Assisted reproductive technologies: professional and legal restrictions in Australian clinics.

The professional and legal regulation of assisted reproductive technologies (ART) in Australia is a vast maze of intersecting laws and guidelines which place restrictions on the provision of services such as infertility treatment, surrogacy, sex selection for social reasons, donor insemination, pre-implantation diagnosis and human embryo research. This study investigated the application of these restrictions on clinical practice in New South Wales, a relatively unregulated State, and Victoria, a relatively highly regulated State. The results of the survey indicate that the range of ART services in Victorian clinics was far more limited than in New South Wales clinics. The Victorian clinics uniformly restricted access of single and lesbian women and did not offer social sex selection procedures. The New South Wales clinics adopted different polices regarding these services. It was found that restrictive laws governing "social" issues have a significant impact on the availability of ART services and some respondents seemed unclear about the nature of restrictions and laws relevant to their work. It was also found that "reproductive tourism" is prevalent and restrictions were circumnavigated by patients with assistance from clinics. It was concluded that more evidence is required to evaluate regulation in this field of medicine.

Topographical memory impairments after unilateral lesions of the anterior thalamus and contralateral inferotemporal cortex.

Monkeys with crossed unilateral excitotoxic lesions of the anterior thalamus and unilateral inferotemporal cortex ablation were severely impaired at learning two tasks which required the integration of information about the appearance of objects and their positions in space. The lesioned monkeys were also impaired at learning a spatial task and a task which required the integration of information about the appearance of objects and the background on which the objects were situated. Monkeys with only one of the unilateral lesions were not impaired and previous work has shown that monkeys with bilateral lesions of the anterior thalamus were not impaired on these tasks. These results indicate that the whole of the inferotemporal cortex-anterior thalamic circuit, which passes via the hippocampus, fornix, mamillary bodies and mamillothalamic tract, is essential for the topographical analysis of information about specific objects in different positions in space. Together with previous work, the results show that a unilateral lesion may affect cognition in the presence of other brain damage when an equivalent bilateral lesion alone does not. The tasks required the slow acquisition of information into long term memory and therefore assessed semantic knowledge although other research has shown impairment on topographical processing within working or episodic memory following lesions of the hippocampal-diencephalic circuit. It is argued that the hippocampal-diencephalic circuit does not have a role in a specific form of memory such as episodic memory but rather is involved in topographical analysis of the environment in perception and across all types of declarative memory.

Prediction of student performance on the Comprehensive Osteopathic Medical Licensing Examination Level I based on admission data and course performance.

To predict student performance on the Comprehensive Osteopathic Medical Licensing Examination (COMLEX-USA) Level 1 examination based on academic performance during the first 2 years, stepwise regression analysis of COMLEX-USA Level 1 performance with preadmission grade point averages, Medical College Admission Test scores, and academic performance was performed on the class of 2000 to develop three formulae that were then used to predict performance on COMLEX-USA Level 1 for the class of 2001. Models ranged in accuracy of predicting the pass/fail status from 95.2% (all available data) to 96.8% (first-year grades and admissions data). A predictive model for student performance on COMLEX-USA Level 1 can be developed and has a high degree of accuracy. The model with the most variables available to choose from predicts the most failures.

Necrospermia and chronic spinal cord injury.

OBJECTIVE: To determine whether improvement in quality of semen over 4 consecutive days of electroejaculation in men with chronic spinal cord injury (SCI) was consistent with epididymal necrospermia. DESIGN: Prospective study of a random sample of men with SCI. SETTING: A southeastern Australian SCI management center in collaboration with the specialist andrology service of a university-based department of obstetrics and gynecology in a tertiary referral hospital. PATIENT(S): Nine men with chronic spinal cord injury. INTERVENTION(S): Semen samples were obtained by using electroejaculation, and testicular biopsy samples were obtained by using fine-needle tissue aspiration. MAIN OUTCOME MEASURE(S): Semen analysis was performed according to World Health Organization criteria. Testicular biopsy and electron microscopy were done by using standard techniques. RESULT(S): During up to 4 days of consecutive-day electroejaculation, sperm motility and viability in semen obtained from men with chronic SCI increased by an average of 23% on days 2 and 3. The severity of the degenerative changes and the numbers of spermatozoa affected on day 1 became less marked by day 4. The changes were not present in late spermatids obtained from testicular biopsies. CONCLUSION(S): The asthenospermia of chronic SCI is similar to epididymal necrospermia and can be improved by consecutive-day electroejaculation.

