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Biomedical subjects

J M Blair

Publications and source records attributed to J M Blair.

At least 19 recordsLinked to original sources
PubMed2006

Androgen decreases osteoprotegerin expression in prostate cancer cells.

Osteoprotegerin (OPG), a key regulator of bone resorption, is hypothesized to have a role in prostate cancer (CaP) bone metastasis. As advanced CaP is treated by androgen ablation, we examined if androgen modulates OPG expression by CaP cell lines in vitro. Basal levels of secreted OPG protein were significantly greater in androgen-independent PC-3 cells compared with androgen-responsive LNCaP-FGC cells (P<0.001); OPG was not detected in the androgen-responsive CaP cell lines LAPC-4 or DuCaP. Treatment with 5alpha-dihydrotestosterone (5alpha-DHT) significantly decreased OPG protein levels in both PC-3 and LNCaP-FGC, with maximal suppression using 10(-9)-10(-7) M 5alpha-DHT in PC-3 (P<0.01; day 3), and using 10(-10)-10(-9) M 5alpha-DHT in LNCaP-FGC cells (P<0.01; day 6). OPG messenger RNA levels were not significantly altered by this 5alpha-DHT treatment. Co-treatment with 10(-6) M flutamide blocked 5alpha-DHT inhibition of OPG protein expression in LNCaP-FGC cells. These data suggest that androgen may modulate OPG protein levels in CaP cell lines in vitro using a post-transcriptional mechanism.

5-alpha-Dihydroprogesterone↗
PubMed2006

RANK ligand.

RANK ligand (RANKL), a key mediator of bone resorption in normal and pathological states, is expressed as membrane-bound or soluble forms by tissues as diverse as lymph nodes, spleen, thymus and bone-forming cells. In normal bone turnover and in bone metastasis, RANKL stimulates the formation and activity of bone-removing cells, osteoclasts, by binding to its cognate receptor, RANK, on osteoclasts and their progenitors; these processes are disrupted by binding of RANKL to osteoprotegerin (OPG), a soluble decoy receptor. Whilst no mutations in the RANKL gene have yet been identified in human disease, mutations that result in enhanced RANK signalling through inactivation of OPG or activation of RANK are associated with Juvenile Paget's disease and familial expansile osteolysis, respectively. This review focuses on the central role of RANKL in bone resorption and on the therapeutic targeting of RANKL in osteoporosis, humoral hypercalcaemia of malignancy and bone metastasis.

Amino Acid Sequence↗
PubMed2006

Over-expression of p53 mutants in LNCaP cells alters tumor growth and angiogenesis in vivo.

This study has investigated the impact of three specific dominant-negative p53 mutants (F134L, M237L, and R273H) on tumorigenesis by LNCaP prostate cancer cells. Mutant p53 proteins were associated with an increased subcutaneous "take rate" in NOD-SCID mice, and increased production of PSA. Tumors expressing F134L and R273H grew slower than controls, and were associated with decreased necrosis and apoptosis, but not hypoxia. Interestingly, hypoxia levels were increased in tumors expressing M237L. There was less proliferation in F134L-bearing tumors compared to control, but this was not statistically significant. Angiogenesis was decreased in tumors expressing F134L and R273H compared with M237L, or controls. Conditioned medium from F134L tumors inhibited growth of normal human umbilical-vein endothelial cells but not telomerase-immortalized bone marrow endothelial cells. F134L tumor supernatants showed lower levels of VEGF and endostatin compared with supernatants from tumors expressing other mutants. Our results support the possibility that decreased angiogenesis might account for reduced growth rate of tumor cells expressing the F134L p53 mutation.

Apoptosis↗
PubMed2005

Patient controlled analgesia for labour: a comparison of remifentanil with pethidine.

