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Biomedical subjects

W J Dodds

Publications and source records attributed to W J Dodds.

At least 307 records · Page 17Linked to original sources

Disseminated intravascular coagulation induced by Liquoid in the rat. II. Effect of heparin on hematologic and complement abnormalities and renal lesions studied by light, fluorescence, and electron microscopy.

A single intravenous injection (12.5 mg.) of Liquoid (polyanethol sulfonate) was given to anticoagulated (heparinized) rats. Fibrinogen concentrations, platelet counts, total serum complement (CH50),C3 protein, and terminal components (C3 to C9) were measured. Histopathology was assessed by light, fluorescence, and electron microscopy. Heparin given before Liquoid remarkably diminished the seferity of the histologic lesions, with good correlation among light, fluorescence, and electron microscopy. Levels of clotting factors, CH50, C3 and C3 to C9, however, were not statistically different in the heparinized rats injected with Liquoid from those of animals receiving Liquoid alone. Actually C3 protein concentration was lower in the anticoagulated (Liquoid-heparin) rats. It is postulated that under the present experimental conditions, heparin did not antagonize the procoagulant and precipitating or complement-activating Liquoid effects. The attenuated histopathology observed was perhaps the result of either local or systemic, as yet undefined, heparin effects other than anticoagulation.

Animals↗

Immunologic characterization of canine factor VIII.

Canine factor VIII (FVIII) preparations isolated from cryoprecipitates by gel chromatography were pooled to provide one batch of antigen for simultaneous immunization of two rabbits and a goat. The goat and rabbit antisera had similar FVIII-neutralizing titers, but the latter had seven to ten times more precipitating titer for FVIII-related antigen (FVIII-RA). Absorption with material low in FVIII had little effect on the precipitating titer of the rabbit antibody, but it abolished the precipitating capacity of the goat antibody and caused a 20% reduction in the neutralizing titer of both antisera. Results obtained in the Laurell assay with the two different antisera were similar. This finding was true whether the FVIII-RA levels were reduced, normal, or elevated, as well as for heat-treated and frozen-thawed plasmas. Both antisera were neutralized by the same canine plasma to a similar extent. Analysis of FVIII concentrates by crossed immunoelectrophoresis suggested that canine FVIII-RA was heterogeneous, with slow-and fast-migrating components. The presence of more than one antigenic site on the FVIII complex was also supported by the disparity between the FVIII-neutralizing and -precipitating titers of goat antiserum and by the demonstration that FVIII-RA, FVIII-neutralizing antigen, and procoagulant activity varied independently.

Animals↗

Characterization of the fawn-hooded rat as a model for hemostatic studies.

A large colony of fawn-hooded (FH) rats, comprising five original families and six generations of their progeny, was developed for genetic and comparative studies of their bleeding tendency. The characteristics of the bleeding diathesis in these rats are similar to those originally reported in related rats by Tschopp and Zucker. FH rats have normal clot retraction, ADP-induced platelet aggregation and platelet ADP; variable aggregation with collagen; minimal aggregation with adrenaline and cobra venom factor; and reduced platelet ATP, ATP/ADP ratio, serotonin content and -14C-serotonin release. In comparison to age- and sex-matched Wistar rats, FH rats have significantly prolonged partial thromboplastin time, shortened Russell's viper venom time and increased factor X and XI levels. Other coagulation screening tests and specific assays for fibrinogen, plasminogen and factors VII, VIII and IX were normal. Some age- and sex-related differences in coagulation and other parameters were observed within each rat strain. Plasma proteins, glycoproteins and ceruloplasmin (copper oxidase activity) showed no abnormalities, nor did initial studies of immunoglobulins and complement. However, FH rats have significantly lower glucose and higher cholesterol levels than comparable Wistar rats.

Adenine Nucleotides↗

Relationship between serum gastrin concentration and lower-esophageal sphincter pressure.

Serum gastrin concentration [G] has been proposed as the major factor regulating resting lower-esophageal sphincter pressure (LESP). Available supporting evidence in man, however, is largely circumstantial. The present study directly compares measurements of LESP with concurrent levels of circulating serum gastrin in fasting human subjects. A direct correlation was not shown between [G] and resting LESP; rather, a trend existed toward an inverse relationship. The study results indicate that the concentration of serum immunoreactive gastrin is not a major determinant of lower-esophageal sphincter tone in humans.

Adolescent↗

Multiple lipomas of the stomach and duodenum.

