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Biomedical subjects

R J Anderson

Publications and source records attributed to R J Anderson.

At least 181 records · Page 10Linked to original sources

The influence of arachidonic acid metabolites on leukocyte activation and skeletal muscle injury after ischemia and reperfusion.

Derivatives of arachidonic acid have been found to play a role in the reperfusion injury of various tissues. These compounds have a broad spectrum of activity, including modulation of white blood cell response to injured tissue. This study was designed to determine the effect of thromboxane and lipoxygenase derivatives on the local and systemic response to ischemia and reperfusion of skeletal muscle. Fifteen dogs were separated into three groups and subjected to gracilis muscle ischemia followed by 2 hours of reperfusion. One group served as controls, one group was treated with OKY-046 (a thromboxane synthetase inhibitor), and one group was treated with diethylcarbamazine (a lipoxygenase inhibitor). White blood cell activation as measured by superoxide anion production, and eicosanoid levels were measured both in the gracilis venous effluent and central venous circulation. These results were compared to infarct size in the gracilis muscle. OKY-046 significantly reduced thromboxane production in both the central venous (102 +/- 30 to 31 +/- 9 pg/ml, p less than 0.05) and gracilis samples (107 +/- 22 to 25 +/- 6 pg/ml, p less than 0.005). This was accompanied by a reduced white cell activation in the central venous blood (15 +/- 1 to 10 +/- 1 nmol O2-, p less than 0.05), but did not affect infarct size or white cell activation in the gracilis. Conversely, diethylcarbamazine significantly reduced both white cell activation (16 +/- 1 to 10 +/- 1 nmol O2-, p less than 0.005) and infarct size in the gracilis muscles (61.6% +/- 4.5% to 28.5% +/- 8.6%, p less than 0.01), as well as reduced systemic white blood cell activation.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

Ultrasonic determination of fetal parameters in baboons (Papio anubis)

The use of nonhuman primates to study reproductive physiology, fetal development, and neonatal management often depends on the availability of pregnant and fetal animals of known gestational history. The purpose of this study was to establish and correlate normal fetal growth parameters with gestational age in olive baboons (Papio anubis). Normal cycling females were bred to proven males by using the degree of perineal swelling and vaginal cytology to determine onset of ovulation. The subjects were evaluated to determine pregnancy beginning 18 days postmating, using an Aloka-650 diagnostic ultrasound unit, equipped with a 7.5 mHz prostate probe and a 5 mHz transabdominal probe. Ten pregnant animals were then evaluated sonographically every 3 days through day 30 and weekly through day 135 (average gestation 184 days). Measurements included gestational sac, greatest-length, biparietal diameter, femur length, head circumference, and abdominal circumference. Using the means and standard deviations, growth curves were constructed, and the data used to develop predicted value charts for gestational age estimation. Using the predicted value charts established in our study, subsequent evaluation of pregnant baboons in our colony disclosed concordance with actual gestational age.

Animals↗

Thromboxane synthetase inhibition decreases polymorphonuclear leukocyte activation following hindlimb ischemia.

Ischemia of the lower extremity has been shown to cause pulmonary leukostasis and increased pulmonary artery pressure. Thromboxane (TX) has been implicated as a mediator in this process. The effect of OKY-046, a TX synthetase inhibitor, on polymorphonuclear leukocyte (PMN) production of superoxide anion (O2-) as determined by ferricytochrome reduction was examined. Fourteen dogs were subjected to 6 hours of bilateral gracilis muscle ischemia followed by 1 hour of reperfusion. O2- production from resting PMNs and PMNs stimulated with opsonized zymosan (OZ, 0.1 mg/ml) was measured prior to ischemia or drug treatment (baseline), and following reperfusion in both treated (n = 7) and control groups (n = 7). Serum TX levels were measured using a radioimmunoassay. Following reperfusion, TX levels in the treated group were decreased as compared with the control group (18 +/- 2 pg/ml vs. 72 +/- 26 pg/ml, P less than 0.05). Superoxide production by both resting and stimulated PMNs was also decreased in the treated group; from 0.98 +/- 0.16 nmol to 0.43 +/- 0.12 nmol O2- in the resting state (P less than 0.05) and from 13.3 +/- 1.5 nmol to 9.0 +/- 1.1 nmol O2- after stimulation (P less than 0.005). O2- production was increased in the control group following reperfusion as compared with baseline samples, and this increase was attenuated by treatment with OKY-046. TX synthetase inhibition decreases activation of PMNs following hindlimb ischemia.

