Biomedical subjects
D Alexander
Publications and source records attributed to D Alexander.
Is fatal pancreatitis a consequence of excessive leukocyte stimulation? The role of tumor necrosis factor alpha.
This study examines the possible role of excessive leukocyte stimulation in the pathogenesis of acute pancreatitis. Levels of tumor necrosis factor alpha (TNF-alpha) and elastase-alpha 1 proteinase inhibitor (E-alpha 1PI) have been measured as markers of macrophage and neutrophil activation, respectively, in serial plasma samples from 27 patients with acute pancreatitis. Levels of TNF-alpha did not support the possibility of excessive macrophage activation, but raised levels of E-alpha 1PI in patients with either the mild or severe form of the illness indicated the activation of neutrophils. Whether this is a consequence of the illness or is a contributory factor in the pathogenesis is not clear.
Strenuous exercise: analogous to the acute-phase response?
1. It has been suggested that the physiological consequences of strenuous exercise are analogous to those of the acute-phase response. 2. In 70 male and 20 female competitive distance runners, a marked, but transient, neutrophil leucocytosis occurred immediately after these athletes completed a standard (42 km) marathon race. Concomitant significant increases were noted in the plasma cortisol levels, creatine kinase activity, C-reactive protein level, total protein level and albumin level (P less than 0.01). 3. The plasma fibrinogen, C-reactive protein and total protein concentrations were markedly increased both 24 h and 48 h after exercise (P less than 0.01). The serum haptoglobin level was significantly decreased after exercise (P less than 0.01), and increased 48 h later (P less than 0.05). There was no change in the serum iron level, total iron-binding capacity, per cent saturation of transferrin and serum ferritin level. 4. A significant increase in interleukin-1-type activity was demonstrated immediately and 24 h after exercise (P less than 0.01). 5. It is concluded that the metabolic sequelae of sustained exercise are similar, but not analogous, to the acute-phase response, and interleukin-1, probably plays a significant role in linking the haematological and immunological changes observed after sustained strenuous exercise.
AIDS education for labor and management: category III workers.
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The effect of two new immunosuppressive agents, FK506 and didemnin B, in murine pregnancy.
The purpose of this study was to investigate two promising immunosuppressive agents, didemnin B (DB) and FK506 (FK), during pregnancy to assess potential adverse maternal or fetal effects. Pregnant C3H mice were randomized into control and high- and low-dose treatment groups for each drug. Animals received daily injections from day 1 to day 16, and on day 17 of gestation the maternal condition, litter size, fetal resorption rates, and fetal/placental unit weights were determined. Immunoglobulin (IgG) levels were obtained for DB treatment groups. Delayed type hypersensitivity was assessed in virgin females. Both DB and FK had dose-dependent immunosuppressive activity in the DTH assay, and DB caused elevated IgG concentrations. High doses of DB caused diarrhea and maternal wasting with no fetal survival; with low-dose DB, maternal weight gain was depressed, but pregnancy outcome was not different from control animals. High-dose FK had no obvious detrimental effects on maternal health but caused resorption of all fetuses; administration of low-dose FK resulted in a higher number of resorptions, but fetuses that survived did not appear different from controls. We conclude that these immunosuppressive drugs can have adverse effects on pregnancy, but the maternal and fetal toxicity are dose-dependent.
Alpha 2 macroglobulin state in acute pancreatitis. Raised values of alpha 2 macroglobulin-protease complexes in severe and mild attacks.
Plasma values of C reactive protein, alpha 1 proteinase inhibitor, alpha 2 macroglobulin, and complexed alpha 2 macroglobulin have been determined in serial samples from 27 patients with acute pancreatitis. Complexed alpha 2 macroglobulin was measured by a novel enzyme linked immunosorbent assay with a monoclonal antibody specific for the complexed form. Patients with severe illness had lower concentrations of total alpha 2 macroglobulin and higher concentrations of complexed alpha 2 macroglobulin than those with mild illness, and in the majority of severe attacks the abnormal amounts of complexed alpha 2 macroglobulin were present throughout the eight days of the study. The proportion of total alpha 2 macroglobulin in the uncomplexed form, however, was generally greater than 90%, and in 26% of the mild cases completely normal concentrations of uncomplexed alpha 2 macroglobulin (greater than 99% of total) were found throughout the eight days of the study. This suggests that exhaustion of alpha 2 macroglobulin in plasma is unlikely to be a major factor in the pathogenesis of acute pancreatitis.
Effect of otitis media on infrared tympanic thermometry.
