Time dependence of ventricular refractory periods: implications for electrophysiologic protocols.

Cardiac refractory periods are routinely measured during electrophysiologic testing. Informal observations suggested that the effective refractory period lengthened with a prolongation of the time in sinus rhythm (basic cycle length time) between successive runs of drive stimuli (S1S1s). If this were true, failure to control the basic cycle length time could affect the results and interpretation of electrophysiologic testing. To study this phenomenon, the effective refractory period was studied in 20 patients during sinus rhythm and two ventricular paced rates with up to three extrastimuli, while varying the basic cycle length time from 2 to 3, to 10 to 20 s. With each of the stimulation sequences used, the effective refractory period lengthened as the basic cycle length time increased ("basic cycle length time-effective refractory period effect"). The effect was most pronounced when extrastimuli were used during the two ventricular paced rates. As the basic cycle length time increased from 2 to 3 to 20 s, the mean effective refractory period determined during sinus rhythm increased from 296 to 300 ms; with the first ventricular paced rate, the effective refractory period increased from 259 to 272 ms (p less than 0.0003) and with the second ventricular paced rate, the effective refractory period increased from 250 to 263 ms (p less than 0.01). The basic cycle length time-effective refractory period effect became more pronounced as the number of extrastimuli increased. With the second ventricular paced rate, as basic cycle length was increased from 2 to 3 to 20 s, the mean prolongation in the cumulative effective refractory period (S1 to final extrastimulus) as the number of extrastimuli increased from 1 to 2 to 3, was 13 (p less than 0.01), 42 (p less than 0.0003) and 82 ms (p less than 0.001), respectively. Results were confirmed in 17 instances by redetermining the effective refractory period at the 2 to 3 s basic cycle length time after the final 20 s basic cycle length time determination, and demonstrating that it was similar to the effective refractory period after the initial 2 to 3 s basic cycle length time. No further prolongation of the effective refractory period could be demonstrated by increasing basic cycle length time from 20 to 60 s, and no significant effect of medications on the basic cycle length time-effective refractory period effect could be demonstrated.

Improved quality of care for patients undergoing an abdominoperineal excision for rectal cancer.

INTRODUCTION: New diagnostics, the emergence of total mesorectal excision and neoadjuvant treatments have improved outcome for patients with rectal cancer. Patients with distal rectal cancer undergoing an abdominoperineal excision seem to do worse compared to those treated with sphinctersparing techniques. The aim of this study was to evaluate the quality of care for patients undergoing an abdominoperineal excision for distal rectal cancer during the last 15 years. MATERIALS AND METHODS: All patients with rectal cancer, who underwent an abdominoperineal excision between December 1996 and December 2010 in 5 Dutch hospitals were analysed. Patients were divided into three cohorts; 1996-2001, 2001-2005 and 2006-2010. All data was extracted from medical records. RESULTS: 477 patients were identified. There was no significant difference in sex, age, BMI, prior pelvic surgery and ASA stages between the cohorts. MRI became a standard tool in the work-up, the use increased from 4.5% in the first, to 95.1% in the last cohort (p < 0.0001). Neoadjuvant treatment shifted from predominantly none (64.9% in cohort 1) to short course radiotherapy (66.7% in cohort 2) and chemoradiation therapy (55.7% in cohort 3). There was a trend towards a decreased circumferential resection margin involvement in the cohorts (18.8%, 16.7% and 11.4%; p = 0.142). Accidental bowel perforations have significantly decreased from 28.6%, and 21.7% to 9.2% in cohort 3 (p < 0.0001). CONCLUSION: Significant improvements in work-up, neoadjuvant and surgical treatment have been made for patients with low rectal cancer, undergoing an abdominoperineal excision. These improvements result in improved short term outcome.

Obesity and weight loss in obstructive sleep apnea: a critical review.

