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Biomedical subjects

J M Price

Publications and source records attributed to J M Price.

At least 73 records · Page 4Linked to original sources

Microvascular responses of intact and adrenal medullectomized rats to hemorrhagic shock.

Evidence indicates that during the later stages of hemorrhagic shock there appears to be a loss of response to the control systems that would normally maintain an adequate peripheral resistance. Therefore, the reactivity of the cremaster muscle microcirculation of pentobarbital-anesthetized Wistar rats, intact and adrenal medullectomized, was studied using videomicroscopy. The left cremaster muscle was spread over an optical port in a bath filled with modified Krebs solution (pH 7.4, 34 degrees C). The right femoral artery was cannulated for determination of mean arterial pressure (Pm) and for hemorrhage of the rat. Following control measurements of Pm and microvessel diameters, cumulative dose-response curves of arteriolar and venular diameters to topical norepinephrine (NE) (10(-9) - 10(-4) M) were obtained. The protocols for intact and medullectomized groups were: 1) hypovolemic shock (shed blood not reinfused)--hemorrhage of 3.2 ml/100 g, compensation allowed, and NE dose-response curves repeated and obtained again during late shock as determined by Pm declining below 60 mmHg; and 2) normovolemic shock (condition after reinfusion of shed blood)--hemorrhage into a reservoir to Pm of 40 mmHg, maintenance at this level until 25% of the bled volume had been taken back (irreversible shock), and then reinfusion of the remainder of the blood. After blood reinfusion, the NE dose-response curves were repeated and obtained again during late shock, as determined by Pm below 60 mmHg. In all of the bled animals, the A1 arterioles were constricted posthemorrhage. The A2 arterioles were constricted only in the hypovolemic intact group. The A3 arterioles of all groups were not significantly changed from control. The constricted arterioles remained so. However, the other arterioles in all groups were unchanged during the several hours until death. The threshold concentration of NE for constriction of arterioles (10% or greater) was significantly increased (decreased sensitivity) during shock in all four groups. The response of the medullectomized rats to normovolemic shock was similar to that of the intact group, indicating that the circulating catecholamines were not essential. The response of medullectomized rats to hypovolemic shock was more severe and indicated the need for circulating catecholamines to compensate for the blood volume loss.

Adrenal Medulla↗

Length-dependent sensitivity of vascular smooth muscle in normotensive and hypertensive animals.

Ring segments were obtained from the aorta of spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Wistar (WST) rats and from the anterior tibial artery of normotensive and hypertensive dogs. Norepinephrine dose-response curves were generated at lengths relative to that for maximum force (Lmax) and at a specific preload (in grams). The doses of stimulus necessary to elicit 10 and 50% maximum force of contraction (ED10 and ED50) are greater at lengths less than Lmax than at Lmax for all groups. When SHR rings are compared with WKY or WST rings, ED10 or ED50 is the same at either length. The same result was found in comparing normal and hypertensive dogs. ED10 and ED50 from hypertensive groups were the same as their respective control groups when compared at the same preload. We conclude that sensitivity of the rat aorta and dog anterior tibial artery to norepinephrine depends on muscle length, this relationship is not altered in hypertension, and the conclusion on sensitivity in hypertension is the same for excised rings compared at the same length or at the same preload. Contractility (active stress) was lower (rats) or the same (dogs) but thickness was greater in the hypertensive groups than in their controls. The results show that a change in the vessel wall that can cause increased flow resistance and pressure is not in sensitivity or contractility but in wall thickness. Apparent differences in sensitivity from normal and hypertensive animals can be explained by an unchanged length-dependent sensitivity. The results also show that differences in body weight will affect a comparison of wall tension but not of sensitivity.

Animals↗

Nasal mast cells: a preliminary report on their ultrastructure.

