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Biomedical subjects

A Costello

Publications and source records attributed to A Costello.

At least 55 records · Page 3Linked to original sources

Prehospital thrombolysis in a rural community: short- and long-term survival.

In order to assess the feasibility and outcome of using prehospital thrombolysis in acute myocardial infarction in a rural community, we performed an open randomized study of patients with symptoms of acute myocardial infarction of less than 6 hours. One hundred and forty-five patients with acute myocardial infarction were allocated to receive IV streptokinase prehospital by means of a mobile coronary care unit (MCCU) (n = 43) or to receive IV streptokinase in hospital (n = 102). The mean delay time to treatment was 138 minutes (MCCU group) and 172 minutes (hospital group) (p less than 0.02). Reperfusion time was 88 minutes for the MCCU group and 92 minutes for the hospital group. Mortality at 14 days was 2.3% for the MCCU group and 11.7% for the hospital group (p less than 0.05). Six month mortality was 4.9% for the MCCU group and 17.3% for the hospital group (p = 0.03). Mortality at 1 year was 6.1% for the MCCU group and 20.0% for the hospital group (p = 0.04). There were no significant adverse events in either treatment group. Thus, prehospital thrombolysis by streptokinase is feasible and allows significant reduction in the delay time to treatment initiation. There are encouraging improvements in both short- and long-term survival with no apparent reduction in safety profile.

Adult↗

Lithotripsy for kidney stones.

Extracorporeal Shock Wave Lithotripsy or extracorporeal lithotripsy has become the preferred method of treatment for most renal calculi. Since its introduction in 1980 in Munich, Germany, over 3 million patients worldwide have been treated on more than 1100 machines, using a variety of shock-wave generators to disintegrate kidney stones.

Humans↗

Predicting cognitive recovery from closed head-injury in children and adolescents.

Longitudinal data from 84 head-injured children and adolescents, who were tested at three points in the first year postinjury, were analyzed to determine the best combination of demographic, injury-related, and behavioral factors predicting cognitive performance. Dependent variables were language, memory, visuomotor, and speeded performance factor scores obtained through confirmatory factor analyses of an extensive test battery. Multiple regression analyses indicated that injury severity and the existence of previous psychological, physical, or cognitive disorders were primary for predicting acute (1 month post-hospital discharge) performance for older subjects. For younger subjects, however, parental marital status was the most important correlate of acute cognitive performance. Those residing in homes with both parents fared better than children in one-parent families. At 6 months and 1 year postinjury, the older subjects who performed most poorly initially remained the most impaired. For younger children, acute cognitive standing was also an important predictor of later performance, but parental marital status remained a crucial influence on their longer-term recovery of cognitive skills.

Adolescent↗

Glucocorticoids suppress levels of immunoreactive bradykinin in inflamed tissue as evaluated by microdialysis probes.

Although circulating bradykinin increases during surgery, concentrations remain unknown in the biologically relevant compartment, the inflamed tissue. We have developed a new method, using microdialysis probes, for collecting tissue samples of immunoreactive bradykinin in both postoperative patients and rats injected with carrageenan. In vitro studies determined optimal flow rate, that dialysate levels of immunoreactive bradykinin were linearly related to external concentrations, and that the probes do not activate bradykinin synthesis. In oral surgery patients, tissue levels of immunoreactive bradykinin peaked approximately 3 hours after surgery. Preoperative administration of methylprednisolone (125 mg) reduced immunoreactive bradykinin levels by 62% (p less than 0.001) compared with placebo. Comparison of bradykinin levels to concurrent pain revealed a counterclockwise hysteresis, suggesting a delay between peak levels of bradykinin in the effect compartment and pain. In rats, dexamethasone suppressed tissue levels of immunoreactive bradykinin. The glucocorticoid suppression was dependent on de novo protein synthesis. Microdialysis appears to be a novel and useful method for measuring the peripheral release of bradykinin and, possibly, other inflammatory mediators.

Animals↗

Neuropsychology.

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Brain↗

Cyclic AMP inhibits the synthesis and release of prolactin from human decidual cells.

