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Biomedical subjects

T Williams

Publications and source records attributed to T Williams.

At least 91 records · Page 5Linked to original sources

Neuropsychological study of frontal lobe function in psychotropic-naive children with obsessive-compulsive disorder.

OBJECTIVE: The authors' goal was to evaluate cognition in children with obsessive-compulsive disorder (OCD) early in their illness. METHOD: They administered neuropsychological tests to 21 pediatric patients with OCD and 21 healthy children matched for age, sex, socioeconomic status, and intelligence. The children with OCD were not depressed, and none had ever received psychotropic medication. The neuropsychological tests were used to assess the relationship between psychiatric symptoms and cognitive function. RESULTS: The children with OCD performed as well as the healthy children on the neuropsychological tests. Psychiatric symptoms and cognitive performance were not related. CONCLUSIONS: Nondepressed children with recently diagnosed OCD who had never received psychotropic medication demonstrated no cognitive impairment according to their performance on neuropsychological tests. The authors conclude that OCD symptoms may not interfere with cognitive abilities early in the illness.

Age of Onset↗

Attitudes about menstruation among fifth-, sixth-, and seventh-grade pre- and post-menarcheal girls.

A descriptive study of 106 fifth-, sixth-, and seventh-grade girls was conducted to determine their attitudes toward menarche. Attitudes of affirmation and worry were examined based on grade level, menarcheal status, and various other variables, including whether the participants had talked with their mother or a close friend, or seen a video on menstruation. Worry scores increased independently of menarcheal status from the fifth to sixth grade. From the sixth to seventh grade, there was no change in the level of worry of post-menarcheal girls, but there was a significant decrease in worry for pre-menarcheal girls. Perhaps these girls sought reassurance from a supportive person that their late menses was not abnormal. If so, this reassurance may have accounted for their decrease in worry scores. There was a decrease in worry in those girls who had sisters. Also, girls who had talked with someone about menstruation had higher affirmation scores than those who had not. Nursing implications include the need for school nurses to provide ongoing education for young females from fifth through seventh grades, and to encourage them to communicate with their support systems.

Adolescent↗

Oral niacin prevents photocarcinogenesis and photoimmunosuppression in mice.

Topical nicotinamide (niacinamide) has demonstrable preventive activity against photocarcinogenesis in mice. To better understand how this vitamin prevents ultraviolet (UV) carcinogenesis, we tested systemic administration of another form of the vitamin, niacin, and its capacity to elevate cutaneous nicotinamide-adenine dinucleotide (NAD) content as well as to decrease photoimmunosuppression and photocarcinogenesis. BALB/cAnNTacfBR mice were fed the AIN-76A diet supplemented with 0%, 0.1%, 0.5%, or 1.0% niacin throughout the experiment. UV irradiation consisted of five 30-minute exposures per week to banks of six FS40 Westinghouse sunlamps for 22 weeks in the carcinogenesis experiments, yielding a total cumulative dose of approximately 1.41 x 10(6) Jm-2 of UV-B radiation. Dietary supplementation with 0.1%, 0.5%, or 1.0% niacin reduced the control incidence of skin cancer from 68% to 60%, 48%, and 28%, respectively, at 26.5 weeks after the first UV treatment. Two potential mechanisms by which niacin prevents tumor formation were identified. Photoimmunosuppression, critical for photocarcinogenesis, is measured by a passive transfer assay. Syngeneic, antigenic tumor challenges grew to an average of 91.6 +/- 19.7, 79.8 +/- 11.5, 41.9 +/- 11.7, or 13.2 +/- 4.1 mm2 in naive recipients of splenocytes from UV-irradiated mice treated with 0%, 0.1%, 0.5%, or 1.0% niacin supplementation, respectively, demonstrating niacin prevention of immunosuppression. Niacin supplementation elevated skin NAD content, which is known to modulate the function of DNA strand scission surveillance proteins p53 and poly(ADP-ribose) polymerase, two proteins critical in cellular responses to UV-induced DNA damage. These results clearly demonstrate a dose-dependent preventive effect of oral niacin on photocarcinogenesis and photoimmunosuppression and establish the capacity of oral niacin to elevate skin NAD levels.

Administration, Oral↗

Activator protein-2 mediates transcriptional activation of the CYP11A1 gene by interaction with Sp1 rather than binding to DNA.

