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Biomedical subjects

B Richardson

Publications and source records attributed to B Richardson.

At least 19 recordsLinked to original sources
PubMed2005

Randomised controlled trial and cost consequences study comparing initial physiotherapy assessment and management with routine practice for selected patients in an accident and emergency department of an acute hospital.

OBJECTIVE: The Department of Health is reviewing the effectiveness of accident and emergency (A&E) departments. This study aimed to compare health and economic effects of physiotherapy initial assessment and management with routine practice in an A&E department. METHODS: Randomised controlled trial and cost and consequences study. Patients presenting at A&E were eligible if suspected at triage to have soft tissue injury without fracture. The efficacy end point was "days to return to usual activities". Secondary end points included patient satisfaction with their care and further health outcomes and cost data. RESULTS: 766 of 844 (915) patients were randomised. The median days before return to usual activities (available for 73% of those randomised) was greater in the physiotherapist group (41 days compared with 28.5 days; hazard ratio 0.85 p = 0.071). The physiotherapy group expressed greater satisfaction with their A&E care (on a scale of 1 to 5, median was 4.2 compared with 4.0, p<0.001), were more likely to be given advice and reassurance, and more likely to be provided with aids and appliances. Costs were the same between the two arms. CONCLUSION: There is evidence that physiotherapy leads to a prolonged time before patients return to usual activities. This study shows no clear danger from physiotherapy intervention and long term outcomes may be different but given these findings, a best estimate is that introducing physiotherapist assessment will increase costs to the health service and society. Routine care should continue be provided unless there is some reason why it is not feasible to do so and an alternative must be found.

Adolescent↗
PubMed2004

Identification of two novel allelic variants of ESX1L in the human placenta: lack of an association with intrauterine growth restriction.

Intrauterine growth restriction (IUGR) is a leading cause of neonatal morbidity and mortality. Although epidemiological studies implicate an important role for genetic factors in determining birth weight, few candidate genes for IUGR have been identified. ESX1L, the orthologue of Esx1, is an X chromosome-linked human homeobox gene expressed in the placenta and testis. The present study was undertaken to determine if aberrations in the ESX1L gene were associated with idiopathic IUGR because targeted deletion of Esx1 in the mouse leads to abnormal placental development and consequent IUGR. Genotyping analysis of ESX1L gene was performed on placental samples from 22 normal term and 12 IUGR term fetuses. Two allelic variants were identified, and they contain an insertion and a deletion, respectively, of the same 27 nucleotides in the highly repetitive region of exon-4 that encodes the previously identified 12 contiguous repeats of a unique 9-amino acid motif, PPMAP(V/L)PPG. Thus, the insertion and deletion variants were predicted to code for an aberrant ESX1L protein containing 13 and 11 contiguous repeats, respectively. However, both variants were detectable and evenly distributed in normal as well as IUGR placentae, indicating that these two variants of ESX1L do not contribute to genetic susceptibility to idiopathic IUGR. Furthermore, no single nucleotide polymorphisms were identified, and there was no difference in the level of ESX1L mRNA between control and IUGR placentae. Taken together, these findings provide the first evidence that two allelic variants of ESX1L exist in the human placenta but they are not associated with idiopathic IUGR.

Alleles↗
PubMed2001

Estimating the efficacy of interventions to prevent mother-to-child transmission of HIV in breast-feeding populations: development of a consensus methodology.