Animals↗

Localization of human blood phenol sulfotransferase activities: novel detection of the thermostable enzyme in granulocytes.

Phenol sulfotransferases (PSTs) catalyze the sulfate conjugation of catecholamines and a variety of phenolic compounds. Thermolabile and thermostable forms of PST exist in human tissue. Blood component thermostable PST activities have proved useful as measures of the enzyme activities in other tissues such as the liver. The most thoroughly studied blood component is the human platelet, which contains both thermolabile and thermostable PST activities. Partial localization of PST activity in blood has been characterized only for thermolabile PST. We performed the studies reported here to define the cellular and subcellular localization of both thermolabile and thermostable PST activities in blood elements. Blood samples from four adults were pooled and aliquots for platelet studies were anticoagulated with ethylenediaminetetraacetic acid. Aliquots for studies of granulocytes, mononuclear cells, and erythrocytes were defibrinated to avoid platelet contamination and were separated through Ficoll-Hypaque gradients. Cytosol thermolabile PST activities assayed with dopamine as the substrate and expressed as a percent of the total thermolabile PST activity per milliliter of whole blood were as follows: platelets, 97%; granulocytes, 0.6%; mononuclear cells, 0.7%; and erythrocytes, 0.4%. Cytosol thermostable PST activities measured with p-nitrophenol were as follows: platelets, 77% of the total activity; granulocytes, 19%; mononuclear cells, 1.2%; and erythrocytes, 0.5%. Plasma and membrane-bound activities were less than 2.3% of total activities for each form. Because granulocyte thermostable PST was present in an amount greater than expected, it was further characterized. The Michaelis-Menten constant values for p-nitrophenol and 3'-phosphoadenosine-5'-phosphosulfate were 1.13 mumol/L and 0.6 mumol/L, respectively. The pH optimum of 6.6, a 50% inhibitory concentration for 2,6-dichloro-4-nitrophenol of 1.0 mumol/L, and retention of 56% of activity after preincubation at 45 degrees C for 15 minutes were the same for the granulocytes as for platelet thermostable PST. In summary, our study confirms and extends our knowledge of localization of blood thermolabile PST. Our data define for the first time the localization of blood thermostable PST and highlight the substantial contribution of granulocyte thermostable PST activity. Granulocytes represent an easily obtained nucleated cell for the study of human thermostable PST.

Arylsulfotransferase↗

Changing immunization referral patterns among pediatricians and family practice physicians, Dallas County, Texas, 1988.

Family practice physicians and pediatricians in Dallas County, Texas, were surveyed to determine how recent vaccine price increases have changed immunization referral patterns. A total of 73% of responding physicians referred some pediatric patients for immunization in 1988. Public health clinics were the largest referral source with more responding pediatricians (84.4%) referring patients than did responding family practitioners (66.5%). Referrals to the clinics were most often made when patients were unable to afford immunizations in a private practice setting. Between 1979 and 1988, the number of responding pediatricians and family practitioners making immunization referrals increased by 193% and 391%, respectively. The percentages of children referred for immunization increased by 693% during the same decade. It was suggested by our survey of Dallas County physicians that a new influx of patients are using public sector immunizations, potentially creating additional financial stress for public health programs. In addition, this shift to the public sector may undermine the health departments' ability to provide new vaccines or protect greater numbers of children with immunization.

Costs and Cost Analysis↗

Intravascular ultrasonography: validation studies and preliminary intraoperative observations.