The ovine P45 side chain cleavage (CYP11A1) enzyme gene, which catalyzes the initial enzymatic step in steroid hormone biosynthesis is transcriptionally regulated in cultured steroidogenic human trophoblastic JEG-3 cells. The ovine CYP11A1 promoter contains two GC-rich footprinted regions referred to as ovine footprints 5 (OF5) and OF3, which are well conserved among the CYP11A1 promoters of different species. These GC-rich sequences resemble activator protein-2 (AP-2)/Sp1 binding sites and were previously implicated in basal and cAMP-regulated activity of the bovine and ovine CYP11A1 promoters. In the current studies, AP-2 induced the ovine CYP11A1 promoter 4.5-fold in JEG-3 cells with full induction requiring the previously defined cAMP-responsive elements. Point mutation of OF3 abolished induction by AP-2, and OF3 was sufficient for induction by AP-2 when linked to a heterologous promoter. AP-2 induction of the CYP11A1 promoter required the basic region (N165-N278) and the carboxy terminus of AP-2 (N413-N437). In the course of investigating the mechanisms by which OF5 and OF3 regulated CYP11A1 transcription, we found that OF5 and OF3 bound Sp1 and Sp3 in JEG-3 cells. AP-2 did not bind OF5 or OF3 directly but rather formed a multiprotein complex with Sp1 in JEG-3 cells. AP-2 associated directly with Sp1 in vitro requiring the AP-2 basic region and the Sp1 carboxy terminus. AP-2 induced Sp1/Sp3 activity independently of AP-2 binding to DNA using a GAL4 paradigm. The Sp1 and Sp3 transactivation domains were linked to the DNA-binding domain of GAL4, and their activity was assessed using a luciferase reporter gene containing only the GAL4 DNA-binding sites linked to the minimal TATA site. AP-2 induced Sp1/ Sp3-GAL4 activity 3- to 4-fold, requiring both the amino and extreme carboxy terminus of AP-2. We conclude that AP-2 can bind to and stimulate Sp1 activity and induces the ovine CYP11A1 promoter through conserved Sp1/Sp3-binding sites in JEG-3 cells. The induction of Sp1 activity by AP-2 may contribute to the induction of other genes that bind Sp1.

Animals↗

Do health professionals' attitudes interfere with the treatment of depression?

Might the attitudes of health care professionals help to explain why most persons with a depressive disorder do not receive adequate care? To assess this question, the authors surveyed the faculty and staff of a midwestern university. One hundred percent of the social workers who responded found psychotherapy or counseling to be extremely or quite effective in treating persons with a major depressive episode, compared to 55% of the psychologists and 31% of the psychiatrists. For medication, the corresponding figures were 88% of psychiatrists, 64% of psychologists, and 46% of social workers. Many respondents noted problems with interprofessional communication, while most psychiatrists felt that individuals treated by two or more professionals for their depression usually receive poorer care. If future studies indicate that nonmedical therapists who view antidepressants as relatively ineffective are less likely to refer depressed clients for medication evaluation, these findings might help to explain why many depressed individuals who could benefit from medication do not receive it. Concerns about interprofessional communication, as well as psychiatrists' beliefs about the quality of care received by persons treated by more than one professional, might also explain why joint treatment occurs less often than would be desirable. The authors discuss some of the implications that these findings may have for the education of health care professionals.

Attitude to Health↗

Expression of AP-2 transcription factors in human breast cancer correlates with the regulation of multiple growth factor signalling pathways.

The AP-2 transcription factors are required for normal growth and morphogenesis during mammalian development. Previous in vitro studies have also indicated that the AP-2 family of proteins may be involved in the etiology of human breast cancer. The AP-2 genes are expressed in many human breast cancer cell lines, and critical AP-2-binding sites are present in both the ERBB-2 (HER2/neu) and estrogen receptor promoters. We have now characterized immunological reagents that enable specific AP-2 family members, including AP-2alpha and AP-2gamma, to be detected in human breast cancer epithelium. Data obtained with these reagents demonstrate that whereas AP-2alpha and AP-2gamma are both present in benign breast epithelia, there is a significant up-regulation of AP-2gamma expression in breast cancer specimens (P = 0.01). There was also a significant correlation between the presence of the AP-2alpha protein and estrogen receptor expression (P = 0.018) and between specimens containing both AP-2alpha/AP-2gamma proteins and ERBB-2 expression (P = 0.003). Furthermore, we detected an association (P = 0.04) between the expression of AP-2gamma and the presence of an additional signal transduction molecule implicated in breast cancer, the insulin-like growth factor I receptor. Analysis of the proximal promoter of the insulin-like growth factor I receptor revealed a novel AP-2-binding site. Thus, AP-2 proteins may directly regulate the transcription of this growth factor receptor. Taken together, these data strongly support a role for the AP-2 gene family in the control of cell growth and differentiation in breast cancer.