The ultrastructure of mast cells found in normal inferior turbinate was compared with the features found in the inferior turbinate in two groups of patients, those with allergic rhinitis due to dust mite hypersensitivity and those with nasal polyps; the latter group also had their polyps studied. Adenoid tissue was examined in children with secretory otitis media to see if there was evidence of mast cell degranulation, which would support the hypothesis that either local allergic or other mast cell-mediated reactions caused the condition. The mast cells from five normal turbinates varied considerably in size, shape and distribution, but were found mainly in the submucosa. There was no difference in the morphology of cells of different sizes and they could not be sub-grouped into either connective tissue or mucosal mast cells. Most granules were electron dense and homogeneous, although scrolls and crystalline structures were seen occasionally. Some of the granules contained lighter material and others had become vacuoles. Mitochondria were present in all cells suggesting active metabolism. The three patients with allergic rhinitis showed extensive but variable degranulation of the mast cells in all depths of the mucosa. Nine of the 10 cases with nasal polyps had mast cells identified in both the polyp and the turbinate. They were only normal in one turbinate and in one patient it was impossible to identify mast cells. All the mast cells were degranulated extensively in all other specimens. The adenoids from seven children had identifiable mast cells, which were less frequently found than in the turbinates. There was some degranulation in four of the patients and in one it was fairly extensive.

Adenoids↗

The liabilities and consequences of medical device development.

A large increase in medical products liability litigation during the past 40 years has resulted in a flood of litigation against drug and device manufacturers. The medical technology and chemical industries are prime targets for products liability litigation. Physicians and other health care providers are willing to accept a reasonable degree of risk associated with the use of a medical product when compared to the benefit to be achieved by that product but lay juries are less likely to tolerate the concept of an acceptable failure rate. Plaintiffs' lawyers believe that the medical products industry should be held to a standard of absolute liability and that anyone injured by a medical product is entitled to recover without regard for the circumstances. Large compensatory and punitive damage awards, the high cost of insurance, large defense costs, and low profit margins have forced some companies to remove their products from the market. The medical or biomaterials manufacturer can significantly reduce its exposure for products liability by adopting a successful product safety program. Manufacturers have significant control over the quality, safety, and reliability of their products through appropriate design, testing, manufacture, labeling, and sale of quality products.

Biotechnology↗

Myxopapillary ependymoma of the filum terminale. A light and electron microscopic study.

The histology of a myxopapillary ependymoma of the filum terminale in a 15-year-old girl was studied by light and electron microscopy. The neoplasm contained both papillary and compact areas of cell growth. The papillary regions consisted of vacuolated cuboidal cells arranged around hyaline/vascular cores that were variably mucin-positive. In the compact regions, the tumor cells were intensely immunoreactive for glial fibrillary acidic protein and occasionally formed perivascular pseudorosettes. Ultrastructural examination revealed interdigitating cell processes, sometimes resting on a basement membrane. Surface specializations included numerous microvilli and occasional cilia. The cilia had an abnormal microtubular pattern (e.g., 8 + 1, 7 + 0). The cytoplasm of the tumor cells contained numerous 7-10 nm intermediate filaments and large numbers of abnormal microtubular aggregates, consisting of 4 to 50 single microtubules enclosed by a limiting membrane. These microtubular aggregates may represent a characteristic feature of myxopapillary ependymoma of the filum terminale.

Adolescent↗

Dependence of the length-tension relationship on agonist concentration in vascular smooth muscle.

This study examines the dependence of the length-tension (L-T) relationship in vascular smooth muscle on its level of activation. A horizontal shift of the L-T relationship with a change in activation level has been shown in striated muscle when L-T curves could not be superimposed. Active force at each length was normalized to the maximum active force in each curve. Indices of a horizontal shift of a L-T curve include the initial length for an active response (Li) and the length for maximum active force (Lmax). In this study normalized L-T curves were obtained from rings of the dog anterior tibial artery at low (approximately ED50) and high (maximal activation) concentrations of potassium (K+), norepinephrine (NE), and calcium (Ca2+). The normalized curve with a low concentration of K+ or NE was shifted to the right of the curve obtained with a high concentration. Li and Lmax were significantly longer for a low concentration of K+ or NE than a high concentration. With the same concentration of NE (10(-5) M) no difference in the normalized L-T curves, in Li, or in Lmax were found when low (0.085 mM) Ca2+ experiments were compared to normal (1.7 mM) Ca2+ experiments. It may be concluded that the length-tension relationship in vascular smooth muscle is shifted to longer lengths with a decrease in the concentration of a chemical agonist but not by a decrease in external calcium. We suggest that a concentration dependent shift in the length-tension relationship may have a role in the regulation of blood flow.

Animals↗

The influence of insulin and insulin-like growth factor-I on hexose transport by Sertoli cells.