Intravascular ultrasonography is emerging as an important imaging modality to assess the presence, distribution, and extent of atherosclerotic vascular disease. To determine the accuracy and clinical utility of intravascular ultrasonography, a flexible catheter-based system was used to generate two-dimensional, cross-sectional vascular images. In 23 arteries of 11 sheep 206 in vivo images demonstrated an echo-free lumen surrounded by three distinct concentric acoustic transitions corresponding to intima, media, and adventitia. Ultrasound measurements of lumen diameter and area correlated significantly with those of corresponding arteriographic measurements obtained by use of digital calipers (r = 0.91, r = 0.86). To evaluate clinical feasibility, intraoperative images (n = 160) were obtained in 10 patients undergoing vascular bypass or hemodialysis access procedures. The images depicted luminal configuration and arterial wall morphologic characteristics. Measurements of lumen diameter and lumen area correlated closely with corresponding intraoperative arteriography (r = 0.81, r = 0.79). The ultrasound images demonstrated arterial stenoses, intimal hyperplasia, intraluminal thrombus, polytetrafluoroethylene graft material, and anastomotic sites. We conclude that flexible catheter-based ultrasonography produces images that accurately demonstrate arterial wall architecture, lumen diameter, and area. Intraoperative application can produce images that provide unique information thus expanding the clinical potential of ultrasonography as a guidance system for vascular procedures.

Animals↗

A comparative study of methods of photoreceptor morphometry.

A comparative study was performed to compare methods of quantitative evaluation of damage to photoreceptor cells in rat eyes exposed to light. Using a manual count of individual photoreceptor nuclei as the standard, the following measurements were compared: (1) outer nuclear layer column count, (2) area, (3) thickness, and (4) the number of nuclei of the outer nuclear layer of the retina using a newly developed computer program that counts a digitized image. Linear-regression analysis of the data showed that the computer method was the most accurate with a Pearson correlation coefficient of 0.9911. The other methods tested also correlated well with the manual count, with coefficients ranging from 0.9367-0.9532. All these methods were reasonably accurate measurements of photoreceptor layer integrity, with the computer count most closely approximating the values obtained by a manual count. However, the outer nuclear layer thickness measurement appeared to be the fastest and most convenient method to evaluate photoreceptor cell damage quantitatively. Computer counting could be reserved for situations in which a high degree of accuracy is required.

Animals↗

The relationship between caries experience in the deciduous molars at 5 years and in first permanent molars of the same child at 7 years.

The sensitivity and specificity of predictors of caries in the first permanent molars based on caries experience in the deciduous molars were tested, using longitudinal data derived from a group of 565 children examined at the ages of 5 and 7 years. The best predictor of caries experience in the first permanent molars at the age of 7 years in this group of children was found to be caries experience in three or more deciduous molars at the age of five.

Age Factors↗

Retention of three fissure sealant resins. The effects of etching agent and curing method. Results over 3 years.

Results are reported of a 3-year blind study comparing three different fissure sealants, using a system of contralateral control teeth. A total of 744 first permanent molars were sealed for 186 children, aged 6-7 years at the start of the study. Resin was applied by a dental therapist and all recall examinations were carried out by the same dentist. Resin was fully retained on 77% of teeth at the end of 3 years. After the same time an unfilled light-cured resin was significantly better retained than a filled light-cured resin. The two light-cured resins in the study were retained better on the right side of the mouth than on the left, but there was no comparable significant difference for retention of the control chemically-cured material. The use of enchant in gel form was as effective as liquid etching.

Acid Etching, Dental↗

Histidine regulation of cyclic AMP metabolism in cultured renal epithelial LLC-PK1 cells.

