Brief psychotic episodes in puberty.
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Adolescent↗
Biomedical subjects
A Lloyd
Publications and source records attributed to A Lloyd.
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↗
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↗
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↗
HIV infection and AIDS.
Many of the clinical features of HIV/AIDS can be ascribed to the profound immune deficiency which develops in infected patients. The destruction of the immune system by the virus results in opportunistic infection, as well as an increased risk of autoimmune disease and malignancy. In addition, disease manifestations related to the virus itself may occur. For example, during the primary illness which occurs within weeks after first exposure to HIV, clinical symptoms occur in at least 50% of cases, typically as a mononucleosis syndrome. HIV-related complications are rarely encountered in patients with preserved immunity (i.e. CD4 T-cell counts greater than 500 cells/mm3). Recurrent mucocutaneous herpes simplex (HSV), herpes zoster (VZV), oral candidiasis and oral hairy leukoplakia occur with increasing frequency as the CD4 count drops below this level. Immune thrombocytopenia (ITP) occurs in association with HIV and often presents early in the clinical course. The risk of developing opportunistic infections and malignancies typical of AIDS increases progressively as CD4 counts fall below 200 cells/mm3. The clinical manifestations of infections associated with AIDS tend to fall into well-recognized patterns of presentation, including pneumonia, dysphagia/odynophagia, diarrhoea, neurological symptoms, fever, wasting, anaemia and visual loss. The commonest pathogens include Candida albicans, Pneumocystis carinii, Mycobacterium tuberculosis, Toxoplasma gondii, Cryptococcus neoformans, Mycobacterium avium intracellulare and cytomegalovirus. Malignant disease in patients with HIV infection also occurs in a characteristic pattern. Only two tumours are prevalent: Kaposi's sarcoma, a multifocal tumour of vascular endothelium which typically involves skin and mucosal surfaces; and non-Hodgkin's lymphoma, which is typically high grade in phenotype, often arising within the central nervous system. The principles of therapy include reduction of HIV replication by antiretroviral agents, prophylaxis against the common opportunistic infections and treatment followed by subsequent lifelong maintenance therapy for infections when they do occur.
AIDS-Related Opportunistic Infections↗
Management development. Scaling the dizzy heights.
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Administrative Personnel↗
Priorities in humanitarian relief.
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Adult↗
On the functional overlap between two Drosophila POU homeo domain genes and the cell fate specification of a CNS neural precursor.
The approximately 200 distinct neurons comprising each hemisegment of the Drosophila embryonic CNS are derived from a stereotypic array of approximately 30 progenitor stem cells, called neuroblasts (NBs). Each NB undergoes repeated asymmetric divisions to produce several smaller ganglion mother cells (GMCs), each of which, in turn, divides to produce two neurons and/or glia cells. To understand the process by which cell type diversity is generated in the CNS, we are focusing on identifying genes that affect cell identity in the NB4-2 lineage from which the RP2 motoneuron is derived. We show here that within the early part of the NB4-2 lineage, two closely linked and structurally related POU homeo domain genes, pdm-2 (dPOU28) and pdm-1 (dPOU19), both encode proteins that accumulate to high levels only in the first GMC (GMC4-2a) and not in its progeny, the RP2 motoneuron. Our results from the genetic and developmental analysis of pdm-1 and pdm-2 demonstrate that these genes are not required for the birth of GMC4-2a; however, they are both involved in specifying the identity of GMC4-2a and, ultimately, in the genesis of RP2 neurons, with pdm-2 being the more dominant player in this process. In mutant animals where both pdm-1 and pdm-2 functions are removed, GMC4-2a fails to express markers consistent with a GMC4-2a identity and no mature (Eve protein expressing) RP2 neurons are produced. We demonstrate that in some mutant combinations in which no mature RP2 neurons are produced, some GMC4-2a cells can nevertheless divide. Hence, the failure of the POU mutants to produce mature RP2 neurons is not attributable to a block in GMC4-2a cell division per se but, rather, because the GMC4-2a cells fail to acquire their correct cellular identity.
Animals↗
Analysing your organisation and environment and setting its strategy.
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Budgets↗
CD8+ and CD45RA+ human peripheral blood lymphocytes are potent sources of macrophage inflammatory protein 1 alpha, interleukin-8 and RANTES.
