Thyroid palpation versus high-resolution thyroid ultrasonography in the detection of nodules

Detection of thyroid nodules by physical examination and high-resolution ultrasonography was compared using small groups of blinded, experienced physician examiners working with a sample of 2441 persons from Estonia, most of whom were Chernobyl nuclear reactor clean-up workers. A random subsample of 113 (5%) persons was subjected to triple control examinations with both physical examination and high-resolution ultrasonography. Positive high-resolution ultrasonographic findings were considerably more reproducible among different observers than were positive physical examination findings. Agreement between methods was poor. Nodules were found in 169 (6.9%) subjects by physical examination and in 249 (10.2%) subjects by high-resolution ultrasonography. Physical examination found only 53 (21%) of the 249 nodules found by high-resolution ultrasonography. High-resolution ultrasonography did not confirm the existence of 115 (68%) of the 169 nodules found by physical examination. Only 6.4% of nodules less than 0.5 cm in diameter, as based on high-resolution ultrasonographic results, were detected by physical examination. Physical examination detection improved with increasing nodule size but was still only 48.2% for nodules larger than 2 cm. Physical examination was relatively effective in detecting nodules in the isthmus of the thyroid gland but much less so for nodules in the upper pole of the gland. Clinical evaluation and epidemiologic studies of nodular thyroid disease stand to benefit from the greater sensitivity and specificity of ultrasonographic examinations.     

On-Line Algorithms for the Dynamic Traveling Repair Problem

We consider the dynamic traveling repair problem in which requests with deadlines arrive through time on points in a metric space. Servers move from point to point at constant speed. The goal is to plan the motion of servers so that the maximum number of requests are met by their deadline. We consider a restricted version of the problem in which there is a single server and the length of time between the arrival of a request and its deadline is constant. We give upper bounds for the competitive ratio of two very natural algorithms as well as several lower bounds for any deterministic algorithm. Most of the results in this paper are expressed as a function of β, the diameter of the metric space. In particular, we prove that the upper bound given for one of the two algorithms is within a constant factor of the best possible competitive ratio.     

Reactivity of twenty-two cytotoxic human monoclonal HLA antibodies towards soluble HLA class I in an enzyme-linked immunosorbent assay (PRA-STAT)

An ELISA, PRA-STAT was recently introduced for the detection of HLA class I specific antibodies of IgG isotype in patients' sera. We studied the antigenicity of the soluble HLA (sHLA) preparations that are used in this ELISA as the detection matrix, with the aid of a panel of complement binding human HLA monoclonal antibodies (HuMAbs). A total of 22 HuMAbs, including both IgG and IgM were used. CDC and PRA-STAT ELISA were in complete agreement on 9 of the mAbs tested, with 16 HLA-A and 16 HLA-B locus antigens or their splits identified identically on CDC and PRA-STAT. In 7 of the remaining 13 HuMAbs, there was a difference of one antigen in the specificity pattern of the two techniques three times a specificity call not made by CDC, and four times a call not made by PRA-STAT. For the remaining 6 HuMAbs the differences involve 2 antigens (4 HuMAbs), and 3 or 4 antigens (1 HuMAb each). This study shows the validity of PRA-STAT for detection of HLA-class I antibodies, irrespective of isotype, in serum. The immunological integrity of the sHLA preparations used in PRA-STAT is also confirmed, albeit with some slight discrepancies in antibody specificity seen between PRA-STAT and CDC.     

Engraftment and retroviral marking of CD34+ and CD34+CD38- human hematopoietic progenitors assessed in immune-deficient mice

Retroviral-mediated transduction of human hematopoietic stem cells to provide a lifelong supply of corrected progeny remains the most daunting challenge to the success of human gene therapy. The paucity of assays to examine transduction of pluripotent human stem cells hampers progress toward this goal. By using the beige/nude/xid (bnx)/hu immune-deficient mouse xenograft system, we compared the transduction and engraftment of human CD34+ progenitors with that of a more primitive and quiescent subpopulation, the CD34+CD38- cells. Comparable extents of human engraftment and lineage development were obtained from 5 x 10(5) CD34+ cells and 2,000 CD34+CD38- cells. Retroviral marking of long-lived progenitors from the CD34+ populations was readily accomplished, but CD34+CD38- cells capable of reconstituting bnx mice were resistant to transduction. Extending the duration of transduction from 3 to 7 days resulted in low levels of transduction of CD34+CD38- cells. Flt3 ligand was required during the 7-day ex vivo culture to maintain the ability of the cells to sustain long-term engraftment and hematopoiesis in the mice.     

T lymphocytes with a normal ADA gene accumulate after transplantation of transduced autologous umbilical cord blood CD34+ cells in ADA-deficient SCID neonates

Adenosine deaminase-deficient severe combined immunodeficiency was the first disease investigated for gene therapy because of a postulated production or survival advantage for gene-corrected T lymphocytes, which may overcome inefficient gene transfer. Four years after three newborns with this disease were given infusions of transduced autologous umbilical cord blood CD34+ cells, the frequency of gene-containing T lymphocytes has risen to 1-10%, whereas the frequencies of other hematopoietic and lymphoid cells containing the gene remain at 0.01-0.1%. Cessation of polyethylene glycol-conjugated adenosine deaminase enzyme replacement in one subject led to a decline in immune function, despite the persistence of gene-containing T lymphocytes. Thus, despite the long-term engraftment of transduced stem cells and selective accumulation of gene-containing T lymphocytes, improved gene transfer and expression will be needed to attain a therapeutic effect.     

