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Biomedical subjects

J R Owen

Publications and source records attributed to J R Owen.

At least 19 recordsLinked to original sources

5-HT activates vagal afferent cell bodies in vivo: role of 5-HT2 and 5-HT3 receptors.

Occipital artery (OA) injections of 5-HT elicit pronounced reductions in heart rate and mean arterial blood pressure (MAP) in urethane-anesthetized rats by activation of vagal afferent cell bodies in the ipsilateral nodose ganglion. In contrast, internal carotid artery (ICA) and i.v. injections elicit similar cardiovascular responses by activation of peripheral vagal afferent terminals. The aim of this study was to examine the roles of 5-HT3 and 5-HT2 receptors in the 5-HT-induced activation of vagal afferent cell bodies and peripheral afferent terminals in urethane-anesthetized rats. OA, ICA and i.v. injections of 5-HT elicited dose-dependent reductions in heart rate and MAP that were virtually abolished after i.v. administration of the 5-HT3 receptor antagonists, MDL 7222 or ICS 205-930. The responses elicited by the OA injections of 5-HT were markedly diminished after i.v. injection of the 5-HT2 receptor antagonists, xylamidine or ketanserin, whereas the responses elicited by i.v. or ICA injections of 5-HT were not affected. The present findings suggest that (1) 5-HT3 and 5-HT2 receptor antagonists gain ready access to nodose ganglion cells upon i.v. administration, and (2) functional 5-HT3 and 5-HT2 receptors exist on the cell bodies of vagal afferent neurons mediating the cardiovascular responses elicited by OA injections of 5-HT. These findings also support a wealth of evidence that 5-HT3 receptors exist on the peripheral terminals of vagal afferents, and although they do not discount the possibility that 5-HT2 receptors exist on peripheral vagal afferent terminals, it appears that activation of these receptors does not have pronounced effects on 5-HT3 receptor activity on terminals that mediate the hemodynamic responses to 5-HT.

Analysis of Variance↗

Occipital artery injections of 5-HT may directly activate the cell bodies of vagal and glossopharyngeal afferent cell bodies in the rat.

The primary objective of this study was to determine whether circulating factors gain direct access to and affect the activity of vagal afferent cell bodies in the nodose ganglia and glossopharyngeal afferents cell bodies in the petrosal ganglia, of the rat. We found that the occipital and internal carotid arteries provided the sole blood supply to the nodose ganglia, and that i.v. injections of the tracer, Basic Blue 9, elicited strong cytoplasmic staining in vagal and glossopharyngeal afferent cell bodies that was prevented by prior ligation of the occipital but not the internal carotid arteries. We also found that occipital artery injections of 5-HT elicited pronounced dose-dependent reductions in heart rate and diastolic arterial blood pressure that were (1) virtually abolished after application of the local anesthetic, procaine, to the ipsilateral nodose and petrosal ganglia, (2) markedly attenuated after transection of the ipsilateral vagus between the nodose ganglion and brain and virtually abolished after subsequent transection of the ipsilateral glossopharyngeal nerve between the petrosal ganglion and the brain, (3) augmented after ipsilateral transection of the aortic depressor and carotid sinus nerves, and (4) augmented after transection of all ipsilateral glossopharyngeal and vagal afferent nerves except for vagal cardiopulmonary afferents. These findings suggest that blood-borne 5-HT in the occipital artery gains direct access to and activates the cell bodies of vagal cardiopulmonary afferents of the rat and glossopharyngeal afferents of undetermined modalities.

Analysis of Variance↗

Influence of a superficial tangential zone over repairing cartilage defects: implications for tissue engineering.

The superficial tangential zone (STZ) plays a critical role in normal cartilage function but is not yet a focus for designing tissue-engineered constructs for cartilage repair. Without material properties of sufficient quality in this zone, transplanted constructs in vivo may have little chance of survival. This finite element study investigates the impact of the superficial tangential zone on the mechanical function of normal articular surfaces as well as those with transplanted constructs. The zone is modeled as a thin transversely isotropic material with strain dependent permeability. The analyses predict that a normal transversely isotropic STZ placed over a repair region reduces the axial compression (55-68%) of, and the rate of fluid loss (45-82%) from the articular surface. A reduction was also found in von Mises stress (26-57%), axial strain (22-56%), and radial strain (69-73%), and an increase in fluid pressure (19-45%) in repair tissue under the STZ. Incorporating a quality superficial tangential zone in tissue-engineered constructs may be a critical factor in achieving mechanical environments conducive for successful cartilage repairs.

