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Biomedical subjects

J Wade

Publications and source records attributed to J Wade.

At least 19 recordsLinked to original sources

Androgenic regulation of hypothalamic aromatase activity in prepubertal and postpubertal male golden hamsters.

Doses of testosterone that fully activate male reproductive behavior in castrated adult male hamsters fail to elicit mounting and intromissions in prepubertal castrates, even when circulating levels of testosterone are equivalent in the two age groups. We hypothesize that this differential responsiveness to testosterone is mediated at least in part by the efficacy with which testosterone in the hypothalamus is aromatized to estradiol, an important hormone mediating male sexual behavior. Therefore, hypothalamic aromatase activity, as measured by the conversion of [3H]testosterone to [3H]estradiol in tissue homogenates, was assessed in four separate experiments: 1) intact prepubertal and adult male golden hamsters, 2 and 3) castrated adult or prepubertal males that received either a 0- or 2.5-mg dose of testosterone, and 4) castrated adult and prepubertal males treated with the 2.5-mg dose oftestosterone. These studies demonstrate that hypothalamic aromatase activity is significantly higher in adult males compared with prepubertal males, and that hypothalamic aromatase activity is increased by testosterone to the same extent in both the adult and prepubertal male hamster. Therefore, the failure of testosterone-treated castrated prepubertal male hamsters to engage in the full suite of male reproductive behaviors is not due to the inability of testosterone to be converted into estradiol in the hypothalamus. Differences in the ability of testosterone to increase aromatase activity in other brain regions, or differences in the action of testosterone and/or estradiol on other cellular processes must account for the inability of testosterone to facilitate male reproductive behavior in juvenile males.

Aging

The significance of aerobic gram-negative bacilli in clinical specimens following orthotopic liver transplantation.

In a prospective study of 284 liver transplant patients, we sought associations between aerobic gram-negative bacillus acquisition or infection and 35 preoperative, perioperative, and postoperative variables. Although the 128 (45%) who acquired aerobic gram-negative bacilli had longer admissions (P = 0.0001), no associations were found with pretransplant variables. Fifty-three (41%) of the 128 acquired coliforms (e.g., Escherichia coli, Klebsiella spp., or Enterobacter spp.), 50 (39%) acquired nonfermentative bacilli (e.g., Acinetobacter spp., Pseudomonas spp., or Stenotrophomonas maltophilia), and a further 25 (20%) acquired both. Acquisition progressed to infection in 58% of patients who acquired coliforms but in only 18% of patients who acquired nonfermentative bacilli (P = 0.005). Acinetobacter spp. were isolated from more patients than other bacilli but rarely caused infection. The positive predictive values for infection of acquiring coliforms or nonfermentative bacilli in clinical material were 42% and 17%, respectively. This study allowed us to determine for each clinical site the positive predictive values for infection of acquisition of different aerobic gram-negative bacilli. Our results should contribute to the rationalization of antimicrobial prescribing for this patient group.

Adolescent

Mobile surgical transport team.

The "golden hour" of trauma is based on the principle that severely injured patients are more likely to survive with rapid, appropriate resuscitation and treatment. An inequality exists between sophisticated urban trauma centers and rural/community hospitals in their efforts and abilities to treat severely injured patients. A level I trauma center developed a unique program in an attempt to equalize this inequality--a mobile surgical transport team (MSTT). This article explains the origin of the MSTT, how and why the MSTT is activated, and the roles and responsibility of MSTT members. To further explain the MSTT, two contrasting case studies on trauma patients are presented.

Adult

Aromatase activity and regulation of sexual behaviors in the green anole lizard.