Aortic dissection in a patient receiving chemotherapy for Hodgkin's disease--a case report

Cancer chemotherapy is associated with a wide range of vascular toxicities, which may be related to endothelial cell damage by these agents. The authors describe a patient with Hodgkin's disease who developed an atypical aortic dissection while receiving MOPP/ABV chemotherapy (nitrogen mustard, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine). They would place aortic dissection on the list of potential vascular complications associated with antineoplastic agents.     

The effects of tolbutamide on the myocardium in experimental diabetes

The effects of chronic tolbutamide treatment were examined in a diabetic animal model in which abnormal myocardial function and composition have previously been demonstrated. Eight diabetic dogs were given tolbutamide 250 mg/day orally and compared with seven untreated diabetics, five healthy dogs receiving tolbutamide, and eight normal controls. After one year, resting hemodynamic studies in the intact anesthetized state showed that treated diabetic dogs had a significantly higher left ventricular end-diastolic pressure of 12.1+/-1.3 mm Hg associated with normal end-diastolic volume, compared to 6.1+/-0.8 mm Hg in untreated diabetics (P less than 0.01) and 6.3+/-0.5 in normals. Stroke work and ejection fraction were similar to normals. Acute volume expansion revealed a larger rise of left ventricular end-diastolic pressure in treated and untreated diabetics than normals, without a significant stroke volume response in treated diabetics. Enhanced stiffness of myocardium appeared to be related to interstitial accumulation of periodic acid-Schiff staining material, further intensified in treated diabetics by triglyceride accumulation observed on electron microscopy and by chemical analysis. Thus treatment of diabetes with tolbutamide, despite improved glucose tolerance, effected further reduction of left ventricular function and altered morphology of myocardium.     

Characterization of a sialyltransferase-deficient mutant of Neisseria gonorrhoeae strain F62: instability of transposon Tn1545 delta3 in gonococci and evidence that multiple genetic loci are essential for lipooligosaccharide sialylation

Neisseria gonorrhoeae strain JB1 was previously shown to be defective in the sialylation of lipoologosaccharide (LOS) by exogenous CMP-NANA. The LOS components synthesized by the mutant now have been shown by mass spectrometry to be similar to those in the parental strain, F62, and to include the 4.5 kDa widely conserved lacto-N-neotetraose component that can be sialylated. The same two LOS components could be sialylated on the surface of the mutant and parental strains. One major component was sialylatable after chemical extraction of the LOS from either strain. These data confirm that the mutant, JB1, retains the ability to synthesize the LOS target required for the conversion by sialylation of serum-sensitive gonococci to serum resistance. A single base frame-shift mutation was found in the lst gene from the mutant, resulting in the replacement of the final 61 amino acids at the C-terminus of the sialyltransferase by four residues. Seventeen independent clones of the lst gene were isolated from the parental strain, but none of them complemented the sialyltransferase defect of the mutant and no sialyltransferase activity expressed from the clones could be detected in Escherichia coli. Although the data suggest that the mutant might be defective in genes at more than one chromosomal locus and that multiple loci are essential for sialyltransferase synthesis and activity, the alternative possibility, that DNA adjacent to the lst gene encodes a product which is toxic to E. coli, cannot be excluded. The site of insertion of the transposon Tn1545-Delta3 in strain JB1 was cloned and sequenced. The transposon is located in an intergenic region adjacent to genes for a putative ATP-dependent transport protein, but encoding no recognizable function relevant to LOS sialylation. Evidence that transposon Tn1545-Delta3 is unstable in gonococci is presented.     

Spatial-frequency discrimination and detection: comparison of postadaptation thresholds

We found that inspecting a sine-wave grating elevated threshold for spatial-frequency discrimination as it does for contrast detection, but discrimination threshold was maximally elevated at about twice the adapting frequency, where detection threshold was little affected; and detection threshold was maximally elevated at the adapting frequency, where discrimination threshold was not elevated at all. Orientation tuning was roughly similar for contrast and for discrimination threshold elevations; elevations fell by half at between 7 and 17 deg from the adapting orientation. We compared our findings with the predictions of three models of discrimination: (1) The data are inconsistent with the idea that the most strongly stimulated channels are the most important channels for discrimination. (2) With an additional assumption, the Hirsch-Hylton scaled-lattice model could account for our finding that discrimination threshold elevations are asymmetric. (3) With no additional assumptions, the idea that discrimination is determined by the relative activities of multiple overlapping spatial-frequency channels or size-tuned neurons can account for our finding that discrimination thresholds are asymmetric. We propose a physiologically based discrimination model: Asymmetrically tuned cortical cells feed a ratio-tuned neural mechanism whose properties are formally analogous to those of ratio-tuned neurons that have recently been found in cat visual cortex. The linear relation between firing frequency and contrast can explain why discrimination threshold is substantially independent of contrast.