Binding Sites↗

AP-2-null cells disrupt morphogenesis of the eye, face, and limbs in chimeric mice.

The homozygous disruption of the mouse AP-2 gene yields a complex and lethal phenotype that results from defective development of the neural tube, head, and body wall. The severe and pleiotropic developmental abnormalities observed in the knockout mouse suggested that AP-2 may regulate several morphogenic pathways. To uncouple the individual developmental mechanisms that are dependent on AP-2, we have now analyzed chimeric mice composed of both wild-type and AP-2-null cells. The phenotypes obtained from these chimeras indicate that there is an independent requirement for AP-2 in the formation of the neural tube, body wall, and craniofacial skeleton. In addition, these studies reveal that AP-2 exerts a major influence on eye formation, which is a critical new role for AP-2 that was masked previously in the knockout mice. Furthermore, we also have uncovered an unexpected influence of AP-2 on limb pattern formation; this influence is typified by major limb duplications. The range of phenotypes observed in the chimeras displays a significant overlap with those caused by teratogenic levels of retinoic acid, strongly suggesting that AP-2 is an important component of the mechanism of action of this morphogen.

Animals↗

Taphonomy and palaeoecology of Olduvai Bed-I (Pleistocence, Tanzania).

Detailed taxonomic and taphomonic studies of rodents and palaeoecological analysis have been undertaken to investigate faunal change in Olduvai Bed-I. The palaeoenvironments inferred from rodent faunas recorded in Olduvai Bed-I suggest a change between the middle (FLK + FLKNN) and the top of the series (FLKN). Changes have also been observed from taxonomic studies of large mammals and from palynological studies. These differences have been attributed in the past to climatic change, but taphonomic studies suggest a more complex scenario. The environment at Olduvai Bed-I is here interpreted through analysis of fossil faunas and fossilization processes. Identification of the causative agents that could have altered the faunal composition provides information on the environment and on the nature of the change observed between the middle and top of Bed-I. This information can then be used to test conflicting hypotheses about the origins and amount of faunal and pollen change. Results show evidence of predation in all units of Bed-I and can be attributed to different predators along the series. Different predator behaviours explain some of the variability observed by previous authors in the small mammal species composition between the middle and the top of Bed-I. After taking taphonomy into account, the remaining faunal differences point to environmental differences between middle and upper Bed-I and even greater within the upper Bed-I sequence. These differences go beyond the range that is present today in the tropical woodland-savanna biome. Our interpretation of the palaeoenvironments is that the middle Bed-I faunas indicate a very rich closed woodland environment, richer than any part of the present-day savanna biome in Africa, changing to less rich woodland in upper Bed-I with a trend towards more open and seasonal woodlands at the top of the series.

Animals↗

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Journal Article↗

Comparison of one week of oral terbinafine (250 mg/day) with four weeks of treatment with clotrimazole 1% cream in interdigital tinea pedis.

Treatment of interdigital tinea pedis often involves long-term therapy with topically applied preparations. Effective oral preparations, such as the allylamine terbinafine (Lamisil), taken over a shorter period, could provide a useful therapeutic alternative. A total of 269 patients from five centres with clinically diagnosed interdigital tinea pedis were entered into this double-blind, randomized, double-dummy, parallel-group study comparing oral terbinafine 250 mg once daily for 1 week with 1% clotrimazole (Canesten) cream applied twice daily for 4 weeks. Of these, 137 patients were evaluable for efficacy (confirmed dermatophyte infection by microscopy and culture): 63 terbinafine and 74 clotrimazole. At week 4, the mycological cure rates (negative culture at week 1 and negative results on microscopy and culture at week 4 onwards) were very similar (71% for clotrimazole and 72% for terbinafine). There was a faster response rate in the terbinafine group with respect to signs and symptoms at week 1. Both treatments were equally well tolerated; adverse events occurred equally in the two groups. In conclusion, oral terbinafine in a single daily dose of 250 mg for 1 week is as effective and as well tolerated as 1% clotrimazole cream applied twice daily for 4 weeks in the treatment of interdigital tinea pedis.

Adolescent↗

Human occult loiasis: field evaluation of a nested polymerase chain reaction assay for the detection of occult infection.

