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Biomedical subjects

D Wakefield

Publications and source records attributed to D Wakefield.

At least 73 records · Page 4Linked to original sources
PubMed1997

Small intestinal bacterial overgrowth in the symptomatic elderly.

OBJECTIVE: 1) To determine the prevalence of small intestinal overgrowth with colonic-type bacteria in symptomatic elderly subjects, particularly those without important "clues" such as clinically apparent predisposition or vitamin B12 deficiency, and 2) to investigate defense mechanisms such as gastric acidity, small intestinal motility, and luminal IgA in this setting. METHODS: Fifty-two symptomatic subjects without vitamin B12 deficiency or clinically apparent predisposition to bacterial overgrowth or disturbed mucosal immunity, including 22 subjects > or = 75 yr old, underwent culture of small intestinal luminal secretions. Indicator paper was used to measure fasting gastric pH. The presence of bacteria of confirmed nonsalivary origin in small intestinal secretions served as an index of small intestinal dysmotility. Small intestinal luminal IgA concentrations were measured by radial immunodiffusion. RESULTS: Small intestinal overgrowth with colonic-type flora was not present in any subject investigated for dyspepsia, irrespective of age. In subjects with chronic diarrhea, anorexia, or nausea, overgrowth with colonic-type flora (Enterobacteriaceae) was present in 0/12 (0%), 1/10 (10.0%), and 9/14 (64.3%) subjects aged < 50 yr, 50-74 yr, and > or = 75 yr, respectively. Enterobacteriaceae were not concurrently recovered from saliva of any subject > or = 75 yr old with small intestinal overgrowth with these bacteria. Fasting hypochlorhydria was present in only 1/9 (11.1%) such subjects. Luminal IgA concentrations were significantly greater in subjects > or = 75 yr old with bacterial overgrowth than in culture-negative subjects (p < or = 0.003). CONCLUSIONS: Small intestinal overgrowth with colonic-type bacterial should be considered in subjects > or = 75 yr old with chronic diarrhea, anorexia, or nausea, even in the absence of clues such as clinically apparent predisposition or vitamin B12 deficiency. Small intestinal dysmotility, rather than fasting hypochlorhydria or mucosal immunosenescence, probably is responsible for the prevalence of bacterial overgrowth in this group.

Aged↗
PubMed1997

Increased expression of matrix metalloproteinases in vivo in scleritis tissue and in vitro in cultured human scleral fibroblasts.

Scleritis is a sight-threatening inflammatory disorder of the eye characterized by the degradation of scleral matrix. Matrix metalloproteinases (MMPs) are ubiquitous proteolytic enzymes important in physiological and pathological processes, the activity of which is stringently controlled by the action of a family of natural antagonists, the tissue inhibitors of matrix metalloproteinases (TIMPs). We hypothesized that enhanced expression of MMPs, without the negative regulatory influence of TIMPs, may be a key feature of tissue destruction in inflammatory eye diseases, such as scleritis. The aim of this study was to localize and characterize cells expressing MMPs and TIMPs in sclera affected by necrotizing scleritis and, in a parallel study, to establish whether cytokines modulate MMP expression in cultured human scleral fibroblasts. In situ hybridization and immunohistochemical analyses indicated that resident scleral fibroblasts as well as inflammatory cells such as macrophages and T lymphocytes express stromelysin, gelatinase B, and TIMP-1 in necrotizing scleritis tissue. In addition, cytoplasmic immunoreactivity for tumor necrosis factor-alpha, an inducer of MMPs, was detected in infiltrating inflammatory cells. Cultured scleral fibroblasts stimulated with the combination of interleukin-1 alpha plus tumor necrosis factor-alpha increased TIMP-1 mRNA twofold above constitutive levels. By contrast, these cytokines induced a sevenfold increase in the steady-state levels of stromelysin mRNA. Using Western blotting, stromelysin and TIMP-1 protein production paralleled mRNA induction in cytokine-stimulated human scleral fibroblasts. Culture supernatants harvested from cytokine-stimulated human scleral fibroblasts were subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis gelatin substrate zymography. Our results revealed a prominent 92-kd gelatinolytic band corresponding to gelatinase B, which was inducible with interleukin-1 alpha. These data provide evidence for our hypothesis, that an imbalance between enzyme/inhibitor ratios may be the underlying mechanism of the tissue destruction characteristic of scleritis. Our results demonstrate the potential involvement of MMPs and their modulation by cytokines produced by infiltrating inflammatory cells in destructive ocular inflammation.

