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Biomedical subjects

M D Owen

Publications and source records attributed to M D Owen.

At least 19 recordsLinked to original sources

Ultraviolet radiation and the risks of cutaneous malignant melanoma and non-melanoma skin cancer: perceptions and behaviours of Danish and American adolescents.

The highest prevalence rates of skin malignancy in the northern hemisphere occur in Scandinavia and the United States (USA). Most Danes and Americans receive 50% of their lifetime ultraviolet (UV) radiation before the age of 21, making it important to address sun exposure risks with adolescents. The project was undertaken to determine differences between Danish and American adolescents in knowledge of sun exposure and skin malignancy, activities accounting for sun exposure, and means used for sun protection. Questionnaires regarding skin cancer and sun exposure were distributed to 674 secondary school age students in Hilleroed, Denmark, and to 483 similarly aged students in Winston-Salem, North Carolina, USA. Differences in responses between and within groups were compared. American adolescents had more knowledge of the characteristics and malignant potential of melanoma than did Danish adolescents. Danish youth and females from both countries were significantly more likely to engage in sunbathing and tanning bed use. Black Danish students reported significantly more sunburn and were more likely to sunbathe or use a tanning bed than were black American students. Danish students were more likely than Americans to use sunscreen, however, Americans were more likely to apply sun protective factor (SPF) 15 or greater. In conclusion, given that sunbathing and tanning bed use are associated with the development of precancerous lesions and skin malignancy, Danish teens are at increased risk. The rates of skin malignancy are relatively high in Scandinavia and efforts to improve understanding of exposure and cancer risks should be undertaken in adolescents.

Adolescent↗

Incidence and characteristics of failures in obstetric neuraxial analgesia and anesthesia: a retrospective analysis of 19,259 deliveries.

A retrospective analysis was performed on 19,259 deliveries that occurred in our institution from January 2000 to December 2002. Anesthesia records and quality assurance data sheets were reviewed for the characteristics and failure rates of neuraxial blocks performed for labor analgesia and anesthesia. The neuraxial labor analgesia rate was 75% and the overall failure rate was 12%. After adequate analgesia from initial placement, 6.8% of patients had subsequent inadequate analgesia during labor that required epidural catheter replacement. Ultimately 98.8% of all patients received adequate analgesia even though 1.5% of patients had multiple replacements. Six percent of epidural catheters had initial intravenous placement but 46% were made functional by simple manipulations without higher subsequent failure. Unintended dural puncture occurred in 1.2% of labor neuraxial analgesia. The incidences of overall failure, intravenous epidural catheter, wet tap, inadequate epidural analgesia and catheter replacement were lower in patients receiving combined spinal-epidural versus epidural analgesia. For cesarean section, 7.1% of pre-existing labor epidural catheters failed and 4.3% of patients required conversion to general anesthesia. Spinal anesthesia for cesarean section had a lower failure rate of 2.7%, with 1.2% of the patients requiring general anesthesia. The overall use of general anesthesia decreased from 8% to 4.3% over the three-year period. Furthermore, regional anesthesia was used in 93.5% of cesarean deliveries with no anesthetic-related mortalities. Future investigations should identify acceptable international standards, risk factors associated with failure and methods to reduce failure before cesarean section.

Adult↗

Low-dose clonidine and neostigmine prolong the duration of intrathecal bupivacaine-fentanyl for labor analgesia.

