Variability in axillary lymph node dissection for breast cancer

BACKGROUND: The axillary nodal status may influence the prognosis and the choice of adjuvant treatment of individual breast cancer patients. The variation in number of reported axillary lymph nodes and its effect on the axillary nodal stage were studied and the implications are discussed. METHODS: Between 1994 and 1997, a total of 4,806 axillary dissections for invasive breast cancers in 4,715 patients were performed in hospitals in the North-Netherlands. The factors associated with the number of reported nodes and the relation of this number with the nodal status and the number of positive nodes were studied. RESULTS: The number of reported nodes varied significantly between pathology laboratories, the median number of nodes ranged from 9 to 15, respectively. The individual hospitals explained even more variability in the number of nodes than pathology laboratories (range in median number 8-15, P < 0.0001). The number of reported nodes increased gradually during the study period. A decreasing trend was observed with older patient age. A higher number of reported nodes was associated with a markedly increased chance of finding tumor positive nodes, especially more than three nodes. The frequency of node positivity increased from 28% if less than six nodes to 54% if >/=20 nodes were examined, the percentage of tumors with >/=4 positive nodes increased from 4 to 31%. Multivariate analysis confirmed these results. CONCLUSIONS: This population-based study showed a large variation in the number of reported lymph nodes between hospitals. A more extensive surgical dissection or histopathological examination of the specimen generally resulted in a higher number of positive nodes. Although the impact of misclassification on adjuvant treatment will have varied, the impact with regard to adjuvant regional radiotherapy may have been considerable.     

A new source of variance in visual acuity

In an ocularly healthy population, decimal visual acuities range from 1 to 3. We wondered how this spread can be understood. Using a maximum likelihood adaptive procedure, "visual acuity" was measured in a healthy population with four stimulus sets: unblurred Landolt Cs and Cs blurred with a Gaussian of width sigma = 2.12', 4.24' and 8.48'. A simple model based on scale invariance of the visual system was applied. This model was tested by predicting the outcomes of the 2.12' measurements based on the other measurements. The minimum angle of resolution (MAR) values found are closely proportional to "equivalent blur" of the stimulus defined as the convolution of a value for intrinsic blur of the eye and added blur. The proportionality factor is different between individuals and is an important source for the spread in acuities found in a healthy population. The differences between the proportionality factors are interpreted as differences in the (neuronal) judgment capability between individuals. The total standard deviation of log(MAR) found in our study was 0.11. This value can be subdivided in 0.06 for the (neuronal) judgment capability, 0.08 for the intrinsic retinal blur and a measurement accuracy of 0.04.     

Comparison of the results of human embryo biopsy and outcome of PGD after zona drilling using acid Tyrode medium or a laser

BACKGROUND: Zona pellucida opening for blastomere removal can be done by mechanical or chemical means, or by laser. So far, only limited data on the use of laser systems for zona drilling in cases of PGD are available. METHODS: Results of embryo biopsy and outcome of PGD in two periods were compared. In the first period, acid Tyrode medium was used for zona drilling. In the second period, zona drilling was performed by a 1.48 micro m infrared laser. RESULTS: In the first period, 59 cycles resulted in 53 biopsy procedures with 356 biopsied embryos. In the second period, these numbers were 69 cycles, 69 biopsy procedures and 402 biopsied embryos. Fewer blastomeres were intact (95.2%) after zona drilling with acid Tyrode than after laser zona drilling (98.3%, P = 0.02). Rates of positive HCG (37.5% versus 35.5%), ongoing pregnancy rates (31.3% versus 25.0%) and ongoing implantation rates (18.9% versus 14.9%) did not differ. CONCLUSIONS: The use of a laser for zona drilling in cases of PGD is an easier procedure and results in more intact blastomeres. Since similar pregnancy rates are obtained, it is advantageous to use a laser for zona drilling. Further follow-up is necessary to prove the safety of this procedure.     