Postnatal transmission of HIV through breast milk complicates both the design of effective interventions to prevent mother-to-child transmission of HIV (PMTCT) and their evaluation. Estimated long-term efficacy in five African trials (four with peri-partum antiretrovirals and one with artificial feeding) varied from 25 to 50 per cent. This variation may be due, at least in part, to differences in analytical methodology. To facilitate direct comparison between trials, a methodological consensus approach to the analysis and presentation of the results of PMTCT trials was developed. The initial methodology used and results presented from African trials with available long-term efficacy data were reviewed during a workshop in Bordeaux, France, in September 2000. A consensus approach for evaluating efficacy applicable across PMTCT studies was developed. There are four typical situations defined by duration of follow-up (short versus long), and the available demographic (vital status) and biological data (single versus repeat HIV testing). Efficacy can be assessed from the risk of infection directly or from HIV-free survival by combining infection and death as a single endpoint. Studies should report results in a standardized format including infection, weaning, mortality and loss to follow-up. New statistical methods that account for the unknown date when a child would first test positive for HIV, for weaning as a competing risk for HIV infection, and for increased risk of death among HIV-infected children should be used in analysing data from PMTCT studies with repeat HIV testing. All estimates should be reported with confidence intervals. This standardized methodology that allows direct comparison between studies is now being applied to four randomized clinical trials.

Antiviral Agents↗
PubMed2001

Morbidity and mortality in breastfed and formula-fed infants of HIV-1-infected women: A randomized clinical trial.

CONTEXT: Breastfeeding among women infected with human immunodeficiency virus type 1 (HIV-1) is associated with substantial risk of HIV-1 transmission, but little is known about the morbidity risks associated with formula feeding in infants of HIV-1-infected women in resource-poor settings. OBJECTIVE: To compare morbidity, nutritional status, mortality adjusted for HIV-1 status, and cause of death among formula-fed and breastfed infants of HIV-1-infected women. DESIGN: Randomized clinical trial conducted between 1992 and 1998. SETTING: Four antenatal clinics in Nairobi, Kenya. PARTICIPANTS: Of 401 live-born, singleton, or first-born twin infants of randomized HIV-1-seropositive mothers, 371 were included in the analysis of morbidity and mortality. INTERVENTIONS: Mothers were randomly assigned either to use formula (n = 186) or to breastfeed (n = 185) their infants. MAIN OUTCOME MEASURES: Mortality rates, adjusted for HIV-1 infection status; morbidity; and nutritional status during the first 2 years of life. RESULTS: Two-year estimated mortality rates among infants were similar in the formula-feeding and breastfeeding arms (20.0% vs 24.4%; hazard ratio [HR], 0.8; 95% confidence interval [CI], 0.5-1.3), even after adjusting for HIV-1 infection status (HR, 1.1; 95% CI, 0.7-1.7). Infection with HIV-1 was associated with a 9.0-fold increased mortality risk (95% CI, 5.3-15.3). The incidence of diarrhea during the 2 years of follow-up was similar in formula and breastfeeding arms (155 vs 149 per 100 person-years, respectively). The incidence of pneumonia was identical in the 2 groups (62 per 100 person-years), and there were no significant differences in incidence of other recorded illnesses. Infants in the breastfeeding arm tended to have better nutritional status, significantly so during the first 6 months of life. CONCLUSIONS: In this randomized clinical trial, infants assigned to be formula fed or breastfed had similar mortality rates and incidence of diarrhea and pneumonia during the first 2 years of life. However, HIV-1-free survival at 2 years was significantly higher in the formula arm. With appropriate education and access to clean water, formula feeding can be a safe alternative to breastfeeding for infants of HIV-1-infected mothers in a resource-poor setting.

Adult↗
PubMed2001

CCR5 promoter polymorphisms in a Kenyan perinatal human immunodeficiency virus type 1 cohort: association with increased 2-year maternal mortality.

The CCR5 chemokine receptor acts as a coreceptor with CD4 to permit infection by primary macrophage-tropic human immunodeficiency virus type 1 (HIV-1) strains. The CCR5Delta32 mutation, which is associated with resistance to infection in homozygous individuals and delayed disease progression in heterozygous individuals, is rare in Africa, where the HIV-1 epidemic is growing rapidly. Several polymorphisms in the promoter region of CCR5 have been identified, the clinical and functional relevance of which remain poorly defined. We evaluated the effect of 4 CCR5 promoter mutations on systemic and mucosal HIV-1 replication, disease progression, and perinatal transmission in a cohort of 276 HIV-1-seropositive women in Nairobi, Kenya. Mutations at positions 59353, 59402, and 59029 were not associated with effects on mortality, virus load, genital shedding, or transmission in this cohort. However, women with the 59356 C/T genotype had a 3.1-fold increased risk of death during the 2-year follow-up period (95% confidence interval [CI], 1.0-9.5) and a significant increase in vaginal shedding of HIV-1-infected cells (odds ratio, 2.1; 95% CI, 1.0-4.3), compared with women with the 59356 C/C genotype.