This study was designed to determine if temperature readings using a new tympanic thermometer are affected by otitis media. These readings were also compared to a rectal or oral temperature. Eighty-four children with unilateral suppurative or non-suppurative otitis media diagnosed clinically by their pediatricians were enrolled in the study. Temperatures were measured in both ears using the Thermoscan PRO-1 Instant Thermometer and rectally or orally by a glass or electronic predictive thermometer. For 67 children with unilateral suppurative otitis media the mean temperature in infected ears was 0.38 degrees Fahrenheit higher than in uninfected ears (p = .005). Neither temperatures measured in affected nor those from unaffected ears differed significantly from oral or rectal control readings. For 17 children with unilateral non-suppurative otitis media there was no statistically significant difference between temperatures in affected and unaffected ears or between the temperatures in either ear and the oral or rectal control. Our data show that temperatures taken in ears with suppurative otitis media are slightly higher than those in normal ears. This difference is of minimal clinical significance and does not affect the accuracy when compared to oral or rectal control readings.
Responses of children, parents, and nurses to tympanic thermometry in the pediatric office.
This study was designed to assess children's behavioral responses to tympanic thermometry. In addition, parents' and nurses' impressions of this new technology were evaluated. 224 patients were enrolled from three private pediatric practices. Patients were alternately assigned to have their temperature taken with either a tympanic thermometer or with a rectal or oral thermometer. Parents and nurses were then asked to fill out a short questionnaire to describe their observations of the child's behavior during temperature taking and to describe their own feelings about the temperature taking method used. Parents were also asked to assess their usual method of temperature taking at home and their child's usual behavioral response. Tympanic thermometry was rated higher by both parents and nurses for speed, ease, cleanliness, and safety. Parents and nurses were more confident in the accuracy of traditional temperature taking methods. Children whose temperatures were taken rectally were more likely to be observed by both parents (p = .02) and nurses (p = .01) to have a negative behavioral reaction to the procedure than children whose temperatures were taken by tympanic thermometry. There was no difference observed between the behavioral responses of children who had temperatures taken orally and those who had tympanic thermometry.
Cost effectiveness of tympanic thermometry in the pediatric office setting.
This study was designed to see if tympanic thermometry might be more cost effective than cheaper more traditional methods of thermometry when office staff time saved is taken into account. There were 224 patients enrolled from three private pediatric practices. Patients were alternately assigned to have their temperature taken with either a tympanic thermometer or with a rectal or oral thermometer depending on the patient's age. For each child enrolled in the study a nurse was asked to time the temperature taking process. Items included in the cost analysis: a) thermometer costs; b) disposable supply costs; c) personnel costs; d) equipment service costs. The mean duration of temperature taking was 35.2 seconds using tympanic thermometers, 73.4 seconds using electronic predictive thermometers, and 247.2 seconds using glass thermometers. In practices taking an average of 10 temperatures per day, tympanic thermometry saved $2,316/year when compared to glass thermometers and $442/year when compared to electronic predictive thermometers. The data presented in this study show that when nursing time is taken into account, tympanic thermometry is less expensive to perform than traditional methods of thermometry despite the initial higher cost of the thermometer.
Measurement of the 'fast' or complexed form of alpha 2 macroglobulin in biological fluids using a sandwich enzyme immunoassay.
A sandwich enzyme immunoassay has been developed for measuring the 'fast' or complexed form of alpha 2 macroglobulin using a complex-specific monoclonal antibody. The working range of this assay is 1.5-15 micrograms/l and is suitable for use with various biological fluids. Using this assay the normal plasma levels were found to range from 4.2 mg/l to 14.4 mg/l (0.17%-0.70% of total alpha 2 macroglobulin) with a mean value of 7.6 mg/l +/- 2.6 (0.37% +/- 0.12% of total alpha 2 macroglobulin). Elevated levels were seen in plasma samples taken on the day of admission from patients with acute pancreatitis and in some synovial fluid samples from patients with various arthritides.
Heterogeneity of protein kinase C expression and regulation in T lymphocytes.
The purpose of the present study was to examine protein kinase C (PKC) isotype expression in T lymphoblasts derived from peripheral blood and the T leukaemic cell Jurkat. Using antisera reactive with PKC alpha, beta 1, and beta 2 and gamma, it was observed that T cells expressed two PKC isotypes, PKC alpha and beta 1. No PKC gamma was detected in T lymphocytes. In lymphoblasts, high levels of PKC beta compared to PKC alpha were found whereas Jurkat cells expressed high levels of alpha compared to PKC beta. Differences in the calcium sensitivity of phorbol ester-induced phosphorylation were observed in Jurkat and T lymphoblasts which correlated with the relative levels of PKC alpha and beta isotypes expressed by the cells.
Lower Na(+)-H+ antiport activity in vascular smooth muscle cells of Wistar-Kyoto rats than spontaneously hypertensive and Wistar rats.
To determine whether increased Na(+)-H+ antiport activity in vascular smooth muscle cells may relate to the pathogenesis of hypertension in the spontaneously hypertensive rat (SHR), we monitored Na(+)-dependent alkalinization of acidified cells from the hypertensive strain and two normotensive controls, the Wistar-Kyoto rat (WKY) and the Wistar rat. Changes in intracellular pH (pHi) of cultured aortic cells were measured using the fluorescent probe 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF). The initial maximal reaction velocity of Na(+)-dependent alkalinization was significantly higher in SHR and Wistar than WKY cells. Similar results were obtained for the maximal velocity of the proton equivalent efflux: SHR, 7.51 +/- 0.71; Wistar, 9.14 +/- 0.85; WKY, 4.38 +/- 0.55 mmol H+/liter x 10 s. There were no differences in the basal pHi or cellular buffering power among the three rat strains. These findings indicate that the activity of the Na(+)-H+ antiport is higher in SHR vascular smooth muscle cells than in WKY cells. However, by itself, this difference cannot explain the hypertensive process in the SHR, since this transport system is also higher in vascular cells of the Wistar rat.