Sexual behaviors in green anoles are regulated by steroid hormones. Androgens activate the display of masculine courtship and copulatory behaviors, and estradiol activates feminine receptivity. Testosterone can also facilitate receptivity in females. The present study was conducted to test the role of converting testosterone to estradiol (aromatization) in the regulation of sexual and aggressive behaviors. Adult males and females were gonadectomized and implanted with a Silastic capsule containing either testosterone propionate (T) or estradiol benzoate (E) or with an empty (blank, BL) capsule. T- and BL-treated animals were then given injections of either Fadrozole (FAD, an aromatase inhibitor) or saline (SAL). E-treated animals received saline injections. Each individual was then tested alternately with male and female stimulus animals. Overall, T stimulated masculine sexual behaviors and receptivity, but the androgen had little effect on the display of aggressive behaviors. The inhibition of aromatase activity by treatment with Fadrozole eliminated the effect of T on receptivity. In contrast, Fadrozole treatment had no effect on mounting behavior or the frequency of courtship bouts. The inhibition of aromatase activity did increase the number of dewlap extensions (the display of a red throat fan) during courtship. These results suggest that the metabolism of testosterone to estradiol is a mechanism through which androgens can facilitate receptivity, and that such aromatization of testosterone is not required for the display of masculine sexual behaviors. In addition, females performed courtship and mounting behaviors less frequently than males, suggesting that an organizational component to steroid hormone regulation of sexual behaviors may exist in the anole.

Aggression

Self-reported sleep and mood disturbance in chronic pain patients.

OBJECTIVE: To evaluate the prevalence of self-reported sleep disturbance and its relationship to mood disturbance in chronic pain patients. DESIGN AND SETTING: Survey of patients referred to a multidisciplinary outpatient pain clinic. PATIENTS: The sample consisted of 105 consecutive patients (59 men and 46 women), with an average age of 41.5 (SD +/-13.4) years. MEASURES: Self-report measures of sleep disturbance and visual analog scales of mood disturbance (anxiety and depression) and pain experience (intensity and unpleasantness). RESULTS: Patients were grouped according to whether they considered themselves "poor" (n = 68) or "good" (n = 37) sleepers. Poor sleepers reported more difficulties initiating and maintaining sleep and greater pain intensity and pain unpleasantness than did good sleepers. The two groups did not differ on measures of depressive or anxious mood. CONCLUSION: The results suggest that sleep disturbance is a prevalent complaint in chronic pain patients, but it is not always associated with an underlying mood disturbance.

Adult

Sexual dimorphisms in the brainstem of the green anole lizard.

Male green anoles (Anolis carolinensis) court females by extending a bright red throat fan, called a dewlap. The dewlap is larger in males than in females who do not display the structure in the context of courtship. The ceratohyoid muscle and second ceratobranchial cartilage which control dewlap extension are significantly larger in male than in female anoles. Neurons innervating the ceratohyoid muscle were retrogradely labeled by injecting the muscle with fast blue and were found to be located in the vagal portion of nucleus ambiguus (Amb X), as well as in the region containing the glossopharyngeal portion of nucleus ambiguus (Amb IX) and the ventral portion of the motor nucleus of the facial nerve (nVIImv). Cells in both areas were larger in males than in females. These parallels between structure and function provide the opportunity to study mechanisms of sexual differentiation of brain and behavior.

Animals

Quality-of-life benefit in chemotherapy patients treated with epoetin alfa is independent of disease response or tumor type: results from a prospective community oncology study. Procrit Study Group.

PURPOSE: To evaluate prospectively the effectiveness of epoetin alfa as an adjunct to chemotherapy in patients with cancer based on changes in quality-of-life parameters and hemoglobin levels, and to correlate these changes with antitumor response. PATIENTS AND METHODS: Two thousand three hundred seventy patients with nonmyeloid malignancies who received chemotherapy were enrolled onto this study from 621 US community-based practices. Patients received epoetin alfa 10,000 U three times weekly, which could be increased to 20,000 U three times weekly depending on the hemoglobin response at 4 weeks. Treatment continued for a maximum of 16 weeks in patients who showed evidence of hematologic response. RESULTS: Two thousand two hundred eighty-nine patients (97%) were eligible for efficacy analyses. Epoetin alfa therapy was associated with improved quality-of-life parameters; these improvements correlated significantly with hemoglobin levels and were independent of tumor response. Provider-reported Karnofsky performance scores did not correlate with the improved quality-of-life changes. Epoetin alfa therapy was also associated with a significant increase in hemoglobin levels and decrease in transfusion use. Tumor type, chemotherapy agent/regimen, prior chemotherapy, baseline hemoglobin level, and baseline erythropoietin level were not predictive of a positive response to treatment. Epoetin alfa was well tolerated. CONCLUSION: Epoetin alfa appears to have a beneficial impact on patient-reported functional capacity and quality of life in patients with cancer who received chemotherapy independent of tumor response. Concordantly, epoetin alfa appeared to increase hemoglobin levels and decrease transfusion use. Patients responded across all tumor types. The results suggest that epoetin alfa effectively improves functional outcomes in patients with cancer who receive chemotherapy.