BACKGROUND: Intrathecal (IT) opioid and local anesthetic combinations are popular for labor analgesia because of rapid, effective pain relief, but the duration of analgesia is limited. This study was undertaken to determine whether the addition of clonidine and neostigmine to IT bupivacaine-fentanyl would increase the duration of analgesia without increasing side effects for patients in labor. METHODS: Forty-five healthy parturients in active labor were randomized to receive a 2-ml IT dose of one of the following dextrose-containing solutions using the combined spinal-epidural technique: (1) bupivacaine 2.5 mg and fentanyl 25 microg (BF); (2) BF plus clonidine 30 microg (BFC); or (3) BFC plus neostigmine 10 microg (BFCN). Pain, sensory levels, motor block, side effects, maternal vital signs, and fetal heart rate were systematically assessed. RESULTS: Patients administered BFCN had significantly longer analgesia (165+/-32 min) than those who received BF (90+/-21 min; P<0.001) or BFC (123+/-21 min; P<0.001). Pain scores, block characteristics, maternal vital signs, Apgar scores, maternal satisfaction, and side effects were similar among groups except for nausea, which was significantly greater in the BFCN group (P<0.05 as compared with BFC). CONCLUSIONS: The addition of clonidine and neostigmine significantly increased the duration of analgesia from IT bupivacaine-fentanyl during labor, but neostigmine caused more nausea. Although serious side effects were not observed in this study, safety must be further addressed before the routine use of multiple IT drugs is advocated.

Adjuvants, Anesthesia↗

Glycyl-glutamine inhibits the respiratory depression, but not the antinociception, produced by morphine.

Glycyl-glutamine (Gly-Gln; beta-endorphin(30-31)) is an endogenous dipeptide that is synthesized through the posttranslational processing of beta-endorphin in brain stem regions that control respiration and autonomic function. This study tested the hypothesis that Gly-Gln administration to conscious rats will prevent the respiratory depression caused by morphine without affecting morphine antinociception. Rats were administered Gly-Gln (1-100 nmol) or saline (10 microl) intracerebroventricularly followed, 5 min later, by morphine (40 nmol icv). Arterial blood gases and pH were measured immediately before Gly-Gln and 30 min after morphine injection. Gly-Gln pretreatment inhibited morphine-induced hypercapnia, hypoxia, and acidosis significantly. The response was dose dependent and significant at Gly-Gln doses as low as 1 nmol. In contrast, Gly-Gln (1-300 nmol) had no effect on morphine-evoked antinociception in the paw withdrawal test. When given alone to otherwise untreated animals, Gly-Gln did not affect nociceptive latencies or blood gas values. These data indicate that Gly-Gln inhibits morphine-induced respiratory depression without compromising morphine antinociception.

Acidosis↗

Ropivacaine.

Ropivacaine (Naropin, AstraZeneca) is a long-acting amide local anaesthetic released for clinical use in 1996. Similar to bupivacaine, ropivacaine is equally effective for s.c. infiltration, epidural and peripheral nerve block for surgery, obstetric and post-operative analgesia. Ropivacaine differs from most other amide-type local anaesthetics in that it is marketed as a pure S-enantiomer, instead of as a racemate. This feature improves the safety of ropivacaine, and, indeed, studies have shown ropivacaine to have less cardiovascular and CNS toxicity than bupivacaine. Ropivacaine is nearly identical to bupivacaine in onset, quality and duration of sensory block, but it produces less motor block. Whether or not the motor sparing effect of ropivacaine is due to a lower relative potency compared to bupivacaine is a matter of intense debate. Despite a better safety profile, the increased cost of ropivacaine may limit its clinical utility.

Amides↗

Effects of weed management systems on canopy insects in herbicide-resistant soybeans.

The effects of transgenic herbicide-resistant soybean varieties and their corresponding weed management strategies on canopy insects were examined in studies at two locations in Iowa in 1997 and 1998. Weed management systems that allowed more weed escapes typically had higher insect population densities. However, systems with fewer weeds seemingly were preferred by potato leafhoppers. Bean leaf beetles and potato leafhoppers showed preferences for certain soybean varieties, but these effects were attributed to soybean plant height. These findings indicate that although the transgenic soybean varieties did not strongly affect insect populations, weed management systems can affect insect populations in soybean. However, this impact is likely related more to weed suppression effectiveness than to a direct effect of the herbicides on the insects.

