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Biomedical subjects

J M Riddle

Publications and source records attributed to J M Riddle.

At least 37 records · Page 2Linked to original sources
PubMed1989

Scanning electron microscopy of surgically excised human mitral valves in patients over 45 years of age.

Leaflets were obtained from 23 diseased mitral valves of patients over 45 years of age removed at the time of prosthetic valve insertion and the topography was studied with scanning electron microscopy. The clinical diagnosis in all cases was probable rheumatic heart disease. Filiform processes (Lambl's excrescences) were seen on 15 of 23 (65%) of these leaflets. Some of these processes appeared to develop when either bundles of collagen or elastic fibers in the connective tissue framework of the cusp were broken. The freed portion of the fiber then served as a nidus for thrombus formation. The endothelium on the surface of the leaflets was consistently altered. Endothelial cells were changed in shape, had microvilli scattered over their exterior, showed discontinuous cell borders and were desquamated, either singly or in groups. Elements of the peripheral blood adhered to the exposed subendothelium. Erythrocytes were usually entrapped in fibrin networks. Single activated platelets and platelet aggregates adhered to the fibers of the exposed subendothelial connective tissue. Surface mineral deposits were composed of granular spherulites, which contained both calcium and phosphorous. This study extends our understanding of the architectural modifications that contribute to the continuing pathologic process of rheumatic mitral valve disease.

Aged↗
PubMed1989

Platelet serotonin metabolism and ultrastructure in migraine.

Biochemical and ultrastructural techniques were used to study the nature of platelet serotonin involvement in migraine. Serotonin levels were increased to a moderate degree in classic migraine, but not in common migraine. The platelet content of 5-hydroxyindoleacetic acid was equally reduced in both classic and common migraine. Platelet-dense bodies, the storage organelles for serotonin, were increased in both migraine groups, particularly in classic migraine. The results were interpreted as evidence for reduced platelet serotonin turnover combined with dense body hyposecretion in migraine sufferers. These findings are further supportive evidence for altered serotonergic function between attacks of migraine, and argue in favor of a role for serotonin in the mechanisms of a migraine attack.

Adolescent↗
PubMed1989

Platelet activation and analysis of organelles in migraineurs.

We used transmission electron microscopy to investigate selected aspects of the platelet response (surface activation as well as aggregation) and quantify cytoplasmic organelles within the cytoplasm of platelets obtained from both healthy control women and women diagnosed as having either common or classic migraine. Comparisons between controls and migraineurs showed no differences for: (1) the number of circulating platelets, (2) degree of surface activation, (3) amount of aggregate formation or (4) percent of hyperactive platelet populations. In contrast, platelets of migraine sufferers uniformly contained a significantly greater number of dense bodies compared to control platelets. Although we did not find functional abnormalities for the platelets obtained from migraineurs, we did demonstrate that they were altered structurally.

Adult↗
PubMed1989

Early afterdepolarizations: mechanism of induction and block. A role for L-type Ca2+ current.

Early afterdepolarizations (EADs) are a type of triggered activity found in heart muscle. We used voltage-clamped sheep cardiac Purkinje fibers to examine the mechanism underlying EADs induced near action potential plateau voltages with the Ca2+ current agonist Bay K 8644 and the effect of several interventions known to suppress or enhance these EADs. Bay K 8644 produced an inward shift of the steady-state current-voltage relation near plateau voltages. Tetrodotoxin, lidocaine, verapamil, nitrendipine, and raising [K]o abolish EADs and shift the steady-state current-voltage relations outwardly. Using a two-pulse voltage-clamp protocol, an inward current transient was present at voltages where EADs were induced. The voltage-dependence of availability of the inward current transient and of EAD induction were similar. The time-dependence of recovery from inactivation of the inward current transient and of EAD amplitude were nearly identical. Without recovery of the inward current transient, EADs could not be elicited. The inward current transient was enhanced with Bay K 8644 and blocked by nitrendipine, but was not abolished by tetrodotoxin or replacement of [Na]o with an impermeant cation. These results support a hypothesis that the induction of EADs near action potential plateau voltages requires 1) a conditioning phase controlled by the sum of membrane currents present near the action potential plateau and characterized by lengthening and flattening of the plateau within a voltage range where, 2) recovery from inactivation and reactivation of L-type Ca2+ channels to carry the depolarizing charge can occur. Our results suggest an essential role for the L-type Ca2+ "window" current and provide a framework for understanding the role of several membrane currents in the induction and block of EADs.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Platelet ultrastructure and secretion in acute ischemic stroke.

