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Biomedical subjects

S Mackay

Publications and source records attributed to S Mackay.

At least 19 recordsLinked to original sources
PubMed2004

Postnatal development of the reproductive system in the grey short-tailed opossum, Monodelphis domestica.

Postnatal phenotypic sex differentiation has been investigated in a laboratory marsupial, Monodelphis domestica, as part of a larger study to resolve apparent discrepancies between eutherian and marsupial mammals. These include the formation of sex-specific structures in marsupials prior to gonadal differentiation and the retention in both sexes of structures which are sex-specific in eutherians. The time-course and nature of differentiation was investigated in 131 specimens ranging in age from the day of birth to 56 days. Patent wolffian ducts extend to the urogenital sinus in both sexes at birth, while müllerian ducts are identified on day 1 and grow in a cranio-caudal direction to reach the urogenital sinus on day 6. The male müllerian duct shows signs of regression at its cranial end on day 10 and throughout its length on day 12; its lumen has completely disappeared by day 15. By this time the epididymis and vas deferens have developed from the wolffian duct; their histological differentiation occurs between days 26 and 56. Prostatic buds are identifiable in tissue surrounding the male urethra on day 14. In the female, the wolffian duct is larger than the müllerian duct until day 14; thereafter the wolffian duct begins to regress at its cranial end, disappearing by day 17, whereas the müllerian duct begins to enlarge, converging with its fellow at the urogenital sinus by day 19. Lateral vaginae, vaginal culs-de-sac, uteri and oviducts have differentiated from the müllerian ducts by day 25. Gonads of both sexes are elongated in shape at birth, attached along the medial aspect of the large mesonephroi in the abdominal cavity. However, from day 3 onwards the testis becomes more rounded than the ovary. Degeneration of the male mesonephros begins about day 10 and is almost completed by day 19; the female mesonephros is still relatively large at day 14 though it too has almost disappeared by day 19. By postnatal day 13 the abdominal phase of testis descent is underway and the inguinal phase begins at day 15. Testes have reached the scrotal sac by day 24 and achieve their final position at the base of the scrotum by day 28. In summary, postnatal reproductive tract development and gonadal descent has been examined in this important biomedical model, where differentiation of the wolffian and müllerian ducts takes place after gonadal differentiation, according to the normal eutherian pattern.

Animals↗
PubMed2003

The role of androgens in development of the scrotum of the grey short-tailed Brazilian opossum ( Monodelphis domestica).

In eutherian mammals, sex differentiation is initiated by expression of the testis-determining gene on the Y chromosome. Subsequent phenotypic development of the reproductive tract and genitalia depends on the production of hormones by the differentiated testis. In marsupials the mechanisms of phenotypic development may vary from this pattern, as differentiation of the scrotal primordia has been shown to occur before that of the gonad. Thus, the development of the scrotum in the marsupial has been regarded as an androgen-independent process. We have sought to clarify the ontogeny of scrotal development and the appearance of androgen receptor immunoreactivity by examining Monodelphis domesticaembryos/pups from 1 day prior to birth until 2 days after birth. We have also used immunocytochemistry to determine the expression of the key steroidogenic enzyme 3beta-hydroxysteroid dehydrogenase as an indicator of when the developing gonad may be capable of synthesizing androgens. Expression of this enzyme was first detected in the gonads and adrenals of both sexes 1 day prior to birth and before the appearance of scrotal bulges. Androgen receptor immunoreactivity was detected in the scrotal anlagen of male opossum pups as early as 1 day following birth. This finding is significantly earlier than previous reports and coincides with the appearance 1 day after birth of distinct scrotal bulges. Androgen receptor immunoreactivity was also observed in the genital tubercles of male pups, but not female pups, 2 days after birth. These results suggest that androgens may play an important role in the development of the male genitalia at a much earlier stage than that indicated by previously published work and that scrotal development in this species may not be androgen-independent.

3-Hydroxysteroid Dehydrogenases↗
PubMed2002

The PreOp flexible sigmoidoscopy trainer. Validation and early evaluation of a virtual reality based system.

