Occlusion pressures in men rebreathing CO2 under methoxyflurane anesthesia

The effect of general anesthesia on control of breathing was studied by CO2 rebreathing and occlusion pressure measurements in six normal human subjects under methoxyflurane anesthesia. CO2 was found to increase the amplitude of the occlusion pressure wave without changing its shape, so that CO2 responses in terms of the occlusion pressure developed 100 ms after the onset of inspiration (Po/0.1) gave results equivalent to the responses in terms of Po/1.o or any other parameter of the pressure wave. Methoxyflurane depressed the ventilatory response to CO2 but not the occlusion pressure response, implying that the most important action of the anesthetic was to increase the effective elastance of the respiratory system rather than to depress the respiratory centers. The elastance was further increased by CO2, and this mechanical change had the effect of shifting the "apneic threshold" extrapolated from the ventilatory response curve to a lower PAco2. Frequency of breathing, inspiratory and expiratory times were not altered by CO2 in anesthetized subjects.     

Investigation of optical clearing of gastric tissue immersed with hyperosmotic agents

In order to understand the role of water desorption and the mass transport process in the optical clearing effect on gastric tissues with the application of hyperosmotic agents, the porcine stomach tissues (pyloric mucosa) applied topically with glycerol and dimethyl sulfoxide (DMSO) are investigated with optical coherence tomography (OCT) and the near infrared reflectance spectroscopy. Three solutions of 80% and 50% glycerol, and 50% DMSO are studied, each of which shows significant improvement in light transmittance and, thus, reduction of the light scattering of tissue. It is found that, among the solutions investigated, 80% glycerol achieves the best clearing effect on improvement of both the light penetration and imaging contrast. More detailed microstructures of the mucosal layer can be observed for glycerol treatment, while these structures are not resolvable by the conventional OCT. Light transmittance is increased by approximately 23% and diffuse reflectance decreased by approximately 24% at 30 min after the topical application of 80% glycerol. 50% DMSO is more effective than 50% glycerol only at the beginning stage; thereafter the rate of optical clearing is slowed down with time. Although DMSO can enhance the light transmittance and thus reduce the scattering, it has a negligible effect on the imaging contrast improvement. The mass transport process of agent to tissue accounts for the different clearing effects for glycerol and DMSO, respectively. It is concluded that the optical clearing by the hyperosmotic agent is strongly correlated with the water desorption kinetics induced by agent and the agent mass transport process within tissue. In other words, the tissue dehydration induced by agent and the refractive index matching between the agent and the main scattering components within tissue facilitated by the agent mass transport are responsible for optical clearing effects.     

Oligodendrogliomas. Part II: A new grading system based on morphological and imaging criteria

Myocardial perfusion scintigraphy is a noninvasive diagnostic method for the evaluation of patients with suspected or proven coronary artery disease (CAD). We utilized case-based reasoning (CBR) methods to develop the computer-based image interpretation system SCINA which automatically derives from a scintigraphic image data set an assessment concerning the presence of CAD. We compiled a case library of 100 patients who underwent both perfusion scintigraphy and coronary angiography to document or exclude the presence of CAD. The angiographic diagnosis of the retrieved nearest neighbor match of a scintigraphic input case was selected as the CBR diagnosis. We examined the effects of input data granularity, case indexing, similarity metric, and adaptation on the diagnostic accuracy of the CBR application SCINA. For the final prototype, sensitivity and specificity for detection of coronary heart disease were 98% and 70% suggesting that CBR systems may achieve a diagnostic accuracy that appears feasible for clinical use.     

Positive chronotropic actions of parathyroid hormone and parathyroid hormone-related peptide are associated with increases in the current, I(f), and the slope of the pacemaker potential

BACKGROUND: The classic calciotropic hormone parathyroid hormone (PTH) and its paracrine factor parathyroid hormone-related protein (PTHrP) both increase heart rate. METHODS AND RESULTS: We used standard electrophysiological techniques to study the effects of PTH and PTHrP on isolated rabbit sinus node, isolated canine Purkinje fibers, and disaggregated rabbit sinus node myocytes. Sinus node maximum diastolic potential, activation voltage, and amplitude were unchanged by PTH or PTHrP (P>.05). However, the slope of phase 4 and the automatic rate were increased at PTH and PTHrP > or = 10 nmol/L (P<.05). Comparable results were seen in canine Purkinje fibers. We then used the perforated-patch technique to study the I(f) pacemaker current in sinus node. PTH 12.5 nmol/L and PTHrP 12.5 to 18 nmol/L increased I(f) at -65 mV by 68+/-41% (n=5) and 69+/-50% (n=5), respectively. Actions of both agents were reversible. The increase in I(f) appeared to result from a change in maximal conductance and not a shift in the voltage dependence of activation. CONCLUSIONS: These observations provide, for the first time, direct electrophysiological support for the chronotropic actions of PTH and PTHrP. They suggest that classic hormones and paracrine factors can have multiple functions and that in the case of PTH and PTHrP, a newly recognized action is to alter automaticity directly.     