Relationship between academic achievement and COMLEX-USA Level 1 performance: a multisite study.

The purpose of this study was to examine the relationship of performance on the Comprehensive Osteopathic Medical Licensing Examination (COMLEX-USA) Level 1 with academic performance at colleges accredited by the American Osteopathic Association (AOA). Eighteen (95%) of 19 AOA-accredited colleges and 2146 students (91% of those taking the June 1999 examination) met criteria and participated. Students were classified by school representatives on the basis of academic performance in the first 2 years of the curriculum. The relationships of Level 1 performance with assigned classifications and grade point averages (GPAs) were studied. Of students classified in the highest 20% academically, the Level 1 pass rate was 100%, with a mean score of 599. Of students classified in the lowest 5%, the pass rate was 63.5%, with a mean of 416.3. For 16 schools that provided GPAs, the within-school correlations between Level 1 scores and GPAs ranged from r = 0.76 to r = 0.85, with a mean correlation of r = 0.79. School representatives were also asked to indicate, for each student, whether they expected the student to pass the examination. Pass rate for students in the "sure pass" category was 98.9%; "borderline," 82.5%; and "concerns," 61.5%. Academic performance in the first 2 years of osteopathic medical school was strongly associated with performance on COMPLEX-USA Level 1. The national pass rate for this examination was similar to those in previous years, and it remains unclear why school representatives overpredicted the number of failures. Further research is needed.

Relationship of preadmission variables and first- and second-year course performance to performance on the National Board of Osteopathic Medical Examiners' COMLEX-USA Level 1 examination.

The purpose of this study was to examine the relationship of performance on the Comprehensive Osteopathic Medical Licensing Examination (COMLEX-USA) Level 1 licensing examination to (1) academic performance during the first 2 years of the curriculum, and (2) preadmission grade point averages (GPAs) and Medical College Admission Test (MCAT) scores for one osteopathic medical school with the unique mission of providing osteopathic family physicians for West Virginia and rural Appalachia. Simple correlations were calculated for the 63 students at West Virginia School of Osteopathic Medicine who completed all requirements of the first 2 years of the curriculum in May 1998 and were first eligible for board exams in June 1998. These included 26 (41.3%) female students and 5 (7.9%) minority students. Students who had failed a year and/or a course but subsequently successfully completed the first 2 years of the curriculum in May 1998 were included in this study. Every student who qualified to take the June 1998 administration of COMLEX-USA Level 1 did so at that time. For the 55 academic or preadmissions variables of interest, correlation coefficients with COMLEX-USA Level 1 scores and significance levels were calculated using SPSS Base 9.0. The correlation of COMLEX-USA Level 1 performance with GPA for Phase I was 0.64; with GPA for Phase II, 0.67; and total GPA for the first 2 years, 0.70. Grades in most individual courses also correlated significantly with COMLEX-USA Level 1 performance. Given the special focus of this curriculum on the needs of the Appalachian region and use of clinical performance measures or participation measures in calculating academic GPAs, these correlations show a remarkable degree of agreement between these two sets of performance measures. Further research is needed to see if similar relationships exist for osteopathic medical schools with other missions and with other curriculum structures. Preadmissions GPAs and MCATs did not significantly relate to performance on COMLEX-USA Level 1.

Thiamin status of gravidas treated for gestational diabetes mellitus compared to their neonates at parturition.

Since thiamin plays a role in glucose metabolism we wanted to know if blood thiamin influx from gravida to neonate was influenced by treatment of gravidas having gestational diabetes mellitus (GDM). In this study we found thiamin hypovitaminemia in 19% of the 77 pregnancies despite vitamin supplementation and treatment for GDM; neonates born to mothers with hypovitaminemia were also thiamin hypovitaminemic. All neonatal blood had significantly higher thiamin concentration than gravidas. Indeed, cord blood from neonates born to mothers treated with insulin for GDM had significantly higher thiamin concentration than other neonates in the study. A significant weight depression was noted in neonates born to treated GDM mothers. Healthy gravidas giving birth to macrosomia neonates, had significant thiamin hypovitaminosis, but only macrosomic neonates of treated diabetic mothers had significantly depressed blood thiamin concentrations. We noted that subclinical thiamin hypovitaminemia is prominent during pregnancy despite vitamin supplementation. Perhaps increased thiamin supplementation during pregnancy seems warranted to avoid metabolic stress in mother and fetus due to thiamin hypovitaminemia.

