Percutaneous coronary angioscopy: applications in interventional cardiology

We performed percutaneous coronary angioscopy in 35 patients to study the surface morphology of coronary artery lesions. Twenty-five patients had angioscopy performed in conjunction with PTCA, including 20 patients with de novo lesions (16 patients with unstable angina, four patients with stable angina), and five patients with restenosis lesions. Ten cardiac transplant patients had angioscopy performed in conjunction with annual follow-up angiography in attempt to identify accelerated atherosclerotic lesions. There were no complications of angioscopy in any patient. There were no intracoronary thrombi seen either by angiography or angioscopy in the stable angina patients. In the unstable angina group, angiography identified thrombus in 2 out of 16 (12.5%) versus 15 out of 16 (94%) (P less than 0.001) with angioscopy. Following angioplasty, dissections were seen angiographically in 7 out of 16 (44%) of patients versus 16 of 16 (100%) of the patients by angioscopy (P less than 0.01). Restenosis lesions were characterized by a white, fibrous appearance instead of the usual yellow color of primary atherosclerotic lesions. In the ten cardiac transplant patients, angioscopy appeared to be more sensitive than angiography for the detection of atherosclerosis. Yellow (atherosclerotic) and white (fibrotic) plaques were seen in the transplant patients, which often were not detected by angiography. In summary, angioscopy is an excellent tool for visualizing the surface morphology of coronary artery lesions. The clinical indications for angioscopy remain undefined at present.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of methotrexate in leukemia cells: Effect of dose and mode of injection

A lumped compartmental model has been derived to predict methotrexate concentration as a function of time for L1210 cells in BD2F ₁ female mice at doses ranging from 3 mg/kg to 400 mg/kg. Using standard methods of parameter estimation as well as experimental determinations, an integrated approach was derived to account for the differences between the subcutaneous (s.c.) and intraperitoneal (i.p.) modes of injection. It was found that a single generalized forcing function can be used to fit plasma concentration after s.c. injection for all doses. Adequate fits (average error<20% while the standard deviation of experimental determinations was±22%) of L1210 cell data after s.c. injection were obtained. The best results were for a maximum facilitated influx constant V_max of 0.424 g/min/ml, a Michaelis influx constant K_m of 1,42 g/ml, and a first-order efflux constant of 0.047 min^–1.The model simulations were not sensitive to V_max, K_m,and so long as the ratio V_max/was approximately 9g/ml. The values of V _max ,K _m ,and which were obtained from our analysis of the in vivodata can be explained on the basis of previously performed in vitroexperiments. The parameters obtained from modeling the s.c. data were then applied for i.p. injection data. The resulting fits were adequate (average error<20% while the standard deviation of experimental determinations was±22%). A single generalized forcing function for drug concentration in the peritoneal cavity after i.p. injection for all doses was derived. The application of these results enables the prediction of methotrexate concentration in neoplastic cells at other doses after either s.c. or i.p. injection.     

New three-dimensional moving field radiation therapy for brain tumors.

A new modified rotation radiation method called "three-dimensional moving field radiation therapy" is described. The new method uses rotation in many planes while maintaining the the same isocenter to achieve a good spatial dose distribution. This delivers a high dose to tumors and spares the surrounding normal structures. This easy method can be carried out using the equipment for conventional rotation radiation therapy. The new method was superior to the one plane rotation radiation therapy using a physical phantom with film, a chemical phantom using the iodine-starch reaction, and a new biological model using tumor cells. Treatment of six brain tumors irradiated with total air doses of 50-60 Gy caused no hair loss or radiation necrosis.     

Inhaled lidocaine for prevention of hemodynamic changes in laryngoscopy and intubation

This study was undertaken to examine the efficacy of lidocaine aerosol pretreatment in attenuating hemodynamic (HD) responses secondary to laryngoscopy and tracheal intubation in patients undergoing surgery for intracranial space occupying lesions (ICSOL). A semiclosed breathing system was improvised to generate aerosol of consistent density. Five percent lidocaine was nebulized in two different dosages (0.2 and 0.1 ml/kg in groups A and B, respectively); group C (control) received aerosol of normal saline. The average aerosol-treatment time was 24, 12, and 16 min in groups A, B, and C, respectively. Changes in heart rate (HR), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and rate pressure product (RPP) were analyzed by analysis of variance (ANOVA). In group A, tracheal intubation did not cause significant HD changes. In group B, a significant increase was observed in each HD parameter which, when compared with control, was less severe. Lidocaine toxicity, regurgitation, nausea, vomiting, or aspiration did not occur in any patient. Patients accepted the procedure well. This study found efficacy of the technique to be related to duration of aerosol treatment.     