Insulin stimulates the synthesis of lactate by cultured Sertoli cells prepared from rats aged 13 days, to a much greater extent if glucose is present in the incubation medium than when it is absent. Insulin also stimulates the transport of 3-O-methyl-D-[14 C]glucose into cultured Sertoli cells. This increased transport results from a decrease in the Michaelis-Menten constant (Km) of methylglucose for the transport system without change in maximum velocity (Vmax). Moreover, insulin stimulates influx of the glucose analog and is without effect on efflux. Insulin does not alter transport of methylglucose in peritubular fibroblasts or in mixed populations of germ cells. It was observed that whereas insulin stimulates transport of methylglucose at micromolar concentrations, insulin-like growth factor I (IGF I) exerts the same effect at nanomolar (physiological) concentrations. Moreover, the response to insulin plus IGF I is the same as the maximal responses to either hormone alone. In view of the effects of insulin and IGF I on glucose transport by Sertoli cells and in view of the importance of lactate as a substrate for germ cells, it is suggested that IGF I may be important for the development of normal germinal epithelium in rat testes.

3-O-Methylglucose↗

Heparin-induced thrombocytopenia. What is its real frequency?

A prospective study of 104 patients was undertaken to determine the frequency of severe heparin-induced thrombocytopenia in patients receiving either bovine lung or porcine mucosal heparin. One of 54 patients randomized to receive bovine heparin and two of 50 patients randomized to receive porcine heparin developed heparin-induced thrombocytopenia (platelet count less than 100,000/microliters). Although three previous studies suggest a remarkably high frequency of bovine heparin-induced thrombocytopenia, or a high frequency compared to porcine heparin, our study supports other evidence that clinically important, severe heparin-induced thrombocytopenia (platelet count less than 100,000/microliters) occurs in 10 percent of patients or less receiving heparin, and that there is no significant difference of occurrence between bovine and porcine heparin.

Acute Disease↗

Length-dependent activation and sensitivity in arterial ring segments.

This study examines the effect of length on the dose-response (D-R) relationship and the effect of agonist concentration on the length-tension (L-T) relationship in vascular smooth muscle. The experiments used 2-mm rings from isolated segments of the dog anterior tibial artery. In D-R experiments the length (internal ring circumference) for maximum active force (Lmax) was determined first. D-R relationships were obtained from cumulative responses to increasing concentrations of norepinephrine (NE) or potassium (K+). L-T relationships were obtained from individual responses to a specific concentration of agonist as the ring was stretched in increments of L0 (the initial length for resting force). Dimensions of the arterial rings were measured with a video caliper. For NE and K+ stimulations at lengths equal to and less than Lmax: (a) The concentration for half maximal response (ED50) was lowest (most sensitive) at Lmax and increased significantly as length decreased from Lmax; (b) When the direction of length change was reversed, the direction of change in ED50 was reversed; and (c) The ED50 of repeated dose-response experiments at Lmax was not significantly different. For NE: (a) the ED50 decreased significantly when length was decreased to Lmax. The results of L-T experiments show Lmax is significantly longer for a low concentration of NE (10(-6) M) than for a high concentration (10(-5) M). With force normalized to the maximum force, the L-T curve is significantly lower, and the initial length for an active response was 80% longer for 10(-6) M than for 10(-5) M NE. It may be concluded that vascular smooth muscle has a length-dependent dose-response relationship and a concentration-dependent length-tension relationship.

Animals↗

Common materials for emergency respiratory protection: leakage tests with a manikin.

In areas where respirators are not routinely used, emergencies (such as fires) may occur in which protection from airborne particles is necessary. The following readily available materials were tested on a manikin connected to a breathing simulator to determine the fraction of an approximately 2-micron diameter aerosol that would leak around the seal between the materials and the manikin's face: cotton/polyester shirt material, cotton handkerchief material, toweling (a wash cloth), a surgical mask (Johnson & Johnson Co., Model HRI 8137), and a NIOSH-approved disposable face mask (3M Corp., Model #8710). The leakage tests were done to supplement the measurements of penetration through the materials reported previously. Leakage fractions were determined by comparing the penetration of the same aerosol for the materials held to the face versus being fully taped to the face. At a breathing rate of 37 liters per minute, mean leakages for the materials ranged from 0.0 percent to 63 percent, depending on the material. Mean penetrations exclusive of leakage ranged from 0.6 percent to 39 percent. Use of nylon hosiery material ("panty hose") to hold the handkerchief material or the disposable face mask to the face was found to be very effective in preventing leakage. Such a combination could be expected to reduce leakage around the handkerchief to about 10 percent or less in practice, and around the mask to less than one percent, which suggests the adaptation and use of such an approach for industrial hygiene.