AIM: To demonstrate face and construct validity of a computer based flexible sigmoidoscopy trainer. METHODS: The PreOp (Immersion Medical, USA) system is a virtual reality based flexible sigmoidoscopy simulator. The system records several performance parameters, such as percentage of colonic mucosa visualized, time taken, and pathlength of endoscope travel. Forty-five subjects were divided into three groups: novice (never performed a lower GI endoscopy), intermediate (5-50 examinations), and trained (greater than 200 examinations). After initial familiarization subjects were assessed three times on a case module. Results showed a nonparametric distribution. RESULTS: There was a significant difference between all three groups with respect to percentage of mucosa visualized (novice 71.0 +/- 3.7%, intermediate 77.3 +/- 5.6%, expert 84.8 +/- 4.6%, Kruskal-Wallis p <0.001) and efficiency ratio (%mucosa/time, novice 0.163 +/- 0.055, intermediate 0.259 +/- 0.07, expert 0.306 +/- 0.058, p <0.001). The novice group was also slower and had a lower pathlength of instrument travel compared to the others. CONCLUSION: PreOp virtual reality simulator is a valid discriminator of flexible sigmoidoscopic experience. Its effect on training needs to be explored.

Clinical Competence↗
PubMed2002

Practice distribution in procedural skills training: a randomized controlled trial.

BACKGROUND: "Massed" and "distributed" practice are important concepts in the acquisition of fine motor skills, and may be important in training in procedural skills. METHODS: A total of 41 novice subjects were recruited and randomized to three groups to receive training on the MIST VR surgical trainer. There were 14 subjects in each of groups A and B and 13 subjects in group C. Training comprised 20 min of massed practice for group A, 20 min of distributed practice in 5 min blocks for group B, and 15 min of distributed practice in 5-min blocks for group C. Following the training period, all groups had a 5-min rest period, followed by a 5-min retention test. Comparisons were made between groups A and B, and groups A and C. RESULTS: There was a statistically significant difference between groups A and B (p = 0.023) on the retention test, with group B performing better. The increment between the groups was 19% for the overall score on MIST VR. There were also significant differences in the time taken to complete the task during the training phase (p = 0.023, training blocks 3 and 4). Graphical representation suggests no effect between groups A and C, and statistical analysis confirms that the observed difference in median score is not significant. CONCLUSION: This study demonstrates a benefit for distributed practice over massed practice in learning laparoscopic surgical skills on the MIST VR surgical trainer. This finding has potential implications for skills training in all areas of medicine.

Adult↗
PubMed2001

The use of electromagnetic motion tracking analysis to objectively measure open surgical skill in the laboratory-based model.

BACKGROUND: Technical performance has traditionally been assessed subjectively within the operating theater, with few successful attempts at objective analysis. The Imperial College Surgical Assessment Device (ICSAD) has already been shown to be a valid quantitative measure of dexterity in laparoscopic surgical simulation. We describe its application to the assessment of open surgical procedures. STUDY DESIGN: Fifty-one participants were recruited from four different levels of general surgical experience: basic surgical trainees (n = 12), junior specialist registrars (n = 13), senior specialist registrars (n = 13), and consultants (n = 13). They completed two tasks: a small bowel anastomosis and a vein patch insertion into an artery. Surgical performance was measured with the Imperial College Surgical Assessment Device, a motion analysis system that measures the number of hand movements made and time taken to complete a task. The four groups were compared statistically using the Kruskal-Wallis test (K-W). Pairwise group comparisons used the Mann-Whitney U test and p values were adjusted for multiple comparisons to determine the statistical significance of these comparisons. RESULTS: Mean values for number of movements and time (secs) for small bowel anastomosis were 2,080/1,236 (basic surgical trainees), 1,673/1,016 (junior specialist registrars), 1,375/862 (senior specialist registrars), and 1,337/782 (consultants), respectively. Comparison of the medians by K-W revealed a p < 0.001 for each variable (No. of movements, time), respectively. Mean vein patch insertion results were 1,653/1,258, 1,297/1,006, 1,090/912, and 925/736 for each of the four groups. Again, comparison of the medians by K-W revealed a p < 0.001 for each variable. CONCLUSIONS: These findings suggest that hand motion analysis may be an effective objective measure of dexterity in open surgical simulation.

Anastomosis, Surgical↗
PubMed2001

Upper-limb function in Australian children with traumatic brain injury: A controlled, prospective study.

OBJECTIVE: To describe upper-limb function in children with mild and severe traumatic brain injury (TBI), by using both quantitative and qualitative measures. DESIGN: Controlled, prospective cohort study with assessment points initially, at 6 months, and at 2 years after TBI. SETTING: A tertiary pediatric trauma center in Australia. PATIENTS: Fifty-one children, ranging in age up to 14 years, who were consecutive admissions with TBI. On the basis of initial and persisting abnormal coma score and persistence of posttraumatic amnesia, they were assigned to either a mild (n = 26) or a severely injured (n = 25) group. Thirty children admitted with non-TBI trauma were recruited as a control group. MAIN OUTCOME MEASURES: Quantitative measures included Bruininks-Oseretsky Test of Motor Proficiency and Peabody Developmental Motor Scales. Qualitative measures included Brunnstrom Recovery Stages (adapted), categoric scales of muscle tone, grasp used when handwriting, quality of writing product, bilateral activity, and splint use. RESULTS: There was little difference between the groups on the standardized assessments for subjects who could complete the tests. Qualitative measures showed the severe TBI group to have more difficulties with gross arm control, hand control, and hand function. CONCLUSION: Children with severe TBI experience more and persisting difficulties with upper-limb function. It is essential to include both quantitative and qualitative measures in this type of research.

