Cardiac flow measurement by ultrafast CT: validation of continuous and pulsatile flow.

To gauge the accuracy of ultrafast CT in measuring cardiac output and myocardial perfusion in humans, measurements of continuous and pulsatile flow were made in a large asymmetrical phantom. The variation in the relationship between Hounsfield number and contrast concentration was assessed in a human thorax phantom. Radiopaque contrast medium was injected during perfusion of the phantom at a range of flow rates between 1.5 and 8 L/min. The phantom was scanned in two modes (50 and 100 ms) during continuous and pulsatile flow and with the phantom surrounded by air and by water. Flow in the tubes was calculated using indicator dilution theory, and flow in the tissue-equivalent chamber was calculated by applying first-pass distribution principles. The standard deviation of the difference between calculated and measured flow varied from 0.2 to 0.6 L/min, giving 95% limits of agreement from 0.4 to 1.2 L/min. The constant (K) relating Hounsfield unit number to iodine concentration varied widely both in different locations within the phantom and under different scan conditions (17.2-27.6 HU/mg I). Within a human thorax phantom, K varied from 14.15 to 23.18 HU/mg I and was dependent on location within the thorax phantom, the scan mode, and the cross-sectional diameter of the phantom. These data suggest that though the ultrafast CT scanner can measure continuous and pulsatile flow accurately in tubes, precise measurements of cardiac output in humans will require K to be assessed for each subject. Measurements of flow in tissue should be possible.     

Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.     

Behavioural factors associated with symptom outcomes in a primary care-based depression prevention intervention trial

BACKGROUND: A randomized trial of a primary care-based intervention to prevent depression relapse resulted in improved adherence to long-term antidepressant medication and depression outcomes. We evaluated the effects of this intervention on behavioural processes and identified process predictors of improved depressive symptoms. METHOD: Patients at high risk for depression recurrence or relapse following successful acute phase treatment (N=386) were randomly assigned to receive a low intensity 12-month intervention or continued usual care. The intervention combined education about depression, shared decision-making regarding use of maintenance pharmacotherapy and cognitive-behavioural strategies to promote self-management. Baseline, 3, 6, 9 and 12-month interviews assessed patients' self-care practices, self-efficacy for managing depression and depressive symptoms. RESULTS: Intervention patients had significantly greater self-efficacy for managing depression (P<0.01) and were more likely to keep track of depressive symptoms (P<0.0001), monitor early warning signs (P<0.0001), and plan for coping with high risk situations (P<0.0001) at all time points compared to usual care control patients. Self-efficacy for managing depression (P<0.0001), keeping track of depressive symptoms (P=0.05), monitoring for early warning signs (P=0.01), engaging in pleasant activities (P<0.0001) and engaging in social activities (P<0.0001) positively predicted improvements in depression symptom scores. CONCLUSIONS: A brief intervention designed to target cognitive-behavioural factors and promote adherence to pharmacotherapy in order to prevent depression relapse was highly successful in changing several behaviours related to controlling depression. Improvements in self-efficacy and several self-management behaviours that were targets of the intervention were significantly related to improvements in depression outcome.     

Sequence comparison of human and yeast telomeres identifies structurally distinct subtelomeric domains

We have sequenced and compared DNA from the ends of three human chromosomes: 4p, 16p and 22q. In all cases the pro-terminal regions are subdivided by degenerate (TTAGGG)n repeats into distal and proximal sub- domains with entirely different patterns of homology to other chromosome ends. The distal regions contain numerous, short (<2 kb) segments of interrupted homology to many other human telomeric regions. The proximal regions show much longer (approximately 10-40 kb) uninterrupted homology to a few chromosome ends. A comparison of all yeast subtelomeric regions indicates that they too are subdivided by degenerate TTAGGG repeats into distal and proximal sub-domains with similarly different patterns of identity to other non-homologous chromosome ends. Sequence comparisons indicate that the distal and proximal sub-domains do not interact with each other and that they interact quite differently with the corresponding regions on other, non- homologous, chromosomes. These findings suggest that the degenerate TTAGGG repeats identify a previously unrecognized, evolutionarily conserved boundary between remarkably different subtelomeric domains.      

GMS syndrome: a new dominant condition with goniodysgenesis, mental retardation, and short stature.

We describe a mother and daughter with a distinct phenotype that is different from previous reports. This is likely to constitute a new syndrome for which we propose the mnemonic GMS for G goniodysgenesis, M mental deficiency, and S short stature. The pattern of occurrence is compatible with either autosomal dominant or X-linked inheritance.     

Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response

Congenital nephrogenic diabetes insipidus (NDI) is a rare disease caused most often by mutations in the vasopressin V2 receptor (AVPR2). We studied a family which included a female patient with NDI with symptoms dating from infancy. The patient responded to large doses of desmopressin (dDAVP) which decreased urine volume from 10 to 4 I/day. Neither the parents nor the three sisters were polyuric. The patient was found to be a compound heterozygote for two novel recessive point mutations in the aquaporin-2 (AQP2) gene: L22V in exon 1 and C181W in exon 3. Residue Cys181 in AQP2 is the site for inhibition of water permeation by mercurial compounds and is located near to the NPA motif conserved in all aquaporins. Osmotic water permeability (Pf) in Xenopus oocytes injected with cRNA encoding C181W-AQP2 was not increased over water control, while expression of L22V cRNA increased the Pf to approximately 60% of that for wild-type AQP2. Co-injection of the mutant cRNAs with the wild-type cRNA did not affect the function of the wild-type AQP2. Immunolocalization of AQP2-transfected CHO cells showed that the C181W mutant had an endoplasmic reticulum-like intracellular distribution, whereas L22V and wild-type AQP2 showed endosome and plasma membrane staining. Water permeability assays showed a high Pf in cells expressing wild-type and L22V AQP2. This study indicates that AQP2 mutations can confer partially responsive NDI.      

Multiple cerebral metastases: detectability with Gd-DTPA-enhanced MR imaging

Sixteen patients with suspected cerebral metastases were studied with magnetic resonance (MR) imaging before and after the intravenous administration of 0.1 mmol/kg of gadolinium diethylenetriaminepenta-acetic acid. The images were interpreted blindly by two neuroradiologists; all clinical, radiologic (computed tomographic and MR imaging), and pathologic data were reviewed to arrive at a final "best diagnosis," which was then compared with the prior blinded interpretations. Of seven patients found to have multiple metastases, six (86%) had at least one tumor nodule depicted by postinfusion MR imaging that was missed by one or both observers on review of preinfusion images alone. Lesions missed on preinfusion studies were usually small nodules hidden by or not detected next to regions of high-signal edema thought to be related to the adjacent tumor nodule. The authors believe that contrast enhancement improves detection of metastatic foci with MR imaging and that the findings indicate broader implications for the detection of multiple lesions from other causes.     

Implementation of outreach telephone counseling to promote mammography participation.

To increase mammography participation, the authors implemented an outreach intervention translating concepts from expectancy value theory into a motivational interviewing telephone intervention that included the opportunity to schedule a screening appointment. Process data are presented from 491 women who had not scheduled a mammogram within 2 months of receiving a mailed invitation from a managed care organization's centralized breast cancer screening program. A total of 83% of targeted women accepted the counseling calls. Counselors rated 84% of completed calls as either receptive or neutral in tone. Women with prior mammography experience were more likely to be receptive and to schedule a screening appointment during the calls than were women with no prior experience. Topics discussed during the calls also differed between women with and without prior mammography experience. Implications for dissemination of counseling interventions in health care organizations are discussed.