Dust↗

Length-dependent sensitivity at lengths greater than Lmax in vascular smooth muscle.

Previous work has shown that vascular smooth muscle sensitivity depends on muscle length (arterial circumference) at lengths equal to and less than that for maximum active force (Lmax). In the present study dose-response curves were obtained from dog anterior tibial artery rings at lengths equal to or longer than Lmax. The curves were compared with dose-response curves obtained at lengths less than Lmax. The agonist concentration for half maximal response (ED50) was determined by graphical estimation and by calculation from a best-fit curve. The results show that with norepinephrine (NE) stimulation 1) ED50 decreased significantly at each step when the rings were stretched from Lmax to 1.15 Lmax and then to 1.30 Lmax; 2) ED50 increased significantly when length was decreased from 1.15 to 1.00 Lmax; 3) ED50 decreased significantly at each step when the rings were stretched from 0.70 Lmax to Lmax and then to 1.30 Lmax; and 4) for NE concentration greater than the ED50 at Lmax, active stress was significantly higher at Lmax than at 0.70 Lmax or 1.30 Lmax. For an NE concentration less than the ED50 at Lmax, the active stress at 1.30 Lmax was higher than the active stress at Lmax and at 0.70 Lmax. The results show that sensitivity of vascular smooth muscle continually increases with stretch and does not have a maximum at the length for maximum active force.

Animals↗

Angiocardiography with the seven-pinhole collimator: evaluation of methodology and accuracy in assessing global and regional left ventricular function.

Determination of left ventricular function with tomographic radionuclide angiocardiography using a seven-pinhole collimator was evaluated by comparing results of invasive contrast studies and planar multigated blood pool imaging to the tomographic study of 25 patients. LAO, seven-pinhole multigated blood pool acquisition was reconstructed to produce eight slices from apex to base in each of eight segments of the cardiac cycle. After applying an edge detection routine, three-dimensional reconstruction of perimeters allowed cyclic viewing of the left ventricular angiogram in any projection. When planar and tomographic radionuclide techniques were compared to contrast studies, sensitivity and specificity for identification of segmental wall motion abnormalities were not different (93% and 90% for both). Ejection fraction was determined from tomography by integration of slices to produce a noncalibrated volume and from planar blood pool imaging and contrast ventriculograms by standard techniques. Ejection fraction as compared to contrast studies was accurately determined on the planar angiogram (R = .87, P less than .001) with tomographic analysis showing similar significant correlation (R = .79, P less than .001). Methodologic evaluation indicated that the tomographic study was readily positioned and acquired and provided the advantage of requiring little operator interaction. It suffers, however, from the disadvantage of long reconstruction times with current software and occasional difficulties in defining the superior extent of the left ventricle.

Evaluation Studies as Topic↗

Stimulation by follicle-stimulating hormone of synthesis of lactate by Sertoli cells from rat testis.

Sertoli cells from rats aged 16 days were cultured in defined medium for 2 days and then treated by addition of fresh medium containing various hormones (treated) or saline (control). The concentration of lactate in the medium was measured as a function of time. The production of lactate measured under these conditions was increased by addition of FSH to the medium. For NIH FSH (13 and 14), ED50 for stimulation of lactate production was approximately 0.05 micrograms/ml. Stimulation was also seen with LH and TSH (ED50, 0.8 micrograms/ml for both hormones). Reasons are given for believing that TSH may possess the inherent capacity to stimulate production of lactate in contrast to LH, which appears to act only by way of contaminating traces of FSH. Dibutyryl cAMP also stimulates lactate production by Sertoli cells. Other hormones tested, including androgens, were without effect. When production of lactate by Sertoli cells was compared with the maximal consumption by spermatids in vitro, it became apparent that Sertoli cells may provide the major source of metabolic substrate for spermatids in the form of lactate. Stimulation of lactate production by FSH was inhibited by puromycin, cycloheximide, and actinomycin D. Evidently this response requires synthesis of new protein and RNA. This effect of FSH may be important in the regulation of spermatogenesis.

Animals↗

Length-tension properties of the anterior tibial artery in normotensive and perinephritic hypertensive dogs.