Adult↗
PubMed2001

The risks of spontaneous preterm delivery and perinatal mortality in relation to size at birth according to fetal versus neonatal growth standards.

OBJECTIVE: The aim of this study was to test the null hypothesis that size at birth relative to fetal or neonatal growth standards is not a significant variable related to the risk of spontaneous preterm delivery. STUDY DESIGN: This was a hospital-based cohort study of consecutive births at a tertiary care perinatal center from January 1, 1985, to December 31, 1996. A total of 37,377 pregnancies met the following inclusion criteria: (1) singleton gestation, (2) 25 to 40 weeks' gestation, and (3) no anomalies. Neonates were divided into 5 birth weight categories according to either fetal (uncorrected for sex) or neonatal (corrected for sex) growth standards, as follows: (1) intrauterine growth restriction, birth weight <3rd percentile; (2) borderline intrauterine growth restriction, birth weight > or = 3rd percentile and <10th percentile; (3) appropriate for gestational age, birth weight from 10th percentile through 90th percentile; (4) borderline large for gestational age, birth weight >90th percentile but < or = 97th percentile, and (5) large for gestational age, birth weight >97th percentile. Logistic regression analysis was used to estimate the independent effect of birth weight category on the risk of preterm delivery after spontaneous onset of labor, with the appropriate-for-gestational-age group serving as a reference. RESULTS: When fetal growth standards were applied, there was a significant increase in the risk of spontaneous preterm delivery when birth weight was outside the appropriate-for-gestational-age range (odds ratios of 2.5, 1.4, 1.2, and 1.9 for intrauterine growth restriction, borderline intrauterine growth restriction, borderline large-for-gestational age, and large-for-gestational-age groups, respectively). In contrast, when neonatal growth standards were applied, the risks of spontaneous preterm delivery in intrauterine growth restriction, borderline intrauterine growth restriction, and large-for-gestational-age groups were significantly lower (odds ratios of 0.5, 0.7, and 0.7 for intrauterine growth restriction, borderline intrauterine growth restriction, and large-for-gestational-age groups, respectively) because of an underestimation in the number of fetuses with abnormal size at birth delivered prematurely. With both fetal and neonatal growth standards there was a 5-to 6-fold greater risk of perinatal death for both preterm and term fetuses with intrauterine growth restriction. CONCLUSION: Fetal growth standards are more appropriate in predicting the impact of birth weight category on the risk of spontaneous preterm delivery than are neonatal growth standards. When fetal standards are applied, the risks of preterm birth in both extreme abnormal birth weight categories (intrauterine growth restriction and large for gestational age) are 2- to 3-fold greater than the risk among appropriate-for-gestational-age infants.

Adult↗
PubMed2001

Fetal umbilical cord oxygen values and birth to placental weight ratio in relation to size at birth.

