Detection of human T-lymphotropic virus (HTLV) tax sequences in New York City blood donors seronegative for HTLV types 1 and 2

A potential public health concern is the reported detection of the human T-lymphotropic virus (HTLV) tax gene in the lymphocytes of up to 11% of a low-risk group of New York City blood donors (NYBD). This study aimed to independently confirm the prevalence of HTLV tax sequences in 293 NYBD. All NYBD tested negative for antibodies to HTLV types 1 and 2 and HTLV Tax. HTLV tax sequences were not detected in the NYBD lymphocytes. These data demonstrate the lack of HTLV-1 tax in this group of NYBD at low risk for HTLV infection.     

Apparent replication of suggestive linkage on chromosome 16 in the NIMH genetics initiative bipolar pedigrees

Analyses of a replication sample of families collected as part of the National Institute of Mental Health (NIMH) Genetics Initiative for bipolar disorder provide further evidence for linkage to a region of chromosome 16. Families who had a bipolar I (BPI) proband and at least one BPI or schizoaffective, bipolar type (SABP) first-degree relative were ascertained for the purpose of identifying genes involved in bipolar affective disorder. A series of hierarchical models of affected status was used in linkage analyses. Initial genetic analyses of chromosomes 3, 5, 15, 16, 17, and 22, completed at Indiana University in 540 subjects from 97 families, suggested evidence of linkage to chromosomes 5, 16, and 22 [Edenberg et al., 1997: Am J Med Genet 74:238-246]. Genotyping was subsequently performed on these chromosomes in a replication sample of 353 individuals from 56 families. Nonparametric linkage analyses were performed using both affected relative and sibling pair methods. Analyses in the new sample on chromosome 16, using the broadest model of affected status, corroborate previously reported suggestive linkage to the marker D16S2619. Combining the initial and replication samples further increased the evidence of linkage to this region, with a peak lod score of 2.8.     

Plasma steroid concentrations during alternate-day treatment with prednisone

Plasma steroid concentrations were measured in asthmatic children 24 and 48 hours after administration of alternate-day treatment with prednisone, and the results were compared with those of control patients who did not receive corticosteroid treatment as well as those of patients who were treated with prednisone each day. It was found that 24 hours after administration of prednisone in any dose, plasma steroid concentrations were significantly lower than those of the control group. The degree of suppression in plasma steroid concentration was less marked in patients who received treatment on alternate days than in those who received the same doses of prednisone each day. Within 48 hours after administration of alternate-day treatment, plasma steroid concentrations approached the values observed in the control group and were independent of the magnitude of the prednisone dose. Although alternateday steroid treatment was associated with transient and incomplete suppression of pituitary-adrenal function, patients whose therapy was changed from a daily to an alternate-day regimen sometimes exhibited prolonged suppression of adrenal cortical function.     

Osteoblast response to hydroxyapatite doped with divalent and trivalent cations

The present in vitro study doped hydroxyapatite (HA) with various metal cations (Mg(2+), Zn(2+), La(3+), Y(3+), In(3+), and Bi(3+)) in an attempt to enhance properties of HA pertinent to orthopedic and dental applications. X-ray diffraction material characterization indicated that the metal cations may have substituted for calcium in the HA crystal structure and that all of the doped HA formulations were single-phase and crystalline. Scanning electron microscopy analysis revealed a variety of grain sizes, depending on the dopant utilized. Energy-dispersive spectroscopy confirmed that the dopants added during synthesis were present and that all of the HA formulations synthesized were within the defined range of HA phase in the CaO-P(2)O(5)-H(2)O system. Lastly, Bi-doped HA had a slower dissolution rate than either undoped HA or HA doped with other cations when exposed to simulated physiological conditions for 21 days. In terms of cell function, results provided the first evidence that osteoblasts, bone-forming cells, adhered and differentiated (as measured by alkaline phosphatase synthesis) in response to HA doped with trivalent cations (specifically, La(3+), Y(3+), In(3+), Bi(3+)) at earlier time points than either HA doped with divalent cations (Mg(2+), Zn(2+)) or undoped HA. Of the dopants examined, Bi(3+) most enhanced osteoblast long-term calcium-containing mineral deposition. For these reasons, this study revealed for the first time the potential benefits of doping HA with Bi(3+) according to criteria critical for bone prosthetic clinical success.     

Self-esteem and causal attributions for success and failure in children

In a comparison of causal attributions following success and failure in hypothetical social, athletic, and academic situations, high self-esteem grade school children were more likely than low self-esteem children to attribute their success to ability and their failure to either lack of effort or bad luck. Low self-esteem children, on the other hand, attributed their success more often than high self-esteem children to good luck (and in social situations to effort and task ease as well) and their failure to lack of ability. Whereas prior studies that focused only on the internal-external dimension found that low and high self-esteem children differed in their attributional style to success but not to failure, the present study found that when distinctions between behavioral and characterological attributions (stability and globality dimensions) were included, the two groups differed significantly in response to both success and failure. Although perhaps not generalizable beyond the present attribution measure, the most pronounced attribution differences between low and high self-esteem children were observed in the social domain, the least in the academic domain, with athletics falling in between. Finally, it was found that sex and age (within the limited fourth- to sixth-grade range examined in the present study) did not alter the overriding difference in attributional style between low and high self-esteem children.This study is based on a doctoral dissertation submitted by the first author under the supervision of the last author in partial fulfillment of the requirements for the Ph.D. degree at the University of Vermont.     