Animals↗

Optimal planning target volume for stage I testicular seminoma: A Medical Research Council randomized trial. Medical Research Council Testicular Tumor Working Group.

PURPOSE: To compare relapse rates and toxicity associated with para-aortic (PA) strip or PA and ipsilateral iliac lymph node irradiation (dogleg [DL] field) (30 Gy/15 fractions/3 weeks) for stage I testicular seminoma. PATIENTS AND METHODS: Between July 1989 and May 1993, 478 men with testicular seminoma stage I (T1 to T3; no ipsilateral inguinoscrotal operation before orchiectomy) were randomized (PA, 236 patients; DL, 242 patients). RESULTS: Median follow-up time is 4.5 years. Eighteen relapses, nine in each treatment group, have occurred 4 to 35 months after radiotherapy; among these, four were pelvic relapses, all occurring after PA radiotherapy. However, the 95% confidence interval (CI) for the difference in pelvic relapse rates excludes differences of more than 4%. The 3-year relapse-free survival was 96% (95% CI, 94% to 99%) after PA radiotherapy and 96.6% (95% CI, 94% to 99%) after DL (difference, 0.6%; 95% confidence limits, -3.4%, +4.6%). One patient (PA field) has died from seminoma. Survival at 3 years was 99.3% for PA and 100% for DL radiotherapy. Acute toxicity (nausea, vomiting, leukopenia) was less frequent and less pronounced in patients in the PA arm. Within the first 18 months of follow-up, the sperm counts were significantly higher after PA than after DL irradiation. CONCLUSION: In patients with testicular seminoma stage I (T1 to T3) and with undisturbed lymphatic drainage, adjuvant radiotherapy confined to the PA lymph nodes is associated with reduced hematologic, gastrointestinal, and gonadal toxicity, but with a higher risk of pelvic recurrence, compared with DL radiotherapy. The recurrence rate is low with either treatment. PA radiotherapy is recommended as standard treatment in these patients.

Adolescent↗

Tax-exempt charities can offer employees 401(k) retirement plan.

Here is a description of some recent changes in U.S. tax law that now allow tax-exempt non-profit organizations to improve one employee benefit--at a minimal cost to the employer. Tax-exempt organizations can now offer employees 401(k) retirement plans.

Charities↗

New antidepressants and the cytochrome P450 system: focus on venlafaxine, nefazodone, and mirtazapine.

OBJECTIVE: This review critically evaluates recent information on the cytochrome P450 system, with an emphasis on drug interactions involving antidepressant medications, particularly venlafaxine, nefazodone, and mirtazapine. METHODS: International literature on the cytochrome P450 system and related drug interactions from 1995-1997 were critically examined. RESULTS: Venlafaxine, nefazodone, and mirtazapine have different effects on the cytochrome P450 system. In vitro, venlafaxine is a weaker CYP2D6 inhibitor than most of the selective serotonin reuptake inhibitors (SSRIs) by a factor of 1-3 orders of magnitude. In vivo drug interaction studies generally confirm in vitro results. However, some exceptions exist. The clinical significance of such interactions remains unknown. Venlafaxine had minimal or no demonstratable inhibition of CYP1A2, CYP3A4, or CYP2C. Nefazodone is a potent inhibitor of CYP3A4 and is therefore absolutely contraindicated with concurrent administration of terfenadine, astemizole, and cisapride. It is a weak inhibitor of CYP1A2, 3A4, and 2D6. A metabolite of nefazodone, mCPP, is a weak and probably clinically insignificant inhibitor of CYP2D6. Mirtazapine has minimal inhibitory effects on CYP1A2, CYP3A4, and CYP2D6 in vitro. Little is known about its interactions with other drugs. CONCLUSIONS: With the addition of the latest antidepressant medications, the clinician may now choose antidepressants with little liability for drug-drug interactions. Venlafaxine and mirtazapine are associated with a lower risk of clinically significant drug interactions than SSRIs. Nefazodone is a potent inhibitor of CYP3A4 and therefore may not be suitable for all patient populations. It is, however, a much weaker CYP2D6 inhibitor than the SSRIs. More studies are needed to assess more accurately and precisely the risk of such untoward drug-drug interactions with these novel antidepressants, particularly in more diverse ethnic patient populations.