A patient complaining of epigastric distress was found to have multiple gastroduodenal lipomas. Although the roentgenologic findings were both bizzare and initially confusing, close scrutinization of the abnormalities suggested a correct diagnosis.

Celiac Artery↗

The effect of manometric assembly diameter on intraluminal esophageal pressure recording.

Recent studies indicate that lower esophageal sphincter pressure is influenced by manometric assembly diameter. This study determines the effect of assembly diameter on both esophageal sphincter pressure and peristaltic pressure in the esophageal body. We performed esophageal manometric studies in 6 normal subjects using graded assembly diameters. High-fidelity recording was achieved by using a noncompliant catheter-infusion system. The results indicate that increases in assembly diameter cause significant increases in peristaltic pressure amplitudes and in resting sphincter pressure in both the smooth and striated muscle portions of the esophagus. This phenomenon is best explained by the length-tension characteristics of esophageal muscle, increased stretch causing greater contraction force.

Adolescent↗

Effect of increased intraabdominal pressure on lower esophageal sphincter pressure.

This study evaluates the effect of intraabdominal pressure increases on lower esophageal sphincter (LES) pressure in normal subjects and in patients with reflux esophagitis. Intraabdominal and intragastric pressure were increased by abdominal compression, the Valsalva maneuver, and leg raising. In normal subjects changes in pressure recorded from the LES equaled the changes in gastric pressure induced by abdominal compression and Valsalva. Consquently the LES-gastric pressure gradient remained unchanged. During leg raising, pressure recorded from the LES increased more than gastric pressure, thereby increasing the LES-gastric pressure gradient. Although statistically significant, the LES pressure increases associated with leg raising were modest, unrelated to initial sphincter pressure, and unaffected by atropine. When individuals demonstrating a "common cavity" phenomenon were exculed, LES pressure changes during abdominal compression were similar in patients with esophagitis and in normal volunteers. Consequently, response of the LES to abdominal compression generally does not separate patients with esophagitis from normal subjects. We believe that the LES responses to increased intra-abdominal pressure observed in this study are better accounted for by mechanical factors than by a physiologic adaptive response of intrinsic LES tone.

Abdomen↗

The value of age- and sex-matched controls for coagulation studies.

Several coagulation parameters and plasminogen levels were studied in 80 normal people divided into eight paired and sex-matched age groups: prepubertal children, postpubertal children, young adults, and adults over 50. The data indicate that factor-VII and -IX activities increase with age, with a cluster of lower activity for children and higher activity for adults. Factor-VIII levels appear to decrease with age, although this effect could be due to greater anxiety in the pre- and postpubertal children at the time of venipuncture. The adults showed no significant change in factor-VIII activity with age, but partial data indicate that factor-VIII levels are higher in adults with blood group A than those with blood group O. The age-related changes in factor-VII, -IX, and possibly -VIII activities did not vary between sexes. By contrast, plasminogen increased strikingly with age in males and decreased with age in females. With fibrinogen, a similar effect was found for adults, though not for the entire population. These findings indicate the importance of using appropriate age- and sex-matched controls for coagulation and plasminogen assays, especially in patients with mild inherited or acquired coagulation disorders.

ABO Blood-Group System↗

Hereditary factor VII and IX deficiencies in a large kindred.

A large kindred with combined deficiencies of factors VII and IX is presented. The deficiencies appeared to be independent and the data were not consistent with a diagnosis of haemophilia BM. The identification of mildly affected family members, including carriers of haemophilia B and heterozygotes for factor-VII deficiency, was facilitated by comparison with the 95% confidence interval of an age- and sex-matched control population. The bleeding patterns were those of mild to moderate haemophilia B and did not appear to have been modified by the presence of factor-VII deficiency.

Factor IX↗

Quantitation of pharyngeal motor function in normal human subjects.

A need exists for accurate pressure recording of pharyngeal motor events. Results of this study indicate that accurate quantitation of pharyngeal motor activity is not possible using a water-filled catheter system, even when high infusion rates are used. An intraluminal strain gauge system, however, achieves high-fidelity recording. Quantitation of pharyngeal peristalsis using the intraluminal strain gauge system reveals peristaltic pressure amplitudes higher than those hitherto recorded. In normal subjects, peristaltic amplitude averages about 200 mmHg in the hypopharynx, complexes in one subject being as high as 600 mmHg. A zone of relatively low pressure exists in the oropharynx. Mean pharyngeal wave duration decreases progressively in an aboral direction, from 1.0 to 0.3 s, and peristaltic wave speeds range between 9 and 25 cm/s. Accurate quantitation of pharyngeal peristaltic variables provides the necessary basis for characterization and assessment of pharyngeal motor disorders.

