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Biomedical subjects

C Richards

Publications and source records attributed to C Richards.

At least 55 records · Page 3Linked to original sources

A comparison of the performance of rating scales used in the diagnosis of postnatal depression.

The results of a study looking into the association between thyroid status and depression in the postpartum period were reanalysed to explore the psychometric properties of the rating scales employed. The performance of the Edinburgh Postnatal Depression Scale was found to be superior to that of the Hospital Anxiety and Depression Scale in identifying RDC-defined depression, and on a par with the observer-rated Hamilton Rating Scale for Depression, which it also matched for sensitivity to change in mood state over time. The anxiety subscale of the Hospital Anxiety and Depression Scale performed well, reflecting the fact that anxiety represents a prominent symptom in postnatal depression.

Adult↗

Cognitive-behavioural approach to understanding obsessional thinking.

BACKGROUND: Obsessional ruminations (obsessions without any accompanying overt compulsive behaviour) were previously considered especially difficult to treat. METHOD: Cognitive-behavioural theory regarding obsessional problems is discussed. Strategies for therapy developed on the basis of this theory are reviewed. RESULTS: The cognitive-behavioural theory of obsessive-compulsive disorder proposes that obsessional problems occur as a consequence of the particular meaning or significance which patients attach to the occurrence and/or content of intrusive thoughts. When intrusions are interpreted (appraised) as indicating increased personal responsibility, this results in both distress and the occurrence of neutralising behaviour. Cognitive-behavioural treatment seeks to change responsibility beliefs and appraisals, and thereby reduce distress and eliminate neutralising responses which usually occur as covert neutralising (mental rituals). Evidence is emerging for the success of therapy developed on this theoretical basis. CONCLUSIONS: Recent developments in the psychological conceptualisation of obsessional ruminations have improved the prospects for successful therapy.

Anxiety Disorders↗

Low-level c-myc amplification in human colonic carcinoma cell lines and tumors: a frequent, p53-independent mutation associated with improved outcome in a randomized multi-institutional trial.

Human colonic cancer is associated with multiple genetic deletions, mutations, and alterations in gene expression; in contrast, gene amplification has not been recognized as a prominent characteristic of human colonic tumors. Although the c-myc gene is overexpressed in approximately 70% of human colonic cancers, previous studies have not detected frequent gene amplification or rearrangement of c-myc in these tumors, although such amplification has been reported in chemically induced rodent colon cancer and quantitative analysis of gene copy number has shown the gene to be amplified at a low level in mucinous and poorly differentiated human colon carcinomas. Using rigorously controlled blot methodology, we have established that the c-myc gene, located at 8q21, exhibited amplification of 87% to 35-fold in 7 of 10 human colonic carcinoma cell lines. This was highly significant even at a low level of amplification in HT29 cells (P < 0.0001). Cytogenetic analysis by G-banding did not detect aneuploidy involving chromsome 8q, suggesting that the amplification for the c-myc gene on 8q was relatively specific, and this was consistent with a lack of amplification detected for the c-mos gene on 8q24, which was assayed similarly. The same methodology then revealed amplification of c-myc from 1.5-fold to 5-fold in 32% of tumors from 149 patients entered into a multi-institutional Phase III study of adjuvant therapy for colon cancer. c-myc status was not related to time to recurrence or death, but low levels of c-myc amplification identified a subset of patients who showed a statistically significant increase in disease-free survival, and a corresponding trend to longer overall survival, in response to adjuvant therapy with 5-fluorouracil plus levamisole. Presence of c-myc amplification was not related to incidence of p53 mutations.

Carcinoma↗

A controlled family history study of childhood-onset depressive disorder.