Clinic-based and epidemiological studies demonstrate a strong association between obesity and obstructive sleep apnea. However, defining the causal relationship between excess body weight and sleep-disordered breathing remains difficult. Potential mechanisms to be considered include: (1) alterations in upper airway structure; (2) alterations in upper airway function; (3) alterations in the balance between ventilatory drive and load and (4) obesity-induced hypoxemia. Additional evidence for the role of obesity in obstructive sleep apnea comes from clinical studies of weight loss in patients with sleep-disordered breathing. Significant weight loss has been reported in most studies, which has been associated with varying degrees of improvement in sleep-disordered breathing, oxygen hemoglobin saturation, sleep architecture and daytime performance. Surgical and nonsurgical approaches to weight loss have been evaluated, although most studies to date suffer from methodological limitations including lack of random assignment to treatment groups, confounding of treatment interventions, absence of untreated controls and lack of adequate follow-up assessment. Implications for research and clinical practice are discussed.

Duplication 11p11.3 leads to 14.1 to meiotic crossing--over.

An infant with macular dysfunction, cleft lip and palate, and developmental delay was shown to have an inverted duplication of 11p11.3 leads to p14.1 on the basis of meiotic recombination subsequent to an intrachromosomal "shift" in his mother. A half-sister had previously been shown [3] to have the reciprocal recombinant with resultant deletion of 11p11.3 leads to 11p14.1.

Early and late respiratory-related cortical potentials evoked by pressure pulse stimuli in humans.

Although respiratory-related cortical evoked potentials (CEPs) have been obtained in humans, early-latency responses have been obtained only with direct electrical stimulation of respiratory afferents. We have recorded both early and late cortical activity in response to a relatively novel stimulus consisting of a 300-ms negative pressure pulse applied to the mouth near the start of selected inspirations, when mouth pressure attained a predetermined threshold. This stimulus caused highly reproducible and rapid changes in mouth pressure and was effective in eliciting CEPs to a wide range of applied pressures. Using pulses of approximately -2 to -25 cmH2O, we obtained an early positive component with a mean latency of approximately 20 ms and a subsequent negative component at approximately 30 ms in normal subjects. Peak-to-peak amplitude varied directly, and component latencies inversely, as a function of pulse magnitude. Using -5- to -10-cmH2O stimuli, we also measured a later positive-negative-positive response with mean component latencies of 96.7 +/- 15.1, 147 +/- 14.8, and 237.6 +/- 23.5 ms, respectively. The early-latency activity was resistant to manipulations of stimulus predictability, whereas the later waves were attenuated or disappeared when load presentation was made completely predictable. We validated our method by eliminating the possibility of tactile stimulation of the lips and teeth as the origin of the evoked responses. We propose that early-latency activity derives from precortical structures and may provide a window on the functioning of respiratory afferents in normal subjects and in patients with respiratory disease.

Force production of the genioglossus as a function of muscle length in normal humans.

Resting muscle length affects both maximum force production and force maintenance. The strength and force maintenance characteristics of the genioglossus as a function of resting muscle length have not been described. We hypothesized that genioglossus optimum length (L(o)) could be defined in vivo and that the ability of the genioglossus to sustain a given workload would decrease as resting length deviated from L(o). To test this, 11 normal men repeated maximal isometric genioglossus protrusions at different muscle lengths to determine L(o). L(o) was also obtained by using submaximal efforts while simultaneously recording electromyographic activity of the genioglossus, with L(o) defined as the length at which the force-to-genioglossus electromyographic activity ratio was maximum. Both methods provided similar results. Force maintenance was measured at four muscle lengths on separate days. Target efforts representing 60% of each subject's maximum at L(o) and lasting 5 s were performed at 12-s intervals. Time limit of endurance of the genioglossus was defined as the time from trial onset at which 90% of the target could not be maintained for three consecutive efforts. Time limit of endurance was greatest at L(o) and fell to 47.5% at L(o) + 1 cm, 53.8% at L(o) - 1 cm, and 47.4% at L(o) - 1.5 cm. We conclude that L(o) of the genioglossus can be determined in vivo and that force maintenance of the genioglossus is decreased when operating length deviates from L(o).

Reproducibility of and experiences with the BHK cell transformation assay.

Transformation of BHK 21 C 13 cells was investigated using the ability of transformed cells to reproduce in semi solid agar (anchorage independent growth). A number of modifications to previously published methods have been made, our assays were carried out on 16 compounds, including both carcinogens and non-carcinogens as judged by in vivo bioassay. Reproducibility of test results within the laboratory and with data derived from literature could be shown. Experiences concerning the optimal growth of transformed cells and the threshold level to differentiate between positive and negative results are discussed.

