Too late for early intervention? The Healthy Ageing Service's mental health response.

Objectives: This paper describes the rationale for and development of an innovative mental health service for people aged over 65 years living in Northern and Eastern Melbourne, Victoria, Australia.

Conclusion: The Healthy Ageing Service (HAS) was established in July 2020 to provide care for people aged over 65 years experiencing mild-to-moderate mental health concerns. It embraces a prevention and early intervention model of care.

Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis.

The discovery of fingolimod (FTY720/Gilenya; Novartis), an orally active immunomodulatory drug, has opened up new approaches to the treatment of multiple sclerosis, the most common inflammatory disorder of the central nervous system. Elucidation of the effects of fingolimod--mediated by the modulation of sphingosine 1-phosphate (S1P) receptors--has indicated that its therapeutic activity could be due to regulation of the migration of selected lymphocyte subsets into the central nervous system and direct effects on neural cells, particularly astrocytes. An improved understanding of the biology of S1P receptors has also been gained.

Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis.

Background: Fingolimod (FTY720), a sphingosine-1-phosphate-receptor modulator that prevents lymphocyte egress from lymph nodes, showed clinical efficacy and improvement on imaging in a phase 2 study involving patients with multiple sclerosis.

Methods: In this 12-month, double-blind, double-dummy study, we randomly assigned 1292 patients with relapsing-remitting multiple sclerosis who had a recent history of at least one relapse to receive either oral fingolimod at a daily dose of either 1.25 or 0.

Phase II study of oral fingolimod (FTY720) in multiple sclerosis: 3-year results.

In a 6-month, placebo-controlled trial, oral fingolimod (FTY720) 1.25 or 5.0 mg, once daily, significantly reduced MRI inflammatory activity and annualized relapse rate compared with placebo in patients with relapsing multiple sclerosis (MS).

Proof of concept studies for tissue-protective agents in multiple sclerosis.

Background: There is considerable interest in tissue-protective treatments for multiple sclerosis (MS).

Methods And Objectives: We convened a group of MS clinical trialists and related researchers to discuss designs for proof of concept studies utilizing currently available data and assessment methods.

Results: Our favored design was a randomized, double-blind, parallel-group study of active treatment versus placebo focusing on changes in brain volume from a post-baseline scan (3-6 months after starting treatment) to the final visit 1 year later.

FTY720 versus MMF with cyclosporine in de novo renal transplantation: a 1-year, randomized controlled trial in Europe and Australasia.

FTY720 is a novel immunomodulator investigated in de novo renal transplantation and other therapeutic areas including multiple sclerosis. This 1-year multicenter, randomized, phase III study in 668 de novo renal transplant patients compared FTY720 2.5 mg plus full-dose cyclosporine (FDC) or FTY720 5.

Mycophenolic acid area under the curve values in African American and Caucasian renal transplant patients are comparable.

The possibility of an effect of ethnicity on the pharmacokinetics of mycophenolic acid, the immunosuppressive metabolite of the prodrug mycophenolate mofetil, was studied over 90 days following renal transplantation in African American (n = 13) and Caucasian patients (n = 20). Since renal dysfunction and time after transplant surgery are two factors known to alter mycophenolic acid pharmacokinetics, two-way analysis of variance of the data at each time point with ethnicity and renal function status as covariates was used to evaluate the possibility of an ethnicity effect on the pharmacokinetic parameters. No statistically significant difference based on ethnicity was detected for the primary pharmacokinetic parameters, abbreviated mycophenolic acid area under the concentration-time curve (MPA AUC), or the predose trough concentration on study days 4, 7, 14, 28, or 90.

Identification of alpha3, alpha4, and alpha5 chains of type IV collagen as alloantigens for Alport posttransplant anti-glomerular basement membrane antibodies.

Background: Alport syndrome is a hereditary disorder of basement membranes especially affecting the kidneys, ears, and eyes. Some patients who undergo renal transplantation lose their kidneys as a result of posttransplant anti-glomerular basement membrane (anti-GBM) disease.

Methods: In the present study, we analyzed serum from 21 unselected Alport patients who underwent renal transplantation.

Clinical management of early progressive renal failure.

In the era of managed health care, the primary physician will be required to play an active role in the management of patients with early renal failure. This section provides a comprehensive and practical approach to the management of such patients. Early recognition of renal failure and monitoring its progression require an understanding of the pitfalls of commonly used diagnostic tests.

Focal acute tubular necrosis in a renal allograft.

Nuclear imaging is used to evaluate renal allografts demonstrating delayed function after transplantation. Interpretation of the nuclear scan in the context of clinical data, provides helpful information in the management of the transplant recipient. The better quality of images obtained with technetium-99m mercaptoacetyltriglycine (Tc-99m MAG3) has made it the radiotracer of choice compared to technetium-99m diethylenetriamine pentaacetic acid (Tc-99m DTPA) for imaging of the renal allograft.

Effect of anti-lymphocyte induction therapy on renal allograft survival: a meta-analysis.

Induction immunosuppression with antilymphocyte antibodies has not been shown to improve cadaveric kidney allograft survival in randomized, controlled trials despite widespread use. This meta-analysis of randomized, controlled trials assessed the effectiveness of induction therapy in prolonging allograft survival. Studies of induction therapy were identified in Medline (1986 through 1996), using the terms "monoclonal antibodies" or "antilymphocyte serum," and "kidney transplantation," "human," and "clinical trial.

Will tolerance become a clinical reality?

The goal of transplant physicians is to create a state of antigen-specific tolerance in the recipient, whereby the graft is not rejected and the patient will not need a lifetime of medical therapy. Although the immunosuppressive medications used are effective in lowering the incidence of rejection, they produce significant side effects and do not induce a state of transplantation tolerance. Progress toward inducing transplantation tolerance has been made in animal models, primarily by the exploitation of the natural mechanisms that vertebrates have to maintain self-tolerance.

OKT3 induction therapy: influence of duration on rejections and infections.

Anti-lymphocytes induction therapy in renal transplants remains controversial relative to efficacy and cost benefit. It has been suggested that shortening the duration of induction therapy from 14 to 7 d would provide adequate efficacy at less cost. Our objective was to compare the efficacy and complications of short (7 d or less, group A) versus standard (14 d or more, group B) duration of OKT3 induction therapy in renal allograft recipients.

Myocardial systolic function in systemic lupus erythematosus: a study based on radionuclide ventriculography.

We assessed left ventricular systolic function by means of radionuclide ventriculography in 20 consecutive unselected patients with systemic lupus erythematosus. All patients had normal left ventricular systolic function (defined as ejection fraction greater than 45%) in a resting state. Regional wall motion abnormalities were, however, seen in 4 patients (20%).