Lack of effect of 1 year intake of a high-dose vitamin and mineral supplement on cognitive function of elderly women.

OBJECTIVE: To determine if long-term, high-vitamin supplementation could reverse cognitive malfunction in old people. METHODS: We performed a longitudinal study relating the 12-month outcome to baseline values. Twenty non-vitamin-deficient elderly females with a Folstein mini mental state examination score indicating cognitive malfunctions were recruited to ascertain if feeding a high-dose vitamin-mineral supplement for 1 year could, by mass vitamin action, reverse some existing cognitive malfunctions. Ten females were fed a high-dose vitamin-mineral supplement pill with each of three daily meals for 1 year; the other 10 did not receive this supplementation. Twelve blood vitamin analyses and a Folstein mini mental state examination were performed for each of the 20 subjects before and after 1 year; each subject served as its own control. RESULTS: No improvement in cognitive malfunction was noted despite elevation of blood vitamins. CONCLUSION: Feeding of a high-dose vitamin and mineral supplement for 1 year did not improve cognitive malfunction in non-vitamin-deficient elderly in this study.

Evaluation of the effects of omega-3 fatty acid-containing diets on the inflammatory stage of wound healing in dogs.

OBJECTIVES: To ascertain the effects of dietary omega-3 (n-3) fatty acids on biochemical and histopathologic components of the inflammatory stage of wound healing. ANIMALS: 30 purpose-bred Beagles. PROCEDURE: Dogs were allotted to 5 groups of 6. Each group was fed a unique dietary fatty acid ratio of omega-6 to n-3--diet A, 5.3:1; diet B, 10.4:1; diet C, 24.1:1; diet D, 51.6:1; and diet E, 95.8:1. Dogs were fed once daily for 12 weeks, then biopsy specimens were taken from 4-day-old wounds of each dog and analyzed by gas chromatography-mass spectrometry for: prostaglandin E2 (PGE2) metabolites, and ratios of omega-6 to n-3 fatty acids, arachidonic acid (AA) to eicosapentaenoic acid (EPA), adrenic acid to docosahexaenoic acid, and PGE2 to prostaglandin E3 (PGE3) metabolites. RESULTS: Qualitative analysis was carried out on AA, EPA, adrenic acid, docosahexaenoic acid, and the major metabolite from the PGE2 and PGE3 pathway. These molecules were further quantified with respect to diet to determine significant differences. By analysis of the AA-to-EPA ratio, diet A was different from diets D and E and diets B and C were different from diet E (P < 0.05). By analysis of the PGE2-to-PGE3 metabolite ratio, diet A was different from diet E (P < 0.05). Though biochemical analysis indicated dietary dependence, histopathologic data indicated no significant difference with respect to diet groups. CONCLUSION: The biochemical component of the inflammatory stage of wound healing can be manipulated by diet. CLINICAL RELEVANCE: Omega-3 fatty acid-enriched diets can be used to control inflammation associated with dermatologic conditions.

AP-1 transcription factor binding activity in rat adrenal medulla and hypothalamus with age and cold exposure.

The AP-1 regulatory element has been implicated in the cold-induced expression of tyrosine hydroxylase in the adrenal medulla. Since in this tissue, the cold-induced increase in tyrosine hydroxylase expression is impaired with age and in other tissues, there is some evidence that AP-1 transcription factor binding is diminished with age, we examined the cold-stimulated AP-1 transcription factor binding to an oligonucleotide with the consensus sequence of the AP-1 response element in nuclear extracts from adrenal medulla and hypothalamus of young and senescent rats. AP-1 transcription factor binding activity diminished by 38% with age in unstimulated adrenal medulla. Following cold stimulation, the AP-1 binding activity increased by 21-25% in the adrenal medulla of both young and senescent rats. However, the level of AP-1 binding in cold-stimulated senescent rats was still less than in cold-stimulated younger rats. There were no changes in AP-3 binding activity with either age or cold exposure in the adrenal medulla. Similarly, in the hypothalamus, there was a 25% decrease with age and a 25% increase following cold stimulation in the level of AP-1 binding. There was a 62% age-related increase in AP-3 binding activity but no change with cold exposure. These data indicate that there is reduced AP-1 binding activity in senescent control rats. Moreover, the demonstration that cold stimulus evokes similar increases in AP-1 binding activity in both young and old rats suggests that the stimulation pathway that increases AP-1 transcription factor is maintained in the senescent animal.