Aged

Notable multicultural training in APA-approved counseling psychology and school psychology programs.

On the basis of the initial work of M.R. Rogers, J. Martin, and L. Druckman (1994) regarding exemplary multicultural training occurring at school psychology programs, the authors examined salient aspects of 5 American Psychological Association (APA)-approved counseling psychology and 5 APA-approved school psychology programs nominated for their reputation for multicultural training. Twenty-two percent of the program faculty represented a racial-ethnic minority group, at least 2 faculty members per program were involved in multicultural teaching, and 90% of the programs offered a multicultural course. Program faculty at the notable programs were actively involved in relevant research, routinely made presentations at national conferences regarding their scholarship, regularly participated in campuswide multicultural committees, and generally reported their university training environment to be supportive of multicultural issues.

Counseling

Effects of embryonic estrogen on differentiation of the gonads and secondary sexual characteristics of male zebra finches.

Male zebra finches sing to court females, whereas females do not normally sing. In parallel, the telencephalic brain regions that control song are larger in volume and contain larger cells in males than in females. The vocal control organ (syrinx) is also larger in males. Some evidence suggests that the sexual differentiation of both anatomy and behavior is under the regulation of gonadal hormones during early development, yet recent data conflict with the idea that the sole source of masculinization of the neural song system is the testes. In the present experiment, we treated genetic males with estradiol benzoate on embryonic day 5 and measured the volume of and neuron soma size in robust nucleus of the archistriatum (RA) and the high vocal center (HVC), two telencephalic song control nuclei. We also weighed the syrinx, the muscles of which are the target of the motor pathway containing the two brain regions. The estrogen treatment disrupted testicular morphology, and induced an oviduct in six of seven animals, but it had no effect on any of four measures of masculinization of the neural song system. These results suggest that normal testicular tissue is not required for masculine development of the neural song system.

Animals

Androgen metabolism in the brain of the green anole lizard (Anolis carolinensis).

Activities of the steroid metabolizing enzymes aromatase and 5 alpha-reductase have been documented in species ranging from fish to humans, yet relatively little work has been done in this area in reptiles. In the green anole lizard, Anolis carolinensis, steroid hormones are critical to the display of both masculine and feminine sexual behaviors. For example, dihydrotestosterone and testosterone can stimulate both masculine courtship and copulatory behaviors, and estrogen and testosterone facilitate feminine receptivity. These results suggest roles for both aromatase (which catalyzes the conversion of testosterone to estradiol) and 5 alpha-reductase (which converts testosterone to dihydrotestosterone). This study documents the presence of both enzymes in the brain of the green anole and indicates that the activity of 5 alpha-reductase is much higher than that of aromatase in whole brain homogenates. However, differences exist among brain regions, such that aromatase activity is higher in preoptic area/hypothalamic dissections, whereas 5 alpha-reductase is much more active in the brain stem. These variations in regional enzyme activity may influence steroid hormone regulation of specific sexual behaviors in male and female anoles.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase

The effects of testicular tissue and prehatching inhibition of estrogen synthesis on the development of courtship and copulatory behavior in zebra finches.

