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Biomedical subjects

B Montgomery

Publications and source records attributed to B Montgomery.

At least 19 recordsLinked to original sources

Consent for genetics studies among clinical trial participants: findings from Action for Health in Diabetes (Look AHEAD).

BACKGROUND: Increasingly, genetic specimens are collected to expand the value of clinical trials through study of genetic effects on disease incidence, progression or response to interventions. PURPOSE: and methods We describe the experience obtaining IRB-approved DNA consent forms across the 19 institutions in the Action for Health in Diabetes (Look AHEAD), a clinical trial examining the effect of a lifestyle intervention for weight loss on the risk of serious cardiovascular events among individuals with type 2 diabetes. We document the rates participants provided consent for DNA research, identify participant characteristics associated with consent, and discuss implications for genetics research. RESULTS: IRB approval to participate was obtained from 17 of 19 institutions. The overall rate of consent was 89.6% among the 15 institutions that had completed consenting at the time of our analysis, which was higher than reported for other types of cohort studies. Consent rates were associated with factors expected to be associated with weight loss and cardiovascular disease and to affect the distribution of candidate genes. Non-consent occurred more frequently among participants grouped as African-American, Hispanic, female, more highly educated or not dyslipidemic. LIMITATIONS: The generalizabilty of results is limited by the inclusion/exclusion criteria of the trial. CONCLUSIONS: Barriers to obtaining consent to participate in genetic studies may differ from other recruitment settings. Because of the potentially complex associations between personal characteristics related to adherence, outcomes and gene distributions, differential rates of consent may introduce biases in estimates of genetic relationships.

Aged↗

Outcome analysis and patient satisfaction following octant transrectal ultrasound-guided prostate biopsy: a prospective study comparing consultant urologist, specialist registrar and nurse practitioner in urology.

PURPOSE: To determine whether transrectal ultrasound-guided biopsy of the prostate is equally reliable and acceptable if performed by urology nurse practitioner or urologist. SCOPE: Octant biopsies were taken by each operator (consultant urologist n=2, urology specialist registrar n=1 and urology nurse practitioner n=2) from 50 consecutive unselected patients and demographics and cancer detection rate were compared between the groups. A postal survey was performed following nurse practitioner biopsy to assess patient satisfaction and acceptance of nurse practitioner biopsy. CONCLUSION: Transrectal ultrasound-biopsy of prostate whether performed by nurse practitioner or urologist is equally reliable if adequate training is provided. Patients are happy to undergo prostate biopsy and receive information about the diagnosis from an appropriately trained prostate cancer nurse specialist.

Aged↗

Collection of wind-borne haematophagous insects in the Torres Strait, Australia.

Circumstantial evidence has implicated wind-borne mosquitoes (Diptera: Culicidae) in the introduction of Japanese encephalitis (JE) virus into Australia from the New Guinea mainland. A study was initiated on Saibai Island in the northern Torres Strait, during January and February 2000, to identify the potential source of insects collected in aerial (kytoon) and surface-level traps. Wind speed and direction were recorded to determine wind profiles during insect sampling. Northerly winds capable of carrying insects from New Guinea to Saibai Island were only present on three out of 18 nights sampled. Only three male mosquitoes, comprising two Verrallina funerea (Theobald) and one Ochlerotatus vigilax (Skuse), were collected in aerial samples, and were most likely of local origin. Culicoides midges were also collected in aerial nets and included gravid/parous C. bundyensis Lee and Reye, and one parous C. histrio Johannsen. Highest densities of arthropods (up to 1562/million m3) were on 30 January 2000 when NW winds, sustained for six hours, probably introduced midges from the New Guinea mainland. Adult mosquitoes (including three female Ve. funerea and a single female Ficalbia) and Culicoides (including two gravid C. bundyensis and one parous C. cordiger Macfie) were also collected in 2 m high mast nets during northerly surface winds. Although the results do not provide evidence that wind-blown mosquitoes introduced JE from New Guinea into Australia, they do not preclude that strong N winds associated with low pressure systems SW of the Torres Strait could have done so. However, results suggest that Culicoides were more likely than mosquitoes to reach high altitude and travel long distances during the light N winds experienced during the study.

Animals↗

Validation of a flexible cystoscopy course.