We used transmission electron microscopy to count the organelles (dense bodies, alpha granules, and mitochondria) contained within platelets from 11 acute ischemic stroke patients and 12 healthy controls. We randomly selected for evaluation 25 platelet profiles in ultrathin sections cut from three separate blocks. Compared with those from controls, platelets from stroke patients contained significantly fewer alpha granules (p less than 0.001) and mitochondria (p less than 0.02) and showed a trend toward fewer dense bodies. Supportive of our previous studies, the amount of adenosine triphosphate secreted following stimulation by collagen also tended to be greater in platelets from stroke patients. These observations support the presence of increased platelet secretion associated with acute cerebral infarction and raise the possibility that platelet secretion may be of separate importance to the mechanical occlusion of blood vessels by platelet aggregates in the pathogenesis of cerebral infarction.

Adenosine Triphosphate↗
PubMed1989

Newsletter.

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Academies and Institutes↗
PubMed1988

Leukocytes, platelets, and surface microstructure of spontaneously degenerated porcine bioprosthetic valves.

The microstructure of 33 spontaneously degenerated porcine bioprosthetic valves was assessed by scanning electron microscopy in order to gather insight regarding the degenerative process. Twenty-four mitral and 9 aortic valves were removed from 32 patients. The duration of insertion was 7.7 +/- 2.4 years (mean +/- SD). All valves showed denudation of endothelial cells and exposure of the subendothelial fibrous tissue. Fibroblastlike cells were occasionally seen. Platelet deposits were observed on 22 of 33 valves (67%). Leukocytes were observed on the surface of 27 of 33 valves (82%). Mononuclear leukocytes were the most common category of cells (66%). Crystalline material was present on the surface of some leukocytes, suggesting that they may serve as a nidus for calcification. Transmission electron microscopy showed leukocytes in the process of phagocytizing collagen fibers. Macrophages, by exerting their scavenger function seem to contribute to destruction of the collagen framework of the valves. Whether the observed lymphocytes and plasma cells reflect an immunological involvement is unclear.

Bioprosthesis↗
PubMed1988

A model for early afterdepolarizations: induction with the Ca2+ channel agonist Bay K 8644.

Early afterdepolarizations (EADs) are one mechanism proposed to cause certain cardiac arrhythmias. We studied the effect of the Ca2+ channel agonist Bay K 8644 (1 x 10(-8) to 5 x 10(-5) M) on normally polarized sheep and canine cardiac Purkinje fiber short segments. EADs occurred with higher Bay K 8644 concentrations and had an average take-off potential of -34 mV. The initiation of EADs was preceded by lengthening of action potential duration and flattening of the plateau. Induction of EADs with Bay K 8644 was enhanced by low stimulation frequencies, lowering of [K]o, addition of tetraethylammonium chloride, or application of depolarizing constant current pulses during the plateau. EADs were abolished by increasing stimulation frequency, raising [K]o, the addition of tetrodotoxin, lidocaine, ethmozin, verapamil, and nitrendipine, or application of repolarizing constant current pulses. Using current pulses to modify the action potential plateau, a steep inverse relationship was found between the EAD peak voltage and its take-off potential, and EADs could be initiated over only a narrow range of take-off potentials. Thus, interventions that suppressed EADs shortened action potential duration or shifted the plateau away from the voltage range needed to initiate EADs. These observations suggest that mechanisms dependent on both time and voltage underlie EADs, and provide a unifying hypothesis for the induction of the EADs. We propose that induction of EADs requires 1) lengthening of action potential duration within a plateau voltage range where 2) recovery from inactivation and reactivation of an inward current possibly carried through Ca2+ channels can occur.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

Small bowel transplantation in the rat: ultrastructural changes during the early phases of rejection.