Exposure of human decidual cells for 0.5 h to dibutyryl cAMP, isobutyl-methylxanthine (IBMX), cholera toxin or forskolin caused a dose-dependent inhibition of prolactin release with maximal inhibition by each agent of 50-60%. Dibutyryl cAMP (5 mM), IBMX (0.5 mM), and cholera toxin (10 micrograms/ml) also inhibited prolactin synthesis to the same extent as prolactin release. Dibutyryl cAMP, IBMX, and cholera toxin, however, had no effect on the release of 35S-methionyl-prolactin from decidual cells preincubated for 24 h in medium with 35S-methionine. These agents, however, had no effects on the synthesis or release of TCA-precipitable 35S-decidual proteins and did not cause the degradation of intracellular or released prolactin. The demonstration that agents which increase intracellular cAMP levels inhibit the synthesis and release of decidual prolactin strongly implicates cAMP as a second messenger in the regulation of the synthesis and release of the hormone. The inhibitory effect of cAMP on prolactin release appears to be on the release from a rapidly releasable, newly synthesized intracellular prolactin pool.

1-Methyl-3-isobutylxanthine↗

Cyclic adenosine-3',5'-monophosphate stimulates the acute release of placental lactogen from human trophoblast cells.

cAMP has been shown to be a second messenger in the release of many hormones and other secretory products. To determine whether cAMP also plays a role in the mechanism of release of human placental lactogen (hPL), we examined the effects of (Bu)2cAMP, isobutyl methylxanthine, forskolin, and cholera toxin on the acute release of hPL from an enriched fraction of hPL-producing trophoblast cells. Static cultures of trophoblast cells exposed to (Bu)2cAMP (5 mM) for 2 h released 2.6 times as much hPL as control cells (P less than 0.01) during the first 0.5 h of exposure. The increase in hPL release was followed by a decrease rate of release during the subsequent 1.5 h. Perifused trophoblast cells (1.5 X 10(6) exposed to 5 mM cAMP for 20 min released 3.2 times as much hPL as control cells. The rate of hPL increased markedly during the first 10 min of exposure, rapidly decreased toward control values during the remainder of the exposure period, and then declined to a subnormal rate for the next 30 min before returning to normal to control values. (Bu)2cAMP, however, had no acute effects on the release of human CG or the release of the cytosolic enzymes alkaline phosphatase and lactic dehydrogenase. The phosphodiesterase inhibitors theophylline (5 mM) and isobutyl methylxanthine (0.5 mM) and the adenylate cyclase activators forskolin (5 micrograms/ml) and cholera toxin (25 micrograms/ml) stimulated hPL release by 75-95%. These results strongly suggest that cAMP is a second messenger in the acute release of hPL.

1-Methyl-3-isobutylxanthine↗

Activation of protein kinase C inhibits synthesis and release of decidual prolactin.

Activation of calcium-activated, phospholipid-dependent protein kinase C by diacylglycerol and phorbol esters has been shown to mediate release of hormones in many systems. To determine whether protein kinase C activation is also involved in the regulation of prolactin release from human decidua, we have examined the effects of various acylglycerols and phorbol esters on the synthesis and release of prolactin from cultured human decidual cells. sn-1,2-Dioctanoylglycerol (diC8), which is known to stimulate protein kinase C in other systems, inhibited prolactin release in a dose-dependent manner with maximal inhibition of 53.1% (P less than 0.01) at 100 microM. Diolein (100 microM), which also stimulates protein kinase C activity in some systems, inhibited prolactin release by 21.3% (P less than 0.05). Distearin and dipalmitin, which are much less effective in activating protein kinase C, and monopalmitin and tripalmitin, which do not activate protein kinase C, had no significant effect on prolactin release. Phorbol 12-myristate 13-acetate (PMA), phorbol 12,13-didecanoate, and 4 beta-phorbol 12,13-dibutyrate, which activate protein kinase C in other systems, also inhibited the release of prolactin, while the protein kinase C inactivate 4 alpha-phorbol-12,13-didecanoate was without effect. The inhibition of prolactin release was secondary to a decrease in prolactin synthesis. The amounts of prolactin synthesized by cells exposed to diC8 (300 microM) or PMA (10(-7) M) for 30 min were 56.3 and 50.0% less than that synthesized by control cells (P less than 0.01 in each instance).(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗

Characterization of placental lactogen release from perifused human trophoblast cells.

