Laboratory based study of undetectable thyroid stimulating hormone.

The clinical importance of an undetectable thyroid stimulating hormone (TSH) concentration (less than 0.2 mU/l) was studied in a consecutive series of 2573 requests for routine thyroid function tests. Two hundred and seventeen (8.4%) patients had an undetectable TSH concentration, and of these 39 (18%) had otherwise normal thyroid hormone concentrations and no history of thyroid disease. In a follow up study 71 patients (34 outpatients and 37 inpatients) with undetectable TSH concentration associated with otherwise normal thyroid hormone concentrations were randomly selected during routine reporting of thyroid function test results. None of these patients had a history of thyroid disease. Sex hormone binding globulin concentrations were increased in five out of 50 of these patients and antithyroid antibodies were detectable in four out of 49, suggesting that in most cases the isolated undetectable TSH concentration was not associated with thyroid dysfunction, particularly hyperthyroidism. Isolated undetectable TSH concentration was observed in both inpatients and outpatients and was not associated with any particular clinical condition. Repeat specimens were received in 54 of the 71 patients and TSH concentration remained persistently undetectable in 35 of these.

Method comparison--a different approach.

The commonly accepted method of analysing data from method comparison studies is regression analysis, a method which has limitations. This study illustrates the use of a graphical presentation of data, the difference plot, which can be used as an alternative to least squares regression analysis. The data from comparison studies performed on five methods were analysed both by Deming's regression analysis, with calculation of the correlation coefficient, and by the difference plot. The results show that in most cases much more relevant information was obtained from the difference plot.

Comparison of total, complexed and free prostate-specific antigens and their ratios in the detection of prostate cancer in a non-screened population.

BACKGROUND: The role of prostate-specific antigen (PSA) isoforms in the detection of prostate cancer in a non-screened population in the UK remains to be determined. METHODS: Consecutive patients undergoing diagnostic transrectal ultrasound-guided biopsy of the prostate were studied. Prior to biopsy, a blood sample was obtained and total, complexed and free PSA concentrations measured. RESULTS: Of the 171 patients included in the study, 103 were found to have prostate cancer. There were significant differences in total and complexed PSA concentrations and in the ratio of free-to-total PSA (all P <0.001) between patients with prostate cancer and those with benign disease. Receiver operating characteristics (ROC) curve analysis showed that the corresponding areas under the curves were similar. Restricting the analysis to the 77 patients who had total PSA concentrations between 2 and 10 micro g/L, ROC curve analysis showed that total and complexed PSA concentrations failed to discriminate between benign and malignant disease. In contrast, the areas under the ROC curve were greater for the free-to-total ratio (P = 0.033). CONCLUSION: These results show that in patients with total PSA concentrations between 2 and 10 micro g/L, the free-to-total PSA ratio was superior to total PSA concentration in discriminating between patients with benign and malignant disease.

Prediction of outcome in neonates using EEG.

To determine the value of EEG in predicting prognosis, the recordings of 30 neonates were re-examined using a specially devised method of visual rating which permitted quantitative assessment of 13 EEG items. Seven clinical variables were also coded. The data were submitted to computer discriminant function analysis, to determine whether the outcome could be predicted and which EEG variables contributed most effectively. Marked asymmetries, many slow transients, and a wide range of variability of suppression durations were the main indicators. The state of consciousness during the recording and the gestational age were the clinical variables which were useful. It was possible to predict outcome using this technique in 28 of the 30 patients. The same procedure was applied to serial recordings with equal value. The combination of visual ratings carried out, without reference to clinical information and requiring no subjective statement as to normality or abnormality of the features in the recording, seems to offer a contribution in the difficult field of neonatal EEG.

Thyroxine treatment in patients with symptoms of hypothyroidism but thyroid function tests within the reference range: randomised double blind placebo controlled crossover trial.

OBJECTIVES: To determine whether thyroxine treatment is effective in patients with symptoms of hypothyroidism but with thyroid function tests within the reference range, and to investigate the effect of thyroxine treatment on psychological and physical wellbeing in healthy participants. DESIGN: Randomised double blind placebo controlled crossover trial. SETTING: Outpatient clinic in a general hospital. PARTICIPANTS: 25 patients with symptoms of hypothyroidism who had thyroid function tests within the reference range, and 19 controls. METHODS: PARTICIPANTS were given thyroxine 100 microgram or placebo to take once a day for 12 weeks. Washout period was six weeks. They were then given the other to take once a day for 12 weeks. All participants were assessed physiologically and psychologically at baseline and on completion of each phase. MAIN OUTCOME MEASURES: Thyroid function tests, measures of cognitive function and of psychological and physical wellbeing. RESULTS: 22 patients and 19 healthy controls completed the study. At baseline, patients' scores on 9 out of 15 psychological measures were impaired when compared with controls. Patients showed a significantly greater response to placebo than controls in 3 out of 15 psychological measures. Healthy participants had significantly lower scores for vitality when taking thyroxine compared to placebo (mean (SD) 60 (17) v 73 (16), P<0.01). However, patients' scores from psychological tests when taking thyroxine were no different from those when taking placebo except for a poorer performance on one visual reproduction test when taking thyroxine. Serum concentrations of free thyroxine increased and those of thyroid stimulating hormone decreased in patients and controls while they were taking thyroxine, confirming compliance with treatment. Although serum concentrations of free triiodothyronine increased in patients and controls taking thyroxine, the difference between the response to placebo and to thyroxine was significant only in the controls. CONCLUSIONS: Thyroxine was no more effective than placebo in improving cognitive function and psychological wellbeing in patients with symptoms of hypothyroidism but thyroid function tests within the reference range. Thyroxine did not improve cognitive function and psychological wellbeing in healthy participants.