OBJECTIVE: To examine the instructional effectiveness of a course for nurses wishing to learn flexible cystoscopy, using a virtual reality flexible cystoscopy simulator to measure the outcome. SUBJECTS AND METHODS: Fourteen urology nurse practitioners with no previous experience of cystoscopy were taught the basic techniques of flexible cystoscopy. They then had supervised group instruction during which they practised flexible cystoscopy on an inanimate latex model, and were taught how to handle the cystoscope, followed by unsupervised practice, including use of the virtual reality (VR) simulator (URO Mentor, Simbionix, Israel). They then undertook a cystoscopy task on the simulator; within the bladder there were 10 flags (numbered 1-10) at key positions. By visualizing and photographing each of the flags the subject would have visualized the entire bladder mucosa. The number of flags seen was thus used as a measure of how much of the bladder mucosa was examined. The VR simulator also measured the total procedure time. After a day of training the subjects were reassessed and the changes in performance evaluated. Subjects were also asked their opinion of the use of VR for flexible cystoscopy. RESULTS: The median (range) time to complete the procedure before the course was 3.33 (2-5.5) min and the number of flags seen 7 (6-9). After the course, the median time decreased to 2.85 (1.5-4.42) min and the number of flags seen increased to 8 (6-9). The change in time was significant (P = 0.03) but the difference in the number of flags was not (P = 0.12). All 14 subjects enjoyed the use of VR for learning flexible cystoscopy; they all reported that they were more confident in handling a flexible cystoscope and in undertaking flexible cystoscopy. CONCLUSION: The virtual reality simulator was an effecctive tool for teaching flexible cystoscopy.

Adult↗

The issue of prophylactic antibiotics prior to flexible cystoscopy.

OBJECTIVE: The aim of this study was to determine whether single-dose parenteral antibacterial therapy significantly alters the rate of infection in patients undergoing flexible cystourethroscopy. PATIENTS AND METHODS: 162 patients were studied prospectively having either received parenteral antibacterial chemoprophylaxis prior to flexible cystourethroscopy or not. Pre- and postprocedure mid stream samples of urine (MSSU) were obtained to objectively evaluate the presence of infection. RESULTS: Gentamicin prophylaxis reduced the rate of post-cystoscopy-positive MSSUs from 21 to 5%. CONCLUSION: The surprisingly high rate of infection after flexible cystoscopy was significantly reduced by a single dose of gentamicin.

Antibiotic Prophylaxis↗

Importance of early phase insulin secretion to intravenous glucose tolerance in subjects with type 2 diabetes mellitus.

Insulin secretion is impaired in type 2 diabetes with the early response being essentially absent. The loss of this early insulin secretion is hypothesized to be important in the deterioration of glucose tolerance. To determine whether enhancement of the early-phase insulin response can enhance glucose tolerance, we administered 1) 120 mg nateglinide, an insulinotropic agent that enhances early insulin secretion; 2) 10 mg glyburide, which enhances the later phases of insulin secretion; or 3) placebo in random order to 21 subjects with type 2 diabetes (14 males and 7 females; aged 59.2 +/- 2.1 yr, x +/- SEM; body mass index 29.7 +/- 1.0 kg/m(2); fasting plasma glucose 8.1 +/- 0.1 mM). beta-Cell function was quantified as the incremental area under the curve for different time periods for the 5 h following iv glucose administration and glucose tolerance as the glucose disappearance constant (Kg) from 10 to 60 min. Insulin release commenced immediately after nateglinide administration, even before glucose injection, but this was not observed with glyburide. Both nateglinide and glyburide enhanced glucose-induced insulin release, compared with placebo (area under the curve -15-300 min: nateglinide 23,595 +/- 11,212 pM/min, glyburide 54,556 +/- 15,253 pM/min, placebo 10,242 +/- 2,414 pM/min). The profiles of insulin release demonstrated significant enhancement of release between -15 and 30 min for nateglinide, compared with glyburide and between 60 and 300 min for glyburide over nateglinide. Kg increased by 15% with nateglinide (0.87 +/- 0.04%/min), but it did not increase significantly with glyburide (0.79 +/- 0.04%/min), compared with placebo (0.76 +/- 0.04%/min). The enhancement of insulin release by glyburide resulted in a lower minimal glucose concentration with glyburide (3.8 +/- 0.2 mM), compared with nateglinide (5.0 +/- 0.2 mM) and placebo (5.9 +/- 0.2 mM). Thus, enhancement of the early phase of insulin secretion improves iv glucose tolerance, whereas delaying it by 30 min results in a slower rate of glucose disappearance for the first 2 h after iv glucose administration. Further, the differences in the kinetics of nateglinide and glyburide action results in continued insulin release with glyburide despite the fact that glucose levels have returned to basal, thus resulting in a further reduction in glucose levels and a lower nadir.