Protein kinase C plays an important role in the human zona pellucida-induced acrosome reaction.

To investigate the involvement of protein kinases in signal transduction in the human zona pellucida (ZP)-induced acrosome reaction (AR), the effects of protein kinase (PK) activators, dibutyryl cAMP (PKA) and cGMP (PKG), phorbol 12-myristate 13-acetate (PMA, PKC), and the PKC inhibitor, staurosporine were studied. Sperm samples were obtained from normozoospermic men with normal sperm-ZP binding. Oocytes were obtained from other patients with failure of fertilization in vitro. Motile spermatozoa selected by a swim-up technique were pre-incubated with 2.5-20 microM PMA, 1 mM dibutyryl cAMP or cGMP, 3 mM pentoxifylline or 0.125-2.0 microM staurosporine for 30 min and then incubated with four oocytes for 2 h in human tubal fluid supplemented with bovine serum albumin. The spermatozoa bound to the ZP were dislodged by repeatedly aspirating the oocytes with a small bore pipette and the state of the AR was determined by fluorescein-labelled Pisum sativum agglutinin. Motility and movement characteristics were assessed by computer-assisted sperm analysis (CASA) after incubation of spermatozoa with PMA for 30 min and 2 h. The dibutyryl cAMP and cGMP analogues had a small positive effect (P < 0.05) but pentoxifylline had no effect on stimulating the ZP-induced AR (P > 0.05). In contrast, PMA stimulated ZP-induced AR in a marked dose-dependent manner. Only the highest concentrations (15-20 microM) of PMA significantly decreased percentage motility (P < 0.001). Doses of 2.5-15 microM of PMA significantly stimulated ZP-induced AR without decreasing motility (P < 0.001). The PKC inhibitor, staurosporine (0.125-0.25 microM) significantly inhibited ZP-induced AR without affecting motility (P < 0.001). Sperm samples from 33 normozoospermic men were used for studies of the ZP-induced AR augmented with 15 microM PMA. One sample did not show a response to PMA stimulation. Among the 14 men with low ZP-induced AR, half had normal responses to PMA and other half had low responses to PMA. In conclusion, activation or inhibition of PKC significantly increases or decreases human ZP-induced AR suggesting that PKC plays a important role in the signal transduction pathway for the physiological AR.

Molecular cloning of ictacalcin: a novel calcium-binding protein from the channel catfish, Ictalurus punctatus.

Calcium is essential for a variety of functions in animals, including signal transduction, transmission of nerve impulses, and bone and scale growth. In freshwater adapted teleosts, blood calcium levels are maintained constant (2-4 mM) even at low external calcium concentration (< 0.01 mM). Epithelial cells in skin and gill have been implicated in calcium homeostasis. We have cloned a cDNA from Ictalurus punctatus, the channel catfish, that codes for ictacalcin, a novel member of the S100 family of calcium-binding protein. In-situ hybridization demonstrates ictacalcin mRNA is abundant in epithelial cells of olfactory rosette, barbel, skin and gill but not brain or muscle. The presence of ictacalcin protein in these tissues was confirmed by immuno-blot analysis. Tissue extracts and recombinant ictacalcin bind calcium with attendant changes in electrophoretic mobility indicative of changes in protein conformation. The calcium-binding activity and abundant localization of ictacalcin in epithelial cells of several tissues indicates that this protein plays an important role in catfish calcium homeostasis.

Micronutrient profiles in HIV-1-infected heterosexual adults.

There is compelling evidence that micronutrients can profoundly affect immunity. We surveyed vitamin supplement use and circulating concentrations of 22 nutrients and glutathione in 64 HIV-1 seropositive men and women and 33 seronegative controls participating in a study of heterosexual HIV-1 transmission. We assayed antioxidants (vitamins A, C, and E; total carotenes), vitamins B6 and B12, folate, thiamin, niacin, biotin, riboflavin, pantothenic acid, free and total choline and carnitine, biopterin, inositol, copper, zinc, selenium, and magnesium. HIV-infected patients had lower mean circulating concentrations of magnesium (p < 0.0001), total carotenes (p = 0.009), total choline (p = 0.002), and glutathione (p = 0.045), and higher concentrations of niacin (p < 0.0001) than controls. Fifty-nine percent of HIV+ patients had low concentrations of magnesium, compared with 9% of controls (p < 0.0001). These abnormal concentrations were unrelated to stage of disease. Participants who took vitamin supplements had consistently fewer low concentrations of antioxidants, across HIV infection status and disease stage strata (p = 0.0006). Nevertheless, 29% of the HIV+ patients taking supplemental vitamins had subnormal levels of one or more antioxidants. The frequent occurrence of abnormal micronutrient nutriture, as found in these HIV+ subjects, may contribute to disease pathogenesis. The low magnesium concentrations may be particularly relevant to HIV-related symptoms of fatigue, lethargy, and impaired mentation.