OBJECTIVE: Our purpose was to examine regulatory linkages between fetal oxygenation and fetal and placental growth. We determined umbilical cord PO (2) and oxygen saturation, fractional oxygen extraction, and birth to placental weight ratio values in relation to size at birth for a large tertiary hospital population delivering at term. STUDY DESIGN: The computerized perinatal database of St Joseph's Health Care London, London, Ontario, was used to obtain the umbilical cord gases, pH, birth weight, placental weight, and other selected information for all term, singleton, liveborn infants between January 1990 and December 1999 (N = 27,043). Oxygen saturation values were calculated from the umbilical cord PO(2) and pH data with a previously derived empirical equation; fractional oxygen extraction values were calculated from the umbilical cord oxygen saturation data. Size at birth was divided into the following 5 birth weight categories using neonatal growth standards: fetal growth restriction, <3%; borderline fetal growth restriction, >or=3% and <10%; appropriate for gestational age, >or=10% and 90% and 97%. RESULTS: Infants in the borderline fetal growth restriction and fetal growth restriction groups had umbilical vein and artery PO(2) and oxygen saturation values that were stepwise lower than respective values for infants in the appropriate for gestational age group. Conversely, infants in the borderline large for gestational age and large for gestational age groups had umbilical vein PO(2) and oxygen saturation values that were stepwise higher than respective appropriate for gestational age group values; infants in these groups showed no change in arterial PO (2) and oxygen saturation values. Therefore infants in the borderline fetal growth restriction and fetal growth restriction groups had fractional oxygen extraction values that were stepwise higher than the appropriate for gestational age group value, whereas values for infants in the borderline large for gestational age and large for gestational age groups remained unchanged. Birth weight was disproportional to placental weight for infants in the borderline fetal growth restriction and fetal growth restriction groups when compared with that of the infants in the appropriate for gestational age group, with the birth to placental weight ratio values stepwise decreased. Conversely, birth weight was proportional to placental weight for infants in the borderline large for gestational age and large for gestational age groups with the birth to placental weight ratio values thus unchanged when compared with that of the infants in the appropriate for gestational age group. CONCLUSION: We conclude that fetal oxygenation is related to size at birth across the entire range of birth weights as studied at term from macrosomic to growth-restricted infants; this conclusion supports oxygen as a primary determinant of fetal growth. However, there are differences in the linkage between fetal oxygenation and metabolic rate or growth for these cohort groups that may relate to underlying etiologic processes.

Adult↗
PubMed2001

Eligibility criteria for elderly mentally ill continuing-care National Health Service patients: are they being met and do they need revision?

BACKGROUND: in 1996, the British government directed health authorities to draw up local eligibility criteria for National Health Service continuing health care. OBJECTIVES: to examine whether elderly mentally ill continuing-care National Health Service patients fulfilled a variety of eligibility criteria for their placement, and to identify the characteristics of patients who met local eligibility criteria. DESIGN: descriptive study. SETTING: four continuing-care units for elderly mentally ill patients in and around London. SUBJECTS: 67 continuing-care inpatients. METHODS: interview with nurse carer and, where possible, the patient with the use of standard global, functional, behavioural and cognitive rating scales. We determined fulfillment of Royal College of Psychiatrists' guideline criteria and three local eligibility criteria for elderly mentally ill continuing care. We identified clinical differences between those eligible and ineligible. RESULTS: although there were wide variations between local eligibility criteria, their effects were the same. In total, 58% of patients fulfilled all local eligibility criteria; 42% fulfilled none. Patients who fulfilled local eligibility criteria scored much higher on ratings of aggression, activity disturbance (wandering, and purposeless and inappropriate activity) and paranoid and delusional ideation. Ten percent of patients fulfilled Royal College of Psychiatrists' criteria but not local eligibility criteria. CONCLUSIONS: comprehensive and unambiguous national eligibility criteria should be introduced to reflect clinical needs and provide equity of access.

Aged↗
PubMed2001

Unexpected effects of a heterozygous dnmt1 null mutation on age-dependent DNA hypomethylation and autoimmunity.