A nested polymerase chain reaction (nested PCR) assay, targeted on the repeat 3 region (15r3) of the gene coding for a Loa loa 15 kD polyprotein, was developed to detect L. loa infection. The assay has a sensitivity of 95% and is 100% specific with regard to sympatric filarial parasites: Mansonella perstans, Onchocerca volvulus and Wuchereria bancrofti. In this field study in a mixed filarial (L. loa and M. perstans) endemic region of Gabon, 157 L. loa amicrofilaraemic blood samples (AMF; diagnosed by leucoconcentration followed by standard microscopic examination) from the residents from four villages were screened by the 15r3-nested PCR assay. The assay detected 106 occult infected subjects among the 157 AMF individuals (68%), including 59 of 87 adults (68%) and 47 of 70 children (67%). In each village the prevalence of occult infection was, respectively, 38%, 52%, 79% and 80% for Moyabi, Djoutou, N'djokaye and Okoumbi. The annual transmission potential (ATP) of loiasis has been estimated to be 250 infective larvae (L 3) per man per year for Moyabi and Djoutou, 1800 for N'djokaye and 433000 L3/man/year for Okoumbi. This implies a correlation between occult infection of loiasis and the intensity of transmission. By contrast, the prevalence of L. loa microfilariae was 21% for Okoumbi, 22%, for N'djokaye and 19% for Djoutou and Moyabi. These results show that the prevalence of loiasis in this region of Gabon is higher than previously described by standard microscopic examination and that the application of this assay will be significant in the development of control strategies for loiasis.

Adolescent↗

A comparison of multimedia and standard advanced cardiac life support learning.

OBJECTIVES: To compare student performance after Multimedia ACLS Learning System (MM) education compared with that after standard (ST) ACLS education. METHODS: Final-year medical students were divided into 2 groups based on convenience scheduling and given ACLS instruction either in a standard format or with the MM course. The sizes of the small groups and the times in small-group instruction were identical. All students were evaluated with the same 50-item multiple-choice written examination, a structured evaluation immediately after the management of a mock cardiac arrest, and a second structured evaluation of the same mock arrest (videotaped) by an instructor blinded to the education method. Students were assigned a mark from 1 to 5 in each of 4 domains: assessment, immediate priorities, continual assessment, and leadership. RESULTS: 75 students took the MM and 38 took the ST course. The mean +/- SD mark for the multiple-choice test was 89.3 +/- 4.9% (MM) vs 89.3 +/- 4.8% (ST); the on-site mock arrest evaluation mark (20 maximum) was 14.1 +/- 2.5 (MM) vs 14.1 +/- 2.0 (ST); and the blinded mock arrest evaluation was 13.1 +/- 2.9 (MM) vs 14.4 +/- 2.9 (ST) (p = 0.024). 1/75 (MM) vs 0/38 (ST) did not successfully complete the on-site mock arrest evaluation. More students in the MM group (46% vs 25%) required multiple attempts to successfully complete the mock arrest evaluation (p < 0.02). CONCLUSION: In medical students with no previous ACLS training, structured access to the multimedia ACLS Learning System provides immediate educational outcomes similar to those of a standard ACLS course. Multimedia computer-interactive learning should be enhanced with a short period of hands-on practice.

British Columbia↗

Behavioural effects of long-term multi-sensory stimulation.

OBJECTIVES: Regular access to a multi-sensory environment (MSE or Snoezelen room) was compared with a non-complex sensory environment for individuals with learning disabilities. We also tested the prediction that those individuals whose challenging behaviour was maintained by sensory consequences would benefit most from exposure to the MSE. DESIGN: The conditions were compared over 16-week periods using a double crossover design, and were matched for social contact and attention from the enabler. Participants were randomly assigned to orders of treatments. METHODS: Participants were 27 adults with severe/profound learning disabilities who exhibited challenging behaviour. Behaviour was assessed before and after each treatment phase using both direct observation and standardized assessments (the Functional Performance Record and the Problem Behaviour Inventory). The behavioural observations formed the basis of a functional analysis of each individual's challenging behaviour. RESULTS: Some participants became more calm and relaxed while in the MSE, however, the objective measures of behaviour outside the treatment settings revealed no difference between the MSE and control conditions. Challenging behaviour maintained by sensory consequences showed no greater responsivity to the MSE than to the control condition. CONCLUSIONS: The multi-sensory environment had no effects beyond those that could be ascribed to the social interaction between participant and enabler. Anecdotal evidence of favourable responses within the MSE itself could not be confirmed outside the environment.

Adult↗