Animals↗

0.125% ropivacaine is similar to 0.125% bupivacaine for labor analgesia using patient-controlled epidural infusion.

UNLABELLED: We compared the effects of 0.125% ropivacaine with 0.125% bupivacaine in laboring patients using patient-controlled epidural analgesia (PCEA). Fifty-one ASA physical status I or II term parturients with functioning epidural catheters were randomized to receive ropivacaine or bupivacaine using a prospective, double-blind design. Basal infusions (6 mL/h) were supplemented with patient-controlled boluses (5 mL) every 10 min as required. For inadequate analgesia, patients were administered 10-mL boluses of study solution until comfortable. There were no differences in verbal pain scores, amount of local anesthetics used, sensory levels, motor blockade, labor duration, mode of delivery, side effects, or patient satisfaction between the two local anesthetics. We conclude that 0.125% ropivacaine and bupivacaine are clinically indistinguishable and are both highly effective for labor analgesia using PCEA. IMPLICATIONS: This study compared labor analgesia from 0.125% ropivacaine and 0.125% bupivacaine using patient-controlled epidural analgesia. We found no significant differences in local anesthetic use, analgesic characteristics, or side effects between 0.125% ropivacaine and 0.125% bupivacaine. We conclude that these two drugs are clinically indistinguishable at this concentration.

Adult↗

Cyclo(Gly-Gln) inhibits the cardiorespiratory depression produced by beta-endorphin and morphine.

Glycyl-L-glutamine (Gly-Gln; beta-endorphin 30-31) is an endogenous dipeptide that is synthesized through the post-translational processing of beta-endorphin. Previously, we showed that Gly-Gln inhibits the hypotension and respiratory depression produced by central beta-endorphin administration. In this study, we tested whether cyclo(Gly-Gln), a non-polar, cyclic Gly-Gln derivative, was similarly effective following intracerebro-ventricular (i.c.v.) or intra-arterial (i.a.) administration to pentobarbital-anesthetized rats pretreated with beta-endorphin (0.5 nmol i.c.v.). Intracerebroventricular cyclo(Gly-Gln) (0.3, 0.6 or 1.0 nmol) injection produced a dose-dependent inhibition of beta-endorphin-induced hypotension, but not bradycardia, with a potency similar to that of Gly-Gln. Cyclo(Gly-Gln) (5 mg/kg) was also effective following i.a. injection and significantly attenuated the fall in arterial pressure elicited by i.c.v. beta-endorphin, consistent with evidence that cyclic dipeptides permeate the blood-brain barrier; i.a. Gly-Gln was ineffective. Intra-arterial cyclo(Gly-Gln) (5 mg/kg) and i.c.v. Gly-Gln (10 nmol) also attenuated the hypotension and respiratory depression induced by morphine (50 or 100 nmol i.c.v.). Cyclo(Gly-Gln) (0.5, 5.0 or 50.0 mg/kg i.a.) had no effect on arterial pressure or heart rate when given alone. These findings indicate that cyclo(Gly-Gln) is a biologically active peptide capable of reversing the cardiorespiratory depression produced by beta-endorphin or morphine.

Animals↗

Postoperative analgesia using a low-dose, oral-transdermal clonidine combination: lack of clinical efficacy.