The role of cytotoxic chemotherapy in the management of aggressive and malignant pituitary tumors

Pituitary tumors are mostly benign lesions, although 5-35% are locally invasive. A small number exhibit a more aggressive course, infiltrating dura, bone and sinuses, and are designated highly aggressive. However, the presence of metastases separate from the pituitary in the central nervous system or at a distance is necessary to designate pituitary tumors as carcinomas, i.e. truly malignant. When conventional therapeutic modalities fail, systemic chemotherapy remains the last option. We report seven such patients, three with highly aggressive and four with malignant pituitary tumors (n=4) four women; median age, 32 yr; range, 23-48 yr), who received one or more courses of chemotherapy with lomustine and 5-fluorouracil (median, two courses; range, one to six courses). Three patients with systemic metastatic disease had a shorter survival (median, 5 months; range, 1-14 months) than the one patient with central nervous system metastases alone (10 yr). A patient with an aggressive nonmetastatic prolactinoma who initially responded to chemotherapy died from another nondisease-associated cause. Two patients, one with an aggressive and one with a metastatic tumor, achieved symptomatic improvement with a median duration of 6 months. A hormonal reduction greater than 50% was observed in two of seven patients; only one patient who had an aggressive tumor obtained an objective tumor response. The median survival from the time of initiation of chemotherapy in patients with malignant tumors ranged from 3-65 months. Two patients with malignant tumors developed disease progression while receiving chemotherapy; no patient with extracranial metastases showed a response. Treatment was well tolerated, with minimal individual side-effects. Three patients with no response to initial treatment received different chemotherapeutic regimens with no additional response. All patients with metastatic malignant tumors eventually died. Treatment with cytotoxic chemotherapy is noncurative, and current experience is limited. Until another more specific form of treatment is available, chemotherapy may still be of some value in patients with highly aggressive and malignant pituitary tumors, at least in achieving a temporary remission or delay in progression. The combination of lomustine/5-fluorouracil proved easy to administer with minimal toxicity, although the response rate was only 14%. Until a more specific treatment is found, an optimal chemotherapeutic regimen needs to be established.     

The Use of Surface Analysis Techniques to Determine the Route of Manufacture of Tablet Dosage Forms

ABSTRACT

Analytical methods for determining the manufacturing process of tablet dosage forms have not been previously reported. The use of surface analysis techniques in particular X-ray Photoelectron Spectroscopy and Time of Flight Secondary Ionization Mass Spectrometry will be described and a model proposed which allows the prediction of the route of manufacture in calcium phosphate and cellulosic-based tablet formulations. Results of the application of this model to evaluate prototype tablet formulations prepared by wet granulation or direct compression will be reported. Strengths and limitations of the model will be discussed.     

Troubleshooting in geoelectrical prospecting using real‐coded genetic algorithm with chromosomal extrapolation

This work presents a genetic operator developed from mathematical methods of curve extrapolation applied in solving problems in geoelectrical prospection. This operator will assist the production of fitter individuals in the population of a genetic algorithm in which inherent patterns of the best individuals of each generation are recognized. The proposed operator in conjunction with a real‐coded genetic algorithm is compared to five alternative optimization techniques known and used in the application to problems in geoelectrical prospection. Copyright © 2014 John Wiley & Sons, Ltd.     

A note on characterizing canonical cuts using geometry

In this technical note we introduce a set of cuts for 0–1 integer programming with a strong geometrical flavor. These are the spherical and cylindrical inequalities. We show that the geometrical cuts are in one‐to‐one correspondence with the canonical cuts introduced by Balas and Jeroslow. Moreover, we show how the well‐known subtour elimination constraints for the Traveling Salesman Problem can be obtained via geometrical cuts. By presenting the subtour elimination constraints in this way, we give another easy and intuitive way to explain the validity of such inequalities. We show that the arguments used to derive the subtour elimination constraint as geometrical cut can be repeated to derive strong valid inequalities that are known for other combinatorial optimization problems.     

Determinant spreading associated with demyelination in a nonhuman primate model of multiple sclerosis

Definition of the immune process that causes demyelination in multiple sclerosis is essential to determine the feasibility of Ag-directed immunotherapy. Using the nonhuman primate, Callithrix jacchus jacchus (common marmoset), we show that immunization with myelin basic protein and proteolipid protein determinants results in clinical disease with significant demyelination. Demyelination was associated with spreading to myelin oligodendrocyte glycoprotein (MOG) determinants that generated anti-MOG serum Abs and Ig deposition in central nervous system white matter lesions. These data associate intermolecular "determinant spreading" with clinical autoimmune disease in primates and raise important issues for the pathogenesis and treatment of multiple sclerosis.