Periadventitial dissection of the superior mesenteric artery for locally advanced pancreatic cancer: Surgical planning with the “halo sign” and “string sign”

Most patients diagnosed with pancreatic cancer are classified as nonoperative candidates based on the contemporary guidelines of resectability. The advent of more potent control of systemic disease using neoadjuvant chemotherapy has enabled more aggressive operative interventions. In our multidisciplinary practice, patients with Stage III, locally advanced pancreatic cancer and superior mesenteric artery (SMA) encasement are now carefully triaged with high quality, preoperative imaging to determine if they can be considered candidates for operative resection with periadventitial dissection of the SMA. Patients displaying a “halo sign,” where the encased SMA remains fully patent and free from arterial invasion, are now candidates for SMA periadventitial dissection. This procedure involves the surgical stripping of the infiltrated neurolymphatic tissue off the SMA leaving behind a bare “skeletonized artery.” Alternatively, the “string sign” involving the SMA confers a more likely case of arterial invasion, where a complete oncologic resection cannot be achieved successfully. This method of patient selection in case of SMA involvement abandons the traditional metrics of circumferential degrees of the arterial encasement to guide surgical decisions. Our institutional approach has allowed us to meaningfully expand our operative methods of resection with the potential for improved longitudinal outcomes to pancreatic cancer patients who were deprived historically from the more effective and possibly curative treatment.     

Assembly of targeting complexes driven by a single-chain antibody

Rapid development in design and production of recombinant antibodies and antibody fragments specific for cell surface markers opens new opportunities for targeted delivery of therapeutic or imaging agents. However, the progress in this field is slowed by inactivation of many antibodies by chemical conjugation of payloads and by lack of internalization of complexes formed on the cell surface. Here, we describe conversion of a non-internalizing single chain Fv (scFv) antibody P4G7 specific for vascular endothelial growth factor receptor 2 (VEGFR-2) into a targeting protein (Hu-P4G7) for assembly of a novel type of targeting complexes. Hu-P4G7 contains an N-terminal "docking" Hu-tag, a 15-aa fragment of human RNase I, capable of high affinity binding of S-protein fragment of human RNase I or bovine RNase A. Purified Hu-P4G7 and complexes of Hu-P4G7 with S-protein bind both soluble and full-length cellular VEGFR-2. To assemble targeted DNA delivery complexes, S-protein modified with a DNA condensing agent was "docked" to Hu-P4G7, and then loaded with luciferase plasmid DNA. As expected for a non-internalizing targeting protein, Hu-P4G7-based complexes did not deliver DNA in VEGFR-2 expressing cells. However, in the presence of vascular endothelial growth factor (VEGF), these complexes selectively delivered DNA into the cells overexpressing VEGFR-2 suggesting that even a non-internalizing scFv antibody can be used for targeted intracellular drug delivery.     

A comparison of the haemodynamic and hormonal effects of low and conventional dose cyclopenthiazide in normal volunteers

Summary In this study we compared low (125 g) and conventional (500 g) doses of cyclopenthiazide on the renin angiotensin system, plasma and extracellular fluid volumes and the pressor responsiveness to angiotensin II since we have previously shown that the two doses have the same antihypertensive effect but different effects on plasma renin activity.Following a two week placebo run-in period, 8 healthy male volunteers received 125 g or 500 g of cyclopenthiazide for 2 treatment periods of 4 weeks as part of a double blind, 2-part crossover study with treatment periods separated by a 4-week placebo washout phase. Measurements were made on two study days at the beginning and end of the active treatment periods. On the first day serum potassium, plasma renin activity and plasma angiotensin II levels were measured after a 1 h period of supine rest. Plasma and extracellular fluid volumes were also measured after appropriate equilibration times. The blood pressure responses to angiotensin II were assessed on day 2.The 500 g dose of cyclopenthiazide had a greater effect than the 125 g dose on plasma renin activity, serum potassium, angiotensin II levels and extracellular fluid volumes. Neither drug had any effect on plasma volume or the responsiveness to infused angiotensin II.Low dose cyclopenthiazide failed to increase angiotensin II levels, contract body fluid volumes or attenuate vascular reactivity in normotensive volunteers.     

Severity adjustment for length of stay: is it always necessary?

OBJECTIVE: Severity adjustment is an oft-cited requirement when comparing physicians or medical delivery systems. Each application of severity adjustment, however, has to be tested to validate the need, the method, and its value. We examined the value of severity adjustment for identifying physician outliers when studying length of stay in the hospital. DESIGN: We compared the placement of physicians in an outlier category using a severity-adjusted average length of stay (SLOS) index with their placement using the unadjusted average length of stay (ALOS). Changes in placement of the list were validated by the utilization review coordinators. SETTING: A 614-bed tertiary-care university teaching hospital. SUBJECTS: We analyzed 11,146 discharges from 138 physicians in 1992. RESULTS: The mean ALOS +/- standard deviation was 9.05 + 4.50 days, and the SLOS Index was 7.56 +/- 3.06. There were 120 inliers, 6 high outliers, and 12 low outliers by the ALOS method. Using the SLOS index, 27 of 138 physicians had their categories changed from inlier to outlier or from outlier to inlier. The difference in group changes was more significant for those going from outlier to inlier status (8/120 vs 6/18; P < .001). The patients of the six physicians whose status changed from outlier to inlier status were sicker, as indicated by the comorbidity, complications, and manifestations of disease processes score. The utilization reviewers validated the status changes in 8 of 14 instances. CONCLUSIONS: Severity-adjusted length of stay by the SLOS index appears to provide a more accurate measure than the unadjusted ALOS. The changes, however, were small. It is not clear that the added effort is worthwhile.