Adult↗
PubMed1997

Luminal antigliadin antibodies in small intestinal bacterial overgrowth.

OBJECTIVE: Elevated antigliadin antibody levels in small intestinal luminal secretions of subjects with normal or only mildly abnormal small intestinal histology are considered indicative of "latent" or "potential" celiac disease. The purpose of this study was to determine whether small intestinal bacterial overgrowth (SIBO) might provide an alternative explanation for positive luminal antigliadin antibodies in such subjects. METHODS: Twenty-six adult subjects without predisposition to disturbed mucosal immunity were investigated with culture of small intestinal luminal secretions. Luminal total IgA and IgA-antigliadin antibody concentrations were measured by radial immunodiffusion and indirect enzyme immunoassay, respectively. Local mucosal counts of IgA-plasma cells were determined by immunohistochemistry. Small intestinal histology and intraepithelial lymphocyte counts were assessed by light microscopy. Corresponding serum antigliadin antibody concentrations were determined. RESULTS: SIBO was present in 17/26 (65.4%) subjects. No subject with SIBO had villous atrophy. Luminal total IgA concentrations (p < 0.0005), mucosal IgA-plasma cell counts (p < 0.01), and intraepithelial lymphocyte counts (p < 0.01) were significantly increased in subjects with SIBO. Luminal IgA-antigliadin antibodies were detected in 6/17 (35.3%) subjects with SIBO and 0/9 (0%) subjects without SIBO. Luminal IgA-antigliadin antibody concentrations correlated significantly with luminal total IgA levels (p < 0.01) but not with serum values (p < 0.1). Serum IgG-antigliadin antibody concentrations were elevated in 2/6 (33.3%) subjects with SIBO and positive luminal antigliadin antibodies. CONCLUSIONS: SIBO may be an alternative explanation to "latent" or "potential" celiac disease for positive luminal antigliadin antibodies in subjects with either normal or only mildly abnormal small intestinal histology, even when serum antigliadin antibody concentrations are elevated. Positive luminal antigliadin antibodies in SIBO probably occur as epiphenomena in the context of a graded mucosal immune response to local bacterial antigens.

Adult↗
PubMed1996

Increased production of interleukin-2 (IL-2) but not soluble interleukin-2 receptors (sIL-2R) in unmedicated patients with schizophrenia and schizophreniform disorder.

This study investigated immune activation, as measured by production of interleukin-2 (IL-2) and soluble interleukin-2 receptors (sIL-2R) from stimulated lymphocytes, in schizophrenia and schizophreniform disorder. The study included 13 neuroleptic-free patients, 13 medicated patients and 13 age- and sex-matched control subjects. Production of IL-2 and sIL-2R by peripheral blood mononuclear cells (PBMCs) was measured after in vitro stimulation with phytohaemagglutinin (PHA). Patients' symptoms were rated on the Scales for Assessment of Positive (SAPS) and Negative Symptoms (SANS) and the Brief Psychiatric Rating Scale (BPRS). IL-2 production by stimulated lymphocytes was significantly elevated in neuroleptic-free patients compared with both medicated patients and control subjects. IL-2 production was inversely correlated with the SAPS subscales of bizarre behaviour and formal thought disorder. The pattern of increased IL-2 production is in contrast to previous findings in patients with schizophrenia. Significant associations with clinical rating scores suggest that IL-2 production may vary in different biological subgroups of schizophrenia and schizophreniform disorder.

