ESTS guidelines for intraoperative lymph node staging in non-small cell lung cancer.

The European Society of Thoracic Surgeons (ESTS) organized a workshop dealing with lymph node staging in non-small cell lung cancer. The objective of this workshop was to develop guidelines for definitions and the surgical procedures of intraoperative lymph node staging, and the pathologic evaluation of resected lymph nodes in patients with non-small cell lung cancer (NSCLC). Relevant peer-reviewed publications on the subjects, the experience of the participants, and the opinion of the ESTS members contributing on line, were used to reach a consensus. Systematic nodal dissection is recommended in all cases to ensure complete resection. Lobe-specific systematic nodal dissection is acceptable for peripheral squamous T1 tumors, if hilar and interlobar nodes are negative on frozen section studies; it implies removal of, at least, three hilar and interlobar nodes and three mediastinal nodes from three stations in which the subcarinal is always included. Selected lymph node biopsies and sampling are justified to prove nodal involvement when resection is not possible. Pathologic evaluation includes all lymph nodes resected separately and those remaining in the lung specimen. Sections are done at the site of gross abnormalities. If macroscopic inspection does not detect any abnormal site, 2-mm slices of the nodes in the longitudinal plane are recommended. Routine search for micrometastases or isolated tumor cells in hematoxylin-eosin negative nodes would be desirable. Randomized controlled trials to evaluate adjuvant therapies for patients with these conditions are recommended. The adherence to these guidelines will standardize the intraoperative lymph node staging and pathologic evaluation, and improve pathologic staging, which will help decide on the best adjuvant therapy.     

Functional magnetic resonance imaging based on changes in vascular space occupancy.

During brain activation, local control of oxygen delivery is facilitated through microvascular dilatation and constriction. A new functional MRI (fMRI) methodology is reported that is sensitive to these microvascular adjustments. This contrast is accomplished by eliminating the blood signal in a manner that is independent of blood oxygenation and flow. As a consequence, changes in cerebral blood volume (CBV) can be assessed through changes in the remaining extravascular water signal (i.e., that of parenchymal tissue) without need for exogenous contrast agents or any other invasive procedures. The feasibility of this vascular space occupancy (VASO)-dependent functional MRI (fMRI) approach is demonstrated for visual stimulation, breath-hold (hypercapnia), and hyperventilation (hypocapnia). During visual stimulation and breath-hold, the VASO signal shows an inverse correlation with the stimulus paradigm, consistent with local vasodilatation. This effect is reversed during hyperventilation. Comparison of the hemodynamic responses of VASO-fMRI, cerebral blood flow (CBF)-based fMRI, and blood oxygenation level-dependent (BOLD) fMRI indicates both arteriolar and venular temporal characteristics in VASO. The effect of changes in water exchange rate and partial volume contamination with CSF were calculated to be negligible. At the commonly-used fMRI resolution of 3.75 x 3.75 x 5 mm(3), the contrast-to-noise-ratio (CNR) of VASO-fMRI was comparable to that of CBF-based fMRI, but a factor of 3 lower than for BOLD-fMRI. Arguments supporting a better gray matter localization for the VASO-fMRI approach compared to BOLD are provided.     

Urinary kallikrein activity in workers exposed to cadmium, lead, or mercury vapour

A significant reduction of kallikrein activity in urine (assayed by its amidolytic activity) was found in 64 normotensive workers who had been exposed to cadmium for 11 years on average and whose cadmium concentrations in urine ranged from 2.2 to 33.1 micrograms/g creatinine. The mean (geometric) urinary kallikrein activity (in U/g creatinine) amounted to 0.52 (range 0.11-1.90) in the control group (n = 193) against 0.39 (range 0.10-1.03) in the cadmium group, and the prevalence of abnormally low activity levels (less than or equal to 0.20 U/g creatinine) amounted to 17.2% in the cadmium group against 5.2% in the control group. A reduction of aldosterone release (aldosterone in urine) associated with an increased natriuresis was also observed. This might constitute a compensatory mechanism maintaining blood pressure in the normal range. These biological effects of cadmium were not reversible after removal from exposure. This study indicates that cadmium can induce an irreversible toxic effect in the distal nephron. It also suggests that an excessive cadmium body burden alone may not be sufficient to induce hypertension, but in individuals whose blood pressure regulation may be impaired by other factors cadmium could stimulate the development of hypertension. This study also supports the recommendation to prevent hypertensive subjects from being exposed to cadmium. There was no indication that moderate exposure to mercury vapour (n = 53; mercury in urine, range 11-224 micrograms/g creatinine; average duration of exposure: six years) or to inorganic lead (n = 23; lead in blood, range 40-67 micrograms/100 ml; average duration of exposure: eight years) was associated with a reduction of kallikrein production by the kidney.     

A muscle spindle model for primary afferent firing based on a simulation of intrafusal mechanical events.