Results from a prospective, randomized, controlled study evaluating the acceptability and effects of routine pre-IVF counselling

BACKGROUND: The aim of this study was to evaluate a model of routine pre-IVF counselling focusing on the narrative capacities of couples. The acceptability of counselling, the effects on emotional factors and the participants' assessments were considered. METHODS: The study included 141 consecutive childless couples preparing for their first IVF. Randomization was carried out through sealed envelopes attributing participants to counselled and non-counselled groups and was accepted by 100 couples. Another 12 couples refused randomization because they wanted counselling and 29 because they did not. Questionnaires including the State-Trait Anxiety Inventory, the Beck Depression Inventory and assessments of help were mailed to couples before IVF and counselling, and after the IVF outcome. RESULTS: Counselling was accepted by 79% (112/141) of couples. There was no significant effect of counselling on anxiety and depression scores which were within normal ranges at both times. Counselling provided help for 86% (75/87) of initially non-demanding subjects and 96% (25/26) of those initially requesting a session. Help was noted in areas of psychological assistance, technical explanations and discussing relationships. CONCLUSIONS: This model of routine counselling centred on the narrative provides an acceptable form of psychological assistance for pre-IVF couples.     

Elevated troponin T concentrations in critically ill patients

Objective To determine the incidence of troponin T elevations among a selected group of critically ill patients, to correlate these findings to electrocardiographs, and to compare troponin T-positive and T-negative patients in relation to clinical parameters.Design Prospective study.Setting Mixed surgical and medical intensive care unit.Patients Thirty-four consecutive critically ill patients who were mechanically ventilated or underwent thoracic or vascular surgery.Interventions Blood samples were collected at admission, the next morning, and 24 h after the second blood sampling. These samples were used for troponin T measurement and electrocardiographs were made when troponin T levels were elevated.Main results Eleven of 34 patients (32%) had elevated troponin T levels, which were already present upon admission in eight out of 11 patients (73%). Most patients underwent surgery prior to ICU admission (21 of 34 patients). Significantly (P=0.0055) more troponin T-positive patients underwent acute surgery, and significantly more (P=0.045) troponin T-positive patients suffered from hypotension. Only four of the troponin T-positive patients were diagnosed as suffering from an acute myocardial infarction based on electrocardiographs. All troponin T-positive patients had coronary artery disease: nine had a history of CAD and two had actual CAD. No difference in mortality rates was observed between troponin T-positive and T-negative patients.Conclusions An unexpectedly high percentage of included patients had troponin T elevations, which could be corroborated by electrocardiographs in only four cases suggesting that a high percentage of critically ill patients with a history of CAD suffer from clinically unrecognised (minor) myocardial damage.     

Collagen morphology in human skin and scar tissue: no adaptations in response to mechanical loading at joints

Dermal collagen displays a random-like structure that has a major role in strength and function of the human integument. It is hypothesised that collagen bundles align in a parallel fashion in the direction of mechanical tension during scarring, which may explain the problematic scar formation that occurs specifically at joints. Scar tissue and normal skin were biopsied from joints and control areas and evaluated by the Fourier analysis. Collagen orientation was represented by an index ranging from 0 (perfectly random) to 1 (perfectly parallel). Collagen bundle packing signifies the average distance between the centres of collagen bundles. No differences were shown in collagen morphology of scar tissue and normal skin between joints and control areas. Normal skin had a significantly lower collagen orientation index than scar tissue (0.26 versus 0.44, P<0.001). The bundle packing of scar tissue differed significantly from normal skin (18.1 microm versus 23.7 microm, P<0.001). Collagen appeared less parallel orientated in deep dermis compared to superficial dermis especially for normal skin (0.27 versus 0.33, P=0.06). Normal skin had a less parallel organisation in sections that were cut parallel compared to those that were cut perpendicular to the epidermis (0.24 versus 0.30, P=0.02). Collagen orientation of scar tissue is more parallel compared to normal skin. Morphology differs with respect to superficial and deep dermal layers and parallel and perpendicular planes, but appears not to respond to mechanical tension.     

Stray light of spectacle lenses compared with stray light in the eye.