Adult↗
PubMed1996

Modulation of endothelial cell expression of ICAM-1, E-selectin, and VCAM-1 by beta-estradiol, progesterone, and dexamethasone.

The aim of this study was to examine the effects of beta-estradiol, progesterone, and dexamethasone on cytokine-stimulated endothelial cell expression of adhesion molecules. TNF-alpha (250 U/mL) and IL-1 alpha (50 U/mL) were used to stimulate the endothelial cells for 6 or 23 hr in vitro. Indirect immunofluorescence and flow cytometry were used to quantitate expression of adhesion molecules. After 6 hr stimulation with TNF-alpha increased expression of E-selectin (P < 0.03) was noted with beta-estradiol. Strong suppression of ICAM-1 (P < 0.005) and E-selectin (P < 0.005) expression was evident with dexamethasone, which did not influence VCAM-1 expression. After 6 hr stimulation with IL-1 alpha suppression of E-selectin was observed with progesterone (P < 0.001). Dexamethasone had strong suppressive effects on ICAM-1 (P < 0.001), E-selectin (P < 0.0001), and VCAM-1 (P < 0.0002). After 23 hr stimulation with IL-1 alpha or TNF-alpha none of the examined steroids showed a significant effect on the fluorescence intensity of adhesion molecules, although there was a slight increase of the percentage of ICAM-1 positive cells with high concentrations of beta-estradiol after stimulation with TNF-alpha. Beta-estradiol and progesterone are modulatory factors of E-selectin expression on endothelial cell in vitro. Dexamethasone reduces adhesion molecule expression over endothelial cells after cytokine stimulation. These effects may be important in understanding the role of these steroids in autoimmune diseases.

Cells, Cultured↗
PubMed1996

Expression of selectins (CD62 E,L,P) and cellular adhesion molecules in primary Sjögren's syndrome: questions to immunoregulation.

Adhesion molecules are important signal transmitters of the immune system and may mediate the homing of leukocytes to sites of inflammation. The aim of this work was to examine the presence of selecting and cellular adhesion molecules on epithelial and endothelial cells in labial salivary glands (LSG) in Sjögren's syndrome (SS). LSG biopsies were obtained from patients with primary SS (n = 31) and normal subjects (n = 21). Cryostat sections were examined with indirect immunoperoxidase. Epithelial cells in LSG from both patients and controls expressed LFA-3 (CD58) and Hermes I (CD44). A significantly increased number of acinar and ductal epithelial cells in LSG from patients expressed class I MHC (74%, as mean percentage of ductal epithelial cells) (P < 0.05), HLA-DR (58%) (P < 0.0001), and HLA-DQ (11%) (P < 0.001). To a lesser extent limited ICAM-1 (CD54) epithelial expression (6%) was noted only in a few biopsies from patients but none of the controls. Epithelial cells did not express any of the selectins CD62 E, L, and P and sometimes they expressed sialyl Le(x) (a ligand for selectins). Although the number of endothelial structures expressing ICAM-1 (CD54), HLA-DR, HLA-DQ, and class I MHC (per surface area) was increased in patients (P < 0.05), this may be due to the total increase of number of endothelial structures (P < 0.05) (Von Willebrand factor +ve) as part of the chronic inflammatory process. A smaller proportion of endothelial structures expressed E-selectin (CD62 E) (32%) and to a lesser extent VCAM-1 (CD106) (approximately 7%) as detectable only in some LSG from patients. P-selectin (CD62 P) was demonstrated on about one-third of endothelial structures in LSG from patients. Infiltrating mononuclear cells expressed CD11a (68%), CD18 (73%), CD11b (13%), CD11c (21%), CD58 (13%), CD4 (44%), CD8 (17%), CD62L (L-selectin) (18%), CD49d (38%), CD49e (15%), CD2 (56%), and CD44 (77%). The relatively reduced number of CD62 L +ve lymphocytes may be due to shedding of that molecule after activation. Sialyl Le(x) was not detectable on infiltrating lymphocytes. Although infiltrating mononuclear cells were activated, as evidenced by their expression of HLA-DR (72%) and ICAM-1 (55%), they did not express IL-2Ralpha (CD25, confirmed by two antibodies 2A3 and ACT1) or IL-2Rbeta (CD122), except rarely (< or = 1%). In some biopsies, CD106 and CD11c were localized on lymphocytes at the central areas of periductal lymphoid follicles with the appearance of dendritic cells. We conclude that adhesion molecules probably play a major role in the pathogenesis of SS. The pattern of expression of these molecules demonstrates a regulated altered activation in the glands associated with this disease. The glands may be subject to specific regulatory factors, in addition to proinflammatory cytokines.

