Essential thrombocythaemia and the Philadelphia chromosome

Six adult patients presented with clinical features of essential thrombocythaemia. Five of the patients, although Ph-positive, have maintained these features without evidence of leukaemia; in one case for 9 years. A sixth patient developed leukaemic blast crisis following a persistently high platelet count over 4 years. Her cells were Ph-negative, but hybridization of gene probes to chromosomes in situ and to leukaemic DNA showed that the abl oncogene had moved to the breakpoint cluster region (bcr) on the normal chromosome 22. This patient has the same molecular gene change as occurs in some cases of Ph-negative chronic myeloid leukaemia (CML) whose leukaemic cells likewise show no evidence of chromosomal translocation. Molecular studies are essential for the correct diagnosis of these patients. The Ph genomic lesion appears to have a range of leukaemic expression which includes thrombocythaemia as well as chronic myeloid leukaemia and acute lymphatic leukaemia.     

Spatial learning with a minislab in the dorsal hippocampus.

We have determined the volume and location of hippocampal tissue required for normal acquisition of a spatial memory task. Ibotenic acid was used to make bilateral symmetric lesions of 20-100% of hippocampal volume. Even a small transverse block (minislab) of the hippocampus (down to 26% of the total) could support spatial learning in a water maze, provided it was at the septal (dorsal) pole of the hippocampus. Lesions of the septal pole, leaving 60% of the hippocampi intact, caused a learning deficit, although normal electrophysiological responses, synaptic plasticity, and preserved acetylcholinesterase staining argue for adequate function of the remaining tissue. Thus, with an otherwise normal brain, hippocampal-dependent spatial learning only requires a minislab of dorsal hippocampal tissue.     

Pregnancy-related liver diseases

Opinion statement  

Percutaneous coronary artery stenting of an anomalous right coronary artery with high anterior takeoff using standard size 7 French left Judkins guiding catheters

The anomalous right coronary artery with high anterior takeoff is an uncommon and technically difficult vessel for interventions. We describe 2 such cases in which standard size, 7 French, left Judkins guiding catheters allowed for successful percutaneous coronary intervention after many other guiding catheters had failed.     

Cytokinin/auxin balance in crown gall tumors is regulated by specific loci in the T-DNA

Insertion of the transposon Tn5 into the T-region of the octopine Ti plasmid of Agrobacterium tumefaciens gives rise to crown gall tumors having altered morphology. Three loci within the T-DNA that control tumor morphology have been detected [Garfinkel, D. J., Simpson, R. B., Ream, L. W., White, F. F., Gordon, M. P. & Nester, E. W. (1981) Cell 27, 143-153]. They influence tumor size (tml), production of roots (tmr), or production of shoots (tms). Cytokinin and auxin levels in such mutant tumors were examined by HPLC/radioimmunoassay and HPLC/fluorescence assay, respectively. Free indoleacetic acid levels (in pmol/g) were: uninfected tobacco stem tissues, 128; wild-type A348 tumors, 295; tml mutant tumors, 307; tmr mutant tumors, 129; and tms mutant tumors, 70. Average trans-ribosylzeatin levels were correspondingly: 0.97, 48, 40, 0.54, and 1,400 pmol/g. trans-Ribosylzeatin/indoleacetic acid ratios were as high as 24 in shoot-producing tumors and as low as 0.003 in root-producing tumors. The evidence strongly suggests that tumor phytohormone levels are determined by genes in the T-DNA.     

Endogenous selective inhibitors of 11beta-hydroxysteroid dehydrogenase isoforms 1 and 2 of adrenal origin

In earlier studies [Latif, S.A., Sheff, M.F., Ribeiro, C.E., Morris, D.J., 1997. Selective inhibition of sheep kidney 11beta-hydroxysteroid-dehydrogenase isoform 2 activity by 5alpha-reduced (but not 5beta) derivatives of adrenocorticosteroids. Steroids 62, 230-237], only derivatives of steroid hormones possessing the 5alpha-Ring A-reduced configuration selectively inhibited 11beta-HSD2-dehydrogenase, whereas their 5beta-derivatives were inactive. This present study focuses on an expanded group of endogenous 11-oxygenated, 5alpha and 5beta-Ring A-reduced metabolites of adrenocorticosteroids, and progestogen and androgen steroid hormones. These substances were tested for their inhibitory properties against 11beta-HSD2, 11beta-HSD1-dehydrogenase and 11beta-HSD1 reductase. The present studies showed that the following compounds stand out as potent inhibitors. These are 5alpha-DH-corticosterone, 3alpha,5alpha-TH-corticosterone, 11beta-OH-progesterone, 11beta-OH-allopregnanolone, 11beta-OH-testosterone, and 11beta-OH-androstanediol, inhibitors of 11beta-HSD1-dehydrogenase; 3alpha,5alpha-TH-11-dehydro-corticosterone, 11-keto-progesterone, 11-keto-allopregnanolone, and 11-keto-3beta,5alpha-TH-testosterone, inhibitors of 11beta-HSD1 reductase; 3alpha,5alpha-TH-aldosterone, 5alpha-DH-corticosterone, 3alpha,5alpha-TH-corticosterone,11-dehydro-corticosterone, 3alpha,5alpha-TH-11-dehydro-corticosterone, 11beta-OH-progesterone, 11-keto-progesterone, 11beta-OH-allopregnanolone, 11-keto-allopregnanolone, 11beta-OH-testosterone, and 11-keto-testosterone, inhibitors of 11beta-HSD2. All of these substances have the potential to be derived from adrenally synthesized corticosteroids. Substances with similar structures to those described may help in the design of exogenous agents for the management of a variety of disease states involving 11beta-HSD isoenzymes.     

