RETRACTED ARTICLE: The porphyrias: pathophysiology

Porphyrias are a group of inherited and acquired metabolic disorders due to a defect in haem biosynthesis. An enzymatic defect at different steps of haem synthesis leads to tissue accumulation and excessive excretion of porphyrins and/or their toxic precursors. The specific patterns of accumulation determine the variety of clinical manifestations, ranging from acute neurovisceral attacks to skin lesions and liver disease. Most enzyme defects represent partial deficiencies, while familial cases are linked to autosomal or recessive traits. The incomplete penetrance of the genetic defects often requires the triggering or aggravating effect of host-related or environmental factors. While genetics has a role in confirming clinical suspicion and in family screening, biochemical and clinical studies are still central in the diagnosis.     

State-of-the-Art: Pharmacologic-Therapecitic Update: Theophyllines-A Review

Management of asthma in emergency departments (ED) has been well documented to be deficient over many years, despite national and international guidelines. This review summarizes the effect of ED protocols aimed at improving the assessment and treatment of asthma in the ED. We performed a PubMed search of the English literature for ED asthma protocols published from 1986 to 2006 and identified 11 studies. Protocols were effective in improving at least some areas of management, including use of appropriate patient assessment, drug therapy per national guidelines, and patient education. A small number of protocols with the specific aims of reducing the length of stay in the ED as well as rates of hospital admission and return visits were effective. Persistent education of ED staff regarding protocols based on current management guidelines and adoption of easy-to-use forms can facilitate improved care of patients with asthma in the ED.     

Review: Gene Therapy for Cancer:

Gene therapy is a new form of therapeutic intervention with applications in many areas of medical treatment. There are still many technical difficulties to be overcome, but recent advances in the molecular and cellular biology of gene transfer have made it likely that gene therapy will soon start to play an increasing role in clinical practice and particularly in the treatment of cancer. The first clinical gene transfer in an approved protocol took place exactly 10 years ago, and it was for the transfer of gene-marked immune cells into patients with advanced cancer. Now there are 218 active clinical protocols in the United States, and they have involved over 2000 patients worldwide. Among the conditions and diseases for which gene transfer is being tried as treatment, cancer comes first with 130 clinical trials. Fundamental research in the mechanisms of cancer and the development of molecular biology tools are crucial for the success of the treatments in the future. The identification of tumor rejection antigens from a variety of cancers and the immune response that is defective in cancer patients are important topics for future studies. The evaluation of gene therapy combinations involving use of tumor suppressor genes and constructs that inactivate oncogenes is also another important area for future research. The future improvement of present viruses as well as the use of new viral vectors will likely expand the applicability and efficacy of gene therapy. During the next decade technological developments, particularly in the areas of gene delivery and cell transplantation, will be critical for the successful clinical practice of gene therapy.     

Spirituality:

This article addresses the use of spirituality in the assessment and treatment of Black alcoholics and their families who are known to health and human services agencies, including alcoholism-specific treatment centers. Common expressions relating to spiritual beliefs are identified and attention is given to the knowledge needed to formulate an assessment and to make a treatment plan. These include sources of hope and strength, the concept of God and Diety, and the relationship between spiritual beliefs and health. Guidelines for therapists are recommended.     

Minireview: GNAS: normal and abnormal functions

GNAS is a complex imprinted gene that uses multiple promoters to generate several gene products, including the G protein alpha-subunit (G(s)alpha) that couples seven-transmembrane receptors to the cAMP-generating enzyme adenylyl cyclase. Somatic activating G(s)alpha mutations, which alter key residues required for the GTPase turn-off reaction, are present in various endocrine tumors and fibrous dysplasia of bone, and in a more widespread distribution in patients with McCune- Albright syndrome. Heterozygous inactivating G(s)alpha mutations lead to Albright hereditary osteodystrophy. G(s)alpha is imprinted in a tissue-specific manner, being primarily expressed from the maternal allele in renal proximal tubules, thyroid, pituitary, and ovary. Maternally inherited mutations lead to Albright hereditary osteodystrophy (AHO) plus PTH, TSH, and gonadotropin resistance (pseudohypoparathyroidism type 1A), whereas paternally inherited mutations lead to AHO alone. Pseudohypoparathyroidism type 1B, in which patients develop PTH resistance without AHO, is almost always associated with a GNAS imprinting defect in which both alleles have a paternal-specific imprinting pattern on both parental alleles. Familial forms of the disease are associated with a mutation within a closely linked gene that deletes a region that is presumably required for establishing the maternal imprint, and therefore maternal inheritance of the mutation results in the GNAS imprinting defect. Imprinting of one differentially methylated region within GNAS is virtually always lost in pseudohypoparathyroidism type 1B, and this region is probably responsible for tissue-specific G(s)alpha imprinting. Mouse knockout models show that G(s)alpha and the alternative G(s)alpha isoform XLalphas that is expressed from the paternal GNAS allele may have opposite effects on energy metabolism in mice.     

Homelessness:

This article provides a background on homelessness that is relevant to gerontological education and training. The variety of homeless subgroups and the problems of definition and enumeration are discussed before focusing on issues concerning the homeless elderly. All levels of human service providers need education and training for meeting the multiplicity of needs of this population. Gerontological and geriatric educators must be informed about the many issues involved in serving the homeless elderly and include these topics in their training programs.     