Transport of fluid and macromolecules in tumors. IV. A microscopic model of the perivascular distribution

The therapeutic efficacy of various genetically engineered macromolecules is determined by their delivery and distribution in tumors. We have recently developed mathematical models which describe the interstitial velocity, pressure, and concentration profiles of macromolecules over the length scale of a solid tumor (Baxter and Jain, Microvas. Res. 1989, 1990, 1991). Nonspecific and specific antibodies and antibody fragments were chosen as typical macromolecules. The focus of the present investigation was microscopic transport, i.e., the distribution of pressure and solutes around individual blood vessels. Analytical solutions were obtained for interstitial velocities and pressures, while the concentration profiles were calculated numerically using the finite element method. The microscopic model describes flow patterns around an individual blood vessel in an infinite medium and concentration profiles around a single blood vessel in a network of capillaries. Our analysis is novel in that it incorporates interstitial convection, asymmetric filtration, and transcapillary convection to describe interstitial transport in tumors. The purpose of this model was to determine the effect of extravascular binding and interstitial convection on the distribution of macromolecules on a microscopic scale and to test the continuum hypothesis assumed in our previously published macroscopic models. An approximate one-dimensional model was compared with a more accurate two-dimensional model. The results of our microscopic model confirm that the continuum hypothesis used in our previous macroscopic model is reasonable. On a microscopic length scale diffusion is dominant, and short range distortions in the flow field do not significantly affect the penetration of macromolecules into the tissue. In addition, our model confirms the results of Fujimori et al. (Cancer Res., 1989) concerning a "binding site barrier." The implications of our results for cancer therapy are also discussed.     

Studies on the colour-change mechanism in a fresh-water teleost,Nandus nandus (Ham.) I. Neural control

Summary The existence and nature of chromatic fibres controlling the colour-change mechanism in the teleost,Nandus nandus has been studied by means of spinal sectioning at various vertebral levels of the animal between vertebrae 3 to 10. Spinal sectioning at or anterior to 5th vertebra completely eliminated the neural control of colour-change. As a result, the animal darkened to its maximum and the neural responses of different backgrounds were abolished. Spinal sectioning at or posterior to vertebra 6 did not affect the melanophores and at the same time did not interfere with the normal background responses of the animal. This study clearly shows that the chromatic fibres in this species run in the spinal cord and leave the latter at 5/6th vertebral level.Effect of adrenaline in the chromatic spinal-sectioned fish shows that the fibres innervating the melanophores are aggregating in nature and adrenergic in character. The results also suggest that the dispersed condition of pigment in the melanophores represents the resting state of the melanophores when they are under no stimulation.     

Subcommissural organ-Reissner's fiber complex of the teleost Clarias batrachus responds to GABA treatment

Subcommissural organ (SCO) is a highly specialized ependymal gland located in the roof of the third ventricle. The secretory products of the SCO, which condense to form Reissner's fiber (RF), were recently found to cross-react with the anti-calcitonin antibody. To understand the mechanisms regulating the formation of the RF and the possible function of these discrete structures, we studied the response of the SCO-RF complex to intracranially administered GABA, using immunocytochemical labeling with anti-calcitonin antibody. Although the SCO-RF complex of control fish was intensely immunostained, 1 h after GABA treatment, the ependymal cells revealed partial loss of immunoreactivity; the RF showed occasional loss of immunoreactivity with its diameter increased by about 56% of the control value. Following 2 h of GABA treatment, the SCO revealed dramatic loss of calcitonin-like immunoreactivity from the ependymal cells. The RF showed a dual response in this group, while in some segments the RF appeared conspicuously thick, elsewhere it appeared thin. The mean diameter was, however, not significantly different from the normal. Following 4 h of GABA treatment, while calcitonin-like immunoreactive material made its reappearance in the SCO, the RF diameter was uniformly reduced to about 35% of the control value. The responses by the RF as well as the SCO to intracranially administered GABA were blocked by pretreatment with bicuculline, a GABA(A) receptor antagonist. The results suggest that GABA, acting via GABA(A) receptors, may trigger the release of secretory material from the SCO and induce histomorphological changes in the RF indicative of discharge of stored material.     

Limb amputation on renal replacement therapy

Ten (10) diabetic and 7 non-diabetic patients on renal replacement therapy have undergone limb amputation in the authors' unit in the 1988 to 1996 period. The article examines the course of illness and survival patterns in this distinct and increasing sub-set in the amputee population. Rehabilitation and survival were significantly better in the diabetic group and it is recommended that it would be helpful for both prognosis and analysis if the sub-set of amputees on treatment for chronic renal failure is further divided into diabetic and non-diabetic sub-sets.