Female enrollment in colleges of osteopathic medicine: five years and five percentage points behind.

An estimated one fifth of graduates of the colleges of osteopathic medicine (COMs) before 1910 were women. However, the proportion of women declined after 1900, so that by 1969, less than 3% of osteopathic medical students were women. Dramatic gains have been made in the past 25 years: for the 1993-1994 academic year, women made up 35% of all osteopathic medical students. Although these gains seem impressive, allopathic medical school enrollment comprised 40% women during the same academic year (5 percentage points higher than in osteopathic medical schools). Allopathic medical schools have had significantly more women enrolled every year between academic years 1969-1970 and 1993-1994. In academic year 1988-1989, allopathic medical schools already had an enrollment that consisted of 35% female students, a percentage that COMs would first reach 5 years later. Based on these findings, enrollment of women in COMs is 5 years and 5 percentage points behind that of allopathic medical schools.

Innervation-independent changes in the mRNAs encoding tyrosine hydroxylase and the norepinephrine transporter in rat adrenal medulla after high-dose reserpine.

To determine whether a trans-synaptic mechanism triggered the effects of reserpine on adrenomedullary mRNAs encoding the norepinephrine transporter and tyrosine hydroxylase, we administered 10 mg/kg reserpine to rats after unilateral splanchnicotomy, and examined their adrenal medullas using quantitative in situ hybridization. Splanchnicotomy did not alter the decrease in norepinephrine transporter mRNA that follows reserpine administration, but diminished the reserpine-induced increase in tyrosine hydroxylase mRNA by almost 80%. Despite the latter effect, reserpine still induced a significant increase in tyrosine hydroxylase mRNA in denervated adrenal medullas, compared to vehicle-treated adrenal medullas. These results show that a trans-synaptic mechanism does not trigger the decrease in adrenomedullary norepinephrine transporter mRNA following reserpine. In addition, an innervation-independent mechanism mediates a portion of the reserpine-induced increase in adrenomedullary tyrosine hydroxylase mRNA.

Daily micronutrient supplements enhance delayed-hypersensitivity skin test responses in older people.

A placebo-controlled double-blind trial of the effects of daily micronutrient supplements on circulating vitamin and trace metal concentrations and delayed-hypersensitivity skin test (DHST) responses was conducted. Subjects, aged 59-85 y, were randomly assigned to placebo (n = 27) or micronutrient (n = 29) treatment groups. DHST and circulating concentrations of nine micronutrients were measured before and after 6 and 12 mo of micronutrient ingestion. For the micronutrient group, there were statistically significant increases at 6 and/or 12 mo in the mean serum concentrations of ascorbate, beta-carotene, folate, vitamin B-6, and alpha-tocopherol. There was a significant increase at 12 mo in the number of subjects in the placebo group with one or more low concentrations. DHST responses to a panel of seven recall antigens were significantly increased at 12 mo in the micronutrient group but not the placebo group. This study demonstrates that daily supplementation with low-to-moderate doses of micronutrients can prevent low concentrations of some micronutrients and can improve DHST responses in healthy, independently living older adults.

Three-dimensional structure of lactoferrin in various functional states.

The three-dimensional structures of various forms of lactoferrin, determined by high resolution crystallographic studies, have been compared in order to determine the relationship between structure and biological function. These comparisons include human apo and diferric lactoferrins, metal and anion substituted lactoferrins, the N-terminal half molecule of human lactoferrin, and bovine diferric lactoferrin. The structures themselves define the nature and location of the iron binding sites and allow anti-bacterial and putative receptor-binding regions to be mapped on to the molecular surface. The structural comparisons show that small internal adjustments can allow the accommodation of different metals and anions without altering the overall molecular structure, whereas large-scale conformational changes are associated with metal binding and release, and smaller, but significant, movements accompany species variations. The results also focus on differences in flexibility between the two lobes, and on the importance of interactions in the inter-lobe region in modulating iron release from the N-lobe and in possibly enabling binding at one site to be signalled to the other.