Adult↗
PubMed1996

Mucosal cytokine production in small-intestinal bacterial overgrowth.

BACKGROUND: Mucosal production of interferon-gamma, interleukin-6, and tumour necrosis factor-alpha is increased in inflammatory bowel disease and parallels disease activity. Interferon-gamma production is also increased in coeliac disease. Conversely, local cytokine profiles have not been investigated in small-intestinal bacterial overgrowth. This study addressed this issue. METHODS: Eighteen adult subjects were studies with culture of proximal small-intestinal luminal secretion and measurement of luminal interferon-gamma, interleukin-6, and tumour necrosis factor-alpha concentrations by enzyme-linked immunosorbent assay. Small-intestinal histology was assessed by light microscopy. RESULTS: Interferon-gamma, interleukin-6, and tumour necrosis factor-alpha were measurable in proximal small-intestinal luminal secretions of all subjects, even in the absence of light microscopic evidence of enteropathy. Small-intestinal bacterial overgrowth was present in 12 of 18 (66.7%) subjects. Luminal concentrations of neither interferon-gamma nor tumour necrosis factor-alpha differed significantly in subjects with and without small-intestinal bacterial overgrowth (P + 0.06 and P = 1.0, respectively). Conversely, luminal interleukin-6 concentrations were significantly increased in subjects with this disorder (P = 0.02). Multivariate linear regression analysis suggested that colonic-type rather than salivary-type flora mediated this increased interleukin-6 response (P = 0.02 and P = 0.64, respectively). No correlation was found between luminal interleukin-6 and tumour necrosis factor-alpha concentrations, even after the confounding influence of colonic-type bacteria was excluded (P = 0.60). CONCLUSIONS: These findings suggest that increased mucosal production of interleukin-6 occurs in small-intestinal bacterial overgrowth, particularly when the overgrowth flora includes colonic-type bacteria. Conversely, luminal levels of neither interferon-gamma nor tumour necrosis factor-alpha are increased in the circumstance, distinguishing the local cytokine profile in this disorder from those that occur in coeliac disease and inflammatory bowel disease.

Adult↗
PubMed1996

The expression of complement protein 4 and IgG3 in luminal secretions.

BACKGROUND: Factors regulating proximal small-intestinal luminal concentrations of IgG3, the predominant IgG subclass at this site, are unclear. This study determined whether luminal IgG3 concentrations are related to those of complement protein 4 (C4), an acute-phase reactant predominantly derived from local mucosa. METHODS: Proximal small-intestinal luminal and peripheral blood IgG subclass and C4 concentrations were measured by radial immunodiffusion in 30 adult subjects without predisposition to disturbed mucosal immunity. Mucosal C4 immunoreactivity and the presence or absence of small-intestinal bacterial overgrowth were determined in all subjects. Caecal luminal concentrations of IgG3 and C4 were measured in a separate cohort of eight asymptomatic subjects. RESULTS: Proximal small-intestinal luminal C4 and IgG subclass concentrations were not significantly influenced by the presence of absence of small-intestinal bacterial overgrowth (P > 0.2). Nor did plasma C4 levels significantly influence C4 concentrations in small-intestinal luminal secretions (P > 0.2). Mucosal immunoreactivity for C4 was present in every subject. A significant correlation was found between C4 and IgG3 concentrations in proximal small-intestinal luminal secretions (P < 0.0005) and also in caecal secretions (P < 0.05) but not in peripheral blood (P > 0.1). CONCLUSIONS: Common factors, not including the presence or absence of small-intestinal bacterial overgrowth, regulate luminal concentrations of C4 and IgG3. Local investigation is mandatory when assessing mucosal immune mechanisms.