The length-active tension relation has been previously reported to be decreased or unchanged in hypertensive vessels whereas resting distensibility was unchanged or increased. We found the maximum active stress and the internal ring circumference, in millimeters, at which it occurs (Lmax) to be lower in arterial rings from perinephritic hypertensive dogs than in rings from normotensive dogs. The internal circumferences (length) at which resting force and active force became zero (L0 and Lmin, respectively) were unchanged. Lmax, L0 and Lmin were used to normalize length-tension diagrams. Active stress was significantly lower in hypertensive vessels at most of the lengths tested with the diagram normalized to Lmax. When the length-tension diagram was normalized to Lmin there was no difference in the active stress at any of the lengths tested. The length-resting stress curves were identical when rhe diagram was normalized to Lmax but the curve for hypertensive vessels was higher when the diagram was normalized to L0. An important characteristic of these length-tension curves is that normalized lengths correspond to the same absolute length in each group of vessels when the reference length has the same absolute value (L0 and Lmin in this study). This separates differences due to absolute length from differences associated with hypertension. We conclude that perinephritic hypertension in the dog is accompanied by a decrease in resting distensibility of the arterial wall. The results indicate that the choice of reference length may affect the values of stress and tension that are obtained for comparison of length-tension relationships in hypertensive and normotensive blood vessels.

Animals↗

Length-dependent sensitivity in vascular smooth muscle.

Dose-response curves were obtained from dog anterior tibial artery rings at various lengths (L) to determine whether sensitivity to norepinephrine (NE) and potassium (K+) depends on arterial circumference. The dose for half maximal response (ED50) was determined by graphical estimation and by calculation from a best fit curve. For both NE and K+: 1) ED50 was lowest (most sensitive) at L for maximum active force (Lmax) and increased significantly as L decreased from Lmax; 2) ED50 at 1.0 and 1.15 Lmax was not significantly different; 3) ED50 of repeated dose-response curves at Lmax was not significantly different; and 4) when the direction of length change was reversed (from decreasing to increasing), the direction of change in ED50 was also reversed (from increasing to decreasing). Change in the dose for 10% maximal response was the same as ED50. The results did not depend on the method of determining ED50 or on whether responses were expressed as absolute values or as relative values. The results show that sensitivity of vascular smooth muscle depends on L and that the length-sensitivity relation is similar to the length-active tension relation. Similarity of results for NE and K+ indicate that length-dependent sensitivity does not depend on the method of stimulation.

Animals↗

Contractility and the length-tension relation of the dog anterior tibial artery.

Active force (S) and rate of change of force (S) throughout the time of isometric contraction in electrically stimulated, circumferentially cut segments of dog anterior tibial artery were analyzed for dynamic indices of the contractile state. Previous works have determined indices that change with temperature but not with length (L) or calcium (Ca) and were designated indices of crossbridge dynamics. They assumed that changes in L and Ca change only the number of crossbridges between contractile filaments and temperature affects only the dynamics of individual crossbridges. We have shown: (1) specific ratios of S/S to be independent of L; (2) S/S at the same instant of time (VCE) is related to an index from previous work which was defined as a velocity of internal shortening; (3) specific indices of S/S were decreased with lower temperature but increased with time in a Ca-free solution. Our results for a Ca-free solution do not agree with previous work but can be explained by changes of the smooth muscle cell membrane. This suggests that L-independent indices are useful for characterizing changes in the overall dynamic state of the tissue but are not necessarily representative of a change in crossbridge dynamics.

Animals↗

The secretion of Mullerian inhibiting substance by cultured isolated Sertoli cells of the neonatal calf.

Sertoli cells have been insolated from the newborn calf testis using a combination of mechanical and enzymatic disruption. Testicular fragments, previously chopped into 1-mm pieces, are digested in an enzyme mixture consisting of hyaluronidase, collagenase, trypsin and DNAse, followed by a second digestion in trypsin and DNAse. Isolation of the resulting cellular fractions by sedimentation with unit gravity produces an aliquot of Sertoli cells which is over 95% pure when examined by light and electron microscopy. Cultures of these cells grow rapidly and produce Mullerian Inhibiting Substance as evidenced by their ability to cause the involution of the Mullerian duct of the female fetal rat when co-cultured in an organ-culture assay system.

Animals↗