STUDY OBJECTIVE: To determine if a lower than previously reported oral-transdermal clonidine regimen could reduce postoperative morphine requirements without producing systemic side effects. DESIGN: Double-blind, randomized, placebo-controlled study. SETTING: University-affiliated hospital. PATIENTS: 29 healthy, ASA physical status I and II females undergoing elective abdominal hysterectomy. INTERVENTIONS: Patients received preoperative oral clonidine 4 to 5 mu/kg and a 7 cm2 transdermal clonidine patch (0.2 mg/24 hours) or a placebo tablet and patch. MEASUREMENTS AND MAIN RESULTS: Postoperative patient-controlled analgesia pumps provided morphine during the 48-hour study period. Morphine use, hemodynamic changes, and nonhemodynamic side effects were recorded. Additionally, visual analog pain scales (VAPS) and plasma concentrations of morphine and clonidine were measured. We found that low-dose clonidine had no potentiating effect on morphine analgesia. Postoperative morphine use, VAPS, and morphine plasma levels were similar between the control and clonidine-treated groups. Nevertheless, patients in the clonidine group experienced a significantly greater incidence of intraoperative and postoperative hypotension and bradycardia than did the control group. No differences were noted in the incidence of nonhemodynamic side effects. CONCLUSIONS: The low-dose oral-transdermal clonidine regimen evaluated failed to reduce postoperative morphine requirements, although patients who received clonidine were still at risk for developing hypotension.

Administration, Cutaneous↗

Studies on the safety of glucose and paraben-containing neostigmine for intrathecal administration.

Initial toxicity testing of neostigmine for intrathecal (IT) injection was performed with preservative-free isobaric solution, yet currently available formulations contain the preservatives methyl- and propylparaben and are usually mixed with glucose to yield hyperbaric solutions. Since it has been proposed that preservatives and hyperbaricity increase the risk of neurotoxicity after IT injection, we examined the safety of chronically administered IT neostigmine containing these additives in sheep and rats. Rats receiving daily IT injections of glucose alone or of glucose with preservative-containing neostigmine, 5 and 10 microg, exhibited dose-related antinociception, tremor, and rigidity. In comparison to our previously published study of neostigmine injection in solution without glucose, rats receiving IT neostigmine with glucose displayed less rigidity, tremor, and salivation. Sheep receiving daily injection of glucose alone or with preservative-containing neostigmine, 1 mg, for 14 days exhibited no histologic evidence of neurotoxicity, nor did they exhibit abnormalities in cerebrospinal fluid chemistry aside from those caused by inflammation. Spinal cord histologic examination in both species revealed fibrosis and inflammation secondary to the catheter without evidence of neuronal damage. These studies support the safety of paraben- and glucose-containing IT neostigmine.

Analgesia, Epidural↗

Glycyl-L-glutamine [beta-endorphin-(30-31)] attenuates hemorrhagic hypotension in conscious rats.

The profound hypotension caused by acute hemorrhage is thought to involve opioid peptide neurons. In this study, we tested whether glycyl-L-glutamine [Gly-Gln; beta-endorphin-(30-31)], a nonopioid peptide derived from beta-endorphin processing, prevents the cardiovascular depression induced by hemorrhage in conscious and anesthetized rats. Previously, we found that Gly-Gln inhibits the hypotension and respiratory depression produced by beta-endorphin and morphine but does not affect opioid antinociception. Hemorrhage (2.5 ml/100 g body wt over 20 min) lowered arterial pressure in conscious rats (from 120.1 +/- 2.9 to 56.2 +/- 4.7 mmHg) but did not change heart rate significantly. Intracerebroventricular Gly-Gln (3, 10, or 30 nmol) pretreatment inhibited the fall in arterial pressure and increased heart rate significantly. The response was dose related and was sustained during the 35-min posthemorrhage interval. Pentobarbital sodium anesthesia potentiated the hemodynamic response to hemorrhage and attenuated the effect of Gly-Gln. Gly-Gln (10 or 100 nmol icv) did not influence arterial pressure or heart rate in normotensive rats. These data indicate that Gly-Gln is an effective antagonist of hemorrhagic hypotension.

Animals↗

Tyrosine hydroxylase in the cerebral ganglia of the American cockroach (Periplaneta americana L.): an immunohistochemical study.

