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Biomedical subjects

David Graham

Publications and source records attributed to David Graham.

26 records · Page 2Linked to original sources
PubMed2002

Randomized crossover trial of two treatments for sleep apnea/hypopnea syndrome: continuous positive airway pressure and mandibular repositioning splint.

Mandibular repositioning splints (MRSs) and continuous positive airway pressure (CPAP) are used to treat the sleep apnea/hypopnea syndrome (SAHS). There are some data suggesting that patients with milder symptoms prefer MRS, but there are few comparative data on outcomes. Therefore, we performed a randomized crossover trial of 8 weeks of CPAP and 8 weeks of MRS treatment in consecutive new outpatients diagnosed with SAHS (apnea/hypopnea index [AHI] >or= 5/hour, and >or= 2 symptoms including sleepiness). Assessments at the end of both limbs comprised home sleep study, subjective ratings of treatment value, sleepiness, symptoms, and well-being, and objective tests of sleepiness and cognition. Forty-eight of 51 recruited patients completed the trial (12 women; age [mean +/- SD], 46 +/- 9 years; Epworth 14 +/- 4; median AHI, 22/hour; interquartile ratio [IQR], 11-43/hour). Significant (p <or= 0.01) differences between MRS and CPAP were observed for 7 of 21 variables (effect sizes, 0.3-0.6 SDs), all favoring CPAP, including AHI (15 +/- 16 and 8 +/- 6/hour, respectively), effectiveness rating, symptoms, Epworth (12 +/- 5 and 8 +/- 5, respectively), functional outcomes of sleepiness questionnaire, short-form 36 health survey mental component, and health transition scores. Objective sleepiness, cognitive performance, and preference for treatments were not different. In patients experiencing a mild form of the syndrome (AHI < 15, n = 18), symptoms, treatment efficacy and satisfaction, and subjective sleepiness were also better with CPAP than with MRS (effect sizes, 0.7-1.1 SDs). These results do not support these MRS devices as first-line treatment for sleepy patients with SAHS.

Adolescent↗
PubMed2002

A rapid and sensitive assay for paralytic shellfish poison (PSP) toxins using mouse brain synaptoneurosomes.

A membrane potential assay using mouse brain synaptoneurosomes was evaluated for the determination of paralytic shellfish poison (PSP) toxin content of mussels and other bivalve species important to the shellfish industry. The assay relies on the ability of PSP toxins to block veratridine-induced depolarization of synaptoneurosomes. Changes in the membrane potential of synaptoneurosomes were monitored using the voltage-sensitive fluorescent probe rhodamine 6G. Standard saxitoxin was found to be a potent inhibitor of the membrane depolarizing effects of the sodium channel activator veratridine (I(50) ca. 4 nM). Likewise, shellfish extracts containing PSP toxins inhibited veratridine-induced depolarization. Neither saxitoxin or shellfish extracts had any discernible effect on the resting membrane potential of synaptoneurosomes. When synaptoneurosomal results for extracts of mussels (n=120) and other shellfish (n=29) were correlated with official mouse toxicity assay data there was very good agreement (r(2)=0.84 and 0.86, respectively), indicating that the in vitro assay has utility for a variety of commercially relevant shellfish species. Our investigation suggests that the mouse synaptoneurosome assay is of similar sensitivity to the official CD1 mouse toxicity assay. The synaptoneurosome fraction can be prepared quickly (approx. 40 min) and an individual assay takes less than 7 min. Since 20 such assays can be performed using material from a single CD1 mouse brain, there is considerable opportunity for reducing the number of animals required in conventional PSP monitoring while retaining the same animal system.

Animals↗
PubMed2002

Piritrexim in advanced, refractory carcinoma of the urothelium (E3896): a phase II trial of the Eastern Cooperative Oncology Group.

UNLABELLED: This was a single-agent phase II clinical trial of the antifol piritrexim in patients with advanced transitional cell carcinoma of the bladder. METHODS: Patients with previously-treated, advanced urothelial carcinoma were treated with oral piritrexim at a dose of 25 mg three times daily for 5 consecutive days each week for 3 consecutive weeks followed by a 1-week rest period. Courses were repeated every 28 days. RESULTS: Thirty-five patients were enrolled in the study, with 28 patients evaluable for survival and toxicity and 27 evaluable for response. TOXICITY: Myelosuppression was the major dose-limiting toxicity, with WHO grade 3/4 thrombocytopenia in 4 patients, granulocytopenia in 1 patient, and anemia in 3 patients. Grade 3 nonhematologic toxicity consisted of neuropathy in 5 patients, hepatotoxicity in 2, nausea in 2, and 1 each with pulmonary toxicity and rash. EFFICACY: Of the 27 patients evaluable for response, 2 (7%) achieved an objective response, lasting 112 and 142 days, respectively. CONCLUSION: Piritrexim has minimal activity in patients with previously treated transitional cell carcinoma of the bladder, regardless of prior exposure to methotrexate, and further evaluation of this compound in this clinical setting is not warranted.