As in many mammalian and avian species, testicular androgens or their metabolites activate courtship and copulatory behaviors in adult male zebra finches. However, studies of sexual differentiation of these behaviors and related anatomical structures provide conflicting results. For example, posthatching estradiol can both masculinize courtship and the neural structures involved in song in females and inhibit the development of masculine copulation in males. These and other results have led to the hypotheses that (1) testicular androgens are converted to estradiol in the brain of developing males, and estradiol serves to masculinize the song system, whereas (2) estradiol secretion by the female ovary allows feminine rather than masculine copulatory behavior to develop. Treating embryonic zebra finches with the estrogen synthesis inhibitor fadrozole causes functional testicular tissue to develop in genetic females. The present study investigated the effects of such treatment on the development of singing and copulatory behavior as well as song system anatomy in males and females. While exogenous testosterone facilitated the display of sexual behaviors in adult males, the testicular tissue in females had no masculinizing effect on the production of audible courtship song or copulation. Their song control nuclei were also not masculinized, even in individuals lacking ovarian tissue. In contrast, embryonic inhibition of estrogen synthesis in males significantly stimulated song production. These results suggest that while manipulations of steroid hormone exposure can influence the display of sexual behaviors, gonadal secretions may not be required for normal sexual differentiation of the song system in zebra finches.

Animals

Diversity associated with the second expressed HLA-DRB locus in the human population.

Although diversity within the HLA-DRB region is predominantly focused in the DRB1 gene, the second expressed DRB loci, DRB3, DRB4, and DRB5, also exhibit variation. Within DRB1(*)15 or DRB1(*)16 haplotypes, four new variants were identified: 1) two new DRB5 alleles, DRB5*0104 and DRB5*0204, 2) a haplotype carrying a DRB1(*)15 or *16 allele without the usual accompanying DRB5 allele, and 3) a haplotype carrying a DRB5(*)0101 allele without a DRB1(*)15 or *16 allele. The evolutionary origins of these haplotypes were postulated based on their associations with the DRB6 pseudogene. Within HLA haplotypes which carry DRB3, a new DRB3(*)0205 allele and one unusual DRB3 association were identified. Finally, two new null DRB4 alleles are described: DRB4(*)0201N, which exhibits a deletion in the second exon, and a second allele, DRB4(*)null, which lacks the second exon completely. Gene conversion-like events and variation in the number of functional genes through reciprocal recombination and inactivation contribute to the diversity observed in the second expressed HLA-DRB loci.

Alleles

Infant emmetropization: longitudinal changes in refraction components from nine to twenty months of age.

Rapid emmetropization is described in pediatrically normal infants from 9 months of age during the following year. The infants, obtained from various categories of the Cambridge population screening program, provided a broad range of refractive errors. The large group of 254 nonanisometropic infants studied allowed the mean rate of change and dependence on the initial refraction value to be determined. Refraction was measured by cycloplegic retinoscopy. Rapid emmetropization changes occurred in the following refractive components: mean spherical equivalent (MSE), astigmatism magnitude, the horizontal astigmatism component, the infant's most positive meridian, and the infant's most negative meridian. The MSE and astigmatism rates of change (diopters/year), were highly dependent on their respective initial powers (r = -0.61 and r = -0.76). The percentage weighted mean proportional rate of change for MSE was -30% (SE 4%) and for astigmatism magnitude it was -59% (SE 14%). There was much individual variation, with some exhibiting fast emmetropization and others not. The MSE and astigmatism changes, however, were almost independent of each other. The refractive errors of the most positive and most negative meridians emmetropize because they are both derived from the MSE and half the astigmatism. With-the-rule astigmatism was more prevalent than against-the-rule astigmatism at 9 months of age, and with-the-rule astigmatism exhibited a significantly greater proportional rate of change. The relationship of emmetropization and refractive screening is considered. A new component "MOMS" is introduced, the maximum ocular meridional separation, when both eyes are considered. Thus incorporating astigmatism and anisometropia may be a good single indicator of conditions associated with later amblyopia. The almost independent emmetropization of the MSE and astigmatism components is an important result to consider in theories of emmetropization, refractive screening, clinical prescribing, and the evaluation of infants in treatment trials.

Accommodation, Ocular

Immunogenetic and microbial factors in acute anterior uveitis.

