Empirically Supported Treatment: Recommendations for a New Model

Over the 20 years since the criteria for empirically supported treatments (ESTs) were published, standards for synthesizing evidence have evolved and more systematic approaches to reviewing the findings from intervention trials have emerged. Currently, the APA is planning the development of treatment guidelines, a process that will likely take many years. As an intermediate step, we recommend a revised set of criteria for ESTs that will utilize existing systematic reviews of all of the available literature, and recommendations that address the methodological quality, outcomes, populations, and treatment settings included in the literature.     

The CD11b promoter directs high-level expression of reporter genes in macrophages in transgenic mice [published erratum appears in Blood 1995 Apr 1;85(7):1983]

CD11b is the alpha chain of the Mac-1 integrin and is preferentially expressed in myeloid cells (neutrophils, monocytes, and macrophages). We have previously shown that the CD11b promoter directs cell-type- specific expression in myeloid lines using transient transfection assays. To confirm that these promoter sequences contain the proper regulatory elements for correct myeloid expression of CD11b in vivo, we have used the -1.7-kb human CD11b promoter to direct reporter gene expression in transgenic mice. Stable founder lines were generated with two different reporter genes, a Thy 1.1 surface marker and the Escherichia coli lacZ (beta-galactosidase) gene. Analysis of founders generated with each reporter demonstrated that the CD11b promoter was capable of driving high levels of transgene expression in murine macrophages for the lifetime of the animals. Similar to the endogenous gene, transgene expression was preferentially found in mature monocytes, macrophages, and neutrophils and not in myeloid precursors. These experiments indicate that the -1.7 CD11b promoter contains the regulatory elements sufficient for high-level macrophage expression. This promoter should be useful for targeting heterologous gene expression to mature myeloid cells.     

Interleukin-2 induction of lymphokine-activated killer (LAK) activity in the peripheral blood and bone marrow of acute leukemia patients: II. Feasibility of LAK generation in children with active disease and in remission

Activation and expansion in culture with rIL-2 of peripheral blood (PB) and/or bone marrow (BM) specimens derived from children with ALL and ANLL, with active disease (AP) and in remission were studied (RP). Baseline NK cytolytic activity from AP was found to be depressed, whereas RP-derived cells had normal NK activity, as assayed against K562 targets. Culture in rIL-2 significantly enhanced the NK activity of both AP- and RP-derived cells and generated LAK activity, as assayed by 4-hour 51Cr release, against NK-resistant Raji cell line and against fresh, allogeneic, and autologous tumor cells. Lytic activity against fresh, cryopreserved leukemia blasts was of lower than that found against cell lines. In three patients higher lytic activity against autologous than against allogeneic blasts was demonstrated. Expansion in culture with rIL-2 varied from twofold to 120-fold. rIL-2 activation and expansion was better in RP than in AP. The predominant phenotype of activated cells, as determined by flow cytometry, was [mean % (SD)]: CD3- = 54 (12), CD8+ = 55 (17), and NKH1+ = 26 (7). The consistently high level of CD8+ cells was accompanied by very low levels of CD4+ cells: mean = 11% (14). Double-marker analysis showed mean of 33% (10) for CD3+/NKH1+ cells and mean = 32 (11) for CD8+/NKH1+ cells, implying that these populations were overlapping. Kinetics of expression of cell surface markers during 2 to 3 weeks in culture showed that CD8+ and NKH1+ enrichment occurred during the first week and lasted for up to 4 weeks, whereas CD4+ expression decreased after the second week. A significant decrease in the expression of IL-2 receptors (CD25) was observed from the second week of culture. This study shows the feasibility of in vitro generation of killer cells from PB and BM of pediatric leukemia patients.     

Regulation of growth hormone (GH) bioactivity by a recombinant human GH-binding protein

The in vitro biological effects of serum GH-binding protein (GHBP) were measured in the mouse 3T3-F442A preadipocyte adipogenesis assay during GH stimulation. Coincubation of increasing concentrations of human (h) GH (0.14-4.5 nM) with 4.2 nM recombinant hGHBP-(1-247) in serum-free medium shifted the hGH dose-response curve to the right over the range 0.14-0.9 nM. When the hGH concentration was fixed at 0.45 nM, a dose-dependent inhibition of GH bioactivity was seen over the range of 0.1-11.3 nM GHBP, with an ED50 of 3 nM. The presence of serum had no effect on the inhibitory properties of GHBP. When 2% pooled human serum was added to incubation medium containing 0.45 nM hGH and GHBP (0.6 nM-5.7 nM), the effect of GHBP was again inhibitory, with an ED50 of 1.2 nM. Two percent serum alone was adipogenic, but at this low serum concentration it is likely that some factor other than GH is responsible. In a homologous receptor assay, the binding of [125I]hGH to IM-9 lymphocytes was inhibited in a dose-dependent manner by increasing concentrations of hGHBP in the physiological range, providing further support for the idea that GHBP can regulate the bioactivity of GH by blocking the binding of free GH to target tissues in vivo. Our results suggest that one function of GHBP is to dampen the biological effects of pulsatile GH secretion by reducing free GH during secretory pulses. This effect combined with an increased half-life of circulating GH would have the effect of flattening the hormone secretory profile at the target tissue level.     