Leisure:

Leisure represents the freedom to make quality of life choices. For the alcoholic, drinking represents total enslavement and results in a deprivation of all freedoms, including the ability to make valid leisure choices. This article presents a programmatic scheme for the assessment of leisure and lifestyle changes necessary to encourage sobriety. The relationships among leisure and lifestyle issues and the clinical process for the recovering alcoholic are explored. Development of a leisure service model for clinical service to the alcoholic is presented.     

REVIEW: Management of gout: beyond allopurinol

The basic concepts of the pathogenesis and management of gout have not altered for many years. Monosodium urate monohydrate crystals drive the disease and identification of these crystals is required for certain diagnosis. In contrast, our understanding of the mediators of gouty inflammation, the appropriate target serum urate concentration during treatment, the drugs available and the best ways to use those drugs have all advanced in recent years and will be the focus of this review.     

Ticagrelor: molecular discovery to clinical evidence: Ticagrelor: a novel antiplatelet agent

Cardiovascular (CV) deaths are one of the leading cause of death, both in developed and developing countries, with acute coronary syndrome (ACS) accounting for about 50% of all CV deaths. Atherothrombosis formation is the prime reason behind ACS and platelets play a central role in formation of thrombus. Antiplatelet drugs, particularly dual antiplatelet therapy (DAPT) with Aspirin and Clopidogrel play a vital role and are widely used in the management of ACS for the past decade. However in spite of currently available options for antiplatelet therapy there remains a significant risk of arterial thrombosis and post ACS mortality grows over a period of time. Thus, there is a need for novel antiplatelet agents which can overcome some limitations of current antiplatelet therapies. Ticagrelor is a novel antiplatelet agent which has a faster onset of action, produces high level of platelet inhibition with minimal inter patient variability. This review summarizes the pharmacokinetic, pharmacodynamic characteristics and clinical evidence of ticagrelor in the management of ACS.     

Reprint of: Betaglycan: a multifunctional accessory

Betaglycan is a co-receptor for the TGFβ superfamily, particularly important in establishing the potency of its ligands on their target cells. In recent years, new insights have been gained into the structure and function of betaglycan, expanding its role from that of a simple co-receptor to include additional ligand-dependent and ligand-independent roles. This review focuses on recent advances in the betaglycan field, with a particular emphasis on its newly discovered actions in mediating the trafficking of TGFβ superfamily receptors and as a determinant of the functional output of TGFβ superfamily signalling. In addition, this review encompasses a discussion of the emerging roles of the betaglycan/inhibin pathway in reproductive cancers and disease.     

Cryoablation:

The use of cryoablation in the electrophysiology lab provides some distinct advantages not seen with conventional radiofrequency ablation. Ice mapping allows a functional assessment of a putative ablation site prior to the formation of a permanent lesion. This provides a distinct advantage adjacent to the AV node for para-hisian pathways and difficult cases of AVNRT. Cryoablation also produces minimal endothelial disruption and thrombus formation and causes no collagen shrinkage. This is likely advantageous when ablation is required within venous structures. There is also mounting experimental evidence that cryoablation is safe adjacent to the arterial system, especially within the middle cardiac vein or distal coronary sinus. As the technology evolves and further iterations of the catheter proceed, the role for this new but well-established technology is likely to grow.     

Minireview: RET: normal and abnormal functions

The RET gene encodes a single-pass transmembrane receptor tyrosine kinase. RET is the oncogene that causes papillary thyroid carcinoma and medullary thyroid carcinoma. The latter may arise as a component of multiple endocrine neoplasia type 2 syndromes; germline mutations in RET are responsible for multiple endocrine neoplasia type 2 inheritance. In this report we review data on the mechanisms leading to RET oncogenic conversion and on RET targeting as a strategy in thyroid cancer treatment.     

Suicide:

Knowledge about suicide is often low and attitudes are ofent negative toward the suicidal person, even among those that come into frequent contact with them. The elderly are among the highest risk groups for suicidal behavior. The need for education and training about suicide among caregivers is discussed. Specific topics for this training should include the dispelling of myths about suicide, demographic high risk factors, the recognition of suicide warning signs, awareness of existing community resources for dealing with suicidal persons, the variety of direct and indirect self-destructive behaviors, and awareness of the grief experience of suicidal survivors. Current levels of suicidal behavior and the prevention of elderly suicide are highlighted.     

EDITORIAL: Another Decade: Challenges and Promises

Internationally, the alcohol and other drug (AOD) field has an increasing focus on recovery-oriented care, however there has been little research addressing the impacts in Australia. This study explores the attitudes of AOD clinicians toward recovery-oriented care in Victoria. Data was collected from 50 AOD clinicians and managers across six AOD services. Data collection included completion of a structured questionnaire addressing recovery attitudes and beliefs and semistructured group interviews. Although participants agreed with the broad concept of recovery, there was disagreement over the appropriateness of recovery as a term. The findings support that the development of a set of guiding recovery principles would be more useful than a simple definition.