Stray light in spectacle lenses may affect the overall vision. It may also affect the measurement of ocular stray light, contrast sensitivity, or glare sensitivity. This article describes common stray light characteristics for glass and plastic spectacle lenses and compares this to the stray light characteristics of the eye, which are well known from the literature. Stray light is described by the skirts of the point-spread function (PSF), which were measured for angles from 4 degrees to 30 degrees. The PSF of spectacle lenses appears to follow the equation PSF = a(10). (theta/10)b, with a(10) and b representing fitting parameters and theta representing the stray light angle. The slope b is on average -2, which similar to that of the eye. For clean spectacle lenses, the PSF is usually at least an order of magnitude lower than that of the eye, whereas "as worn" (uncleaned) spectacle lenses may approach the PSF of the eye. To reach the PSF of the eye, the spectacle lens needs to be contaminated by as much as one or two fingerprints. The article also shows that plastic spectacle lenses degrade much faster than glass spectacle lenses when looking at the amount of stray light.     

Biologic and physical fractionation effects of random geometric errors

PURPOSE: We are developing a system to model the effect of random and systematic geometric errors on radiotherapy delivery. The purpose of this study was to investigate biologic and physical fractionation effects of random geometric errors and respiration motion and compare the resulting dose distributions with Gaussian blurring of the planned dose. MATERIALS AND METHODS: A hypothetical dose distribution with Gaussian penumbra was used. Random errors drawn from a normal distribution, optionally combined with simulated respiration motion (in the cranio-caudal direction), were used to displace the dose distribution for N simulated fractions. To simulate biologic effects of fractionation, the physical dose was converted to a biologically effective dose using the linear-quadratic model (including repopulation), then summed and converted back to physical dose for comparison. Differences between dose distributions were quantified in terms of the distance between selected isodose levels. RESULTS: A limited number of fractions led to an uncertainty in the position of isodose levels in the total dose with as standard deviation (SD) the SD of the random error divided by radical N. Due to biologic fractionation effects, the total dose distribution became slightly wider: 0.4 mm for alpha/beta = 1 Gy and a random error SD of 3 mm. The widening increased with random error and reduced with increasing alpha/beta but does not depend on the number of fractions or on repopulation. Respiration motion caused an asymmetric deviation in the shape of the total dose distribution, but no additional dose widening was seen from the biologic effect of fractionation. With a random error SD of 3 mm and respiration amplitude, A, of 1 cm or less (SD < 0.36 cm), the asymmetry was negligible. For larger respiration amplitudes (combined with the same random error), the shift of the 95% isodose level was about 0.25*A caudally, and 0.45*A cranially. CONCLUSIONS: Gaussian blurring with a combined SD of organ motion, setup error, and respiration motion is a valid approximation for the effect of purely random errors in fractionated radiotherapy. For respiration motion in excess of 1 cm in amplitude, isodose lines shift in a distinctly asymmetric fashion and asymmetric margins need to be used.     

Driving ability after acute and sub-chronic administration of levocetirizine and diphenhydramine: a randomized,double-blind,placebo-controlled trial

Rationale Sedation following antihistamine use poses a danger to ambulant patients involved in daily activities such as driving. Objective To investigate effects of levocetirizine (5 mg), diphenhydramine (50 mg), and placebo on driving ability during normal traffic. Methods Forty-eight healthy volunteers participated in a double-blind, placebo-controlled, randomized clinical trial. Treatments were administrated on days 1, 2, 3 and 4, exactly 1.5 h before the start of the standardized driving test (performed on day 1 and day 4). In the standardized driving test, subjects were instructed to drive with a steady lateral position, while maintaining a constant speed (95 km/h). Primary parameter was the standard deviation of lateral position (SDLP; cm). Statistical analyses were performed separately for day 1 and day 4, using analysis of variance and an equivalence test. Equivalence to placebo was evidenced if the 95% confidence interval lay between −2.6 cm and +2.6 cm. Results SDLP after levocetirizine was equivalent to placebo on both day 1 (−0.66 cm; +1.12 cm) and day 4 (−0.37 cm; +1.28 cm). In contrast, SDLP after diphenhydramine differed significantly from placebo on both day 1 (P<0.0001) and day 4 (P<0.0003). On day 1, the 95% confidence interval of diphenhydramine (+1.85 cm; +3.63 cm) was partially above the upper equivalence limit (+2.6 cm), indicating clinically relevant driving impairment. On day 4, however, the 95% confidence interval of diphenhydramine (+0.74 cm; +2.38 cm) was contained within the acceptance range. Conclusion In contrast to diphenhydramine, driving performance was not significantly affected while using 5 mg levocetirizine once daily.