Small bowel transplantation has great potential for the treatment of short bowel syndrome, but the poorly understood rapid rejection of the bowel has hindered progress in this field. In this study, the rat model was used to evaluate the earliest detectable changes of bowel rejection. Eleven pairs of outbred rats underwent heterotopic transplantation of 10-15 cm segments of proximal jejunum on a pedicle of superior mesenteric artery and vein, anastomosed microsurgically to recipient aorta and inferior vena cava, respectively. The bowel extremities were exteriorized. Eight successfully transplanted rats were studied with serial punch biopsies, immediately post-transplantation and daily for 7 successive days. Biopsies were evaluated by light (LM) and transmission electron microscopy (TEM). Ultrastructural changes were evident before any gross or histologic changes. Endothelial damage, detected only by TEM, was common and resulted in exposure of the thrombus-promoting subendothelial components. Activated platelets as well as platelet aggregates adhered to these damaged areas. The lumen of some vessels was filled with tightly packed erythrocytes, at times showing intravascular hemolysis, suggestive of stasis. Extravascular features included edema and small numbers of immunocompetent cells. The epithelium showed a variable morphology depending on the degree of change in the underlying vessels and submucosa. The findings suggest that vascular damage and thrombosis as well as immunologic events are important in the early phase of the rejection process. Sustaining a viable segment of transplanted intestine may depend on suppressing both the microthrombotic aspect (with anticoagulants and/or antiplatelet agents) and the ensuing immunologic process with newer modalities such as cyclosporine.

Animals↗
PubMed1988

Newsletter.

Explore the source record for details and available documents.

Academies and Institutes↗
PubMed1988

Anteroposterior radiographic view of the knee. An unreliable indicator of bone damage.

The clinician and/or radiologist uses standard radiographic views to assess bony changes in the joints of patients with both potential and established arthritis. Using AP (standing) views, we recorded the number of osteophytes and/or subchondral cysts seen on both nonarthritic and arthritic tibial tables and their respective plateaus. These data were compared with the number of osteophytes and/or subchondral cysts observed on "en face" views taken of the same tibial tables after they were resected from the knee joints. Not all of the osteophytes or subchondral cysts present in these tibial tables were detected with the AP view. Narrow osteophytes and those located at extreme anterior or posterior positions on a plateau were missed. Single cysts scattered across a plateau were also not seen. We found that the standard AP view gave an inaccurate measure of the amount of bone damage actually present in the tibial tables of arthritic knees.

Adult↗
PubMed1988

The erosive front: a topographic study of the junction between the pannus and the subchondral plate in the macerated rheumatoid metacarpal head.

The junction between cellular pannus and cartilage/bone was identified grossly on rheumatoid metacarpal heads. Its topography was displayed by scanning electron microscopy using macerated samples. A uniform pattern of resorption bays, typical of osteoclastic activity, was seen spreading over the surfaces of both calcified cartilage and subchondral bone. The contact area between pannus and cartilage/bone was found to represent an erosive front. Morphologic evidence suggested that osteoclasts were primarily responsible for the destructive process.

Adult↗
PubMed1987

Effects of chronic smoking on platelet function.

Platelet function was investigated in 20 healthy cigarette smokers and 23 nonsmokers. Cigarette consumption was 1.4 +/- 0.5 packs/day (mean +/- SD) and the duration of smoking was 19 +/- 12 years. Platelet surface activation in vitro, aggregation in vivo and in vitro, as well as the release of platelet-specific proteins in vivo were evaluated. The mean number of platelet aggregates counted on an activating surface (Formvar film) was higher in smokers (80 +/- 59) than in nonsmokers (43 +/- 27) (P less than .01), indicating enhanced activity following exposure to an activating surface. Smokers who were 50 years of age or older showed an enhanced platelet aggregation following an in vitro stimulation in comparison to younger smokers (105 +/- 54 vs 54 +/- 55 aggregates) (P less than .05). Those who smoked 20 years or more also showed enhanced aggregation in comparison to those who smoked less than 20 years (112 +/- 60 vs 53 +/- 45 aggregates) (P = .02). Circulating platelets showed no significant difference among smokers and nonsmokers in the following tests: platelet aggregate ratio (0.67 +/- 0.30 vs 0.86 +/- 0.76), platelet count per mm3, (310,000 +/- 82,000 vs 278,000 +/- 78,000/mm3), levels of platelet factor 4 (9.8 +/- 5.2 vs 9.4 +/- 5.3 ng/ml), and plasma concentrations of beta-thromboglobulin (53.9 +/- 23.5 vs 49.1 +/- 25.5 ng/ml). The data suggest that chronic smoking primes platelets, causing them to aggregate more readily when exposed to an activating stimulus in vitro.