DNA methylation modifies gene expression. Methylation patterns are established during ontogeny, but they change with aging, usually with a net decrease in methylation. The significance of this change in T cells is unknown, but it could contribute to autoimmunity, senescence, or both. We examined the effects of a null mutation in DNA methyltransferase 1 (Dnmt1), a gene maintaining DNA methylation patterns, on immune aging. Whereas aged control mice developed hypomethylated DNA, autoimmunity, and signs of immune senescence as predicted, the knockout mice surprisingly increased DNA methylation and developed signs of autoimmunity and senescence more slowly. To identify potential mechanisms, we compared transcripts of DNA methyltransferase and methylcytosine binding protein family members in control and knockout mice. MeCP2, a methylcytosine binding protein involved in gene suppression and chromatin inactivation, was the only transcript differentially expressed between old knockout mice and controls, and thus it is a candidate for a gene product mediating these effects.

Aging↗
PubMed2001

Is human chorionic gonadotropin useful for identifying and treating nonpalpable testis?

PURPOSE: We evaluated the efficacy of human chorionic gonadotropin (HCG) for identifying and treating nonpalpable testis. We then compared the cost-effectiveness of this approach to that of laparoscopy. MATERIALS AND METHODS: We reviewed patient charts during a 15-month period and identified 51 boys (64 testes) who underwent surgery to correct cryptorchidism. There were nonpalpable testes in 17 cases and bilateral cryptorchidism in 2 for a total of 19 impalpable testes. All patients were offered a full course of HCG. Those electing hormonal treatment received intramuscular injection of 2,000 IU/m.2 HCG (maximum 1,500 IU/injection) 3 times weekly for 3 weeks. RESULTS: A full course of HCG was given in 8 patients (10 testes). Of the 10 testes 8 became palpable after HCG treatment, including 1 atrophic nubbin located in the inguinal canal. Of the 2 testes that remained impalpable 1 discovered at the level of the renal vessels had complete epididymal nonunion and 1 was located closer to the inguinal ring. All 9 untreated patients underwent laparoscopy, which identified 3 intra-abdominal, 3 vanished and 2 peeping testes, and 1 atrophic testis in the inguinal canal. CONCLUSIONS: HCG therapy is valuable for identifying and treating nonpalpable testis. Using this agent enabled the testicle to be detected while avoiding the risks and cost associated with the laparoscopic procedure.

Child, Preschool↗
PubMed2001

Autoreactive murine Th1 and Th2 cells kill syngeneic macrophages and induce autoantibodies.

D10 cells, a cloned Th2 line, become autoreactive following treatment with DNA methylation inhibitors like 5-azacytidine (5-azaC), and induce anti-DNA antibodies if injected into unirradiated syngenic mice. The mechanism by which the autoreactive cells break tolerance is unknown. To further define effector functions required, we asked if 5-azaC-treated Th1 cells could also induce autoimmunity. AE7 cells, a cloned Th1 line, were treated with 5-azaC and shown to become autoreactive and induce anti-DNA antibodies in vivo. Comparison of effector mechanisms demonstrated that the two cell lines secreted a distinct repertoire of cytokines, and that only killing of syngeneic Mø was common to both AE7 and D10 cells. This suggests that Mø killing may be an early step in the induction of anti-DNA antibodies, providing antigenic nucleosomes and decreasing clearance of apoptotic material. Secretion of cytokines promoting B cell differentiation may play a role, but no one cytokine is required.

Animals↗
PubMed2000

Mean arterial pressure, pregnancy induced hypertension, and preeclampsia. Evaluation as independent risk factors and as surrogates for high maternal serum alpha-protein in estimating breast cancer risk.

