Acetylsalicylic acid does not alter thermo-effector responses during mild whole-body passive heat stress in young men.

Acetylsalicylic acid (ASA), aspirin, exerts potent systemic effects that may interfere with normal thermo-effector responses. We investigated the influence of commonly ingested ASA doses on measures of skin blood flow (SkBF) and local sweat rate (SR) during whole-body, passive heat stress. Seven male participants completed counter-balanced trials to compare ASA treatments (single dose 325 mg or 4 consecutive days 81 mg (4-d 81 mg)) to control (no ASA). Laser-Doppler flowmetry provided an index of SkBF. A ventilated capsule measured local sweat rate via capacitance hygrometry. Mean body temperature ([Formula: see text]) was increased by 1 °C above baseline using a water-perfused suit. [Formula: see text] was similar at the onset of cutaneous vasodilation among trials. Cutaneous vascular conductance, expressed as a percentage change from baseline, was not different among trials. Additionally, [Formula: see text] at the onset of local SR and SR sensitivity did not differ among trials. While ASA has previously been shown to influence SkBF during heat stress, it is possible our cohort's relatively young age may have contributed to our dissimilar results.

Bevacizumab for the treatment of recurrent ovarian cancer: a retrospective cohort study.

OBJECTIVE: To determine response rates (RR), progression-free survival (PFS), overall survival (OS), and toxicity in patients treated with cytotoxic chemotherapy, in combination with bevacizumab compared to cytotoxic chemotherapy alone, in the setting of recurrent ovarian cancer. MATERIALS AND METHODS: After obtaining Institutional Review Board approval, two cohorts of patients with recurrent ovarian cancer were identified: 1) patients that received cytotoxic chemotherapy with bevacizumab from January 2006 to June 2009; 2) patients that received cytotoxic chemotherapy alone. RR were measured using RECIST criteria or by CA-125 levels using modified Rustin criteria. RR, OS, and PFS were determined using Kaplan-Meier survival analysis. RESULTS: Thirty-two patients that received bevacizumab in combination with cytotoxic chemotherapy and 32 patients that received cytotoxic chemotherapy alone were identified. The control patients were matched for age, platinum response, histology, surgical outcome, grade, and number of previous chemotherapy regimens. There were no differences between the two cohorts in the rates of venous thromboembolism (VTE) (p = 0.39), bleeding (p = 0.15) or bowel obstruction (p = 0.40). The rate of hypertension in the bevacizumab cohort was greater than in the comparison cohort (p < 0.005). There were no differences in response rates PR/CR vs SD/PD (p = 0.46), OS (p = 0.79) or PFS (p = 0.43). CONCLUSIONS: With increased toxicity, increased cost of therapy and no improvement in PFS or OS, the role of bevacizumab in patients with recurrent ovarian cancer warrants further investigation.

Adjuvant treatment for uterine leiomyosarcoma.

The aims of this study were to evaluate outcomes in women diagnosed with uterine leiomyosarcoma (LMS). A retrospective chart review was conducted. Fifty-eight women with LMS were identified. Of the evaluable 52 patients (six patients were excluded), 73% had Stage I/II disease, and 27% had Stage III/IV disease. Sixty-three percent of patients received chemotherapy (97% doxorubicin-based therapy), eight percent received radiation alone, and 29% received no therapy. For patients with Stage I/II disease, no improvement in OS was demonstrated when adjuvant therapy was administered. There was a significant difference in OS (p = 0.0005) for patients with advanced Stage (III/IV) disease that received adjuvant chemotherapy. OS of the entire group, when adjusted for stage, failed to reveal a significant survival advantage for those receiving chemotherapy-based (p = 0.22). The present findings suggest further research into the role of chemotherapy in early stage disease is needed to better refine optimal treatment.

Ontogenetic expression of trk neurotrophin receptors in the chick auditory system.