Adult↗
PubMed1987

Photodynamic therapy of normal cerebral tissue in the cat: a noninvasive model for cerebrovascular thrombosis.

The early neuropathological response of normal cat brain to photodynamic therapy was investigated. Photofrin II was injected (IV) into a cat and photoactivated with red light from a filtered incandescent lamp. Animals were subjected to phototherapy either through the intact skull or with energy deposition onto the intact dura. Following photoactivation the animals were maintained for 6 h after which time the brain was removed and sections submitted for electron microscopic and or light microscopic study. Gross anatomical analysis of the photoactivated brain revealed hemorrhagic dusky discoloration limited to the area of the tissue illuminated. Animals that failed to show a lesion were cats characterized by low Photofrin II dosage and low photoactivation intensity. The microscopic cortical features of cats with lesions included prominent capillary congestion and regions of marked vacuolization and rarefaction. Blood vessels were structurally altered and the lumen of many vessels was completely filled with tightly packed erythrocytes. Our study suggests that the acute neuropathological response of cerebral tissue to photoactivation resembles that of microvascular thrombosis. It is thus reasonable to explore PDT of normal tissue as a non invasive model of cerebrovascular thrombosis in the cat.

Animals↗
PubMed1987

The tibial subchondral plate. A scanning electron microscopic study.

Non-arthritic tibial plateaus were obtained from fifteen cadavera and five above-the-knee amputation specimens. After radiographs had been made, each sample was macerated and the topography of the subchondral plate was displayed by scanning electron microscopy. The surface features included small peripheral and submeniscal osteophytes, indentations, and holes penetrating the plate. The pattern of distribution of holes per square centimeter was different for the subchondral plate of the medial plateau than it was for that of the lateral plateau. More holes were present in the submeniscal area of the medial tibial plateau; the lateral tibial plateau showed a greater concentration of holes in its central area. By light microscopy, many holes were seen to be blood vessels that were lined by endothelium and contained erythrocytes.

Adult↗
PubMed1986

A modified technique for small-bowel transplantation in the rat.

The rat model for small-bowel transplantation is becoming increasingly popular. The currently accepted microsurgical technique, however, is complicated by extensive dissection in the donor rat vascular system requiring a great deal of manipulation of the vessels themselves, with consequent complications of thrombosis and vascular injury. We describe a procedure for small-bowel transplantation in the rat that simplifies the currently accepted technique. The peripheral portion of the superior mesenteric artery (SMA) and superior mesenteric vein (SMV) is used as the vascular pedicle of the segment of bowel to be transplanted rather than the SMA with an aortic cuff and the portal vein as previously described. The SMA and SMV are anastomosed to recipient aorta and inferior vena cava respectively. The bowel extremities are exteriorized, thus leaving access to the lumen for further studies. All anastomoses are performed with interrupted 10-0 nylon sutures. The procedure was performed in 11 animals. Good revascularization of the transplant was defined as immediate filling of the transplant vasculature with normal (pink) appearing bowel. Eight of the recipients had excellent revascularization. Venous occlusion was the cause of early failure in the remaining three animals. All animals were killed, autopsies performed, and the anastomoses examined. The longest survivors were killed at 7 months. Biopsies were obtained immediately and at daily intervals. Early ultrastructural changes of rejection in the transplanted bowel were studied by electron microscopy. Changes in the microvasculature were seen early after transplantation. Immunologic changes were apparent only later in the course of rejection. We conclude that this technique is successful in achieving functional small-bowel transplants in the rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