When nurses are addicted to drugs. Confronting an impaired co-worker.
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Dephosphorylation of the human T lymphocyte CD3 antigen.
Previous studies demonstrated that activation of T lymphocytes by phorbol ester or mitogenic lectin leads to phosphorylation of Ser 126 of the CD3 antigen gamma chain, whereas treatment with ionomycin results in phosphorylation of both Ser 123 and 126 [Davies, A. A. et al. (1987) J. Biol. Chem. 262, 10918-10921]. In the present study, the dephosphorylation of Ser 123 and Ser 126 of the gamma chain was investigated. Phorbol-ester-induced phosphorylation of the gamma-chain Ser 126 in vivo was reversed following removal of phorbol ester. Dephosphorylation of both Ser 123 and 126 was also observed in vitro using the microsome fraction of T lymphocytes. In order to identify the phosphatases acting at these two sites, the immunoprecipitated gamma chain was used as substrate either following treatment with protein kinase C in vitro, in which case phosphorylation occurs mainly at Ser 123, or following in vivo phosphorylation of Ser 126. Purified oligomeric forms of the polycation-stimulated phosphatases were more effective in dephosphorylating both phosphorylated forms of the gamma chain compared with equivalent amounts of ATP,Mg2+-dependent phosphatases or calcineurin. By using phosphopeptide analogues of the CD3 gamma chain containing Ser 123 or Ser 126 as substrates (A3 and A6), it was shown that polycation-stimulated phosphatases selectively dephosphorylated Ser 123 compared to Ser 126. In order to determine which phosphatases dephosphorylate the gamma chain in microsomes, A3 and A6 were used as substrates for characterising phosphatases in microsomes from human T leukaemia Jurkat 6 cells. Three phosphopeptide phosphatases (250-400 kDa) co-eluted through five purification steps with three forms of polycation-stimulated phosphorylase phosphatase. The partially purified A3/A6 phosphopeptide phosphatases were insensitive to Ca2+, calmodulin and inhibitor-1, and dephosphorylated A3 preferentially compared with A6. A latent form of microsomal ATP,Mg2+-dependent phosphorylase phosphatase was stimulated 10-fold by trypsinisation, but did not dephosphorylate phosphopeptides A3 and A6. The results show that high-Mr forms of polycation-stimulated phosphatases are the only enzymes in human T leukaemia cell microsomes which dephosphorylate gamma chain phosphopeptides. The data point to an important role for polycation-stimulated phosphatases in regulating the phosphorylation state, and so function(s), of the CD3 antigen.
Open forum. EMT/paramedic fitness.
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Levobunolol and betaxolol. A double-masked controlled comparison of efficacy and safety in patients with elevated intraocular pressure.
In a double-masked, randomized, controlled clinical trial, the authors evaluated the ocular hypotensive efficacy of twice-daily treatment with levobunolol (0.25 and 0.5%) and betaxolol (0.5%) in 85 patients with open-angle glaucoma or ocular hypertension. During the 3-month study, intraocular pressure (IOP) reductions in the two levobunolol groups were significantly greater than in the betaxolol group. From a mean baseline IOP of approximately 25 mmHg, overall mean reductions were 6.2 and 6.0 mmHg for the 0.25 and 0.5% levobunolol groups, respectively, and 3.7 mmHg for the betaxolol group. No clinically or statistically significant among-group differences were noted in the systemic safety variables evaluated. These data suggest that although all three treatments are effective, levobunolol provides a greater reduction in IOP than betaxolol.
Befrienders lend a helping hand.
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Distress and self-soothing bedtime behaviors in hospitalized children with non-rooming-in parents.
The nature of behaviors during sleep onset latency (SOL) at night bedtime was studied in a group of 40 hospitalized children ages 3 to 8 years whose parents did not room-in. Research questions were: (a) What is the nature of behaviors during sleep onset latency of young children whose parents do not room-in? and (b) How are these behaviors related to family structure, social status, age, gender, previous hospitalizations, and number of days hospitalized? Child subjects were observed using the Senders, Signals, and Receivers (SSR) computer-compatible system to measure SOL, distress, and self-soothing behaviors for 2-3 consecutive nights. The median falling asleep time was 26 minutes. Variations in SOL and self-soothing behaviors were not significantly related to family structure, social status, gender, age, length of hospitalization, night of hospitalization, or previous hospitalizations. Greater distress behaviors were, however, significantly related to children of two-parent families and those from middle social status.