PURPOSE: Data from a nested case-control study were analyzed to examine high mean arterial pressure (MAP), hypertension of pregnancy and preeclampsia as independent predictors, and as surrogate markers for elevated Alpha-fetoprotein (AFP) levels in evaluating breast cancer risk.METHODS: Cases (n = 205) were identified by the California Cancer Registry from a cohort of pregnant women who were part of the Kaiser Health Plan and took part in the Child Health and Development Studies initiated by the University of California, Berkeley, from June 1959 to September 1966. Controls (n = 337) were selected by randomized recruitment from the same cohort probability matched to cases by distribution of birth dates of cases.RESULTS: High MAP was associated with breast cancer risk, and was different across quartiles of age at first full term pregnancy. Odds Ratios across quartiles were 0.24 (95% CI = 0.08-0.71), 0.84 (95% CI = 0.39-1.66), 1.00 (referent), and 2.50 (95% CI = 1.21-5.13). Neither diagnosed preeclampsia nor hypertension of pregnancy showed any association with breast cancer risk. When both high Alpha-fetoprotein and high mean arterial pressure were entered into the same analysis neither changed the odds ratio for the other more than eight percent. Additionally, AFP level was not a linear function of MAP.CONCLUSIONS: Although the pattern of odds ratios across quartiles of age at first full term pregnancy were similar for the two variables it can not be concluded that high MAP is an adequate surrogate for high levels of maternal serum AFP, but rather represents some related process which is in and of itself a risk factor for breast cancer.

Journal Article↗
PubMed2000

Effect of breastfeeding and formula feeding on transmission of HIV-1: a randomized clinical trial.

CONTEXT: Transmission of human immunodeficiency virus type 1 (HIV-1) is known to occur through breastfeeding, but the magnitude of risk has not been precisely defined. Whether breast milk HIV-1 transmission risk exceeds the potential risk of formula-associated diarrheal mortality in developing countries is unknown. OBJECTIVES: To determine the frequency of breast milk transmission of HIV-1 and to compare mortality rates and HIV-1-free survival in breastfed and formula-fed infants. DESIGN AND SETTING: Randomized clinical trial conducted from November 1992 to July 1998 in antenatal clinics in Nairobi, Kenya, with a median follow-up period of 24 months. PARTICIPANTS: Of 425 HIV-1-seropositive, antiretroviral-naive pregnant women enrolled, 401 mother-infant pairs were included in the analysis of trial end points. INTERVENTIONS: Mother-infant pairs were randomized to breastfeeding (n = 212) vs formula feeding arms (n = 213). MAIN OUTCOME MEASURES: Infant HIV-1 infection and death during the first 2 years of life, compared between the 2 intervention groups. RESULTS: Compliance with the assigned feeding modality was 96% in the breastfeeding arm and 70% in the formula arm (P<.001). Median duration of breastfeeding was 17 months. Of the 401 infants included in the analysis, 94% were followed up to HIV-1 infection or mortality end points: 83% for the HIV-1 infection end point and 93% to the mortality end point. The cumulative probability of HIV-1 infection at 24 months was 36.7% (95% confidence interval [CI], 29.4%-44.0%) in the breastfeeding arm and 20.5% (95% CI, 14.0%-27.0%) in the formula arm (P = .001). The estimated rate of breast milk transmission was 16.2% (95% CI, 6.5%-25.9%). Forty-four percent of HIV-1 infection in the breastfeeding arm was attributable to breast milk. Most breast milk transmission occurred early, with 75% of the risk difference between the 2 arms occurring by 6 months, although transmission continued throughout the duration of exposure. The 2-year mortality rates in both arms were similar (breastfeeding arm, 24.4% [95% CI, 18.2%-30.7%] vs formula feeding arm, 20.0% [95% CI, 14.4%-25.6%]; P = .30). The rate of HIV-1-free survival at 2 years was significantly lower in the breastfeeding arm than in the formula feeding arm (58.0% vs 70.0%, respectively; P = .02). CONCLUSIONS: The frequency of breast milk transmission of HIV-1 was 16.2% in this randomized clinical trial, and the majority of infections occurred early during breastfeeding. The use of breast milk substitutes prevented 44% of infant infections and was associated with significantly improved HIV-1-free survival.

AIDS Serodiagnosis↗
PubMed2000

Oestrogenic steroids and melanoma cell interaction with adjacent skin cells influence invasion of melanoma cells in vitro.