Time out! When slowing down can be the quickest way.

Proxima, a leading manufacturer of desktop projection devices, formed a team to select and implement a new manufacturing resource planning II system. Although standard implementation methods were employed throughout the process, the implementation was plagued by software problems, systems operating problems, and team dysfunction and was halted after the first year. This article examines how and why the implementation effort failed, what the company learned from the experience, and what changes were made that allowed the company to succeed on its second attempt.

Local neurovascular island flap.

Fingertip amputation, with loss of the terminal pulp and bone exposure presents a difficult problem. Reconstruction with use of a local neurovascular island flap has been done in twenty-one patients to restore sensibility and function with preservation of length. All patients achieved two-point discrimination values within two millimeters of the normal contralateral fingertip, with adequate pad for pain-free pinch. We advocate this procedure for deep pulp loss over the distal phalanx. It is reliable, single-staged, and provides skin coverage closer to normal than any regional flap technique.

Essential role of a kinesin-like protein in Arabidopsis trichome morphogenesis.

Little is known about how cell shape is controlled. We are using the morphogenesis of trichomes (plant hairs) on the plant Arabidopsis thaliana as a model to study how cell shape is controlled. Wild-type Arabidopsis trichomes are large, single epidermal cells with a stalk and three or four branches, whereas in zwichel (zwi) mutants the trichomes have a shortened stalk and only two branches. To further understand the role of the ZWI gene in trichome morphogenesis we have cloned the wild-type ZWICHEL (ZWI) gene by T-DNA tagging, and report here that it encodes a member of the kinesin superfamily of microtubule motor proteins. Kinesin proteins transport diverse cellular materials in a directional manner along microtubules. Kinesin-like proteins are characterized by a highly conserved "head" region that comprises the motor domain, and a nonconserved "tail" region that is thought to participate in recognition and binding of the appropriate cargo.

Timing of cerclage removal after preterm premature rupture of membranes: maternal and neonatal outcomes.

OBJECTIVE: Our aim was to evaluate immediate versus delayed removal of cerclage for women with preterm premature rupture of membranes with respect to maternal and neonatal outcomes. STUDY DESIGN: We retrospectively analyzed women with preterm premature rupture of membranes at <34 weeks' gestation with prior cerclage placement. Exclusion criteria included presentation with chorioamnionitis, active labor, or nonreassuring fetal status. Timing of cerclage removal, immediate (<24 hours) or delayed (>24 hours), was compared. RESULTS: There were 25 women in the delayed-removal group and 37 in the immediate-removal group. Average times to removal were 206.8 +/- 7.4 and 5.4 +/- 0.2 hours, respectively. Use of betamethasone was similar for both groups; however, antenatal antibiotic use (100% vs 80%; P =.03) and short-term tocolytic use (20% vs 3%; P =.04) were higher in the delayed-removal group. Duration of latency was significantly longer with delayed removal (10.1 vs 5.0 days; P <. 001). Delivery occurred >48 hours from preterm premature rupture of membranes in 96% (24/25) versus 54% (20/37; P <.001) and >7 days from rupture in 56% (14/25) versus 24% (9/37; P =.02), respectively. Rates of neonatal sepsis (at <10 days) and maternal infection were not statistically different. Neonatal outcomes did not significantly differ regarding mortality, respiratory distress syndrome, birth weight, or duration of stay in the intensive care nursery. CONCLUSION: With the current management scheme for preterm premature rupture of membranes, cerclage retention significantly increases duration of latency without significantly altering maternal or neonatal outcomes.

The cell morphogenesis gene ANGUSTIFOLIA encodes a CtBP/BARS-like protein and is involved in the control of the microtubule cytoskeleton.

The ANGUSTIFOLIA (AN) gene is required for leaf hair (trichome) branching and is also involved in polarized expansion underlying organ shape. Here we show that the AN gene encodes a C-terminal binding proteins/brefeldin A ADP-ribosylated substrates (CtBP/BARS) related protein. AN is expressed at low levels in all organs and the AN protein is localized in the cytoplasm. In an mutant trichomes, the organization of the actin cytoskeleton is normal but the distribution of microtubules is aberrant. A role of AN in the control of the microtubule cytoskeleton is further supported by the finding that AN genetically and physically interacts with ZWICHEL, a kinesin motor molecule involved in trichome branching. Our data suggest that CtBP/BARS-like protein function in plants is directly associated with the microtubule cytoskeleton.