Aged↗
PubMed2002

A novel human nicotinic receptor subunit, alpha10, that confers functionality to the alpha9-subunit.

We present herein the cloning of the human nicotinic acetylcholine receptor alpha9-ortholog and the identification of a new alpha-like subunit (alpha10) that shares 58% identity with alpha9. Whereas alpha10 fails to produce functional receptors alone, it promoted robust acetylcholine-evoked currents when coinjected with alpha9. The presence of alpha10 modifies the physiological and pharmacological properties of the alpha9 receptor indicating that the two subunits coassemble in a single functional receptor. Fusing the N-terminal domain of alpha9 with the rest of the alpha10-cDNA yielded a functional alpha9:alpha10-chimera that displays the acetylcholine binding properties of alpha9 and ionic pore characteristics of alpha10-containing receptors. In addition, alpha9- and alpha10-subunit mRNAs show limited similar tissue distribution patterns and are expressed in cochlea, pituitary gland, and keratinocytes. These data suggest that, in vivo, alpha9-containing receptors coassemble with alpha10-subunit.

Amino Acid Sequence↗
PubMed2002

In-training assessment for specialist registrars: views of trainees and trainers in the Mersey Deanery.

Annual review of specialist registrars and production of a record of in-training assessment (RITA) is a mandatory component of training that has attracted criticism. Mersey Deanery has established a system of review that includes wider evaluation of the trainee's needs and of training requirements. We conducted a survey to ascertain whether this broadened review process was thought beneficial. In one year 1093 questionnaires were distributed to trainees and trainers. 605 (81%) of 744 trainees and 309 (89%) of 349 trainers responded. At least 89% of both groups said that the procedure had been effective in reviewing the previous year and the most recent post and in identifying training requirements. More than 90% rated the overall process positively. Trainees particularly appreciated the advice on future training, on careers and on research. This form of review is expensive in consultant time but was valued by both trainees and trainers.

Attitude of Health Personnel↗
PubMedDate not supplied

Persistence of oral polio vaccine virus after its removal from the immunisation schedule in New Zealand.

On Feb 1, 2002, inactivated poliomyelitis vaccines replaced live-attenuated oral poliovirus vaccine (OPV) in New Zealand's immunisation schedule, allowing systematic monitoring of OPV virus circulation. Findings of paediatric-inpatient surveillance indicate that 7% of children excreted polioviruses before this switch, but none did so 1 month afterwards. Acute flaccid paralysis surveillance detected no poliovirus during and after the switch, whereas enterovirus surveillance detected poliovirus only once during the switch. Environmental surveillance identified polioviruses in sewage samples until May, 2002, after which they were detected infrequently. Intratypic differentiation and sequencing showed that all polioviruses were Sabin-like. Multiple surveillance methods hence showed that OPV strains did not persist for extended periods after a vaccine switch in a developed country with a temperate climate. Sequence homology with Sabin vaccine parent strains indicated that polioviruses detected more than 4 months after the switch were of recent origin, consistent with importation from OPV-using countries.

Feces↗
PubMedDate not supplied

Disinfection by-products in small Alberta community drinking-water supplies.

Complacent attitudes toward drinking-water quality can lead to compromised disinfection practices, as noted in such episodes as Walkerton and North Battleford. The first priority for drinking-water providers must be to ensure microbial safety. However, it is recognized that effective disinfection may not be risk free. Consequently, drinking-water guidelines seek to balance the certain danger posed by microbial pathogens with the potential adverse health hazards that may arise from disinfection by-products (DBPs). Providers of drinking water in small communities often do not have the means to reduce concentrations of DBPs, compared to utilities in larger municipalities. A significant portion of Alberta's population receives drinking water from smaller scale treatment plants or from private wells. A survey of selected DBPs was conducted in 11 rural Alberta communities, with populations ranging from 60 to 2300. The objectives were to evaluate source water quality, as measured by total organic carbon, and to measure representative concentrations of trihalomethanes (THMs) and haloacetic acids (HAAs) at a point within each distribution system as well as within each water treatment plant. During the 5-wk study, our data show: (1) averages of THM3 (chloroform, bromodichloromethane, chloro dibromomethane) concentrations often exceed 100 microg/L (Health Canada's running annual average guideline for total THMs); (2) source waters with the highest TOC concentrations (15 mg/L) had the highest average THM3 concentrations (200 microg/L); and (3) poor source water quality may necessitate using alternative disinfection options to ensure compliance with microbial and chemical drinking-water guidelines.

Alberta↗