We compared the analgesic efficacy and safety of remifentanil and pethidine via patient controlled analgesia for women in established uncomplicated labour. Women received either remifentanil 40 microg with a 2-min lockout (n = 20) or pethidine 15 mg with a 10-min lockout (n = 19). Visual analogue scores for pain during the study and for overall pain were similar for both groups (mean (SD) 6.4 (1.5) cm for remifentanil and 6.9 (1.7) cm for pethidine). The area under the curve for visual analogue scores of satisfaction with analgesia was higher for remifentanil than for pethidine (p = 0.001). Maternal arterial oxygen saturation was similar in both groups. Neurologic and Adaptive Capacity Scores at 30 min were higher for remifentanil than for pethidine (median (interquartile range [range]) 36 (34.5-37 [32-39]) vs 34 (33-35 [30-35]), respectively; p = 0.003).

Adult↗
PubMed2004

Plant community responses to resource availability and heterogeneity during restoration.

Availability and heterogeneity of resources have a strong influence on plant community structure in undisturbed systems, as well as those recovering from disturbance. Less is known about the role of resource availability and heterogeneity in restored communities, although restoration provides a valuable opportunity to test our understanding of factors that influence plant community assembly. We altered soil nitrogen (N) availability and soil depth during a prairie restoration to determine if the availability and/or heterogeneity of soil resources influenced plant community composition in restored grassland communities. Plant community responses to three levels of N availability (ambient, enriched by fertilization, and reduced by carbon amendment) and two levels of soil depth (deep and shallow) were evaluated. In addition, we evaluated plant community responses to four whole plot heterogeneity treatments created from the six possible combinations of soil N availability and soil depth. The soil depth treatment had little influence on community structure during the first 3 years of restoration. Total diversity and richness declined over time under annual N enrichment, whereas diversity was maintained and richness increased over time in soil with reduced N availability. Non-native species establishment was lowest in reduced-N soil in the initial year, but their presence was negligible in all of the soil N treatments by the second year of restoration. Panicum virgatum, a native perennial C(4) grass, was the dominant species in all soil N treatments by year three, but the magnitude of its dominance was lowest in the reduced-N soil and highest in enriched-N soil. Consequently, the relative cover of P. virgatum was strongly correlated with community dominance and inversely related to diversity. The differential growth response of P. virgatum to soil N availability led to a higher degree of community similarity to native prairie in the reduced-N treatment than in the enriched-N treatment. There were no differences in plant community structure among the four whole plot-level heterogeneity treatments, which all exhibited the same degree of similarity to native prairie. Diversity and community heterogeneity in the whole-plot treatments appeared to be regulated by the dominant species' effect on light availability, rather than soil N heterogeneity per se. Our results indicate that a strong differential response of a dominant species to resource availability in a restored community can regulate community structure, diversity, and similarity to the native (or target) community, but the importance of resource heterogeneity in restoring diversity may be dampened in systems where a dominant species can successfully establish across a range of resource availability.

Conservation of Natural Resources↗
PubMed2004

Assessment of tracheal intubation in children after induction with propofol and different doses of remifentanil.

Tracheal intubating conditions were assessed in 112 children after induction of anaesthesia with propofol and remifentanil 1.0, 2.0 or 3.0 micro g.kg-1. Subjects in a control group were given propofol and mivacurium 0.2 mg.kg-1. Haemodynamic and respiratory parameters were recorded. Plasma catecholamine levels were measured in a subgroup of 40 children. Intubating conditions were acceptable in 14/28 (50%), 18/26 (69%) and 22/27 (82%) in those subjects given remifentanil 1.0, 2.0 or 3.0 micro g.kg-1, respectively, and in 27/28 (96%) of the control group. Intubating conditions in subjects given remifentanil 3.0 micro g.kg-1 were better than in those given remifentanil 1.0 micro g.kg-1 (p < 0.05). There were no significant differences in intubating conditions between those given remifentanil 3.0 micro g.kg-1 and the control group. Systolic blood pressure and heart rate increased in response to tracheal intubation in subjects given remifentanil 1.0 micro g.kg-1 and in the control group (p < 0.05). Time to resumption of spontaneous respiration was prolonged in subjects given remifentanil 3.0 micro g.kg-1 (p < 0.001). In conclusion, remifentanil 2 micro g.kg-1 provides acceptable intubating conditions and haemodynamic stability without prolonging the return of spontaneous respiration.