The chemokines macrophage inflammatory protein 1 alpha (MIP 1 alpha), interleukin-8 (IL-8) and RANTES are potent regulators of leukocyte trafficking. Examination of chemokine secretion by human peripheral blood lymphocytes after stimulation with anti-CD3 or phorbol 12, 13 myristate acetate and ionomycin showed CD8+ cells were the dominant source of MIP 1 alpha and RANTES. Although production of MIP 1 alpha and IL-8 were similar in pharmacologically stimulated CD4+ CD45RA+, CD4+ CD45RO+, and CD8+ CD45RA+ cells, the largest amounts of MIP 1 alpha and RANTES were secreted by CD8+ CD45RO+ lymphocytes. A parallel pattern of prolonged chemokine mRNA expression for at least 18 h after activation was observed in the T cells subsets. These results confirm that human T lymphocytes have a unique capacity for secretion of these three chemokines. In addition, CD8+ cells have an unrecognized role in recruiting cells to sites of inflammation, and adult human CD45RA+ cells have a physiologically significant secretory capacity.
Blotting, Northern↗
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↗
Are cytokines associated with neuropsychiatric syndromes in humans?
Traditional aetiological models in neuropsychiatry have placed little emphasis on the abnormal behavioural responses (decreased psychomotor activity, anorexia, weight loss, decreased social exploration and sexual behaviour, impaired cognitive function and increased somnolence) that are common to both psychiatric syndromes, notably depression, and the illness behaviour of sick animals. In recent years, the possible role of cytokines, as mediators of not only the immunological and metabolic responses to infection and inflammation but also a co-ordinated behavioural response, has been described. Further, a range of possible mechanisms for these effects has been postulated, notably involving corticotropin releasing factor (CRF) and prostaglandins of the E series (PgE) with the central nervous system (CNS). Here we outline a series of human clinical conditions where neuropsychiatric syndromes co-occur with a host response to infection or inflammation. These may be characterized by cytokine production (e.g. acute, recurrent and chronic viral illness, systemic autoimmune diseases and chronic fatigue syndrome). Other clinical situations characterized by exposure to or in vivo production of cytokines (e.g. treatment of chronic infections and malignancies, progression and/or recurrence of malignancies) are also discussed. We postulate that the stereotyped behavioural repertoire observed is mediated by cytokine-dependent mechanisms within the CNS. Systematic studies of the behavioural responses of such patient groups are suggested, noting specifically correlations between the time course and severity of immune and neuroendocrine and behavioural responses and dose-response effects.
Animals↗
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↗
Cell-mediated immune function and the outcome of chronic fatigue syndrome.
This study examined the importance of cell-mediated immunity in determining the long-term outcome of patients diagnosed with chronic fatigue syndrome (CSF). A total of 103 patients (74%) of 139 previously enrolled in one of two treatment trials conducted within a university hospital referral center was reviewed a mean of 3.2 yr after trial entry. Ongoing symptom severity, levels of disability and immunological function were assessed at follow-up. The relationship between immunological function at trial entry and measures of outcome was also evaluated. Sixty-five patients (63%) had improved, while only 6 (6%) reported no current symptoms. Thirty-one subjects (30%) were unable to perform any form of work and 26 (25%) were on a disability benefit directly attributable to CFS. Cell-mediated immune function, as measured at trial entry or follow-up, did not appear to affect outcome. Whilst improvement occurred in the majority of patients with CFS, a substantial proportion (37%) remained functionally impaired. Impairment of cell-mediated immunological function measured during the course of the illness may not be an important factor in determining long-term outcome.
Adult↗
Can the chronic fatigue syndrome be defined by distinct clinical features?