We have investigated the distribution of tyrosine-hydroxylase-like immunoreactivity in the cerebral ganglia of the American cockroach, Periplaneta americana. Groups of tyrosine-hydroxylase-immunoreactive cell bodies occur in various parts of the three regions of the cerebral ganglia. In the protocerebrum, single large neurons or small groups of neurons are located in the lateral neuropil, adjacent to the calyces, and in the dorsal portion of the pars intercerebralis. Small scattered cell bodies are found in the outer layers of the optic lobe, and clusters of larger cell bodies can be found in the deutocerebrum, medial and lateral to the antennal glomeruli. Thick bundles of tyrosine-hydroxylase-positive nerve fibers traverse the neuropil in the proto- and deutocerebrum and innervate the glomerular and the non-glomerular neuropil with fine varicose terminals. Dense terminal patterns are present in the medulla and lobula of the optic lobe, the pars intercerebralis, the medial tritocerebrum, and the area surrounding the antennal glomeruli, the central body and the mushroom bodies. The pattern of tyrosine-hydroxylase-like immunoreactivity is similar to that previously described for catecholaminergic neurons, but it is distinctly different from the distribution of histaminergic and serotonergic neurons.

Animals↗

Melittin synthesis in the venom system of the honey bee (Apis mellifera L.).

The amount of melittin (measured by a direct hemolytic assay) contained in the venom system of single honey bees (Apis mellifera), of known age, increases from the time of eclosion to an age of about 4 weeks when about 500 micrograms of melittin is present. In older bees (5-6 weeks) the melittin level falls to about 250 micrograms. Measurements of the incorporation of [3H]leucine (injected into the haemolymph) into melittin show that melittin synthesis is most active in bees aged between 1 and 2 weeks after eclosion. The melittin content of the venom system changes as the summer progresses. Melittin levels in a bee of any age greater than 1 week are lower in mid-August than in a bee of the same age in early June.

Animals↗

Beta-endorphin-induced cardiorespiratory depression is inhibited by glycyl-L-glutamine, a dipeptide derived from beta-endorphin processing.

Glycyl-L-glutamine (Gly-L-Gln), or beta-endorphin-(30-31) [beta-End-(30-31)], is synthesized through the post-translational processing of beta-End-(1-31). Evidence that gly-L-gln is a prominent end product of beta-End-(1-31) processing in cardioregulatory regions of rat brain prompted us to investigate whether it modulates the cardiorespiratory depression induced by central beta-End-(1-31) injection. As shown previously, beta-End-(1-31) (0.5 nmol) lowered mean arterial pressure (MAP) and HR when administered i.c.v. to pentobarbital-anesthetized rats. Gly-L-gln (0.3, 0.6, 1.0 and 10.0 nmol) produced a dose-related inhibition of beta-End-(1-31)-induced hypotension, but not bradycardia, when injected i.c.v. 15 min after beta-End-(1-31). This effect was not attributable to hydrolysis, because equimolar amounts of L-glycine and L-glutamine were ineffective. A comparable response was observed when gly-L-gln was administered to urethane-anesthetized rats and when it was injected before beta-End-(1-31). Gly-L-gln also attenuated the respiratory depressant effect of beta-End-(1-31), significantly inhibiting beta-End-(1-31)-induced hypoxia and hypercapnia. Gly-L-gln (1, 10 and 100 nmol) was inactive when injected alone, however, and produced no significant variation from base-line MAP or HR values. These results demonstrate that gly-L-gln inhibits beta-End-(1-31)-induced cardiorespiratory depression, consistent with accumulating evidence that gly-L-gln functions as a neuromodulator.

Animals↗

Phospholipase A2 in venom extracts from honey bees (Apis mellifera L.) of different ages.

We measured phospholipase A2 activity in the venom of worker honey bees (Apis mellifera L.) of known ages using chemical (titrimetric) and radioallergosorbent methods. The two techniques give similar results. Low levels of phospholipase A2 are present in the venom system at the time of eclosion. Phospholipase A2 activity in the venom increases steadily through the 10 days after eclosion. Maximal phospholipase A2 levels (about 40 micrograms phospholipase A2/venom sac) are maintained through the rest of the life of a worker bee in summer.