L-Histidine and imidazole (the histidine side chain) significantly increase cAMP accumulation in intact LLC-PK1 cells. This effect is completely inhibited by isobutylmethylxanthine (IBMX). Histidine and imidazole stimulate cAMP phosphodiesterase activity in soluble and membrane fractions of LLC-PK1 cells suggesting that the IBMX-sensitive effect of these agents to stimulate cAMP formation is not due to inhibition of cAMP phosphodiesterase. Histidine and imidazole but not alanine (the histidine core structure) increase basal, GTP-, forskolin-, and AVP-stimulated adenylate cyclase activity in LLC-PK1 membranes. Two other amino acids with charged side chains (aspartic and glutamic acids) increase AVP-stimulated but neither basal- nor forskolin-stimulated adenylate cyclase activity. This suggests that multiple amino acids with charged side chains can regulate selected aspects of adenylate cyclase activity. To better define the mechanism of histidine regulation of adenylate cyclase, membranes were detergent-solubilized which prevents histidine and imidazole potentiation of forskolin-stimulated adenylate cyclase activity and suggests that an intact plasma membrane environment is required for potentiation. Neither pertussis toxin nor indomethacin pretreatment alter imidazole potentiation of adenylate cyclase. IBMX pretreatment of LLC-PK1 membranes also prevents imidazole to potentiate adenylate cyclase activity. Since IBMX inhibits adenylate cyclase coupled adenosine receptors, LLC-PK1 cells were incubated in vitro with 5'-N-ethylcarboxyamideadenosine (NECA) which produced a homologous pattern of desensitization of NECA to stimulate adenylate cyclase activity. Despite homologous desensitization, histidine and imidazole potentiation of adenylate cyclase was unaltered. These data suggest that histidine, acting via an imidazole ring, potentiates adenylate cyclase activity and thereby increases cAMP formation in cultured LLC-PK1 epithelial cells. This potentiation requires an intact plasma membrane environment, occurs independent of a pertussis toxin-sensitive substrate and of products of cyclooxygenase, and is inhibited by IBMX. This IBMX-sensitive pathway does not involve either inhibition of cAMP phosphodiesterase activity or a stimulatory adenosine receptor coupled to adenylate cyclase.

1-Methyl-3-isobutylxanthine↗

Statistical evaluation of diagnostic criteria for bacterial vaginosis.

Bacterial vaginosis is the most common cause of vaginitis in women of reproductive age. In an attempt to clarify diagnosis of this condition, various parameters of signs and symptoms and groups of parameters were compared with classical diagnostic criteria in 310 patients. There was no significant difference in positive diagnosis rates between the Amsel et al. criteria and those of Thomason et al. (p = 0.25). The single most reliable indicator of bacterial vaginosis was the presence of clue cells on wet mount examination of vaginal secretions (sensitivity 98.2%, specificity 94.3%, positive predictive value 89.9%, negative predictive value 99.0%). The best two combinations of parameters for rapid accurate clinical diagnosis were clue cells and odor on alkalinization (sensitivity 99.5%) positive predictive value 98.8%, negative predictive value 92.1%). Gram stain criteria (bacterial morphologic types) were less accurate predictors of the disease (sensitivity 97.0%, specificity 66.2%, positive value 57.2%, negative predictive value 97.9%). Even when the bacterial morphologic type criteria were combined with presence of clue cells, predictive accuracy did not exceed that of clue cells on wet mount examination alone (sensitivity 93.9%, specificity 84.7%, positive predictive value 74.2%, negative predictive value 96.8%). Homogeneous discharge was found to be of little diagnostic value.

Bacterial Infections↗

Sustained benefit of temporary limited reperfusion in skeletal muscle following ischemia.

Limiting the rate of reperfusion blood flow following prolonged ischemia in skeletal muscle has been shown beneficial. However, the persistence of this benefit with reinstitution of normal blood flow remains undefined. We investigated the role of temporary limited reperfusion on ischemia-reperfusion injury in an isolated gracilis muscle model in six anesthetized dogs. Both gracilis muscles were subjected to 6 hr of ischemia followed by 2 hr of reperfusion. Reperfusion blood flow was limited for the first hour in one gracilis muscle to its preischemic rate followed by a second hour of normal reperfusion (LR/NR). The contralateral muscle underwent 2 hr of normal reperfusion (NR/NR). Muscle injury was quantified by technetium-99m pyrophosphate (TcPyp) uptake and by histochemical staining using triphenyltetrazolium chloride (TTC) with planimetry of the infarct size. Capillary permeability was evaluated by muscle weight gain. Results are reported as the mean +/- SEM: [table: see text] These data demonstrate a sustained benefit from temporary limited reperfusion. This methodology should be considered in the surgical management of the acutely ischemic limb.

Animals↗

Role of eicosanoids and white blood cells in the beneficial effects of limited reperfusion after ischemia-reperfusion injury in skeletal muscle.