OBJECTIVE: To characterize the rheumatic diseases associated with acute anterior uveitis and examine the potential role of Yersinia enterocolitica in the pathogenesis of acute anterior uveitis. METHODS: 44 patients with acute anterior uveitis were assessed for evidence of an underlying rheumatic syndrome by history and examination. HLA profiles were identified by serologic and molecular techniques. Serological analysis of patients' sera for the presence of antibodies to Y. enterocolitica was by Western blot. RESULTS: 30 of the 44 patients had musculoskeletal symptoms. Of these, 8 had ankylosing spondylitis, 4 reactive arthritis, 2 undifferentiated spondyloarthropathy (SpA), 2 inflammatory bowel disease, one seronegative polyarthritis, and 13 mechanical back pain. Of 42 patients typed, 29 (69%) were HLA B27 positive and an additional 7 patients expressed a crossreactive group antigen (86% of total group B27 or CREG positive). Western blot analysis of the sera revealed increased frequency of antibodies to Yersinia compared with a control population. Antibodies directed against the 36 and 27 kDa Yersinia antigens were recognized with greater frequency (p < 0.05) in patients with acute anterior uveitis than in controls. IgG reactivity was more pronounced than IgA reactivity. Adsorption studies showed significant cross reactivity of anti-Yersinia antibodies with Salmonella typhimurium. Among the patients with acute anterior uveitis anti-Yersinia reactivity did not correlate with the HLA profile, nor with the presence of an underlying rheumatic disease. CONCLUSION: SpA represent the commonest underlying rheumatic disorders associated with acute anterior uveitis. The majority of patients with acute anterior uveitis possess HLA-B27 regardless of whether there is underlying SpA. Patients with acute anterior uveitis show increased frequency of anti-Yersinia antibodies compared with controls. Many of these antibodies appear to be directed against antigenic determinants shared among gram negative bacteria and thus cannot constitute definitive evidence for a causal role specifically for Yersinia in acute anterior uveitis. Acute anterior uveitis represents an interplay of host susceptibility and microbial triggers, as is the case for the SpA in general.

Acute Disease

Thrombotic microangiopathy in renal transplant recipients treated with cyclosporin A.

Thrombotic microangiopathy is an uncommon but well described complication of renal transplantation. This study is a review of the case records of 18 patients with biopsy proven post transplant thrombotic microangiopathy, without cellular rejection. There was no single characteristic underlying cause of renal failure in native kidneys. Although only two (11%) patients had undergone previous transplantation, 16 (89%) had panel reactive antibodies (PRA). All patients received prophylactic antilymphocyte globulin, a single patient had cyclosporin A (CSA) at the time of transplant and in 16 patients CSA was introduced when graft function was established. On this protocol 16 (89%) patients had early graft function. All patients developed acute renal failure and 16 (89%) required dialysis. Nine (50%) patients developed hematological abnormalities. All patients were treated aggressively with anti-rejection therapy, CSA was temporarily withdrawn, and 2 (11%) patients received plasmapheresis. Seven (39%) patients lost their grafts. Renal function in the remaining patients recovered to serum creatinine levels ranging from 104 mumol/l to 430 mumol/l (1.2 mg% to 4.8 mg%). All patients with surviving grafts had CSA successfully reintroduced. This study indicates that there is an association between patients who develop posttransplant thrombotic microangiopathy after CSA administration and high PRA levels. The condition appears to respond to anti-rejection therapy and stopping CSA in the majority of cases. The safe reintroduction of CSA suggests that endothelial cell damage in the posttransplant period may be multifactorial and not solely due to CSA therapy.

Adolescent

How many general surgeons do you need in rural areas? Three approaches to physician resource planning in southern Manitoba.

OBJECTIVE: To assess critically the results of using three different approaches to planning for the number of general surgeons in rural areas. DESIGN: Estimates of the number of general surgeons needed using a ratio approach, a and a population-needs-based approach. SETTING: Rural southern Manitoba. OUTCOME MEASURE: Number of general surgeons needed. RESULTS: The ratio approach supported the recruitment of 7.8 to 14.5 additional general surgeons to rural southern Manitoba. The repatriation approach suggested that the area might support five additional general surgeons, if residents could be persuaded to undergo their surgery closer to home. The population-needs-based approach suggested that the health status of area residents was similar to that of residents of other areas of the province and that they had a higher rate of surgery than residents of other areas; no additional surgeons were apparently needed. CONCLUSIONS: Each method has certain advantages, and none is necessarily useful in isolation. Hence, the most effective approach to planning for general surgeons is likely a combination of all three methods. Other factors that may be important include the type of payment structure and the need for professional groups to monitor variations in rates of surgery.

Aged