Neurotrophins and their cognate receptors are critical to normal nervous system development. Trk receptors are high-affinity receptors for nerve-growth factor (trkA), brain-derived neurotrophic factor and neurotrophin-4/5 (trkB), and neurotrophin-3 (trkC). We examine the expression of these three neurotrophin tyrosine kinase receptors in the chick auditory system throughout most of development. Trks were localized in the auditory brainstem, the cochlear ganglion, and the basilar papilla of chicks from embryonic (E) day 5 to E21, by using antibodies and standard immunocytochemical methods. TrkB mRNA was localized in brainstem nuclei by in situ hybridization. TrkB and trkC are highly expressed in the embryonic auditory brainstem, and their patterns of expression are both spatially and temporally dynamic. During early brainstem development, trkB and trkC are localized in the neuronal cell bodies and in the surrounding neuropil of nucleus magnocellularis (NM) and nucleus laminaris (NL). During later development, trkC is expressed in the cell bodies of NM and NL, whereas trkB is expressed in the nerve calyces surrounding NM neurons and in the ventral, but not the dorsal, dendrites of NL. In the periphery, trkB and trkC are located in the cochlear ganglion neurons and in peripheral fibers innervating the basilar papilla and synapsing at the base of hair cells. The protracted expression of trks seen in our materials is consistent with the hypothesis that the neurotrophins/tyrosine kinase receptors play one or several roles in the development of auditory circuitry. In particular, the polarized expression of trkB in NL is coincident with refinement of NM terminal arborizations on NL.

Cold exposure regulates the renin-angiotensin system.

The effect of cold exposure on the systemic renin-angiotensin system and on regulation of the angiotensin II (Ang II) receptor was examined in target organs for Ang II with cardiovascular relevance (left ventricle, kidney, lung) and metabolic relevance [interscapular brown adipose tissue (ISBAT), liver] to the functional consequences of cold exposure. In time course studies, the effects were examined of 4 hr or 1, 3 and 7 days of exposure to cold (4 degrees C) on plasma Ang II concentration and Ang II receptor binding characteristics in rat liver. Plasma Ang II concentration increased 10-fold after 4 hr of cold exposure, returned to control levels at days 1 and 3 of cold exposure, and was again increased (2-fold) at 7 days of cold exposure. The affinity of [125I]Sar1, Ile8-Ang II binding in membranes prepared from rat liver was not altered in cold-exposed rats. The density (Bmax) of binding sites in liver from cold-exposed rats was increased by day 1 and remained elevated over time-matched controls. Alterations in Ang II receptor density did not parallel plasma Ang II concentration in their time course, suggesting that cold-induced regulation of the Ang II receptor was not substrate mediated. In rats from the 7-day time point of cold exposure, Ang II receptor binding characteristics were examined in ISBAT and lung. Increases in Ang II receptor density were evident in ISBAT but not lung. To determine whether cold-induced increases in food intake contributed to elevations in plasma Ang II concentration and/or Ang II receptor density, a group of cold-exposed rats (7 days) were pair-fed to food intake levels of control rats. Pair-feeding of cold-exposed rats eliminated increases in plasma Ang II and norepinephrine concentration but did not prevent increases in Ang II receptor density in liver, ISBAT, kidney and left ventricle. Moreover, increases in Ang II receptor density were augmented in kidney and left ventricle from cold-exposed rats that were pair-fed. Results from these studies demonstrate that cold exposure resulted in an increase in plasma Ang II concentration through mechanisms related to increased food intake. Elevations in food intake in cold-exposed rats contributed to tissue-specific increases in Ang II receptor density. Moreover, cold-induced increases in Ang II receptor density were not related to plasma Ang II concentration.

Load to failure of common meniscal repair techniques: effects of suture technique and suture material.

Success of meniscal repair with early or immediate motion depends on the ability of the suture fixation to withstand the loads applied. Vertical and horizontal mattress suture techniques were tested using 2-0 Ethibond, and 0-PDS and 1-PDS sutures (Ethicon, Somerville, NJ). Mulberry knot technique was tested with 0-PDS and 1-PDS sutures. Twenty menisci (60 sutures) were tested for each suture material. Sutures were placed 3 to 4 mm from the peripheral edge of the meniscus with double barreled cannulas for vertical and horizontal mattress techniques or a spinal needle for the mulberry knot technique, reproducing clinical techniques of meniscal repair. Mechanical testing of suture fixation was performed to failure at a rate of 10 mm/min on a MTS material testing system (MTS Systems Corp, Minneapolis, MN). Suture pullouts were reported as the load displacement to failure from the inner fragment only, because clinical failure would ensue should a suture pull through the inner fragment of a tear. Vertical mattress technique with 1-PDS suture had significantly greater load to failure than any other combination (P < .05). Analysis of variance showed that the vertical mattress technique had statistically superior pullout strength (P < .0001) compared with the horizontal mattress and mulberry knot techniques, which were statistically similar. There were significant differences (P < .0001) between suture types, with 1-PDS proving best compared with 0-PDS, which was stronger than 2-0 Ethibond. Selection of suture material had the greatest impact on vertical mattress load to failure and was not important to the strength of the other techniques.

