Showing papers by "Rakesh K. Jain published in 1986"

Extravascular transport in normal and tumor tissues

Abstract: The transport characteristics of the normal and tumor tissue extravascular space provide the basis for the determination of the optimal dosage and schedule regimes of various pharmacological agents in detection and treatment of cancer. In order for the drug to reach the cellular space where most therapeutic action takes place, several transport steps must first occur: (1) tissue perfusion; (2) permeation across the capillary wall; (3) transport through interstitial space; and (4) transport across the cell membrane. Any of these steps including intracellular events such as metabolism can be the rate-limiting step to uptake of the drug, and these rate-limiting steps may be different in normal and tumor tissues. This review examines these transport limitations, first from an experimental point of view and then from a modeling point of view. Various types of experimental tumor models which have been used in animals to represent human tumors are discussed. Then, mathematical models of extravascular transport are discussed from the prespective of two approaches: compartmental and distributed. Compartmental models lump one or more sections of a tissue or body into a "compartment" to describe the time course of disposition of a substance. These models contain "effective" parameters which represent the entire compartment. Distributed models consider the structural and morphological aspects of the tissue to determine the transport properties of that tissue. These distributed models describe both the temporal and spatial distribution of a substance in tissues. Each of these modeling techniques is described in detail with applications for cancer detection and treatment in mind.

Effect of glucose on systemic hemodynamics and blood flow rate in normal and tumor tissues in rats

Abstract: The effect of hyperglycemia on systemic hemodynamics and blood flow rate of Walker 256 carcinoma and several normal tissues of unanesthetized, unrestrained female Sprague-Dawley rats was measured, using the radioactive microsphere technique prior to and at 30 and 60 min after glucose administration (6 g/kg body weight i.v.). Whereas the mean arterial pressure and heart rate remained unchanged following glucose injection, cardiac output (CO), cardiac index, and stroke volume decreased by approximately 25% (P less than 0.05), and the total peripheral resistance increased by more than 25% (P less than 0.05). Redistribution of blood flow, expressed as a percentage of CO, among normal tissues was traced to the brain, kidneys, spleen, and liver and away from the skin, pancreas, and stomach. Changes in percentage of CO to the jejunum, colon, peritumor muscle, hindlimb, and forelimb muscles were not significant. Reduction in blood flow in large tumors (greater than 0.6 g) was proportional to the reduction in CO, and in small tumors (less than 0.6 g) was more than the reduction in CO. These results suggest that the reduction in blood flow due to hyperglycemia in large tumors is primarily due to reduction in CO and in small tumors due to both systemic and local effect; and changes in the blood flow to normal tissues should not be disregarded when using hyperglycemia in combination with hyperthermia and/or chemotherapy for cancer treatment.

Non-linear studies of orthotropic shallow spherical shells on elastic foundation

Abstract: Governing non-linear integro-differential equations for cylindrically orthotropic shallow spherical shells resting on linear Winkler-Pasternak elastic foundations, undergoing moderately large deformations are presented. Three problems, namely, non-linear static deflection response, non-linear dynamic deflection response and dynamic snap-through buckling of orthotropic shells have been investigated. The influences of material orthotropy, foundation parameters and shell-material damping on the deflection response are determined for the clamped and the simply- supported immovable edge conditions accurately. Orthotropy, foundation interaction and material damping play significant roles in improving the load carrying capacity of the shell structures.

Extensive verrucosis, squamous cell carcinoma, and immunologic abnormality in Klinefelter's syndrome.

Abstract: A 20-year-old Indian Sikh man, M.S., presented to the skin Out-patient Department with extensive warty growths on the î ace and extremities. His previous medical history included a variety of Infections (Table 1) and a squamous cell carcinoma in the lower lip for which he had received radium implants. The patient was the youngest of six siblings, having three brothers and two sisters. None of the brothers was similarly affected. On examination, the patient was of thin build. Beard growth was scanty, and the pubic hairs were of feminine distribution. The phallus was normal sized, while the testes were palpated as small fibrotic masses with no testicular sensation and gynaecomastia was not present. Multiple warts were seen over the face, especially over the right malar prominence, over dorsa of both hands and feet, and on the posterior aspect of both legs. Most of the warts were verruca vulgaris, with some of those on the face and around the eyes being filiform. The lower lip was swollen and showed an old, healed scar. A few lesions with central clearing and papular margins typical of tinea corporis were seen on the trunk and left leg. The central portion of the scalp showed thick longitudinal folds of skin typical of cutis verticis gyrata.

Effect of transmembrane potential on the deformability of RBC's suspended in carbohydrate-saline solutions

Abstract: The effect of transmembrane potential on the deformability of red blood cells (RBC) suspended in isotonic glucose-saline and galactose-saline solutions was determined using the micropipette aspiration technique. In this method, a negative pressure was applied to the RBC membrane via a micropipette and the resulting deformation was analyzed using a Kelvin model to yield a membrane elastic modulus E. When glucose concentration was increased from 0 to 0.3 M/dm3 in the extracellular media, the membrane elastic modulus increased seven-fold (p < 0.0001) with most increase occurring in the 0–0.1 M/dm3 range. Whereas, galactose had no significant effect on the membrane elasticity up to a concentration of 0.28 M/dm3. However, in pure galactose (isotonic) solution (0.308 M/dm3), the membrane elastic modulus decreased by a factor of 3 (p < 0.001). Increase in the RBC elastic modulus in the presence of glucose may be due to binding of glucose to the membrane and intracellular proteins, and decrease in the presence of pure galactose may be due to the transmembrane potential generated by chloride ions.