摘要:

Adrenal androgens dehydroepiandrosterone (DHEA; prasterone) and its sulphated form (DHEA-S) are among the most abundant hormonal steroids in men and nonpregnant women. Deficiencies of these adrenal androgens are associated with autoimmune disorders such as rheumatoid arthritis (RA). Recent studies from our laboratory have also identified low levels of adrenal androgens in the serum and synovial fluid of patients with juvenile rheumatoid arthritis (JRA). These findings support and complement those already published for RA and other autoimmune diseases.Because of the paucity of data on the hormonal status of patients with JRA, studies on the relationship between hypoandrogenicity and predisposition to develop JRA, and/or disease progression have not been conducted. In addition, despite the rapid expansion of research in the clinical use of these adrenal androgens in hyperlipidaemia, atherosclerosis, obesity, diabetes mellitus, insulin resistance and hypertension, their potential beneficial effects in JRA/RA have not been fully investigated. In fact, clinical trials of adrenal androgens in RA have only been conducted for the treatment of systemic lupus erythematosus.Further studies using prospective approaches are necessary to provide a unified consensus on the hormonal status of patients with JRA (as well as those with RA). This overview of our knowledge of the putative role(s) of hormones in arthritis will hopefully stimulate researchers in basic science and rheumatologists to synergistically collaborate in the effective translation of such knowledge to new clinical approaches.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Phosphodiesterases (PDEs) are involved in the regulation of intracellular levels of the second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). These enzymes hydrolyse the cyclic nucleotides to the corresponding nucleoside 5′-monophosphates. Nine PDE subtypes have been identified; these differ in their substrate specificity and mode of activation. The type 4 PDE (PDE4) hydrolyses cAMP, is activated by elevated levels of cAMP, and is inhibited by rolipram. Inhibition of enzyme activity has been shown to modulate the activity of cells of the immune system. The production of tumour necrosis factor (TNF)αby activated monocytes and macrophages is inhibited, and cytokine secretion and proliferation of type 1 T helper cells are suppressed. Both immune cell activation and their concomitant induction of cytokine secretion are implicated in multiple sclerosis (MS), which is the major demyelinating disease of the central nervous system. Studies with the selective PDE4inhibitor rolipram in experimental autoimmune encephalomyelitis (an animal model of MS) in mice, rats and nonhuman primates have demonstrated the efficacy of the compound in this disease model, suggesting that PDE4inhibitors could ameliorate the clinical course of MS. Unfortunately, clinical trials with PDE4inhibitors revealed the major adverse effects of these drugs, namely nausea and vomiting. However, novel PDE4inhibitors, which target only a subpopulation of PDE4enzymes, may provoke fewer adverse effects. The efficacy of a PDE4inhibitor in MS still needs to be demonstrated in a well designed clinical trial.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

In some patients with Crohn's disease the anorectal complications are the major cause of symptoms and morbidity. Anorectal Crohn's disease may be present in patients with intestinal Crohn's disease, may be the initial manifestation of the disease, or rarely occurs without involvement of Crohn's disease elsewhere in the intestinal tract. The pathogenesis of these anorectal complications remains to be clarified.The anorectal examination is very important in the assessment of patients with suspected or documented inflammatory bowel disease. Meticulous physical examination, examination under anaesthesia and radiological imaging modalities may be utilised to specifically identify the location of abscesses and fistulae.Treatment strategy should be directed toward symptomatic relief; the most important symptom is pain. In most patients this pain will be attributable to an incompletely drained rectal abscess. Simple incision and drainage procedures are often all that is required as initial treatment of anorectal abscesses.Treatment of the anorectal fistulae that occur secondary to Crohn's disease requires combined medical and surgical therapy. Drug therapy is more often initiated for Crohn's disease that involves other areas of the gastrointestinal tract. The anorectal manifestations often respond to these same medications. Lay-open procedures (fistulotomies) are often all that is required surgically for simple (low) anorectal fistulae.High (complex) fistulae that involve large portions of the anorectal muscular ring are more difficult to treat. Patients with these fistulae must be treated on an individual basis, usually local surgical therapy combined with a medical regimen. Many surgical procedures are performed and many classes of medications are utilised on patients with these complex anorectal fistulae. Choosing the appropriate surgical and medical interventions is often quite difficult. Although sulfasalazine, mesalazine and corticosteroids have no lasting or maintenance value for fistulae, the immunosuppressive agents mercaptopurine, azathioprine and cyclosporin, the antibacterial metronidazole and the anti−tumour necrosis factor-α monoclonal antibody infliximab have varying degrees of effect. The goal of the combined regimen is to cure the fistula, or at least make it minimally symptomatic, without altering the patient's continence.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