To determine whether patients diagnosed as having chronic fatigue syndrome (CFS) constitute a clinically homogeneous class, multivariate statistical analyses were used to derive symptom patterns and potential patient subclasses in 565 patients. The notion that patients currently diagnosed as having CFS constitute a single homogeneous class was rejected. An alternative set of clinical subgroups was derived. The validity of these subgroups was assessed by sociodemographic, psychiatric, immunological and illness behaviour variables. A two-class statistical solution was considered most coherent, with patients from the smaller class (27% of the sample) having clinical characteristics suggestive of somatoform disorders. The larger class (73% of sample) presented a more limited combination of fatigue and neuropsychological symptoms, and only moderate disability but remained heterogeneous clinically. The two patient groups differed with regard to duration of illness, spontaneous recovery, severity of current psychological morbidity, utilization of medical services and CD8 T cell subset counts. The distribution of symptoms among patients was not unimodal, supporting the notion that differences between the proposed subclasses were not due simply to differences in symptom severity. This study demonstrated clinical heterogeneity among patients currently diagnosed as CFS, suggesting aetiological heterogeneity. In the absence of discriminative clinical features, current consensus criteria do not necessarily reduce the heterogeneity of patients recruited to CFS research studies.
Fatigue Syndrome, Chronic↗
Sealability of the Trifecta technique in the presence or absence of a smear layer.
The aim of this in vitro study was to assess the sealability of a recently introduced thermoplasticized gutta-percha technique (Trifecta, Hygenic Corp., OH, USA) in the presence or absence of a smear layer. A total of 100 teeth with single straight root canals were included in the study. The teeth were decoronated and the canals prepared with a modified double-flared technique under constant irrigation with 2.5% sodium hypochlorite solution. The apical matrix was prepared to size 40 and apical patency subsequently confirmed with a size 10 file. Four teeth were discarded for technical reasons and the remaining 96 allocated randomly into two groups of 44 teeth and a group of eight teeth which acted as controls. Canals in group 1 were obturated randomly with either cold lateral condensation of gutta-percha or with the Trifecta technique. Canals in Group 2 were rinsed with 17% REDTA to remove the smear layer and then obturated with lateral condensation or the Trifecta technique. All teeth were suspended in India ink for 9 days, demineralized, and rendered transparent prior to the assessment of apical linear dye penetration. Apical extrusion of sealer and gutta-percha occurred commonly but there was no significant difference between the four obturation groups. However, overall, there was significantly more extrusion of sealer with the Trifecta technique compared with lateral condensation (P < 0.05). The majority of canals (79 out of 88) had no evidence of apical leakage and there was no significant difference between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Calcium Hydroxide↗
Longitudinal study of outcome of chronic fatigue syndrome.
OBJECTIVE: To examine the predictors of long term outcome for patients with the chronic fatigue syndrome. DESIGN: Cohort study. SUBJECTS: 139 subjects previously enrolled in two treatment trials; 103 (74%) were reassessed a mean of 3.2 years after start of the trials. SETTING: University hospital referral centre. MAIN OUTCOME MEASURES: Age at onset, duration of illness, psychological and immunological status at initial assessment. Ongoing symptom severity, levels of disability, and immunological function at follow up. RESULTS: 65 subjects had improved but only six reported no current symptoms. An alternative medical diagnosis had been made in two and psychiatric illness diagnosed in 20. The assignment of a primary psychiatric diagnosis at follow up and the strength of the belief that a physical disease process explained all symptoms at entry to the trials both predicted poor outcome. Age at onset of illness, duration of illness, neuroticism, premorbid psychiatric diagnoses, and cell mediated immune function did not predict outcome. CONCLUSION: Though most patients with the chronic fatigue syndrome improve, a substantial proportion remain functionally impaired. Psychological factors such as illness attitudes and coping style seem more important predictors of long term outcome than immunological or demographic variables.
Adaptation, Psychological↗
The treatment of chronic fatigue syndrome: science and speculation.
The chronic fatigue syndrome (CFS) is a heterogeneous disorder characterized by fatigue, neuropsychiatric symptoms, and various other somatic complaints. Treatment studies to date reflect both the diversity of medical disciplines involved in the management of patients with CFS and the multiple pathophysiologic mechanisms proposed. There have been few attempts to study integrated treatment programs, and although several controlled studies have been reported, no treatment has been shown clearly to result in long-term benefit in the majority of patients. Good clinical care integrating medical and psychologic concepts, together with symptomatic management, may prevent significant secondary impairment in the majority of patients. Future treatment studies should examine differential response rates for possible subtypes of the disorder (eg, documented viral onset, concurrent clinical depression), evaluate the extent of any synergistic effects between therapies (ie, medical and psychologic), and employ a wide range of biologic and psychologic parameters as markers of treatment response.
Combined Modality Therapy↗