by different associated MHC alleles. There are also many cases of clinical overlap with related diseases, and certain of these diseases have a different HLA association, which could detract from the primary HLA type associated with SSc.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1992

A double blind, multicentre, placebo controlled trial of lornoxicam in patients with osteoarthritis of the hip and knee.

Lornoxicam is a new non-steroidal anti-inflammatory agent (NSAID) with a similar pharmacological profile to other oxicams and a potency 10 times greater than piroxicam. A multicentre, randomised, double blind, parallel group study was undertaken to compare the efficacy and tolerance of four weeks' treatment with lornoxicam (6 mg once daily, 4 mg twice daily, and 6 mg twice daily) and placebo in patients with osteoarthritis of the hip or knee. A dose related efficacy of lornoxicam was shown by the numbers of patients in each treatment group who withdrew from the trial owing to inadequate symptom relief (12/40 (30%) receiving placebo, 6/40 (15) receiving lornoxicam 6 mg daily, 4/40 (10%) receiving lornoxicam 8 mg daily, and none receiving lornoxicam 12 mg daily). This effect was confirmed by pain relief scores, which were significantly better than placebo during treatment with lornoxicam 8 mg and 12 mg daily, the effect of 12 mg daily being significantly superior to that of 8 mg daily. Similar results were obtained from functional status scores. Mean functional index (Lequesne) scores were significantly greater than placebo only at a daily dose of 12 mg lornoxicam. Lornoxicam was generally well tolerated, though some gastrointestinal side effects were seen as has been reported with other NSAIDs. Laboratory investigations showed no evidence of drug toxicity.

Administration, Oral↗
PubMed1992

Urinary leukotriene E4 after lysine-aspirin inhalation in asthmatic subjects.

The FEV1 and urinary leukotriene E4 (LTE4) concentrations were determined in six aspirin-sensitive and six non-aspirin-sensitive asthmatic subjects before and after inhalation challenge with lysine-aspirin or placebo solution. Lysine-aspirin produced a mean fall in FEV1 of 26.7 +/- 4.9% (mean +/- SEM) in subjects with aspirin sensitivity and of 8.5 +/- 6.5% (mean +/- SEM) in non-aspirin-sensitive asthmatic subjects. The mean baseline urinary LTE4 concentration of 83 pg/mg creatinine (geometric mean [GM], range 15 to 326 pg/mg creatinine) in aspirin-sensitive subjects was significantly higher than the 33.8 pg/mg creatinine (GM, range 10 to 111 pg/mg creatinine) in non-aspirin-sensitive subjects (p = 0.02). In aspirin-sensitive subjects, inhalation challenge with lysine-aspirin produced a significant increase in urinary LTE4 concentration to 240 pg/mg creatinine (GM, range 60 to 1,113 pg/mg creatine), which was not observed after placebo challenge. There was no significant change in urinary LTE4 concentration after inhalation challenge with either lysine-aspirin or placebo solution in non-aspirin-sensitive asthmatic subjects. Thus, sulfidopeptide leukotrienes are released after inhalation of lysine-aspirin in aspirin-sensitive asthmatic patients.

Administration, Inhalation↗
PubMed1992

Reproductive function prior to disease onset in women with scleroderma.

We tested in a retrospective study the hypothesis that women with scleroderma have an increased risk, before disease presentation, of problems in pregnancy. Reproductive history, as reported from a validated postal questionnaire, was obtained from 204 women with scleroderma [mean year of birth (yob) 1942] and compared to that reported by 233 women with primary Raynaud's phenomenon (mean yob 1948) and 189 healthy women from a population register (mean yob 1950). Only pregnancies occurring before symptom onset in the scleroderma group were considered for analysis. All analyses were adjusted for job, social class, age at first pregnancy, smoking habit, and where relevant, parity. The results are expressed as odds ratios (OR) [with 95% confidence limits (CL)] giving the risk of developing scleroderma, with previous exposure to each of the specific reproductive variables analyzed, relative to the 2 comparison groups. The women with scleroderma were more likely than the population women to have had a delay in conception (> or = 12 months): OR 2.6 (1.1, 5.7) or be infertile: OR 2.3 (0.7, 7.2). These differences were not apparent when the scleroderma group was compared to the women with Raynaud's: OR's 0.7 and 1.1, respectively. Similarly there was a greater self report of maternal ill health in pregnancy in the group with scleroderma compared to the population women: OR 2.1 (1.2, 3.5) but not compared to the women with Raynaud's: OR 1.0 (0.7, 1.6).(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1991

Expression and function of surface antigens on scleroderma fibroblasts.