Aging↗

Effect of cerebrospinal fluid hyperosmolality on sweating in the heat-stressed patas monkey.

Dehydration increases the osmolality of body fluids and decreases the rate of sweating during thermal stress. By localizing osmotic stimuli to central nervous system tissues, this study assessed the role of central stimulation on sweating in a heat-stressed nonhuman primate. Lenperone-tranquilized patas monkeys (Erythrocebus patas n = 5), exposed to 41 +/- 2 degrees C, were monitored for calf sweat rate, rectal and mean skin temperatures, oxygen consumption, and heart rate during infusions (255-413 microliters) of hypertonic artificial cerebrospinal fluid (ACSF) into the third cerebral ventricle. ACSF made hypertonic with NaCl to yield osmolalities of 800 and 1,000 mosmol/kgH2O significantly decreased sweat rate compared with control ACSF (285 mosmol/kgH2O), achieving maximal reductions during infusion of 37 and 53%, respectively. Rectal temperature significantly increased during the recovery period, reaching elevations of 0.69 and 0.72 degrees C, respectively, at 20 min postinfusion. In contrast, ACSF made hypertonic with sucrose (800 mosmol/kgH2O) failed to change sweat rate or rectal temperature during infusion in three animals. Thus, intracerebroventricular infusions of hypertonic ACSF mimicked dehydration-induced effects on thermoregulation. The reduction in heat loss during infusion appeared to depend on an elevation in cerebrospinal fluid [Na+] and not osmolality per se.

Animals↗

Effects of CSF ANG II and AVP on sweating in the heat-stressed patas monkey.

Increasing cerebrospinal fluid [Na+] reduces sweat rate (msw) in the heat-stressed patas monkey (Erythrocebus patas). This study determined the potential role of two neuropeptides, angiotensin II (ANG II) and arginine vasopressin (AVP), in mediating this response. Artificial cerebrospinal fluid, containing either ANG II or AVP, was infused into the third cerebral ventricle of lenperone-tranquilized monkeys (n = 4) exposed to 41 +/- 2 degrees C. Solutions were infused at 16.5 microliters/min for 25 min (total vol approximately 413 microliters). ANG II (1.25, 2.5, 5, and 10 ng/microliters) tended to decrease .msw. However, during infusion, only the decline at 10 min associated with the 1.25-ng/microliters dose (26%) was different (P less than 0.004) from control. This dose elevated (P less than 0.004) core rectal temperature by 1.14 degrees C at 20 min postinfusion. In contrast, AVP (0.5 and 1.5 micrograms/microliters artificial cerebrospinal fluid) had no significant effect on .msw compared with control infusions. Both doses of AVP produced a slight but significant increase in rectal temperature of 0.14 and 0.22 degrees C, respectively, at 20 min postinfusion. In conclusion, the magnitude and time course of the change in .msw with central ANG II suggest that it does not act as the sole mediator of the decline in .msw observed with elevated cerebrospinal fluid [Na+]. The minimal effects produced by third ventricular AVP exclude this route as a means by which AVP could modulate .msw during dehydration.

Angiotensin II↗

5-Hydroxytryptamine in the venom of the honey bee (Apis mellifera L.): variation with season and with insect age.

We used liquid chromatography with electrochemical detection to show that 5-HT is present in the venom of worker honey bees (Apis mellifera L.). Immunohistochemical demonstration of 5-HT-like immunoreactivity within the venom reservoir supports this finding. Measurements were made on bees of known age at various times during the summer season. The amount of 5-HT in the venom system varies with the age of the bee and with the time of year at which the bees reached a specific age. 5-HT is shown to be a component of pure venom, rather than simply present in venom gland and reservoir tissues, by its presence in venom collected by electrical 'milking' of worker bees.

Age Factors↗