Antidepressive Agents, Second-Generation↗

The influence of breast size on late radiation effects and association with radiotherapy dose inhomogeneity.

A prospective assessment of late changes in breast appearance in 559 patients after tumour excision and radiotherapy for early breast cancer noted a strong association with breast size. Only 3/48 (6%) patients with small breasts developed moderate or severe late changes compared with 94/423 (22%) with medium sized breasts and 34/88 (39%) patients with large breasts (p < 0.001). One possibility is that greater radiation changes are related to greater dose inhomogeneity in women with large breasts. To explore this hypothesis, radiation dose distributions were assessed in a separate group of 37 women in whom three-level transverse computer tomographic images of the breast in the treatment position were available. A significant correlation was found between breast size and dose inhomogeneity which may account for the marked changes in breast appearance reported in women with large breasts.

Adult↗

Correlated response in growth and body measurements accompanying selection for milk yield in Jerseys.

Growth and body measurements from a long-term selection project were analyzed to determine correlated responses to single-trait selection for milk yield. Data were from 1056 daughters (765 selection, 291 control) of 37 bulls (17 selection, 20 control) of 37 bulls (17 selection, 20 control) and included BW and measures of heart girth, chest depth, wither height, and length from withers to pins and from withers to hooks taken at 6 mo, 15 mo, first calving, end of first lactation, and maturity. Other data were birth weight, change in measurements and weights from first calving to end of first lactation, monthly rate of gain from 1 to 13 mo of age, and age reaching breeding weight (250 kg). Principal component scores were calculated from standardized measurements at each age. The first three principal components has meaning (size, length vs. girth, and height vs. girth). All analyses used linear mixed models with fixed effects of genetic group, generation within group, year-season of birth or calving, parity of dam, and birth status (multiple or single birth). Sires were assumed to be random and nested within genetic group. Mean squares for sires was used to test for group differences. Generation did not differ in any analysis and was removed from all models. Selection cows were heavier, larger in some measurements, and had greater overall size at 6 mo of age. Selection cows had greater monthly rate of gain and attained breeding weight at an earlier age. Genetic groups did not differ for any other measurement or weight. Control cows gained more weight and increased more in some measurements between first calving and end of first lactation. Selection for milk yield did not result in an undesirable correlated response in an growth or body measurement.

Animals↗

Correlated responses in reproduction accompanying selection for milk yield in Jerseys.

Reproductive traits of heifers and primiparous cows from a long-term selection project were analyzed to determine correlated response to single-trait selection for milk yield. Data were from 1056 daughters (765 selection, 291 control) of 37 bulls (17 selection, 20 control). Traits in heifers were ages at first observed estrus and at first breeding, services to conception, interval from first service to conception, and length of first gestation. Traits in primiparous cows were ages at first calving and at first breeding, after calving; services to conception; length of second gestation; and intervals from calving to first observed estrus, to first breeding, and to conception, from first service to conception, and from first to second calving. Analyses for services to conception in heifers and primiparous cows were categorical using models containing genetic group and generation. Analyses of other traits were by linear mixed models using fixed effects of genetic group, generation within group, and year-season of birth. Sires were assumed random and nested within genetic group. The mean square for sires within group was used to test for group differences. No significant differences were found between genetic groups in traits measured in heifers; however, the interval from first service to conception approached significance (control superior). In primiparous cows, differences between genetic groups were significant for the intervals of calving to first breeding and calving to conception and for length of second gestation (control superior). For other traits, reproductive performance of the control was better but not significantly different from that of the selected group. Reproductive performance should be monitored during selection for high milk yield.

Age Factors↗

Direct response in yield and correlated response in components accompanying selection for milk yield in Jerseys.

In 1967, the Jersey herd at the Dairy Experiment Station, Lewisburg, TN was divided into two groups on the basis of ancestry, type, and breeding value for milk as part of a project to determine effects of single trait selection for high milk yield on yield and correlated traits. Control group was mated randomly to 20 unproven young sires selected randomly from those available from breeding studs in 1967. Selection group was mated to sires selected solely on the basis of their high transmitting ability for milk. Selection sires were selected at intervals and used for 4 yr. By the end of the project (1984), lactation information was available on 672 daughters (520 selection and 152 control) of 37 bulls (17 selection and 20 control). Differences in breeding values for milk, fat, and fat test as calculated from the PTA reported in the July 1989 USDA genetic evaluations and differences in first lactation mature equivalent production of milk, fat, fat test, and 4% FCM were examined. Linear mixed models were used for all analyses and contained the fixed effects group, generation within group, and year. Sires were random, nested within group, and used to test for group differences. Groups differed for all traits. Selection was superior to control in breeding value for milk and fat (828 and 31 kg) and for production of milk, fat, and 4% FCM (1066, 42, and 1061 kg). Control was superior to selection in breeding value and production fat test (.15 and .12%). Group differences existed within generation class for all yield traits but not for fat percentage. Realized response closely matched or exceeded expected response as estimated from pedigree information.