The main cause of Addison's disease is an autoimmune organ-specific destruction of the cells in the adrenal cortex by an autoreactive process of activated immune cells directed against the steroid-synthesising enzyme 21-hydroxylase. The diagnosis of Addison's disease is suspected in a patient presenting with symptoms of fatigue, bodyweight loss, anorexia, salt craving, and signs of low blood pressure and hyperpigmentation of the skin. Laboratory findings include electrolyte disturbances, and typically an elevated serum potassium level and sometimes a low serum sodium level is found together with low plasma levels of basal and corticotropin-stimulated hydrocortisone (cortisol). An aetiological diagnosis can rapidly be made using commercially available assays demonstrating the presence of autoantibodies directed against 21-hydroxylase. Determination of 21-hydroxylase autoantibodies also permits early diagnosis before a complete adrenocortical destruction has occurred. Thus, a window of opportunity for an early immunomodulatory intervention therapy may exist. Patients presenting with an acute adrenocortical crisis should be treated with 100mg of hydrocortisone and saline intravenously without awaiting laboratory results. Maintenance therapy includes substitution of glucocorticoid and mineralocorticoid steroids, using divided and lower total dosages of glucocorticoids than previously used.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Intravenously administered alteplase (recombinant tissue plasminogen activator; rtPA) is the only medical treatment that has been approved for the management of acute ischaemic stroke. Although rtPA has demonstrated efficacy in improving outcomes of patients with a wide range of neurological impairments, it cannot be given with impunity. Thrombolytic therapy is associated with a considerable risk of intracranial bleeding that is likely to be catastrophic. Careful selection of patients to treat and intensive ancillary care are the keys for successful administration of rtPA. An algorithm for selection is based on the interval from the onset of stroke, history of recent medical illnesses or use of medications, findings of the medical and neurological examinations and the results of laboratory and brain imaging studies. Because rtPA must be given within 3 hours of onset of stroke, most patients cannot be treated. Thus, additional therapies are needed for treatment of patients with acute ischaemic stroke.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

The treatment of chronic obstructive pulmonary disease (COPD) is receiving increasing attention since the burden of this disease is expected to rise on a global scale in the coming decades. Preventing deterioration of lung function parameters has been the main goal of research in COPD management. In practice, however, the success of drug treatment is not dependent on lung function only, but also relies on the patients' well-being. Therefore, an important role for health-related quality of life (HRQL) is emerging. Until now, several frequently prescribed drugs have been tested in trials using valid and disease-specific HRQL instruments. Evidence of beneficial effects on HRQL is available for the use of short-acting bronchodilators, theophylline and long-acting β-adrenergic bronchodilators in the treatment of COPD. One source reported beneficial effects of inhaled corticosteroid treatment on HRQL. The value of these and other drugs in the management of COPD will need to be assessed in the coming years.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

α1-Antitrypsin (A1AT) deficiency is inherited as an autosomal codominant disorder characterised by reduced levels of A1AT in the serum. Low levels of A1AT in blood perfusing the lung cause low levels in the lung interstitium, making it susceptible to proteolytic damage from resident neutrophil elastase. A ‘protective threshold’ serum A1AT level of 11 µmol/L has been identified by epidemiological studies as a minimum value below which there is an increased risk of emphysema. Intravenous augmentation therapy for patients with severe deficiency of A1AT has been shown to have biochemical efficacy. Although the clinical efficacy of intravenous augmentation therapy has not been demonstrated in a randomised clinical trial, available studies suggest that augmentation therapy is associated with a slowed rate of decline of lung function and enhanced survival. The criteria for patient selection include: age >18 years, serum A1AT level ≤11 µmol/L, a high-risk phenotype (usually PI*ZZ), and documented fixed airflow obstruction (consistent with chronic obstructive pulmonary disease). Although intravenous augmentation is currently the only form of specific therapy approved in the US, active research in the fields of aerosol and gene therapy promise to offer new treatment prospects. In this article, we review the available literature on A1AT augmentation therapy and discuss our recommendations.

ISSN:1173-8804    

出版商:ADIS    

年代:2000

数据来源: ADIS