1. A muscle spindle model for primary afferent firing is presented that contains two components representing a gamma d-dependent (bag1) and gamma s-dependent (bag2/nuclear chain) intrafusal fiber. Each of the intrafusal fibers is composed of a linear elastic element representing the sensory part and a muscle fiber representing the muscular part. 2. The muscular part of the bag1 was modeled as a slow twitch, that of the bag2 as a fast twitch muscle fiber. 3. The sensory regions were linear length transducers, generating a rising depolarization on increasing stretch. The input of both bags was fused by taking the largest depolarization to determine a generator potential. The rate of primary afferent firing depended on this generator potential as well as on its rate of change. 4. To simulate the high sensitivity of muscle spindles to small amplitudes of stretching, a model analogue of cross-bridge fixation (or stiction) has been included in the muscular part of the bag1 fiber. This makes use of one hundred cross-bridge regions that release one after the other, provided a certain breaking force is exceeded. 5. The values of the mechanical parameters that defined the model were selected by a computerized search procedure. 6. The values found by means of this procedure allowed the model to provide an accurate simulation of experimental data on ramp-and-hold stretches (for 6 different stretch velocities under variable conditions of fusimotor activity). 7. On sinusoidal stretches at a frequency of 1 Hz the spindle model responded with about one-half the discharge modulation reported in experimental studies. Its phase advance tended to be slightly lower than that observed for real spindles. 8. Frequency response curves showed the same high sensitivities at high frequencies as those observed in real spindles. 9. Close evaluation of the model compared with experimental results in literature reveal its merits as well as its limitations. Because the model is structural rather than phenomenologic, it provides insight into how intrafusal events may contribute to observed firing properties of real muscle spindles.     

Analysis of saccadic short-term plasticity in three dimensions

The capacity for short-term adaptation is a well-established property of the horizontal (H) and vertical (V) components of saccades. It allows these directional components, which clearly serve the goal of foveation, to maintain their precision even under changing circumstances. Torsional (T) saccade components, on the other hand, which deal with the orientation of the target on the fovea, have hardly been investigated in adaptation experiments. They appear to be severely restricted by Listing's law during fixations and saccades. The main purpose of Listing's law is far from obvious but could be visual or oculomotor. Better knowledge of the adaptive capacity of the saccadic system in the torsional direction could throw new light on the functional significance of this interesting neural strategy. To study short-term plasticity in the torsional components of saccades, binocular 3D-eye positions were measured, using magnetic search foils. Five normal human subjects were instructed to make uni-directional refixation saccades, while they viewed a large visual scene. To induce a change in the torsional component, the complete stimulus was rapidly rotated during these saccades. We thoroughly investigated the torsional responses of the saccadic system, to see if any short-term adaptive response in torsional direction was induced, in which case the notion of a visual purpose for Listing's law would be strengthened. In none of our experiments, however, did we find any clear adaptive response in torsional direction. To further investigate the reliability of this result and to ascertain that our experimental conditions allowed classical gain adaptation, we also did experiments designed to achieve a combination of torsional adaptation and classic gain shortening in one of the directional components. While gain adaptation was very obvious, none of the experiments provided evidence for a short-term effect in torsion. We conclude that our experiments do not support a purely visual basis for Listing's law.     

A comparison of T4:T8 lymphocyte ratio in the periodontal lesion of healthy and HIV-positive patients.

Previous reports describe a characteristic, rapidly progressive, periodontitis that is unique to patients who are seropositive for HIV antibody (Western blot +). The purpose of this study was to compare the T4 and T8 lymphocyte subpopulations in the peripheral blood and periodontal lesions of these HIV patients with those of healthy controls. T-cell subsets in peripheral blood were quantified by flow cytometry. The values from this analysis were used to calculate the peripheral T4:T8 lymphocyte ratio for each patient. Gingival tissue (papilla) was obtained from 8 HIV+ patients and from 6 healthy HIV- control patients during routine gingival surgery. The T-cell subpopulations in the gingival tissue were determined using serial cryostat sections that were labeled with monoclonal antibodies for T4 and T8 cells and developed using an avidin-biotin-peroxidase system. Six sections were taken from each of the 14 tissue specimens (one per patient). The sections were examined at 450 x and the mean number of T4 and T8 cells calculated for each section. These mean values were then used to determine the T4:T8 lymphocyte ratio for each tissue specimen. The peripheral blood analysis revealed a mean serum T4:T8 ratio of (2.07 +/- 0.455) for the controls and (0.58 +/- 0.26) for the HIV patients. The significantly lower T4:T8 ratio in HIV patients is consistent with their diagnosis. Although the results indicated that the mean T4:T8 lymphocyte ratio in the gingiva of controls was highly variable (2.70 +/- 1.344), the gingiva of HIV patients consistently exhibited a complete absence of T-cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of estradiol and progesterone on muscle weight and acetylcholine receptors in “myasthenic” rats

Summary Clinical evidence suggests that endocrinal factors are involved in fluctuations of the symptoms of women with myasthenia gravis. We studied the effect of estradiol and progesterone in an animal model for myasthenia gravis in rats. Although it was found that the mass of muscles was dependent on sex, and in female rats affected by estradiol, the number of acetylcholine receptors in these muscles was independent of sex and hormone administration. Sex hormones failed to influence the severity of muscle weakness in myasthenic rats.