Analgesics, Opioid↗
PubMed2003

Does resource availability, resource heterogeneity or species turnover mediate changes in plant species richness in grazed grasslands?

Grazing by large ungulates often increases plant species richness in grasslands of moderate to high productivity. In a mesic North American grassland with and without the presence of bison ( Bos bison), a native ungulate grazer, three non-exclusive hypotheses for increased plant species richness in grazed grasslands were evaluated: (1) bison grazing enhances levels of resource (light and N) availability, enabling species that depend on higher resource availability to co-occur; (2) spatial heterogeneity in resource availability is enhanced by bison, enabling coexistence of a greater number of plant species; (3) increased species turnover (i.e. increased species colonization and establishment) in grazed grassland is associated with enhanced plant species richness. We measured availability and spatial heterogeneity in light, water and N, and calculated species turnover from long-term data in grazed and ungrazed sites in a North American tallgrass prairie. Both regression and path analyses were performed to evaluate the potential of the three hypothesized mechanisms to explain observed patterns of plant species richness under field conditions. Experimental grazing by bison increased plant species richness by 25% over an 8-year period. Neither heterogeneity nor absolute levels of soil water or available N were related to patterns of species richness in grazed and ungrazed sites. However, high spatial heterogeneity in light and higher rates of species turnover were both strongly related to increases in plant species richness in grazed areas. This suggests that creation of a mosaic of patches with high and low biomass (the primary determinant of light availability in mesic grasslands) and promotion of a dynamic species pool are the most important mechanisms by which grazers affect species richness in high productivity grasslands.

Animals↗
PubMed2003

The extent of bisexual behaviour in HIV-infected men and implications for transmission to their female sex partners.

Heterosexual transmission of HIV is a growing problem for women, but many women do not know how their partners acquired HIV. We described a group of HIV-infected men and women, and focused on: (1) sexual identity and bisexual behaviour in men, and (2) the proportion of women who acknowledged having a bisexual male partner. This study examined HIV-infected persons who participated in a cross-sectional interview project from January 1995 through July 2000; 5,156 men who have sex with men (MSM), and 3,139 women. The proportion of MSM who reported having sex with women (MSM/MSW) varied by race: 34% of black MSM, 26% of Hispanic MSM, and 13% of white MSM. While 14% of white women acknowledged having a bisexual partner, only 6% of black and 6% of Hispanic women reported having a bisexual partner. Most behaviourally bisexual men identified as either bisexual (59%) or homosexual (26%). Among MSM/MSW, 30% had more female partners than male partners, while only 10% had more male partners than female partners. These data suggest that bisexual activity is relatively common among black and Hispanic HIV-infected MSM, few identify as heterosexual, and their female partners may not know of their bisexual activity.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Patient-controlled analgesia for labour using remifentanil: a feasibility study.

We have investigated the efficacy and safety of remifentanil in a patient-controlled analgesia device for labour in 21 women. Remifentanil was available in increasing doses (bolus doses 0.25-1.0 microg x kg(-1)) with and without a background infusion (0.025-0.05 microg x kg(-1) x min(-1)). A lockout time of 2 min was used. Thirteen out of 21 (62%) women chose to continue using remifentanil up to and during delivery. Nineteen out of 21 (90%) achieved a reduction in pain score from baseline. Using a VAS of 0-10 cm the median maximum reduction in pain score was 3 cm (range 0-8 cm). There was a significant reduction (P<0.05) from baseline pain scores (median= 8 cm) to scores at bolus doses in the range 0.25-0.5 microg x kg(-1) (median=5 cm). There were no significant reductions in the fetal heart rate. Apgar scores and cord blood gas analyses remained within normal limits. We conclude that a remifentanil patient-controlled analgesia system (bolus doses 0.25-0.5 microg x kg(-1), without a background infusion) may safely provide worthwhile, although incomplete, analgesia for labour.