Cecum↗
PubMed1996

Luminal immunity in small-intestinal bacterial overgrowth and old age.

BACKGROUND: The independent influences of small-intestinal bacterial overgrowth and old age on mucosal immunoglobulin production and secretion have not been assessed. This is an important issue, since luminal IgA deficiency may exacerbate small-intestinal bacterial overgrowth, the prevalence of which is high in selected elderly populations. METHODS: Proximal small-intestinal aspirates were obtained from 33 subjects for bacteriologic analysis and measurement of total IgA, IgM, total IgG. IgG subclass, and IgD concentrations. IgA subclasses were measured in 24 unselected subjects. Serum immunoglobulin and salivary IgA concentrations were measured in all subjects. RESULTS: IgA2 and IgG3 were predominant IgA and IgG subclasses in proximal small-intestinal luminal secretions. Luminal concentrations of IgA2 and IgM, but not IgG3 or any other IgG subclass, were significantly increased in small-intestinal bacterial overgrowth, which was present in 19 of 33 (57.6%) subjects. Old age did not influence these levels. Luminal immunoglobulin concentrations did not correlate significantly with either serum or salivary values. IgD was not measureable in proximal small-intestinal secretions. CONCLUSIONS: Increased luminal concentrations of the secretory immunoglobulins, IgA2 and IgM, occur in small-intestinal bacterial overgrowth. Local investigation is mandatory when assessing the mucosal immunopathology of this disorder. Luminal IgG3 is unlikely to be predominantly derived from serum. Old age does not independently influence luminal immunity.

Age Factors↗
PubMed1996

Increased matrix metalloproteinases in the aqueous humor of patients and experimental animals with uveitis.

PURPOSE: Matrix metalloproteinases (MMPs) play a major role in connective tissue remodelling, wound healing and embryogenesis. They have also been implicated in pathological tissue degradation in diseases such as rheumatoid arthritis (RA), osteoarthritis (OA), and tumor invasion. The aim of this study was to define the potential role of MMPs in the inflammatory process of uveitis by identifying these proteases in the aqueous humor (AH) of patients with uveitis and in rabbits with endotoxin-induced uveitis (EIU). METHODS: Aqueous humor samples from 6 patients with uveitis and 5 control patients who had undergone elective cataract surgery were examined. The profile of MMPs in the AH of experimentally-induced acute anterior uveitis in rabbits was also assessed. Western blot analysis and SDS-PAGE substrate zymography were used to detect metalloenzymes and their natural inhibitor, tissue inhibitor of metalloproteinase (TIMP-1) in aqueous samples. RESULTS: Aqueous humor from all patients contained interstitial collagenase (MMP-1), stromelysin (MMP-3), gelatinase B (MMP-9) and TIMP-1. Although the amount of MMPs varied considerably, TIMP-1 levels remained unchanged in the aqueous of uveitis patients. Using substrate gel zymography, we were able to reveal several gelatinolytic bands, including one major band at approximately 92-kDa whose activity differed between uveitis and cataract AH. The gelatinase activity found in human AH samples was shown to be inhibited by 10 mM EDTA and activated in vitro by APMA, indicating that these enzymes were indeed of the metalloproteinase class. Aqueous humor samples from the rabbit EIU model revealed a 100-kDa molecular weight species likely to correspond to gelatinase B. This gelatinolytic activity was maximal at 6 hours after the lipopolysaccharide (LPS) injection, declined at 12 and 24 hours post LPS, and was absent at later time points. The induction of gelatinase activity in rabbit AH preceded the increase in cell number during the inflammatory process in the anterior chamber. CONCLUSIONS: Metalloproteinases found in normal human AH may participate in physiological turnover of extracellular matrix in the eye. Elevated levels of MMPs were found in the AH of patients with uveal inflammation and animals with LPS-induced uveitis, where they are likely to be critical to tissue destructive and repair processes. It is likely that pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 alpha (IL-1 alpha), which are known modulators of MMPs, induce their secretion in acute anterior uveitis.