Dermal fibroblasts from patients with systemic sclerosis (SSc) bound a much greater number of T lymphocytes than did normal dermal fibroblasts. Monoclonal antibodies (MAb) against classes I and II antigens of the major histocompatibility complex (MHC) and their receptors, CD8 and CD4, had no effect on T cell interaction with SSc and normal cells, while MAb against lymphocyte function-associated antigen type 3 (LFA-3) and CD2 both strongly inhibited lymphocyte attachment. MAb against intercellular adhesion molecule type 1 (ICAM-1) and LFA-1 also prevented binding of T lymphocytes, but had a more marked effect on adhesion to SSc fibroblasts than to normal fibroblasts; they also completely abolished the increased binding to fibroblasts treated with interleukin-1 alpha, tumor necrosis factor alpha, and interferon-gamma. No difference was found in the proportion of normal and SSc fibroblasts that expressed MHC classes I and II and LFA-3, but more SSc cells expressed ICAM-1, and at a higher level, than did normal fibroblasts. These results show that cultured SSc cells have elevated binding to T lymphocytes, which possibly results from expansion of a subset of fibroblasts that produces high levels of ICAM-1.

Adult↗
PubMed1991

Enumeration of human peripheral blood lymphocytes secreting immunoglobulins of major classes and subclasses in healthy children and adults.

The reverse enzyme-linked immunospot assay was modified to enumerate peripheral blood mononuclear cells (PBMC) secreting IgG1-4, IgA1-2, and IgM. Anti-human IgG F(ab')2 and mouse monoclonal antibodies specific to each of the isotypes were used as solid-phase capture antibodies and developing antibodies, respectively. Although attempts were also made to detect IgD- and IgE-secreting cells (SC), their numbers in the peripheral blood were too few to be reliably estimated. The assay was applied to study healthy subjects including 21 neonates within 3 days of birth, 44 1- to 48-month-old children, and 32 adults. Sixty percent of these neonates had IgM SC in small numbers (less than 20 per 10(6) PBMC), but only three neonates had IgSC of other isotypes. In contrast, by 1-2 months of age children had IgSC of all isotypes, including IgA2 and IgG4, often in higher numbers than adults. The relative frequencies of IgSC were IgA1 greater than IgG1 greater than IgM greater than IgG2 greater than IgG3 greater than IgG4 greater than IgA2 in the children and IgA1 greater than IgG1 greater than IgA2 greater than IgM greater than IgG4 greater than IgG2 greater than IgG3 in the adults. The order of the serum concentrations in the adults was IgG1 greater than IgG2 greater than IgA greater than IgM greater than IgG4 greater than IgG3. No correlation was found between the serum level and the IgSC number of individual isotypes (except for serum IgA and IgA1-SC). This new methodology should facilitate investigating the current status of immunoglobulin synthesis and the Ig repertoire in adults and children, in health and in disease.

Adult↗
PubMed1991

Clinical and immunologic responses to Haemophilus influenzae type b-tetanus toxoid conjugate vaccine in infants injected at 3, 5, 7, and 18 months of age.

The safety and immunogenicity of Haemophilus influenzae type b-tetanus toxoid conjugate vaccine (Hib-TT) were evaluated in 77 healthy infants receiving injections at 3, 5, 7, and 18 months of age. No serious local or systemic reactions were noted. After the first injection the geometric mean Hib antibody level rose to 0.55 micrograms/ml, and each subsequent injection elicited a statistically significant rise in the geometric mean. The percentage of vaccinees with Hib antibody levels greater than 0.15 micrograms/ml serum was 75.5% after the first, 97.4% after the second, and 100% after the third Hib-TT injection. This percentage fell to 90.9% at 18 months of age but rose again to 100% after the fourth injection. Control infants (n = 10) injected with diphtheria-tetanus toxoid-pertussis vaccine only had nondetectable levels after the second injection. Hib-TT elicited increases of Hib antibody in all isotypes: IgG greater than IgM greater than IgA. Among IgG subclasses the highest increases were of IgG1. All vaccinated subjects had greater than 0.01 U/ml of TT antibody (estimated protective level) throughout the study. We conclude that Hib-TT, injected at 3, 5, 7, and 18 months, is safe and induces protective levels of antibodies during the age of highest incidence of meningitis caused by Hib.