BACKGROUND: We studied the family psychiatric history of 125 youths with childhood-onset depressive disorder (a portion of whom developed bipolar disorder) and 55 psychiatric controls with nonaffective disorder. METHODS: Probands were classified according to prospectively observed clinical course in childhood. Family psychiatric history was determined by interviewers blind to probands' diagnosis, with mothers typically informing about themselves and about remaining first- and a all second-degree adult relatives. RESULTS: Families of affectively ill juveniles had 5-fold greater odds of lifetime depressive disorder and 2-fold greater odds of recurrent unipolar depressive disorder than did families of psychiatric controls. The higher risk of depression was most evident in first-degree and female relatives. Mothers of affectively ill youths were younger at onset of depression than were mothers of controls. Alcoholism and substance use disorders were more prevalent in relatives of affectively ill probands than in controls and cosegregated with familial depression. However, other covariates were more important at predicting patterns of familial depression. Familial illness patterns also varied somewhat with proband characteristics. CONCLUSIONS: Child probands with affective disorder identify families enriched with affective disorder (even compared with families of psychiatric controls), suggesting that juvenile- and adult-onset forms of this condition share the same diathesis. Rates of affective illness in the families of depressed youngsters also are notably higher than population-based estimates. The findings therefore indicate that very-early-onset affective disorder is familial and that pedigrees ascertained through affectively ill children are good candidates for family and genetic studies.

Adolescent↗

Reduced preference for sucrose in autoimmune mice: a possible role of interleukin-6.

In a continuous one-bottle sucrose intake test, 4-month-old autoimmune MRL-Ipr mice show a shift to the right along the X-axis of the concentration-intake function, compared to congenic MRL +/+ controls. Using a brief (60-min) and a continuous (48-h) two-bottle test, the present report examines potential factors that could account for the reduced responsiveness to a palatable stimulus. Study 1 examines whether preference for sucrose is associated with age, changes in food/water intake, or impaired renal function. Reduced preference for sucrose was observed in 5-6-week-old MRL-Ipr males, although food/water intake or blood creatinine levels did not differ from control values. Immunosuppressive treatment abolished this deficit, suggesting a role of immune factor(s). Study 2 tests the hypothesis that chronic upregulation of the neuroactive cytokine interleukin-6 (IL-6), reported to occur from 3 weeks of age in young MRL-Ipr mice, reduces preference for sucrose. Sustained administration of IL-6 was produced by infecting healthy MRL +/+, C3H.SW and Balb/C mice with adenovirus vector carrying cDNA for murine IL-6. This resulted in high serum IL-6 levels over 5 days, a rapid decline in preference for sucrose and low blood glucose levels. The results from Study 1 indicate that impaired sensitivity to sucrose in MRL-Ipr mice can be detected before autoimmune disease is florid in MRL-Ipr mice. The results from Study 2 are consistent with altered motivation/emotional states after infection, and point to sustained IL-6 production as an early mechanism in behavioral alterations during chronic autoimmune/inflammatory conditions.

Aging↗

Effect of pollination on accumulation of ACC synthase and ACC oxidase transcripts, ethylene production and flower petal abscission in geranium (Pelargonium x hortorum L.H. Bailey).

Self-pollination of diploid zonal geranium (Pelargonium x hortorum L.H. Bailey) florets leads to a dramatic rise in ethylene production, followed by abscission within 4 h. Neither wounding of the stigma, pollination with tetraploid pollen, nor heat-killed self pollen could elicit as much ethylene production and petal abscission as self-pollination. A cDNA sharing sequence identity with ACC synthase (GACS2) and three different cDNAs sharing sequence identity with ACC oxidase (GACO1, GACO2, GACO3) were isolated from geranium pistils. Transcripts hybridizing with these probes increased slightly in response to self-pollination, but the degree of accumulation in response to various treatments did not correlate with ethylene production. When calculated on a per-plant-part basis, transcripts hybridizing with GACS2 were equally distributed among the stigma+style, sterile ovary, and ovary tissues, but transcripts hybridizing with the three ACC oxidase clones were differentially distributed. All transcripts were differentially expressed among the other tissues of the plant, with GACO1 being the most widely distributed. Ethylene production in geranium pistils was not autocatalytic. Propylene failed to induce ethylene production and ethylene did not induce the accumulation of ACC synthase or ACC oxidase transcripts. ACC accumulated in the stigma and style, and to a smaller extent in the sterile ovary, after pollination. These data support a model of pollination-induced ethylene production by post-transcriptional regulation of ethylene biosynthetic gene expression.

Amino Acid Oxidoreductases↗

Mixed messages: implications of social conflict and social support within close relationships for adjustment to a stressful life event.