Acute Disease↗
PubMed1996

Chemokines and T lymphocyte recruitment to lymph nodes in HIV infection.

Recruitment of T lymphocytes to lymph nodes in patients with HIV infection is critical to the pathogenesis of disease. Chemokines are a family of cytokines, which are potent regulators of leukocyte migration. We studied the leukocyte populations and expression of chemokines known to be active upon T cells in lymph nodes of four HIV infected patients and seven control subjects using in situ hybridization, immunohistochemistry, and FACS analysis. The HIV lymph nodes showed CD8+ T lymphocyte accumulation and strongly enhanced chemokine expression, notably for the CD8+ T cell chemoattractant, macrophage inflammatory protein (MIP)-1 alpha. Resident macrophages appeared to be a major cellular source of chemokines in the HIV nodes. RANTES expression was present in both HIV and control lymph nodes, suggesting a physiological role for this chemokine in T lymphocyte recirculation. Chemokines may be important determinants of T lymphocyte accumulation in lymphoid tissue of patients with HIV/AIDS.

Adult↗
PubMed1996

Is there a postinfection fatigue syndrome?

Prolonged fatigue syndromes are common in general practice. Most of these syndromes are secondary to other common medical or psychological disorders. It appears, however, that some specific infectious illnesses are associated with prolonged recovery. Theories as to the mechanisms for such post infection fatigue syndromes include a range of immunological, psychological and neurobiological processes. Current evidence suggests disruption of fundamental central nervous system mechanisms, such as the sleep-wake cycle and the hypothalamic-pituitary-adrenal axis, may underpin the clinical features of this disorder. Treatment should focus on the provision of continuous medical care, physical rehabilitation and adjunctive psychological therapies.

Fatigue↗
PubMed1995

Chronic fatigue syndrome: current perspectives on evaluation and management.

OBJECTIVE: To describe clinical and laboratory guidelines for assessment and management of patients presenting with chronic fatigue syndrome (CFS). DATA SOURCES: Relevant international consensus diagnostic criteria and research literature on the epidemiology, pathophysiology, concurrent medical and psychological disturbance and clinical management of CFS. CONCLUSIONS: Medical and psychiatric morbidity should be carefully assessed and actively treated, while unnecessary laboratory investigations and extravagant treatment regimens should be avoided. No single infective agent has been demonstrated as the cause of CFS, and immunopathological hypotheses remain speculative. The aetiological role of psychological factors is debated, but they do predict prolonged illness. The rate of spontaneous recovery appears to be high. Effective clinical management requires a multidisciplinary approach, with consideration of the medical, psychological and social factors influencing recovery.

Fatigue Syndrome, Chronic↗
PubMed1995

In vivo and in vitro expression of adhesion molecules by peripheral blood lymphocytes from patients with primary Sjogren's syndrome: culture-associated enhancement of LECAM-1 and CD44.