Adult↗
PubMed2000

Tracheal intubating conditions after induction with sevoflurane 8% in children. A comparison with two intravenous techniques.

We studied tracheal intubating conditions in 120 healthy children, aged 3-12 years, in a blinded, randomised clinical trial. Children were randomly allocated to one of three groups: group PS, propofol 3 mg.kg-1 and succinylcholine 1 mg.kg-1 (n = 40); group PA, propofol 3 mg.kg-1 and alfentanil 10 microg.kg-1 (n = 40); group SF, sevoflurane 8% in 60% nitrous oxide in oxygen for 3 min (n = 40). Tracheal intubating conditions were graded according to ease of laryngoscopy, position of vocal cords, coughing, jaw relaxation and movement of limbs. Overall intubating conditions were acceptable in 39 of 40 children in the propofol/succinylcholine group, 21 of 40 children in the propofol/alfentanil group and 35 of 40 children in the sevoflurane group. Children receiving propofol and succinylcholine or sevoflurane had better intubating conditions overall than those given propofol and alfentanil (p < 0.01). In conclusion, anaesthetic induction and tracheal intubation using sevoflurane 8% for 3 min is a satisfactory alternative to propofol with succinylcholine in children.

Alfentanil↗
PubMed1997

The natural history of asymptomatic thoracic disc herniations.

STUDY DESIGN: Magnetic resonance imaging was used to determine the natural history of asymptomatic thoracic disc herniations. OBJECTIVES: To determine whether thoracic disc herniations change in size over time. SUMMARY OF BACKGROUND DATA: Based on previous work by the authors of the present study, the incidence of asymptomatic thoracic disc herniations is approximately 37%. The natural history of thoracic disc herniations is unknown. The natural history of lumbar and cervical disc herniations in symptomatic individuals who become asymptomatic has been shown in multiple studies frequently to result in a decrease in size of the herniation. METHODS: Twenty patients with 48 asymptomatic thoracic herniations previously diagnosed with magnetic resonance imaging underwent repeat magnetic resonance imaging using sagittal T1-weighted spine echo and axial multiplanar gradient refocused images at each thoracic disc level from T1 to T12 for a mean follow-up period of 26 months. Midsagittal canal diameter was recorded, and disc herniation square area was measured using a computer-assisted digitizing program. Disc herniations were categorized according to percentage of canal compromise. The change in size of the disc herniations over time was analyzed. RESULTS: All patients remained asymptomatic during the follow-up period. A total of 48 disc herniations were identified from the original magnetic resonance images. There were 21 small (0-10% canal compromise) disc herniations, 20 medium (> 10-20%) disc herniations, and seven large (> 20%) disc herniations. Of the 21 small disc herniations, 18 showed no significant change in size, whereas three showed a measurable increase in size. Of the 20 medium-sized disc herniations, 16 showed either a small or no change in size, one showed a significant increase in size, and three showed a significant decrease in size. Of the seven large disc herniations, three demonstrated no change in size, and four demonstrated a significant decrease in size. In addition, five new disc herniations were detected in four patients; one was small, and four were moderate in size. CONCLUSIONS: Based on the results of this study, the authors believe that asymptomatic disc herniations may well exist in a state of relative flux, yet exhibit little change in size and remain asymptomatic. There was a trend, however, for small disc herniations either to remain unchanged or increase in size and for large disc herniations often to decrease in size.

Adult↗
PubMed1996

A prospective comparison of bone density in adolescent girls receiving depot medroxyprogesterone acetate (Depo-Provera), levonorgestrel (Norplant), or oral contraceptives.