Rapid-eye-movement-specific sleep-disordered breathing: a possible cause of excessive daytime sleepiness.

Some patients referred for polysomnography with complaints of excessive daytime sleepiness (EDS) and clinically suspected obstructive sleep apnea (OSA) have a respiratory disturbance index (RDI) < 10. Many would consider these patients not to have OSA. We reviewed 34 such patients to determine whether respiratory disturbances confined primarily to rapid eye movement (REM) sleep correlated with an objective criterion for EDS: a mean sleep latency (MSL) < 10 min. REM-specific events were quantified with indices calculated for REM sleep alone. Univariate linear regression showed that a REM-specific respiratory disturbance index (REM-RDI) and the transient arousal index (TAI) computed for REM sleep (REM-TAI) were associated with a low MSL (R2 = -0.35, p = 0.001; and R2 = -0.27, p = 0.01, respectively). In our subjectively sleepy patients with an overall RDI < 10, a REM-RDI > or = 15 had the highest predictive accuracy (82%) for an MSL < 10 min. Seventeen of the 34 study patients had a REM-RDI > or = 15. Their mean MSL was 8.3 +/- 0.8 min. We conclude that within a group of patients with daytime sleepiness, suspected OSA, and a normal RDI, there may be a subset who have clinically significant REM-specific sleep-disordered breathing.

An algorithmic approach to chronic cough.

OBJECTIVES: To evaluate a stepwise approach to chronic cough that emphasized initial treatment of all patients with an antihistamine-decongestant for postnasal drip and to determine the value of routine bronchoprovocation challenge in the evaluation of chronic cough. DESIGN: Prospective trial using an algorithm for chronic cough in immunocompetent nonsmoking out-patients. SETTING: University-based pulmonary practice. PATIENTS: Forty-five patients met the inclusion criteria. The mean duration of cough was 140 weeks (range, 3 to 2080 weeks), and the mean severity of cough as assessed by patients on a four-point scale was "severe." RESULTS: Marked improvement and resolution (mean, 3.1 and 7.1 weeks, respectively), with resolution in 96% of patients. Antihistamine-decongestant therapy was beneficial in 39 of 45 patients and was the only therapy needed for 16 patients. Bronchoprovocation challenge had a negative predictive value of 100% and a positive predictive value of 74% for cough caused by asthma. No significant relationship was found between the time to cough resolution and duration or severity of cough. Eighteen percent of patients experienced a recurrence of cough at a follow-up interval of 3 months. CONCLUSIONS: A sequential approach to chronic cough that emphasizes initial treatment with an antihistamine-decongestant is effective. Bronchoprovocation challenge is useful in evaluating patients with chronic cough but can be delayed until the initial response to antihistamine-decongestant therapy has been assessed. The 18% incidence of recurrence highlights the fact that cough often is the manifestation of a chronic or recurring process that requires chronic or episodic therapy.

Specificity and sensitivity of the assay for elastin-derived peptides in chronic obstructive pulmonary disease.

One prediction of the protease-antiprotease hypothesis of chronic obstructive pulmonary disease (COPD) pathogenesis is the appearance of elastin-derived degradation products in the plasmas of affected patients that are due to the breakdown of alveolar interstitial elastin by an excess of elastolytic activity in the lung. We previously demonstrated a significant elevation of plasma elastin-derived peptides (EDP) in subjects with COPD in comparison with asymptomatic smokers with normal spirometry or normal nonsmokers. To better determine the selectivity of the assay for EDP as a marker of COPD, we measured plasma EDP levels in different patient populations. These included subjects with COPD, subjects with diseases that may involve accelerated elastolysis (pneumonia, atherosclerotic vascular disease, and inflammatory arthritis), subjects with diseases hypothesized to involve pulmonary inflammation without elastolysis (asthma and acute tracheobronchitis), asymptomatic smokers with normal spirometry, and healthy, nonsmoking subjects. Mean plasma EDP levels in subjects with COPD were elevated above those in all other subjects (p less than 0.01). The prospective analyses of specificity and sensitivity of plasma EDP levels as markers of COPD gave values of 91 and 65%, respectively. Utilizing receiver operating characteristic curve analysis to assess the diagnostic and screening performance of plasma EDP as a test for COPD (perfect test equals an area under the curve of 1.0), the area under the curve was 0.87, which compares favorably with many widely used clinical tests. These data demonstrate that the assay for plasma EDP is a quantitative, easily measured, and highly specific marker for subjects with COPD.