The authors examined the impact of women's perceptions of negative (conflict) and positive (support) exchanges with their mothers, partners, and friends before having an abortion on negative (distress) and positive (well-being) indexes of adjustment after the abortion. Preabortion conflict and support from the partner predicted postabortion adjustment in the same affective domain: Conflict uniquely predicted distress, whereas support uniquely predicted well-being. Within-source interactions were observed between support and conflict from mothers and friends. Women who perceived high support from their mothers or friends were more distressed if they also perceived them as sources of high conflict than if they perceived them as sources of low conflict. Among women who perceived their mothers or friends as nonsupportive, no relationship was observed between conflict and distress. Cross-source buffering was not observed.

Abortion, Induced↗

First-episode major depressive and dysthymic disorder in childhood: clinical and sociodemographic factors in recovery.

OBJECTIVE: To characterize the temporal pattern of depressive disorder in childhood, the first episode of depression was examined, focusing on recovery and its baseline predictors. METHOD: The sample includes 112 clinically referred 8- to 13-year-olds with first-episode major depressive or dysthymic disorder participating in a naturalistic follow-up study. Psychiatric diagnoses were based on standardized interviews and operational criteria. Recovery was modeled by multivariate procedures using baseline clinical and demographic predictors. RESULTS: Recovery rates were 86% and 7% for major depression and dysthymia, respectively, 2 years after onset. Median duration of major depression was 9 months and was predicted only by underlying dysthymia. Median duration of dysthymic disorder was 3.9 years and was predicted only by comorbid externalizing disorder. In post hoc analyses, no positive treatment effects were detected. CONCLUSIONS: First-episode depression in youths is persistent, it generally appears to run its own course, and its naturalistic treatment requires scrutiny. However, because comorbid externalizing disorder apparently affects duration of dysthymia, intervention for behavior problems may shorten this type of depression.

Adolescent↗

Increased expression of activated matrix metalloproteinase-2 by human endothelial cells after sublethal H2O2 exposure.

Basement membranes form a boundary between intravascular and extravascular compartments that is remodeled by matrix metalloproteinases (MMP) expressed by endothelial cells. These cells are at risk of exposure to reactive oxygen intermediates generated as a consequence of interactions with drugs, x-radiation, activated neutrophils, or cancer cells. Herein we have investigated the hypothesis that endothelial cells alter their expression of MMP after sublethel exposure to H2O2 and that this leads to degradation of adjacent basement membranes. Cultured human umbilical vein endothelial cells were treated with concentrations of H2O2 ranging from 1.5 to 32 microM or with 2 x 10(-6)M phorbol myristate acetate (PMA). After 24 hours, the cells were placed into serum-free medium for an additional 24 hours. This conditioned medium or cell lysates were studied by matrix degradation assays, gelatin zymography, immunoblots, and Northern analysis. H2O2-treated or PMA-treated cells, or their serum-free conditioned medium, caused a 2-fold increase in degradation of [3H]-proline-labeled endothelial basement membranes or purified type IV collagen compared to untreated cells. Endothelial cells constitutively expressed gelatinases at Mr 96,000 and 72,000, consistent with MMP-9 and inactive MMP-2. H2O2 exposure caused increased expression of these MMP and appearance of Mr 64,000 to 66,000 gelatinases corresponding to activated MMP-2. In cell lysates, H2O2 or PMA treatment led to increased expression of membrane-type MMP-1, an activator of latent MMP-2. The results suggest that oxidants such as H2O2 may stimulate MMP expression and influence the remodeling of vascular basement membranes by endothelial cells.

Basement Membrane↗

Evidence for genomic instability in human colonic aberrant crypt foci.

Aberrant crypt foci (ACF) are morphologically abnormal structures that can be identified in whole amounts of colonic tissue from rodents treated with colon carcinogens and from patients at risk for development of colon tumors. ACF are heterogeneous and exhibit properties, such as altered patterns of cell proliferation, the presence of dysplasia, and mutations in protooncogenes and tumor formation. In this study, we have investigated the presence of genomic instability in DNA isolated from human ACF from patients with colon cancer. Altered allele length detected by electrophoretic separation of PCR amplified oligo A or microsatellite loci was used to identify candidate samples which were then more rigorously investigated by sequence analysis for instability. Of 20 patients examined, two exhibited alterations at two loci, and this instability could be confirmed by sequence analysis. An additional seven of the 20 patients had evidence for instability at a single locus. Quantitative sequence analysis of the DNA from an ACF of one of these seven patients was consistent with alteration of allele length in this patient, but the alteration was not sufficiently different from normal to reach statistical significance. Thus, genomic instability, manifest as altered length of microsatellite and oligo A sequences, in present in some ACF, and therefore can be a very early event in the development of some human colon cancers.