Gastrointestinal Motility↗

Further studies of canine von Willebrand's disease.

Additional characterization of von Willebrand's disease (VWD) in a family of German shepherd dogs is presented. Genetic studies of three generations of affected dogs indicate that about 50% of the progeny are affected if one parent has VWD and about 60% if both parents have the defect. Some of these progeny manifested an incomplete form of VWD, suggesting autosomal dominant inheritance with variable expressivity. The disease become progressively less severe with advancing age and repeated pregnancies. Ristocetin-induced platelet aggregation was significantly reduced in VWD dogs as compared with normal, thrombopathic, and hemophilic carrier dogs. Immunodiffusion and electroimmunodiffusion studies with rabbit anticanine factor VII showed the level of factor VII-related antigen to be low in VWD dogs but present in increased amounts in hemophilic dogs. VWD affected dogs had markedly delayed hemostatic plug formation, but their plugs appeared normal by light and electron microscopy. Their platelet nucleotides, ATP/ADP ration, and platelet protein content were normal. Platelet and fibrinogen survival times with [75Se] selenomethionine were also normal, although platelets from VWD dogs incorporated more radioactivity than did those from normal dogs or from dogs with incomplete VWD.

Acute Kidney Injury↗

A rapid pull-through technique for measuring lower esophageal sphincter pressure.

Because disadvantages are inherent in the conventional station pull-through technique (SPT) currently used for recording lower esophageal sphincter pressure (LESP), a more suitable recording method is needed. In study, we evaluated a rapid pull-through technique (RPT) for recording LESP and compared the results with those obtained by SPT. The RPT features rapid withdrawal of recording sensors across the LES during a 10- to 20-sec interval of suspended respiration. This method avoids recording "artifact" caused by respiratory LES motion and provides precise end points for scoring and measurement. In 12 normal subjects, LESP measured by RPT (24.3 plus or minus 0.5 mm Hg) was comparable, but significantly greater, than LESP measured by SPT (21.1 plus or minus 9.1 mm Hg). Analysis of LESP scores for the two recording methods revealed that both intraobserver and interobserver error were substantially less for RPT than SPT (P less than or equal to 0.01). Further correlation of LESP between studies was greater for the RPT than the SPT recording method. We conclude that RPT represents a convenient method for recording LESP which is easier to perform and yields more reproducible values than LESP recording by SPT.

Adolescent↗

Disseminated intravascular coagulation induced by liquoid in the rat. I. Correlation of hematologic and complement abnormalities with renal lesions studied by light, fluorescence, and electron microscopy.

Under the proper experimental conditions, disseminated intravascular coagulation,"an intermediary mechanism of disease," results in the classic endotoxin-induced generalized Shwartzman reaction. Other substances, such as liquoid, a highly negatively charged anticoagulant, trigger a generalized Shwartzman reaction-like phenomenon in rabbits. We studied the effects of a single high intravenous dose of liquoid (12.5 mg.) upon the rat's coagulation and complement systems and their correlation with the kidney morphology by light, fluorescence, and electron microscopy. Thrombin time was prolonged; fibrinogen, plasminogen, and factors VIII and XII concentrations were markedly decreased, whereas fibrin degradation products were increased in the experimental animals when compared with the saline-injected controls (p greater than 0.001). Total hemolytic complement, hemolytic activity of terminal components (C3 to C9), and C3 protein concentration were significantly reduced (p greater than 0.001). The liquoid-injected rats developed cortical necrosis and manifested oliguria and anuria, with elevated blood urea nitrogen levels, when survival was longer than 3 hours. Histologically, thrombi of fibrin-like material filled the glomerular capillaries. Deposits of fibrin, and also of immunoglobulin G and C3, were readily identifiable by specific immunofluorescence, Linear or granular fluorescent deposits (or both) along the glomerular basement membranes and in the mesangium were observed. Electron microscopy demonstrated necrosis of glomeruli and abundant thrombi of fluffy, compact granular, or fibrillar electron-dense material. No typical fibrin periodicity was detected. These experiments support the concept of activation of the coagulation and the complement systems. We postulate that liquoid produced not only a consumptive coagulopathy in the rat but also a direct or perhaps anindirect activation of complement. Whether this latter has occurred through the classic or an alternate pathway remains to be elucidated.

Animals↗