Aged↗

Do patients with rheumatoid arthritis established on methotrexate and folic acid 5 mg daily need to continue folic acid supplements long term?

BACKGROUND: It is postulated that some aspects of methotrexate toxicity may be related to its action as an anti-folate. Folic acid (FA) is often given as an adjunct to methotrexate therapy, but there is no conclusive proof that it decreases the toxicity of methotrexate and there is a theoretical risk that it may decrease the efficacy of methotrexate. OBJECTIVES: To look at the effect of stopping FA supplementation in UK rheumatoid arthritis (RA) patients established on methotrexate <20 mg weekly and FA 5 mg daily, to report all toxicity (including absolute changes in haematological and liver enzyme indices) and to report changes in the efficacy of methotrexate. METHODS: In a prospective, randomized, double-blind, placebo-controlled study, 75 patients who were established on methotrexate <20 mg weekly and FA 5 mg daily were asked to stop their FA and were randomized to one of two groups: placebo or FA 5 mg daily. Patients were evaluated for treatment toxicity and efficacy before entry and then at intervals of 3 months for 1 yr. RESULTS: Overall, 25 (33%) patients concluded the study early, eight (21%) in the group remaining on FA and 17 (46%) in the placebo group (P = 0.02). Two patients in the placebo group discontinued because of neutropenia. At 9 months there was an increased incidence of nausea in the placebo group (45 vs. 7%, P = 0.001). The placebo group had significantly lower disease activity on a few of the variables measured, but these were probably not of clinical significance. CONCLUSIONS: It is important to continue FA supplementation over the long term in patients on methotrexate and FA in order to prevent them discontinuing treatment because of mouth ulcers or nausea and vomiting. Our data suggest that FA supplementation is also helpful in preventing neutropenia, with very little loss of efficacy of methotrexate.

Aged↗

Relationship of telomeres and p53 in aging bovine corneal endothelial cell cultures.

PURPOSE: To demonstrate a relationship between telomere lengths and levels of p53 in cultured bovine corneal endothelial cells (CECs) during aging. METHODS: Bovine CECs were grown and aged as long-term cultures. Telomere lengths were determined directly on gels with 32P probes after treatment of isolated DNA with RsaI and HinfI. Protein p53 was determined using an enzyme-linked immunosorbent sandwich assay. Cellular aging and the development of replicative senescence were monitored by the appearance of senescent morphology and the beta-galactosidase assay. RESULTS: Bovine CEC telomeres lost 4 kb (from 12.8 to 8.8 kb) over 1 year (89 population doublings [PDs]). The p53 levels in bovine CECs were initially small (approximately 60 pg/million cells), but rose 3.5-fold by culture age of 260 days (64 PDs). On initiation, cultured bovine CECs did not stain for the senescent marker beta-galactosidase. However, these cells stained at 89 PDs and senescent morphology was observed in the cultures at 64 PDs. CONCLUSIONS: The data indicate an inverse relationship between telomere lengths (decreasing) and levels of p53 (increasing) in bovine CECs during aging. These properties may influence the ability of these cells to divide as they enter into replicative senescence.

Animals↗

Effects of mannitol on cultured corneal endothelial cell Na,K-ATPase activity.

Mannitol was introduced into the media of bovine corneal endothelial cells grown in culture. This was accomplished in order to compare its influence on Na,K-ATPase activity with that of high levels of glucose that inhibit the enzyme. The study was conducted with the intent of showing possible adverse osmolar effects on enzyme activity. Mannitol was found to inhibit NA,K-ATPase when compared with mannitol-free medium (11 U vs. 202 U). However, this inhibition was significantly greater than that produced by high levels of glucose. When mannitol was introduced directly into the assay for the plasma membrane-extracted enzyme, the inhibition was as severe (14 U) as for that placed in the culture medium. By way of comparison, glucose introduced into the enzyme assay caused no significant inhibition (189 U). The mannitol concentration used was 20 mM and in the media there was an osmotic pressure of 347 mOsmol/kg. The high glucose concentration was 25 mM and the osmotic pressure in the media was 341 mOsmol/kg. These osmotic pressures were compared with that of the control medium (with 5 mM glucose), which generated a pressure of 308 mOsmol/kg. None of these values were judged sufficiently high to rupture cell plasma membranes or alter cell morphology as seen by vital staining and phase contrast microscopy. In addition, it was found that mannitol had no effect on cellular DNA, whereas a previous study showed that high glucose caused an increased unwinding of duplex DNA. This study suggests that mannitol inhibits endothelial cell Na,K-ATPase by a different mechanism than that of glucose. It further points out that osmotic effects may not be involved with either mechanism.