Adult↗

General practice: at yet another cross-roads?

There have been enormous changes in general practice over the past couple of decades but we are now in danger of seriously overloading the system with continuous change. Public health practitioners have a role in recognising the contribution of personal and primary care to the delivery of health care and should work with general practice to ensure a creative partnership.

Family Practice↗

The diabetic BB rat. Neither Th1 nor Th2?

A long term objective of our work has been to identify and characterize the T cells responsible for causing autoimmune type I diabetes in the spontaneously diabetic BB rat. Based on the Th1/Th2 paradigm encompassing "regulated" and "regulatory" T cells, our analyses show that there are very few "regulatory" peripheral Th2 cells. The "regulated" T cells that remain express an unusual, immature phenotype that is neither Th1 nor Th2. Our data also indicate that transcript expression for p56lck, an enzyme required for T cell development, is abnormal in BB peripheral T cells. We discuss the role abnormal transcript expression of p56lck might play in retarding the development of mature regulatory Th2 cells while simultaneously influencing the escape of autoreactive T cells from the thymus.

Animals↗

Allergic reactions to oral, surgical and topical bovine collagen. Anaphylactic risk for surgeons.

BACKGROUND: Two cases of allergic (IgE-mediated) reaction to bovine collagen are described. Both patients developed conjunctival oedema in response to the topical application of highly purified bovine collagen to the eye during opthalmic surgery (corneal shields and catgut suture material). One patient developed periocular angioedema and angioedema of the throat after the ingestion of bovine collagen in the form of gelatin-containing foods. METHODS: The presence of allergen-specific IgE was evaluated by skin prick testing with collagen-derived products, and by topical challenge with a highly purified bovine collagen-derived corneal shield. RESULTS: In both patients, application of collagen to the eye reproduced the original subconjunctival oedema. In one patient, skin testing with purified and crude extracts of bovine collagen in the form of a corneal shield, catgut suture material and edible gelatin demonstrated evidence of collagen-specific IgE. CONCLUSIONS: Clinical reactions to collagen are rare. Nevertheless, patients with a history of allergic reactions to bovine collagen-derived products should be investigated because of the widespread use of collagen-derived therapeutic devices, the potential for immunological cross-reactivity with dietary collagen (gelatin) and the potential for anaphylaxis.

Administration, Oral↗

Monoclonal equine IgM and IgG immunoglobulins.

In order to define equine immunoglobulins (Igs) and to produce monoclonal reference Igs we fused equine peripheral blood mononuclear cells with X63-Ag8.653 non Ig producing murine myeloma cells. A total of 29 equine Ig producing equi-murine heterohybridomas were obtained, of which ten expressed equine Ig for more than 3 months. One of these heterohybridoma lines produced monoclonal IgM, an equine isotype which has not been available in monoclonal form before. Four lines secreted equine IgG of two distinct Ig heavy chain types as assessed by the molecular weight (MW), while the remaining five lines expressed only equine Ig light chains. A sixth Ig light chain expressing variant was obtained by cloning of one of the IgG producing heterohybridoma lines. These monoclonal IgGs were compared with previously described equine IgG monoclonal antibodies (mabs) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). According to their MW we identified five groups of gamma-chains and four groups of Ig light chains.

Animals↗

Assessment of in-line filters to prolong the life of intravenous cannulae in cystic fibrosis patients.

Twelve patients with cystic fibrosis received 12 courses of intravenous antibiotics, each over 10-14 days, both with and without the use of an extended-life disposable filter. The design of the trial was to replace the Venflon cannulae as they became non-patent and inserting a filter on alternate occasions. Thus each patient acted as her/his own control. Comparison of times during which cannulae remained patent showed a 50% improvement with use of a filter for 4 patients and no change for 7 patients. There was no significant difference associated with the use of a filter for the group as a whole but our small sample size excludes modest improvements.

Adolescent↗