A scoping review of time-use research in occupational therapy and occupational science

Background: Time use is a defining interest within occupational therapy and occupational science. This is evident through the range of contributions to the disciplinary knowledge base. Indeed it has been suggested that time-use methods are amongst the most established research techniques used to explore aspects of human occupation. However, the extent and nature of such activity in occupational therapy and occupational science has not been examined to date. Aim: This study sought to map the extent and nature of time-use research in occupational therapy and occupational science journals and the extent to which studies explored the relationship between time-use and health. Method: A scoping review method was used. Results: Sixty-one studies were included. Scandinavian countries contributed the largest number of studies (n = 16, 26%). While time-use diaries were used most frequently (n = 30, 49%) occupational therapists and occupational scientists have developed a range of data-collection instruments. Forty-nine studies (80%) focused on time-use in clinical or defined population sub-groups. Ten studies (16%) included an empirical examination of the relationship between time-use and health. Conclusion: Future research should examine time-use and health amongst well populations across the lifespan and in different parts of the world.     

'Coumadin ridge' in the left atrium demonstrated on three dimensional transthoracic echocardiography.

An echogenic band like structure was seen in the left atrium on two dimensional transthoracic echocardiography (2D TTE). Full volume three dimensional (3D) TTE and colour Doppler established the surrounding anatomical landmarks, and demonstrated the absence of obstruction related to this band. 3D TTE confirmed that this band like structure was consistent with the ridge between the left atrial appendage and left superior pulmonary vein ('warfarin/coumadin ridge').     

Effects of nifedipine on hemodynamics and cardiac function in patients with normal left ventricular ejection fraction already treated with propranolol

The interaction between nifedipine and propranolol on cardiac hemodynamics and function was investigated in 9 patients with normal left ventricular (LV) function who were undergoing cardiac catheterization for complaints of chest pain. Only 2 patients had angiographic evidence of significant coronary artery disease but no patient had clinical evidence of ischemia during the study. All patients were pre-treated with propranolol, 30 to 320 mg/day (mean +/- standard deviation 210 +/- 122); the propranolol serum level ranged from 43 to 246 ng/ml (mean 203 +/- 62). The administration of nifedipine resulted in a decrease in blood pressure (from 94 +/- 11 to 85 +/- 13 mm Hg, p less than 0.05), increase in heart rate (from 59 +/- 6 to 65 +/- 7 beats/min, p less than 0.05), and an increase in both mean right atrial and mean pulmonary artery wedge pressures (from 8 +/- 3 to 9 +/- 3 mm Hg and from 13 +/- 3 to 14 +/- 4 mm Hg, respectively, both p less than 0.05). Cardiac index increased (from 2.3 +/- 0.3 to 2.7 +/- 0.2 liters/min/m2, p less than 0.01). Stroke volume index also increased significantly (from 39 +/- 5 to 43 +/- 6 ml/m2) and systemic vascular resistance decreased (from 1,715 +/- 369 to 1,255 +/- 271 dynes s cm-5, p less than 0.01). No significant change was noted in pulmonary vascular resistance (148 +/- 94 vs 140 +/- 62 dynes s cm-5), LV stroke work index (44 +/- 9 vs 42 +/- 10 g-m/m2), LV end-diastolic pressure (15 +/- 2 vs 16 +/- 2 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)     

Catheter balloon valvuloplasty of stenotic aortic valves. Part I: Anatomic basis and mechanisms of balloon dilation

Catheter balloon valvuloplasty of stenotic aortic valves has met with generally poor short- and long-term clinical results. Part of this problem resides with the lack of recognition of various etiologies of aortic stenosis. Part I of this review discusses the various etiologies of aortic stenosis and provides an anatomic basis for successful valve dilation. Results of an in vitro study indicate stenotic aortic valves are dilated by various mechanisms (cracking, stretching) based in part upon the etiology of the aortic valve stenosis.     

Circumferential quantitative analysis of planar 201T1 myocardial scintigraphy in the diagnosis of coronary artery disease

Methodology for the computer analysis of 201T1 myocardial perfusion images has been developed by several laboratories. Substantial evidence of the advantage of this approach over visual inspection alone has been reported. The currently available computer analyses use different algorithms to analyze 201T1 kinetics in the myocardium. The authors evaluated and compared two widely used software programs, Medical Data System (MDS): a mean-count profile, and the Cedars Sinai (CS): a maximal-count profile, of planar 201T1 scintigraphy for their ability to detect coronary artery disease (CAD).