Antibodies, Bacterial↗
PubMed1991

Serum immunoglobulin G subclasses in children infected with human immunodeficiency virus type 1.

We studied serum concentrations of IgG subclasses in 47 human immunodeficiency virus 1-infected (17 asymptomatic and 30 symptomatic) children. Thirty-nine of 47 (83%) had an abnormality of at least 1 subclass. Sixteen had only elevated IgG1, 6 had only elevated IgG3 and 12 had elevated IgG1 and IgG3 concentrations. IgG2, IgG4 and combined IgG2-IgG4 deficiency was found in 3, 4 and 4 patients, respectively. IgG2 concentrations did not differ between patients with (n = 23) or without (n = 24) bacterial infections. Additionally the number of bacterial infections was similar between the patients with normal or low IgG2 and/or low IgG4. These data indicate that IgG subclass abnormalities are found in most children with human immunodeficiency virus 1 infection, but quantitative deficiencies of specific subclasses do not appear to explain the high frequency of bacterial infections occurring in these patients.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Transcutaneous determination of tissue dihematoporphyrin ether content. A device to optimize photodynamic therapy.

Photodynamic therapy involves the use of light of appropriate wavelength to excite a photosensitizer resulting in tissue destruction. The photosensitizer dihematoporphyrin ether is selectively retained in tumors allowing for tumor destruction while sparing normal structures. Accessibility of skin tumors makes them well suited for photodynamic therapy. Tissue and tumor dihematoporphyrin ether content is estimated based on the amount of dihematoporphyrin ether administered. In our study, skin dihematoporphyrin ether content was measured in guinea pigs transcutaneously by a hand-held fluorometer and compared with dihematoporphyrin ether determinations done on skin biopsy specimens. Fluorometry was performed on guinea pigs receiving 0, 2.5, 5, 10, and 25 mg/kg of dihematoporphyrin ether. Transcutaneous measurements of skin fluorescence increased with increasing dihematoporphyrin ether dose and correlated well with skin dihematoporphyrin ether content as determined by extracting dihematoporphyrin ether from skin samples. Transcutaneous fluorescent measurements of guinea pigs given 0 and 2.5, 2.5 and 5, 5 and 10, and 10 and 25 mg/kg of dihematoporphyrin ether differed in a statistically significant manner. Transcutaneous fluorometric determination of dihematoporphyrin ether content and extraction of dihematoporphyrin ether from skin samples were able to reflect differences in dihematoporphyrin ether dosing and presumably skin dihematoporphyrin ether content. However, transcutaneous fluorometry provides an instantaneous estimate of tissue dihematoporphyrin ether without the need for a tissue sample. This may provide a clinical tool to predict more accurately the optimal light dose necessary to maximize photodynamic therapy.

Animals↗
PubMed1991

In vitro photodynamic treatment of normal and human papilloma virus-transfected keratinocytes with photofrin II and red light.

Photodynamic therapy involves the use of light of appropriate wavelength to excite a photosensitizer to result in tissue destruction. The photosensitizer dihematoporphyrin ether and red light were used to treat normal and human papilloma virus type 18-transfected keratinocytes in vitro. Although both cell lines were sensitive to treatment, normal keratinocytes retained more dihematoporphyrin ether and were more sensitive to photodynamic therapy than were transfected cells. In vitro data fail to show the selective retention of dihematoporphyrin ether reported elsewhere in the literature in papillomas and tumors. We did not find selective uptake or retention of dihematoporphyrin ether by human papilloma virus-transfected cells, despite previously published in vivo data to the contrary. Dihematoporphyrin ether retention and thus selective photosensitivity of papillomas in vivo is not caused by individual cellular differences in the processing of dihematoporphyrin ether. In addition, because in vitro results may not parallel in vivo results, both in vivo and in vitro models must be investigated in the study of phototherapeutic agents.

Antiviral Agents↗
PubMed1991

Subject attrition in prevention research.

Subject attrition threatens the internal validity of substance abuse prevention studies because differences in the rate of attrition and the substance use behavior of remaining subjects in the different conditions could account for any differences found in substance use rates. Attrition threatens the external validity of prevention studies because, to the extent that study dropouts are different from remaining subjects, the results of the study may not be generalizable to study dropouts. Analysis of these threats to the validity of prevention studies should be routinely conducted. However, studies of alcohol and drug abuse prevention have generally failed to report or analyze subject attrition. Smoking prevention studies have more frequently reported attrition, and they have recently begun to analyze the degree to which attrition may affect the internal and external validity of the study. Evidence thus far suggests that differences in attrition across conditions do occur occasionally. The evidence is substantial that study dropouts are systematically more likely to smoke, to use other substances, and to score highly on other risk-taking measures.