Animals↗

Effects of gonadotropin-releasing hormone and human chorionic gonadotropin on pregnancy rate in dairy cattle.

This study was to determine if gonadotropin-releasing hormone, human chorionic gonadotropin, or their interaction would affect pregnancy rate or milk progesterone profiles in dairy cattle. Cows and heifers eligible for first, second, and third services were assigned to four treatments: 1) saline i.m. within 5 min after AI (d 0) and saline 15 d after AI (n = 222 AI); 2) gonadotropin-releasing hormone (100 micrograms) i.m. within 5 min after AI and saline on d 15 (n = 223); 3) saline after AI and human chorionic gonadotropin (3500 IU) i.m. on d 15 (n = 196); 4) gonadotropin-releasing hormone at AI and human chorionic gonadotropin on d 15 (n = 195). Progesterone was quantified in milk samples collected twice weekly for 5 wk from all cows. Neither gonadotropin-releasing hormone, human chorionic gonadotropin, gonadotropin-releasing hormone x human chorionic gonadotropin interaction, age, nor service number affected pregnancy rate, which averaged 46.2%. Pregnancy and human chorionic gonadotropin affected milk progesterone profiles. Pregnancy maintained progesterone concentrations and human chorionic gonadotropin on d 15 increased them. This study does not support the general use of gonadotropin-releasing hormone at AI or human chorionic gonadotropin 15 d after AI as methods for enhancing pregnancy rates of dairy cattle.

Animals↗

Correlated response in feed efficiency accompanying selection for milk yield in Jerseys.

Gross feed efficiency (milk energy output divided by energy consumed) was measured in 232 Jersey cows resulting from direct selection for milk yield and a control line of 121 daughters of 20 Jersey bulls taken randomly from commercial artificial insemination sampling programs in 1967. Data were collected between 1971 and 1982 from primiparous cows in middle to late lactation in 21 feeding trials of 28 d. Cows were fed hay and silage ad libitum plus grain according to production at the rate of 1 kg grain/3 kg milk. Models for least squares analyses included trial, line, days in milk, and either body weight change (model 1) or energy balance (model 2), estimated as the difference between energy requirements and actual energy intake. Body weight change was an insignificant source of variation, and gross feed efficiency did not differ between genetic lines using model 1. Significant line differences in gross efficiency were obtained after adjusting for energy balance; however, problems of multicollinearity invalidates meaningful inference. Results indicate genetic lines of Jerseys did not differ in gross feed efficiency when fed according to yield and suggest selection has not affected efficiency of direct conversion of nutrients into milk.

Animal Feed↗

Effect of method of feeding protein and protein insolubility on milk production by Jersey cows.

Each of two feeding trials used 32 first and second lactation Jersey cows to evaluate four methods of protein supplementation of corn silage: A) 20% crude protein grain mixture, B) 1.36 kg of soybean meal replaced an equal amount of grain mixture, C) 2.27 kg of alfalfa-orchardgrass hay daily and 16% crude protein grain mixture, and D) 2.72 kg of soybean meal mixed with the silage daily. Concentrates were fed at 1 to 4 kg fat-corrected milk for treatments A, B, and C. All cows received 1.18 kg of 16% crude protein concentrate mixture daily in the milking parlor. Protein contents, as percents of dry matter intake, for respective treatments were 12.9, 15.0, 12.7, and 17.2. Treatments did not differ significantly for milk production, fat-corrected milk, and change of body weight; however, percents milk fat for 1.36 and 2.72 kg soybean meal were higher. In trial 2, protein insolubility of ration components was determined by four extracting methods: A) autoclaved rumen fluid, B) sodium chloride solution, C) Burroughs' solution, and D) boiling water. Insoluble protein intake determined by autoclaved rumen fluid and hot water methods accounted for more of the variance of milk and fat-corrected milk production than total protein intake.

Animals↗