Adolescent↗
PubMed2001

Nuclear factor-kappa B is upregulated in colorectal cancer.

BACKGROUND: Chemoresistance may involve the anti-apoptotic transcriptional regulator, nuclear factor-kappa B (NF-kappa B). The purpose of this study was to determine whether chemotherapy induces NF-kappa B activation in a human colon cancer cell line (SW48) and whether NF-kappa B is constitutively activated in colorectal cancer. METHODS: SW48 cells were incubated with gemcitabine hydrochloride (Gemzar) in the presence and absence of the 26s proteasome inhibitor, MG132, and NF-kappa B binding (electrophoretic mobility shift assay), DNA synthesis (tritiated thymidine uptake), cell viability (3-[4,5-dimethylthiazol-2-yl]-diphenyl-tetrazolium bromide assay), and apoptosis (caspase-3 activity) were measured at 24 hours. NF-kappa B binding (electrophoretic mobility shift assay) was also assayed in 10 colorectal cancer tumors. RESULTS: SW48 cells demonstrated constitutive NF-kappa B binding that was enhanced by gemcitabine hydrochloride in a dose-dependent manner. MG132 inhibited NF-kappa B binding and enhanced gemcitabine hydrochloride's inhibition of DNA synthesis (gemcitabine hydrochloride = 73% +/- 1.4% vs gemcitabine hydrochloride + MG132 = 6% +/- 0.4%, P <.05), cell killing (gemcitabine hydrochloride = 87% +/- 2.0 vs gemcitabine hydrochloride + MG132 = 25% +/- 1.3%, P <.05), and caspase-3 activity (gemcitabine hydrochloride = 870 +/- 17.4 vs gemcitabine hydrochloride + MG132 = 1075 +/- 20.4, P <.05). NF-kappa B binding was increased in 8 of 10 colorectal cancer tumors compared with adjacent normal mucosa. CONCLUSIONS: Gemcitabine hydrochloride enhances NF-kappa B binding in a colorectal cancer cell line, whereas inhibition of NF-kappa B enhances gemcitabine hydrochloride's antitumor activity. NF-kappa B is also activated in human colorectal cancer. NF-kappa B may identify chemoresistant tumors, whereas inhibition of NF-kappa B may be a novel, biologically based therapy. (Surgery 2001;130:363-9).

Antimetabolites, Antineoplastic↗
PubMed2001

Assessment of surgical competence.

This paper examines the issues that arise in the broad area of competence assessment in surgical practice, with particular reference to the objective assessment of technical skill which has historically been the weakest aspect of assessment in surgical training. To facilitate a thorough appraisal of competence, a simple model of surgical practice is advanced, followed by a review of both current and experimental methods of assessing technical skill. The review comprises not only the published literature, but also work (both from the authors' and other groups) that is in progress or under consideration for publication. Significant issues in the implementation of these new technologies, especially the necessary further validation, and the imperative to demonstrate that the process introduced does indeed improve the outcomes are discussed.

Clinical Competence↗
PubMed2001

Web-based surgical educational tools.

This paper describes work being undertaken as part of the WebSET (Web-based Standard Educational Tools) project. The project is producing a standardised suite of interactive three-dimensional educational tools, delivered across the WWW. The major focus will be the use of open technology and standards, and the production of learning components that can be used as building blocks for further development in a wide range of application areas. Two learning disciplines have been selected for the development of the WebSET tools: surgical training, and physiological education. A high quality consortium from across Europe has been assembled with complementary skills in the technologies needed by the project. The project is partly funded by the European Commission.

Curriculum↗
PubMed2000

Gonadal development in mammals at the cellular and molecular levels.