Cell transformation of BHK 21 C 13 cells by various chemicals with and without S-9 mix.

Transformation of BHK 21 C 13 cells was evaluated by the ability of transformed cells to reproduce in semi solid agar (anchorage independent growth). The in vitro test system was carried out according to Styles with modifications. All compounds were tested with and without metabolic activation (S-9 mix). The results demonstrate the importance of a metabolizing system in this cell transformation assay.

Transformation of BHK 21/CL 13 cells by various polycyclic aromatic hydrocarbons using the method of Styles.

Nine polycyclic aromatic hydrocarbons (PAHs) were investigated by the cell-transformation assay method of Styles. Benzo(a)pyrene [B(a)P], chrysene (CH), 3-methylcholanthrene (3-MC), benz(a)anthracene (BA), benzo(b)fluoranthene [B(b)F], and dibenz(a,h)anthracene (DBA) were tested, including liver homogenate, and showed dose-effect relationships and a more than 2-fold increase of transformation rates at LC50. Due to variations of the test method our results differed quantitatively from the data published by Purchase and Styles. Discrimination between the known carcinogens listed above and the noncarcinogens, phenanthrene (PA) and anthracene (AC), lacking a dose-effect relationship was, however, possible. Benzo(e)pyrene [B(e)P] was regarded as positive although producing only a 2-fold increase in the number of transformed colonies.

Mutagenicity of 8-ethoxycaffeine in vitro. Induction of point mutations in the Salmonella/microsome test and of sister-chromatid exchanges as well as chromosomal aberrations in Chinese hamster ovary cells (CHO line).

The caffeine derivative 8-ethoxycaffeine (EOC) was tested in 3 different test systems in vitro. Each experiment was carried out with and without S9 mix. Incubation temperatures were 20 and 37 degrees C. (1) In the Salmonella/microsome test, EOC behaved as a pro-mutagen in the Salmonella typhimurium strain TA1535. No mutagenic activity was found in experiments without S9 mix. The influence of temperature was negligible. The mutagenic activity of EOC depended mainly on the mammals used to prepare the S9 fraction and on the agents given to them to induce liver enzymes. (2) EOC did not induce sister-chromatid exchanges in cell cultures, either at 20 or at 37 degrees C. (3) On the other hand, EOC induced chromosomal aberrations when the cells were incubated at 37 degrees C without S9 mix.

Photomutagenesis test development: I. 8-Methoxypsoralen, chlorpromazine and sunscreen compounds in bacterial and yeast assays.

Two in vitro genotoxicity tests have been adapted to the evaluation of photomutagenic activity of test compounds. The study was initiated to obtain an experimental basis relating to newly proposed guidelines of the EC which request the screening of UV-absorbing compounds, for example, those employed in sunscreen preparations, for their photomutagenic potential. The well established photomutagens 8-methoxypsoralen and chlorpromazine were used to define relevant test protocols. The compounds were evaluated with the Ames test and the Saccharomyces cerevisiae D7 test for gene conversion. The influence of various parameters such as UV light sources, spectral composition, UV sensitivity of the test systems, absorbance by test materials and different exposure conditions is indicated. Two exemplary screening experiments with cosmetic ingredients are presented. Both test systems can be employed for the evaluation of compounds for photomutagenic activity although the standard excision-deficient strains of S. typhimurium pose problems because of their high UV sensitivity. The present experience in this complex field suggests that rigid test protocols and a restrictive test battery would be inadequate.

Novel naphthoquinones from a Streptomyces sp.

Cdc25A assay-guided fractionation of a fermentation broth derived from a Streptomyces sp. resulted in the isolation of four novel naphthoquinones 1-4. Structures of these compounds were deduced by NMR and mass spectrometry. Two of them, 3 and 4, incorporate a modified cysteine residue which is observed for the first time in this class of natural products. Naphthoquinones 1-4 showed weak activity against cdc25A phosphatase.

Evaluation of a saliva alcohol test stick as a therapeutic adjunct in an alcoholism treatment program.