The Evaluation of a Compassion-Focused Therapy Group for Couples Experiencing a Dementia Diagnosis

Objectives: This study evaluated the effectiveness of a Compassion-Focused Therapy (CFT) group on reducing anxiety, depression, and respiratory rate (RR) in people with dementia (PwD) and their spouses, and improving quality of life (QoL) of PwD.

Method: Sixty-four participants completed six weekly CFT sessions. Baseline and post-intervention assessments were analyzed using t-tests and Reliability Change Index.

Results: Mean baseline and post-assessment anxiety and depression scores fell in the ‘normal range’; although a significant reduction in depression with moderate effect was observed for PwD. Fifty-seven percent of PwD with borderline to abnormal baseline scores showed clinically significant improvement in anxiety and depression. For spouses, 80% showed clinically significant improvement in depression and 50% in anxiety. RR reduced for PwD and spouses with large and medium effects respectively. QoL of PwD improved with a large effect.

Conclusions: CFT appears effective in improving QoL and depression in PwD and reducing RR in PwD and spouses. CFT reduces anxiety and depression in most PwD and spouses with borderline to abnormal symptoms.

Clinical Implications: This study indicates benefits of a group-CFT intervention delivered to people with a range of dementia diagnosis and their spouses. The service should investigate whether individuals in greater distress are not accessing the group and improve engagement.     

Integrating the Accreditation Council for Graduate Medical Education Core competencies into the model of the clinical practice of emergency medicine

In response to public pressure for greater accountability from the medical profession, a transformation is occurring in the approach to medical education and assessment of physician competency. Over the past 5 years, the Accreditation Council for Graduate Medical Education (ACGME) has implemented the Outcomes and General Competencies projects to better ensure that physicians are appropriately trained in the knowledge and skills of their specialties. Concurrently, the American Board of Medical Specialties, including the American Board of Emergency Medicine (ABEM), has embraced the competency concept. The core competencies have been integral in ABEM's development of Emergency Medicine Continuous Certification and the development of the Model of Clinical Practice of Emergency Medicine (Model).¹ ABEM has used the Model as a significant part of its blueprint for the written and oral certification examinations in emergency medicine and is fully supportive of the effort to more fully define and integrate the ACGME core competencies into training emergency medicine specialists.To incorporate these competencies into our specialty, an Emergency Medicine Competency Taskforce (Taskforce) was formed by the Residency Review Committee–Emergency Medicine to determine how these general competencies fit in the Model.¹ This article represents a consensus of the Taskforce with the input of multiple organizations in emergency medicine. It provides a framework for organizations such as the Council of Emergency Medicine Residency Directors (CORD) and the Society for Academic Emergency Medicine to develop a curriculum in emergency medicine and program requirement revisions by the Residency Review Committee–Emergency Medicine. In this report, we describe the approach taken by the Taskforce to integrate the ACGME core competencies into the Model. Ultimately, as competency-based assessment is implemented in emergency medicine training, program directors, governing bodies such as the ACGME, and individual patients can be assured that physicians are competent in emergency medicine.     

Prognostic factors in allogeneic transplantation for patients with high-risk multiple myeloma after reduced intensity conditioning

OBJECTIVES: The aim of this study was to identify prognostic factors for outcome of high-risk patients with multiple myeloma after allogeneic transplantation prepared by reduced intensity conditioning (RIC). MATERIALS AND METHODS: Data from 45 consecutive patients (median age 52 years, range 38-68), who received grafts from a sibling (n = 34) or unrelated donor (n = 11) were analyzed. Fourteen patients received an RIC allotransplant while chemosensitive (>/=partial remission [PR]), whereas 31 chemoresistant patients (相似文献