In mammals, although sex is determined chromosomally, gonads in both sexes begin development as similar structures. Until recently it was widely held that female development constituted a "default" pathway of development, which would occur in the absence of a testis-determining gene. This master gene on the Y chromosome, SRY in the human and Sry in the mouse, is thought to act in a cell-autonomous fashion to determine that cells in the gonadal somatic population develop as pre-Sertoli cells. Triggering of somatic cell differentiation along the Sertoli cell pathway is therefore a key event; it was thought that further steps in gonadal differentiation would follow in a developmental cascade. In the absence of Sertoli cells, the lack of anti-Mullerian hormone would allow development of the female Mullerian duct and absence of Leydig cells would prevent maintenance of the Wolffian duct. Recent findings that female signals not only maintain the Mullerian duct and repress the Wolffian duct but also suppress the development of Leydig cells and maintain meiotic germ cells, together with the finding that an X-linked gene is required for ovarian development and must be silenced in the male, have shown that the female default pathway model is an oversimplification. Morphological steps in gonadal differentiation can be correlated with emerging evidence of molecular mechanisms; growth factors, cell adhesion, and signaling molecules interact together, often acting within short time windows via reciprocal control relationships.

Animals↗
PubMed1999

E-cadherin in the developing mouse gonad.

Expression of the cell adhesion molecule E-cadherin in the developing mouse has been investigated by immunocytochemistry and disaggregated organ culture. The principal aims were firstly, to determine whether E-cadherin is expressed in the indifferent gonad and if so with which cell population(s) it is associated. Secondly, to investigate the pattern of expression in the mesonephros, especially in relation to ventral mesonephric tubule cells, which contribute to the somatic cell population of the gonad. Thirdly, to discover whether there are any sex differences in expression of E-cadherin in differentiating gonads. Germ cells in the indifferent gonad showed strong immunoreactivity whereas somatic cells were unstained unless their membranes were in contact with those of germ cells. Positive staining for E-cadherin was found in epithelial cells of the mesonephric duct and tubules. Staining was weak at the ventral margins of the ventral mesonephric tubules. At later stages, germ cell immunoreactivity could be correlated with stages of ovarian differentiation, being reduced or absent between germ cells at 16 days post coitum, when ovigerous cords become dissociated as a prelude to follicle formation. Stronger staining reappeared briefly at 17 days post coitum, the time of follicular cell attachment to oocytes, before waning again 2 days later. Similarly, immunoreactivity in the differentiating testis was initially restricted to the germ cell population but pre-Sertoli cells were strongly positive between 16 and 19 days post coitum. The most striking sex difference was seen in the somatic cell population, where Leydig cells of the testis became strongly positive for E-cadherin from 17 days post coitum onwards. At this time, unlike controls, dissociated cells from gonads of either sex were unable to reform their initial contacts when cultured in the presence of the antibody to E-cadherin, confirming its functional importance.

Animals↗
PubMed1999

Ultrastructural studies demonstrate that epithelial polarity is established in cultured mouse pre-Sertoli cells by extracellular matrix components.

The effect of three different substrates, laminin, fibronectin and reconstituted basement membrane, on isolated mouse pre-Sertoli cells maintained in vitro has been investigated. Cultures were monitored on a daily basis by phase contrast microscopy, and processed for light and electron microscopy at the end of the culture period. Extra-cellular matrix components have been found to influence Sertoli cell differentiation: both fibronectin and laminin promoted cell adhesion and differentiation, though laminin cultures showed poor viability. Pre-Sertoli cells cultured on reconstituted basement membrane showed the highest degree of differentiation, developing a polarized epithelial phenotype and forming cord-like aggregates; such cultures provide a model system for the investigation of factors involved with gonadal differentiation.

Animals↗
PubMed1998

Postnatal development of Leydig cells in the opossum (Monodelphis domestica): an immunocytochemical and endocrinological study.

This study involved characterization of Leydig cells of the opossum Monodelphis domestica, functionally by immunocytochemical identification of the enzyme 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and by measurement of testosterone levels using RIA. Immunostaining for 3 beta-HSD was first detected in a few Leydig cells on Day 16, was increased by Day 24, reached a peak at 4 mo, and was present even in senescent (3 yr) animals. Plasma testosterone was first measurable (0.35 nM) at prepuberty (3.5 mo). Prior to that, plasma testosterone concentrations were uniformly below the level of detection (< 0.3 nM) in both sexes from Day 5 to 2.5 mo. By 4 mo (puberty), plasma testosterone levels in males had risen significantly to 1.53 +/- 0.35 nM, continuing to increase to 1.79 +/- 0.4 nM at 6 mo and peaking at 2.71 +/- 0.29 nM in the adult (1-2 yr). Ovarian testosterone concentrations were consistently lower than those in the testis, as were those of adrenals of both sexes. Thus the testis would appear to be the major source of androgen production throughout life in this species. Our immunocytochemical study suggests that in Monodelphis, puberty is reached at 4 mo, and this was further supported by a rise in circulating testosterone levels at this time.

3-Hydroxysteroid Dehydrogenases↗