OBJECTIVE: To examine bone density among adolescents receiving different forms of hormonal contraception along with that of control subjects. METHODS: Baseline and 1-year measures of lumbar vertebral bone density were obtained in girls receiving depot medroxyprogesterone acetate (Depo-Provera) (n = 15), levonorgestrel (Norplant) (n = 7), or oral contraceptives (n = 9) and in girls receiving no hormonal treatment (n = 17). In a subsample of Depo-Provera users (n = 8), Norplant users (n = 3), and control subjects (n = 4), bone density measurements were repeated after 2 years. Bone density was measured by dual-energy x-ray absorptiometry. RESULTS: Body mass indexes, level of pubertal development, substance use, and reproductive histories were not significantly different among the groups. More black girls were represented in the initial Depo-Provera group (p < 0.02), girls in the Norplant group exercised more hours per week (p < 0.02), and control subjects were older (p < 0.01) than those in the other groups. These variables did not significantly affect bone density results. After 1 year, bone density decreased 1.5% in Depo-Provera users, compared with increases of 2.5% in Norplant users, 1.5% in oral contraceptive users, and 2.9% control subjects (p < 0.02). After 2 years, bone density increased a total of 9.3% in Norplant users and 9.5% in control subjects but decreased a total of 3.1% in Depo-Provera users (p < 0.0001). CONCLUSION: These data suggest that Depo-Provera may, at least temporarily, suppress the expected skeletal bone mineralization in adolescents, whereas Norplant and oral contraceptives are associated with the expected increase in bone density in this population.

Adolescent↗
PubMed1995

The application of atomic force microscopy for the detection of microcrystals in synovial fluid from patients with recurrent synovitis.

Synovial fluid from 33 patients with inflammatory arthritis was examined with a polarized light microscope (PLM) and an atomic force microscope (AFM). Two samples were imaged with a transmission electron microscope (TEM) to determine calcium/phosphate ratios and identify microcrystals of calcium pyrophosphate dihydrate and octacalcium phosphate. Additional correlative x-ray diffraction studies were performed on several samples including purified hydroxyapatite and sodium chloride crystals. Monosodium urate, calcium pyrophosphate dihydrate, hydroxyapatite, octacalcium phosphate, and cholesterol crystals were identified with AFM. AFM images of these microcrystals revealed detailed surface topology, including lattice parameters and structural irregularities at the crystals' surface. These features were consistent with those obtained by TEM and x-ray diffraction studies. In addition, AFM images revealed that some specimens contained microcrystals that were undetected by PLM and/or TEM. These results suggest that AFM may provide a simple yet powerful technique for the detection of microcrystals in synovial fluid taken from patients with crystal-induced arthritis.

Arthritis↗
PubMed1994

A prospective study of adolescents who choose among levonorgestrel implant (Norplant), medroxyprogesterone acetate (Depo-Provera), or the combined oral contraceptive pill as contraception.