The invasion of melanoma is complex and multi-staged and involves changes in both cell/extracellular matrix (ECM) and cell/cell interactions. Female steroids and alpha-MSH have also been reported to influence metastatic melanoma progression, but their mechanisms of action are unknown. Accordingly, our aim was to establish in vitro models to examine (a) the influence of sex steroids and alpha-melanocyte-stimulating hormone (alpha-MSH) on tumour invasion and the influence of (b) ECM proteins and (c) adjacent cells on melanoma invasion. In the first model, melanoma cell invasion through fibronectin over 20 hr under serum-free conditions was used to investigate the effects of 17beta-oestradiol and oestrone on the invasion of human melanoma cell lines, A375-SM and HBL. A375-SM, but not HBL cells, proved very susceptible to inhibition by female steroids. However, invasion of the HBL line was inhibited by alpha-MSH. Using the second model of reconstructed human skin based on de-epidermised acellular dermis, we found that the HBL cells on their own failed to invade into the dermis (irrespective of the presence or absence of the basement membrane). However, there was a significant synergistic interaction between keratinocytes, fibroblasts and HBL cells, such that a modest invasion of HBLs into the dermis was seen within 2 weeks when other skin cells were present. In contrast, A375-SM cells showed a significant ability to invade the dermis in the absence of other cells, with less invasion when other skin cells were present. In summary, these models have provided new information on the extent to which melanoma cell invasion is sensitive to oestrogenic steroids and to alpha-MSH and to interaction, not only with adjacent skin cells but also to the presence of basement membrane antigens.

Estradiol↗
PubMed2000

Effects of a selective 5-HT(1B/1D) receptor agonist on spinal and trigeminal reflexes in the anaesthetized rabbit.

The effects of the 5-HT(1B/1D) receptor agonist L-741,604 on a trigeminally-mediated (jaw depressor) reflex and a spinally-mediated (flexion withdrawal) reflex have been compared between spinalized and intact, anaesthetized rabbits. L-741,604 depressed the jaw depressor reflex dose-dependently in all animals, to a median of 5% (inter-quartile range, IQR, 3 - 28%, n=18) of pre-drug levels after a cumulative dose of 3.1 micromol kg(-1) i.v. This effect was reversed by the 5-HT(1B/1D) antagonist GR 127,935 (1 - 2 micromol kg(-1) i.v.). The flexion withdrawal reflex was depressed by L-741, 604 in non-spinalized animals, to a median of 22% (IQR 10 - 36%, n=10) of pre-drug levels after the highest dose, an action that was reversed by GR 127,935. In spinalized rabbits, L-741,604 up to 0.3 micromol kg(-1) i.v. cumulative increased the flexion reflex to a median of 189% (IQR 169 - 198%, n=8) of pre-drug controls. With higher doses the reflex decreased, so that after 3.1 micromol kg(-1) it was 75% (IQR 55 - 96%) of pre-drug levels. Subsequent GR 127,935 increased reflexes to a median of 180% (IQR 136 - 219%) of controls. L-741,604 increased arterial blood pressure and decreased heart rate in both preparations, effects that were reversed by GR 127,935. Thus, when the spinal cord was intact L-741,604 inhibited spinal and trigeminal reflexes in the same way. Although spinalization enabled a non-5-HT(1B/1D)-mediated excitatory effect of L-741,604 on spinal reflexes, there was a clear inhibitory effect of the drug at high doses. These data suggest that L-741,604 inhibits spinal reflexes by increasing descending inhibition and by a direct action in the cord. The same processes could apply to inhibition of trigeminally-mediated events.

Animals↗
PubMed2000

Raised line drawings are spontaneously explored with a single finger.

In this study we examine the strategies used by blindfolded subjects asked to freely explore raised line drawings and identify what is depicted in them. We were particularly interested in how often a single finger is spontaneously used because in several studies subjects are forced to use only one fingertip and the extent to which this restriction may depress haptic perception is unclear. The results suggest that despite a variety of strategies, people 'naturally' use single fingertips sufficiently often to allow confidence in conclusions that are based on studies imposing this restriction.

Adolescent↗