This study was designed to evaluate the clinical usefulness of a saliva alcohol dipstick by comparing dipstick saliva alcohol concentrations to simultaneous blood and urine alcohol concentrations. The sample consisted of 211 saliva tests and blood alcohol concentrations and 189 urine alcohol concentrations. The dipsticks had a specificity of 0.965, a sensitivity of 0.895, a positive predictive value of 0.850, a negative predictive value of 0.977 and a Pearson's product moment correlation coefficient of 0.609 for blood alcohol concentrations and salivary alcohol concentrations, suggesting that the saliva dipstick is useful as a qualitative test in certain settings but is less useful than previously reported as a semiquantitative test.

Joint NASA-ESA-DARA Study. Part three: characterization of sleep under ambient CO2-levels of 0.7% and 1.2%.

An experiment was conducted to study sleep quality and sleep architecture in volunteers living in a closed system under elevated ambient CO2 levels of 0.7% and 1.2%. In a closed system, human life is possible only if the CO2 level is permanently adjusted. For the Russian space station MIR, for example, the CO2 levels of the present study are actual upper limits for the adjustment. Sleep architecture was found to be altered in astronauts on the orbiting MIR station. Sleep quantity and quality were reduced. The latency to the first REM sleep was shorter in space and slow wave sleep was redistributed from the first to the second sleep cycle. The elevated CO2 concentration in the atmosphere on MIR may be one of the reasons for those observations regarding sleep in space. Thus, this experiment was also conducted in order to clarify the interpretation of data obtained from astronauts on MIR. In this study sleep polygraphies could be recorded in 4 subjects who lived for 23 d under 0.7% and then for the same period of time under 1.2% CO2. Findings suggest that these levels of ambient CO2 do not reduce sleep quality. Sleep architecture, however, was slightly changed and showed that the amount of slow wave sleep increased with the duration of the exposure to CO2. But it can be excluded that findings on MIR were caused by elevated CO2-levels.

The prevalence of psychiatric disorders among Vietnamese Amerasians: a pilot study.

A pilot study of the prevalence rate of DSM-III psychiatric disorders among Vietnamese Amerasians prior to migration from Vietnam found current prevalence of such disorders to be lower than previously reported among Vietnamese refugees in the United States and Australia. Methodological and cultural factors contributing to the lower than expected prevalence rate are discussed, and implications for clinical assessments and future research are noted.

[Preoperative diagnosis with stereotactic biopsy is a good predictor of breast cancer in radiologically non-benign breast lesions]. / Preoperatieve diagnostische stereotactische biopsie goede voorspeller van mammacarcinoom bij radiologisch niet-benigne mamma-afwijkingen.

OBJECTIVE: To evaluate histological needle biopsy in breast lesions classified radiologically as 'non-benign'. DESIGN: Prospective, descriptive. SETTING: Hospital Velp, Velp, the Netherlands. METHODS: 232 women with an 'uncertain', 'suspicious' or 'malignant' result of mammography, if necessary supplemented by echography, were subjected to histological biopsy from a breast between 1 January 1994 and 1 January 1997. The earlier biopsies were made with a 16 Gauge (G) needle, those after April 1996 with a 14 G needle, as a rule under stereotactic control. In principle, operation was performed after a positive result. Concerning the women operated after the biopsy, the results of the histological examinations were compared in a 2 x 2 table. RESULTS: 165 of the 232 patients (71%) had breast cancer. Of the 59 patients classified roentgenologically as 'uncertain', 15 (25%) had breast cancer, of the 'suspicious' cases this ratio was 44/67 (66%) and of the 'malignant' results it was 106/106 (100%). Operation was performed in 186 women. The biopsy findings and the surgical preparation were in agreement in 169 patients (91%). The sensitivity of the stereotactic biopsy was 90%, its specificity 93%. One woman was over-treated (axillary lymph node resection) because of a biopsy classified as malignant performed on a rare tumour ultimately diagnosed as 'adenomyo-epithelioma with epithelial atypia'. The proportion of false-negative results was 36%. The predictive value of a positive result was 99%, that of a negative result 63%. CONCLUSION: A diagnostic stereotactic biopsy after roentgenological classification based on mammography and echography had a good predictive value regarding the probability of breast cancer.