OBJECTIVES: Levonorgestrel implants (Norplant) and medroxyprogesterone acetate injections (Depo-Provera) represent additional contraception options for adolescents. The purpose of this study was to examine prospectively clinical profiles among adolescents who chose one of the two long-term contraceptives compared with profiles among those who chose the combined oral contraceptive pill (OCP). METHODS: Girls who needed contraception and did not require confidentiality were presented with a contraceptive menu consisting of Norplant (n = 58), Depo-Provera (n = 66), or OCP (n = 75). At baseline and follow-up visits over 6 months, patients were interviewed regarding gynecologic history, side effect symptoms, and satisfaction. The average age of subjects was 15.5 years (range 11 to 20 years); 66% were African-American and 34% white. RESULTS: Significantly more teens who chose Depo-Provera (73%) reported having used some method of birth control previously than those selecting either Norplant (30%) or OCP (26%). Adolescents who chose either Norplant (34%) or Depo-Provera (43%) were significantly more likely to have been pregnant previously than those choosing OCP (12%). Those selecting Depo-Provera were significantly more likely to report a history of genital infection with Chlamydia trachomatis (42%) than those in the other two contraceptive groups (22%). Prevalences of reported recent depression and fatigue before initiation of treatment were high, exceeding 35% across the three groups. A total of 105 and 40 adolescents were assessed at 3 and 6 months, respectively. At follow-up, more than 80% of OCP users maintained regular menstrual cycles, whereas over 80% of those choosing Norplant or Depo-Provera had disrupted cycles. Complaints of nausea and dizziness among Norplant users and fatigue among Depo-Provera and OCP users increased significantly between the baseline and follow-up visits. Reports of local reactions to the Norplant device were common but not clinically significant. Blood pressure readings, facial acne, and body mass index did not change over time in any treatment group. Subjects in the Norplant and Depo-Provera groups appreciated freedom from daily compliance to maintain contraceptive effectiveness and the "hidden" nature of the method. Appointment compliance at the end of 6 months was 78% for Depo-Provera, 40% for Norplant, and 46% for OCP. CONCLUSIONS: The implant and injection forms of contraception appear to be especially popular among girls with previous pregnancies or birth control use. The common occurrences of medical symptoms and sexually transmitted diseases before initiation of therapy underscore the importance of baseline evaluation. Norplant users may be warned about nausea and dizziness as well as minor local symptoms around the insertion site and unpredictable uterine bleeding patterns. Adolescent patients choosing Depo-Provera may expect amenorrhea by the end of 6 months of therapy along with possible fatigue. Early intervention may be needed with adolescents who choose Norplant or OCP to encourage better compliance with follow-up appointments.

Adolescent↗
PubMed1994

Surgical anatomy of the superficial peroneal nerve in the ankle and foot.

The subcutaneous (sensory) portion of the superficial peroneal nerve was dissected in 25 cadaver lower limbs under loupe magnification. Three distinct branching pattern types were noted. Type A (72%) consisted of a pattern where the nerve penetrated the crural fascia to become subcutaneous at an average distance of 12.3 cm proximal to the ankle joint, then divided at a mean distance of 4.4 cm proximal to the ankle into two major branches: a large medial dorsal cutaneous nerve and a smaller more laterally located intermediate dorsal cutaneous nerve. Type B (16%) consisted of a pattern where both the medial and intermediate dorsal cutaneous nerve arose independently from the superficial peroneal nerve, with the medial dorsal cutaneous nerve having a similar course to that found in Type A, while the intermediate dorsal cutaneous nerve penetrated the crural fascia posterior to the fibula 5.5 cm proximal to the ankle joint and coursed medially to cross the lateral aspect of the fibula at mean distance 4.5 cm above the ankle joint. Type C (12%) consisted of a pattern where the medial dorsal cutaneous nerve and the intermediate dorsal cutaneous nerve arose independently and the medial dorsal cutaneous nerve coursed similar to that in Type A; however, the intermediate dorsal cutaneous nerve penetrated the crural fascia anterior to the fibula an average of 4.9 cm above the ankle joint and continued in close proximity to the anterior fibular border. In all patterns the mean diameters of the medial dorsal cutaneous nerve and intermediate dorsal cutaneous nerve at the ankle were 2.9 mm and 2 mm, respectively. At the level of the malleoli, the medial dorsal cutaneous nerve was located approximately one half the distance from the lateral malleolus to medial malleolus while the intermediate dorsal cutaneous nerve was approximately one third the distance. Appreciation of these branch patterns and the quantified relationships should assist nerve protection during surgical procedures as well as aid rapid nerve isolation for exploration or decompression. Branches especially at risk for iatrogenic injury include: (1) the intermediate dorsal cutaneous nerve of Type B where the nerve crosses the lateral surface of the distal fibula; (2) the intermediate dorsal cutaneous nerve of Type C where the nerve travels adjacent to the anterior border of the fibula; and (3) the intermediate dorsal cutaneous nerve and the medial dorsal cutaneous nerve at the level of the ankle, where they are at risk during anterior ankle arthrotomy or arthroscopy.

Adult↗