The interaction of adhesion receptors on lymphocytes with their ligands over endothelial cells provides the mechanism by which lymphocytes infiltrate target tissues in autoimmune diseases. Primary Sjogren's syndrome (SS) is associated with lymphocytic infiltration in exocrine glands. The aim of this study was to examine levels of expression of adhesion molecules by peripheral blood lymphocytes from patients with SS (before and after stimulation). Peripheral blood lymphocytes from 16 patients with primary SS and from 15 controls were stained directly or cultured for 72 h with and without phytohaemagglutinin (PHA). Indirect immunofluorescence with monoclonal antibodies and flow cytometry were used. The following molecules were detected in patients before culture: CD18 (mean percentage 94%), CD11a (94%), CD11b (39%), CD54 (23%), CD58 (62%), CD44 (Hermes-1; 82%), CD49-d (VLA-4; 80%), CD25 (11%) and LECAM-1 (62%). After stimulation with PHA, there was an increase in the levels of CD18 (2.5-fold), CD11a (2.3-fold), CD54 (10.2-fold), CD58 (2.5-fold), CD44 (2.4-fold), CD49d (3.4-fold) and CD25 (62-fold) on lymphocytes from both patients and controls. The number of positive cells and level of expression did not differ from the controls, except in the case of unstimulated, cultured lymphocytes in which the levels of CD44 and LECAM-1 were increased more in patients than in normal controls. The increase in the level of in vitro expression of CD44 (P < 0.05) and LECAM-1 (P < 0.002) on lymphocytes from patients with primary SS reached statistical significance when compared to similarly cultured lymphocytes from controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Delayed-type hypersensitivity skin testing: normal values in the Australian population.

In our human psychoimmunological studies we have utilized a standardized assessment kit, the cell-mediated immunity (CMI) Multitest system, for determining delayed-type hypersensitivity (DTH) skin responses to a panel of ubiquitous antigens. Although the kit had been assessed in large populations of healthy controls in the U.S.A. and Europe, few data were available with regard to normative values in the Australian population. There are cogent reasons to suspect that results for the test will vary depending on geographical location, age cohort, compliance with specific immunization schedules and rates of natural exposure to certain diseases in differing populations. Most of our patient cohorts have a preponderance of female subjects and most standardization had been conducted in males. We tested medically and psychologically healthy males (n = 66) and females (n = 53). The percentage of positive responses to individual antigens was similar to other Australian studies but lower than that reported internationally. The mean number of positive responses was 3.7 for men and 2.8 for women, while the mean induration diameter was 17.5 mm for men and 12.2 mm for women. Three per cent of men and 5.6% of women were anergic (no positive responses), while a further 10.6% of men and 9.4% of women fell into the "hypoergic" category. These results, and those from other studies, indicate that the pattern of response to the CMI Multitest differs in healthy Australians. Therefore, researchers need to exercise caution when selecting patient and control samples (controlling for exposure factors), applying the test, reporting results (i.e. including all relevant parameters-with an emphasis on dimensional rather than categorical scores) and when designating subjects as having "impaired" responses.

Adolescent↗
PubMed1995

Biochemical correlates of in vivo cell-mediated immune dysfunction in patients with depression: a preliminary report.

We have previously demonstrated that at least 50% of patients with melancholia have impaired cell-mediated immunity (CMI) as assessed by delayed-type hypersensitivity (DTH) skin responses to a standardized battery of antigens. Hypercortisolaemia and increased circulating catecholamines both occur in patients with severe depressive disorders and each has been proposed as a possible mediator of observed immune abnormalities in patients with mood disorders. As part of a larger study, we collected 24 h urine samples from 28 patients with major depression and measured concentrations of urinary free cortisol (UFC), the noradrenaline metabolite dihydroxyphenylglycol (DHPG), adrenaline, and the dopamine metabolite DOPAC. CMI multitest skin testing revealed a reduced or absent response in 54% of subjects. Those with reduced DTH skin responses demonstrated increased urinary adrenaline (P < 0.02), with trends toward increased UFC (P = 0.052) and increased DHPG (P = 0.06). These differences could not be attributed to differences in age or depression severity. Correlational analyses demonstrated inverse associations between the extent of DTH responsiveness and 24 h levels of urinary adrenaline and DHPG, with similar trends evident for UFC and DOPAC. These results suggest that both circulating catecholamines and cortisol may play roles in the reduction of CMI in patients with severe depression.

3,4-Dihydroxyphenylacetic Acid↗