The dynamics of the release of human placental lactogen (hPL) under basal conditions and response to various secretogogues has been studied in perifused enriched hPL-producing cells from term placentae prepared by the isopycnic centrifugation of collagenase/hyaluronidase-dispersed placental cells on Percoll gradients. Under basal conditions, the perifused cells released hPL at a relatively constant rate for up to 24 h in culture. The mean rates of hPL release from cells (5 x 10(6) cells) from 18 normal full-term placentae varied from 1.8 to 20.2 ng/5 min (mean 7.7 ng/5 min). The cells from term placentae, however, did not release detectable amounts of chorionic gonadotrophin or the cytosolic enzymes lactic dehydrogenase and alkaline phosphatase. The amounts of hPL released by the perifused cells were inversely related to cell density with mean rates of hPL release by 2, 5, and 10 x 10(6) cells of 15.8, 8.6, and 5.7 ng/10(6) cells/0.5 h. The perifused cells responded to provocative stimuli (high-density lipoproteins (HDL), apolipoproteins AI, AII, and CI, partially purified hPL-releasing factor, phorbol esters, sn-1,2-diacylglycerol, and cAMP) in a manner qualitatively similar to enriched trophoblast cells and placental explants in static culture. Release of hPL in response to HDL, apoproteins AI, AII, and CI, and partially purified hPL-releasing factor was dose-dependent and occurred within 5 min of exposure. Basal and stimulated hPL release by perifused trophoblast cells that had been previously frozen at -70 degrees C for four weeks was identical to that of freshly dispersed cells from the same placenta. These experiments indicate that perifused trophoblast cells may be used as a model system to examine the dynamics of hPL release under basal conditions and in response to provocative stimuli.

Cells, Cultured↗

Considering the impact of medicine label design characteristics on patient safety.

Medication errors involving patients receiving the wrong medicines, the wrong dosages or failure to take medicines according to the prescribed schedule are a substantial threat to patient safety. In the medical domain, research evidence on the benefits of improved labelling are piecemeal and often single-product or single-manufacturer driven and often do not inform the more general process of label design. Government and other guidelines on this topic are often low level and non-specific, often failing to give evidence-based guidance. However, there is a wealth of evidence-based research findings in related areas such as food labelling, chemical labelling and more general warnings research, which can provide systematic evidence on the effects of design characteristics such as font size, colour, signal words and linguistic usage on crucial performance variables such as compliance, understandability and discriminability. This research is reviewed and its relevance to medicine labelling is presented.

Color↗

Nutritional status and age at menarche in a rural area of Bangladesh.

The age at menarche and its association with nutritional status in a rural area of Bangladesh was determined. A cross-sectional study was conducted in four villages of Rupganj Thana of Narayanganj district. Data was collected through October to December 1996 using a pre-tested structured questionnaire interview schedule, and nutritional status was measured by weight, height, body mass index (BMI) and physical examination. Data were obtained on 436 adolescent girls aged 10-17 years. Among them, 165 (37.8%) girls had commenced menarche. The mean age at menarche as determined by retrospective recall was 13 years SD 0.89 (n = 165). The median age at menarche determined by the status quo method was 13.0. Among the adolescents 60.1% were thin (BMI < 5th centile WHO recommended reference) and 48.2% were stunted (< 3rd centile NCHS/WHO). The mean weight and BMI were significantly higher among the menstruating girls of 13, 14 and 15 years (p < 0.01) than non-menstruating girls. The mean height was found to be significantly higher at 11-14 years among the menstruating girls (p < 0.05). A lower prevalence of angular stomatitis was found among the menstruating adolescent girls compared with the non-menstruating girls, 36.4% versus 46.5%, although this was statistically non-significant (odds ratio = 0.66, 95% CI 0.43-1.00). For glossitis, no significant difference was found. Among the menstruating girls 12.1% were suffering from menorrhagia and 31.5% from dysmenorrhoea. We conclude that the age of menarche among this rural Bangladeshi community is not as delayed as expected. Not surprisingly, menarche is associated with better nutritional status. The surveyed population had extremely high rates of undernutrition which suggests that adolescents in this and similar situations require specific intervention programmes to improve their nutritional status.

Adolescent↗