Animals↗

The danger of freely rocking cradles.

OBJECTIVE: To assist the Adelaide State Coroner with his inquest into the death of two infants in South Australia, and to assist the Department of Public and Consumer Affairs develop Australian Standards for rocking cradles. METHODOLOGY: A sample of each brand of new cradle commercially available in South Australia was examined. Videotapes were made of 11 healthy infants in rocking cradles to examine how they moved and how they reacted in different positions. RESULTS: Many cradles had insecure locking pins. Infants in a cradle tilted at 10 degrees greater, face down with the side of the face against the bars, and an aim trapped between the body and bars or through the bars, were unable to obtain a clear airway unless a dummy was in the mouth. CONCLUSIONS: Infants should never be left unattended in freely rocking cradles. Australian Standards should recommend locking pins be bolted into place and that cradles cannot tilt to greater than 5 degrees.

Age Factors↗

Low-molecular-weight peptides in corneal tissue culture media and in bovine aqueous fluid.

Eight putative, low-molecular-weight peptides have been found in the media of bovine corneal tissue cocultures and in bovine aqueous fluid. By investigating amine fluid extracts from these sources by HPLC, possible amino acids, vitamins and urea were eliminated as the unknown peaks of interest. The molecular weights of these substances were equal to or less than 1,000 D. The peaks did not correspond to glutathione or bradykinin either which fall in this molecular weight range. As the cultures aged from 10 to 32 days, it was found that 5 of the 8 peptides varied in concentration. Five peptides increased in concentration to day 17 and slowly decreased afterwards. Efforts are not directed toward the identification of these peptides.

Animals↗

Alteration of ATPase activity and duplex DNA in corneal cells grown in high glucose media.

An investigation was made on the possible effects of high levels (450 mg/dl) of glucose on the activities of Na,K-ATPase [E.C. (Enzyme Commission) 3.6.1.37] and Mg-ATPase (E.C. 3.6.1.4) in plasma membrane preparations of bovine corneal endothelial cells grown in tissue culture. The activities of these enzymes were compared with the activities of the same enzymes from cells grown in low or "fasting" levels (90 mg/dl) of glucose. All activities were assayed from cells that were secondary cultures (15-25 days after trypsinization). The results indicated a 76% decrease in activity for Na,K-ATPase (0.04 units in high glucose vs. 0.17 units in low glucose). The activity for Mg-ATPase also decreased by 33% (0.24 units in high glucose vs. 0.36 units in low glucose). A t-test for significance indicated that the loss of activity in both enzymes was highly significant (p < 0.001) in the high glucose media. Assays for ATPase activity of plasma membranes were also made directly in high glucose after removal of the membranes from cells grown in low-glucose media. However, those membrane ATPases showed no significant decrease in activity. Tests for DNA damage of cells grown in the presence of high levels of glucose indicated a 15.5% change (decrease) in the amount of double-stranded DNA remaining after alkali treatment. This change was highly significant also (p < 0.001). These data suggest that the diabetic state may negatively affect membrane-bound ATPases of the corneal endothelium and further point to the possibility of an altered synthetic rate of ATPase polypeptides as a result of DNA damage.

Animals↗

The inhibition of Na, K-ATPase, and Mg-ATPase by timolol maleate in cultured non-pigmented epithelial cells of the ciliary body.

Bovine, non-pigmented, ciliary body epithelial cells were isolated and grown in culture to determine whether timolol maleate might affect the activity of their plasma membrane ATPases. The possible effects were tested in drug concentrations in a range of 5 x 10(-19) to 5 x 10(-5) M over an incubation period of 30 min at 37 degrees. Assays of specific activity showed that the drug significantly (p less than .001 for most concentrations) inhibited both Na,K-ATPase and Mg-ATPase. However, the inhibition was partially reversed in concentrations greater than 10(-6) M for Na,K-ATPase and 10(-5) M for Mg-ATPase. The latter enzyme also indicated a second partial reversal in activity at concentrations between 10(-12) and 10(-9) M. These reversals in activity suggest that more than one binding site is involved in the inhibition of both enzymes. Since Na,K-ATPase in non-pigmented, ciliary body cells is responsible for the generation of aqueous fluid and the intraocular pressure (IOP), this inhibition demonstrates a possible mechanism for the pharmacological action of timolol maleate in lowering IOP.

Amino Acid Sequence↗