Limiting the rate of reperfusion blood flow has been shown to be beneficial locally in models of ischemia-reperfusion injury. We investigated the effects of this on eicosanoids (thromboxane B2, 6-keto-PGF1 alpha, and leukotriene B4), white blood cell activation, and skeletal muscle injury as quantitated by triphenyltetrazolium chloride and technetium-99m pyrophosphate after ischemia-reperfusion injury in an isolated gracilis muscle model in 16 anesthetized dogs. One gracilis muscle in each dog was subjected to 6 hours of ischemia followed by 1 hour of limited reperfusion and then by a second hour of normal reperfusion. The other muscle was subjected to 6 hours of ischemia followed by 2 hours of normal reperfusion. Six dogs each were used as normal reperfusion controls (NR) and limited reperfusion controls (LR), with 5 dogs being treated with a thromboxane synthetase inhibitor (LR/TSI) and another five with a leukotriene inhibitor (LR/LI). LR in all three groups (LR, LR/TSI, and LR/LI) showed a benefit in skeletal muscle injury as measured by triphenyltetrazolim chloride and technetium-99m pyrophosphate when compared with NR. However, there was no significant difference between the groups with LR regarding eicosanoid levels and white blood cell activation when compared with NR. These results demonstrate that LR produces benefits by mechanisms other than those dependent upon thromboxane A2, prostacyclin, or white blood cell activation.

Animals↗

Popliteal artery agenesis: a new anatomic variant.

Agenesis of the popliteal artery has not been described as a vascular anomaly in the lower extremity. This case report describes congenital absence of the popliteal artery discovered during operative exploration after a traumatic injury to the lower extremity. The preoperative arteriogram suggested acute occlusion of the popliteal artery. Intraoperative exploration and arteriography were consistent with agenesis of the popliteal arterial segment, and postmortem examination confirmed these arteriographic and intraoperative observations. Embryologically, failure of the middle portion of the sciatic artery to persist would account for this anomaly. A review of series reporting congenital anomalies of the lower extremity vasculature failed to discover previous mention of this particular abnormality. Agenesis of the popliteal artery should be included among those vascular anomalies that may affect management of lower extremity vascular disease.

Adult↗

Hypodense eosinophils and interleukin 5 activity in the blood of patients with the eosinophilia-myalgia syndrome.

The recent recognition of the eosinophilia-myalgia syndrome (EMS) associated with the ingestion of L-tryptophan prompted an analysis of the peripheral blood eosinophil phenotypes and of the serum eosinophil hematopoietins in this disorder. Five patients with an illness characterized by the abrupt onset of aching skeletal muscles, edema, thickening and induration of the skin, and marked blood eosinophilia associated with L-tryptophan ingestion provided eosinophils, serum, or both, for evaluation. Gradient sedimentation density analysis of the peripheral blood eosinophils from four of these patients revealed that 43 +/- 13% (mean +/- SEM) of the cells had converted to the abnormal (hypodense) sedimenting phenotype. When normodense eosinophils from the reference donors were cultured for 3 days in medium supplemented with increasing concentrations of serum from the patients with EMS, their viability increased in a dose-dependent manner to 45%, which was significantly augmented over the effect of normal serum. This eosinophil viability-sustaining activity was inhibited by 76 +/- 7% (mean +/- SEM; n = 3) by the addition of anti-interleukin 5 (IL-5) but not by neutralizing antibodies monospecific for either granulocyte/macrophage colony-stimulating factor (GM-CSF) or IL-3. IL-5, an eosinophilopoietic factor, converts normodense peripheral blood eosinophils in vitro to a hypodense sedimenting form with extended viability and augmented biologic responses to activating stimuli. Thus, the presence of IL-5 in the sera of patients with EMS may contribute to the development and maintenance of the eosinophilia and may regulate the conversion of the peripheral blood eosinophils to the hypodense phenotype with augmented pathobiologic potential.

Antibodies↗

A survey of the dental health of the workers on two groups of offshore installations.

The study of the medical evacuation records from offshore installation workers indicated that dental pathology may be a significant problem. This investigation was set up to gather more accurate information. The intention was to examine the mouths of as many of the workforce as possible. This covered both day and night shifts and both tours of duty. The examinees numbered 493 out of an offshore population of 967. Half of the examinees attended the dentist regularly. Eight per cent of those examined had been evacuated for dental reasons. Thirty-six per cent were in the authors' high or medium occupational risk groups. There are opportunities for action to be taken to improve the situation.

Adult↗