Chronic cough as the sole manifestation of Hodgkin's disease.

A patient presented with a cough of three months' duration as the sole manifestation of mediastinal Hodgkin's disease. Systematic evaluation resulted in prompt diagnosis and specific successful treatment of both the Hodgkin's disease and the cough. This case emphasizes that specific therapy based upon an accurate diagnosis almost always results in effective treatment of chronic cough.

Biliary lithotripsy can be enhanced with proper ultrasound probe position.

We have demonstrated in our in vitro system that an extracorporeal lithotripter utilizing a movable ultrasound probe can fragment gallstones more effectively when the ultrasound probe is not partially blocking shock waves. Using a pressure transducer we measured the pressures in the focal volume of a Wolf Piezolith 2300 lithotripter with the ultrasound probe fully extended and fully retracted. We also chose 12 pairs of twin gallstones, each taken from the same gallbladder. One stone from each pair was subjected to shock waves while the ultrasound probe was fully extended and the other treated while the probe was fully retracted. Shock wave pressures (which are converted to a measurable voltage output by our transducer) were clearly lower when the ultrasound probe was extended (5.45 volts; SEM = 0.10 volts) as compared to when the ultrasound scanner was retracted (6.7 volts: SEM = 0.08 volts). Significantly more shock waves were required to completely fragment stones when the ultrasound scanner was extended than when it was retracted (p = 0.01 using the nonparametric Wilcoxon's signed rank test). These results show that, in the lithotripter tested, an extended in-line ultrasound scanner can partially block shock waves. Retraction of an extendible ultrasound probe may enhance stone fragmentation when operating at the highest shock wave intensity.

Experimental laboratory lithotripter: design, construction, and operation.

A laboratory lithotripter has been constructed and used to comminute (crush to a powder) both kidney stones and gallstones. The stones are placed in the second focus (f2) of an ellipse of revolution whose linear eccentricity is 4.7 cm and then acoustically shocked an average of 200 times by an underwater spark discharge at the first focus (f1). The energy levels available from the capacitors (3 to 52 joules) of this unit extend below and above the range of commercially available clinical devices. The electrical and mechanical design of this unit is presented. At a relatively low cost (approximately $15,000) the unit appears to have considerable application in non-clinical research in lithotripsy. Quantitative results of the application of this device to the comminution of human kidney stones are presented.

Minitron II system for precise control of the plant growth environment.

A transparent, cylindrical chamber system was developed to allow measurement of gas-exchange by small crop canopies in the undisturbed plant growth environment. The system is an elaboration of the Minitron system developed previously to compare growth of small plants in different environments within the same general growth area. The Minitron II system described herein accommodates hydroponic culture and separate control of atmospheric composition in individual chambers. Root and shoot environments are compartmented separately to accommodate atmospheres of different flow rate and/or gaseous composition. A series of 0-rings and tension-adjustable springs allow carbon dioxide in the flowing atmosphere to be analyzed without cross-contamination between chamber compartments or from external gas sources. Carbon dioxide has been maintained at set point +/- 9 g m-3 over a range of CO2 concentrations from 382 to 2725 g m-3 and with an atmosphere turnover rate of 136.7 cm3 s-1 by computer-assisted mass flow controllers. Each chamber has dimensions large enough (61 cm internal diameter, 0.151 m3 internal volume) to allow adequate replication of individual plants for statistical purposes (e.g., up to 36 equally-spaced plant holders). No significant variation in growth or photosynthetic rate of leaf lettuce occurred between chambers for a given set of environmental conditions. Gas-exchange rates in different chambers changed to a similar extent as CO2 concentration in the flowing atmosphere or chamber temperature were varied by the same amount. When coupled with appropriate control systems, Minitron II chambers can provide separate controlled environments for multiple small plants with adequate precision and at relatively low cost.

Altered therapy of suspected pulmonary embolism using leg venography.

The traditional approach to the diagnosis of pulmonary embolism involves attempts to document the embolus in the lungs. An alternative diagnostic approach is to document the source of the embolus in the iliofemoral venous system. The present case shows how a search for leg thrombosis in suspected pulmonary embolism can also have an impact in choosing the optimal therapy to prevent recurrent embolization.