Alcoholism↗
PubMed1991

Expression of osteonectin, decorin, and transforming growth factor-beta 1 genes in fibroblasts cultured from patients with systemic sclerosis and morphea.

A characteristic feature of fibroblasts cultured from affected skin areas of patients with systemic sclerosis (SSc) and localized scleroderma (morphea) is excessive activation of collagen biosynthesis. To elucidate the nature of fibroblast activation in scleroderma we have studied the expression of 3 noncollagenous connective tissue components, osteonectin, small dermatan sulfate proteoglycan (proteoglycan II, decorin), and transforming growth factor-beta 1 (TGF-beta 1), by measuring their mRNA levels in fibroblast cultures from 6 patients with SSc and 3 with morphea. A clear correlation was observed between the increase in type I collagen and osteonectin mRNA in these cell lines. The apparent overproduction of osteonectin by scleroderma fibroblasts is in accordance with the suggested activation of osteonectin expression during tissue remodeling. The levels of decorin mRNA showed marked variation in the cell lines, but were in no correlation with collagen or osteonectin mRNA. The levels of TGF-beta 1 mRNA were found to be slightly elevated in fibroblasts grown from affected scleroderma skin. This may suggest that this potent activator of collagen production has a role during the initial activation of dermal fibroblasts both in SSc and morphea.

Adolescent↗
PubMed1991

Counseling the Hispanic male adolescent.

A rationale is given for providing counseling to Hispanic male adolescents. Characteristics of this population are discussed and specific techniques for counseling are suggested.

Adaptation, Psychological↗
PubMed1990

The efficacy of social-influence prevention programs versus "standard care": are new initiatives needed?

This study evaluates the effects of a school-based smoking prevention program after 1 year, using school (22 middle/elementary schools, 15 high schools) as both the unit of randomization and the unit of analysis. The multigrade level (grades 6 through 9) intervention was designed to address comprehensively the social influence factors that encourage smoking. Teacher survey data indicated that treatment schools had a median of 10 classroom sessions devoted to tobacco/drug use education, 5 of which were the sessions designed for this evaluation, and control schools had also dedicated a median of 10 classroom sessions to tobacco/drug education. Thus, the study evaluated the incremental effects of the social influence intervention compared to "standard-care" curricula. Among those who reported smoking one or more cigarettes in the month prior to the intervention, there was a significant treatment effect on rate of smoking at one year, but no grade level, gender, or interaction effects. The 1-year covariate-adjusted smoking rate among pretest smokers in the treatment schools was 76.6 cigarettes per month, compared to 111.6 cigarettes per month in control schools, a 31.4% difference. These effects were not accounted for by differential subject attrition. The analyses for nonsmokers, however, showed no significant effects, and the program did not affect self-reported alcohol or marijuana use. Taken together with the results of other prevention studies, these results point to the need for the development and evaluation of new initiatives to prevent substance use.

Adolescent↗
PubMed1990

Interpretation of IgG subclass values: a comparison of two assays.

Because we have noted discordant results in the measurement of IgG subclass concentrations by means of a widely available commercial radial immunodiffusion (RID) kit in comparison with an enzyme-linked immunosorbent assay (ELISA) developed at the Centers for Disease Control (CDC), we conducted in a blinded manner a comparison of the two assays, using sera from 48 healthy children. The correlation coefficients between the assays were 0.92, 0.82, 0.93, and 0.86 for the IgG1, IgG2, IgG3, and IgG4 assays, respectively. However, the RID assay assigned lower values for IgG1 and IgG4 determinations than the ELISA did. Furthermore, the "normal lower range values" provided by the RID assay were higher for each IgG subclass. When the sera from the healthy control subjects were analyzed with the RID assay, 12 (25%) of 48 subjects had values below the normal range for at least one subclass measurement. In contrast, with the CDC ELISA, all values were within the 95% confidence limits determined for the CDC ELISA. We suggest that age-specific normal limits be established with the use of sera from many healthy subjects for any assay measuring IgG subclass concentrations. As new groups of immunodeficiencies are defined and potential therapies are advocated, careful attention to assay standardization will result in a clearer delineation of these disease groups and of their response to treatment.

Child↗