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Biomedical subjects

S R Walker

Publications and source records attributed to S R Walker.

At least 37 records · Page 2Linked to original sources
PubMed1998

Renal complications following endovascular repair of abdominal aortic aneurysms.

PURPOSE: To investigate the renal complications associated with endovascular repair of abdominal aortic aneurysms (AAAs). METHODS: Data were prospectively collected on 164 AAA patients (154 males; median age 72 years; interquartile range 51 to 88) undergoing endovascular grafting. Any history of renal failure and diabetes mellitus was recorded. Serum urea and creatinine levels were measured preoperatively and at regular intervals postoperatively. Renal impairment was defined as serum creatinine > 130 micromol/L. RESULTS: There were no significant differences in pre- and 1-day postoperative serum urea and creatinine levels. Among 15 (9.1%) patients with preoperative renal failure, 7 (47%) died, 4 (27%) in the perioperative period. Of the 149 patients with normal renal function preoperatively, 4 (2.7%) developed renal failure as part of multisystem organ failure. Another 9 (6.2%) developed significant postoperative elevations (> 20%) in their creatinine levels compared to baseline; 4 of these patients died, 2 in the perioperative period. There was no significant difference in the median dose of intravascular contrast used for those patients that did and did not have a deterioration in their renal function (250 mL versus 300 mL). CONCLUSIONS: In this study, approximately 6% of patients with normal preoperative renal function who undergo endovascular AAA repair develop renal dysfunction. For patients with preoperative renal impairment, the perioperative mortality rate is high, 27%, following endovascular aortic aneurysm repair.

Acute Kidney Injury↗
PubMed1998

A randomized controlled trial comparing a 21 G needle with a 23 G needle for fine needle aspiration of breast lumps.

A randomized study was performed on patients in whom the clinical decision had already been made to excise a breast lump. The objective was to assess the difference in diagnostic results of 21 and 23 G needles in the fine needle aspiration cytology (FNAC) of breast lumps. Following induction of anaesthetic, (local or general), FNAC was performed with either a 21 or 23 G needle. The breast lump was then excised and the histology and cytology results analysed routinely. One hundred and twenty-five excised breast lumps were included. Sixty-one had FNAC performed with a 21 G needle and 64 had FNAC performed with a 23 G needle. Of the 61 21 G FNAC, histology revealed 45 breast cancers. Of the 64 23 G FNAC, 50 patients had breast cancer. There was no statistical difference between these two results. There is no difference in the cytological yield when a 21 G needle is compared with that of a 23 G needle.

Biopsy, Needle↗
PubMed1997

Intercessory prayer in the treatment of alcohol abuse and dependence: a pilot investigation.

OBJECTIVE: To conduct a pilot study of the effect of intercessory prayer on patients entering treatment for alcohol abuse or dependence. DESIGN: In addition to standard treatment, 40 patients admitted to a public substance abuse treatment facility for treatment of alcohol problems who consented to participate were randomized to receive or not receive intercessory prayer (double-blind) by outside volunteers. Assessments were conducted at baseline, 3 months, and 6 months. RESULTS: No differences were found between prayer intervention and nonintervention groups on alcohol consumption. Compared with a normative group of patients treated at the same facility participants in the prayer study experienced a delay in drinking reduction. Those who reported at baseline that a family member or friend was already praying for them were found to be drinking significantly more at 6 months than were those who reported being unaware of anyone praying for them. Greater frequency of prayer by the participants themselves was associated with less drinking, but only at months 2 and 3. CONCLUSION: Intercessory prayer did not demonstrate clinical benefit in the treatment of alcohol abuse and dependence under these study conditions. Prayer may be a complex phenomenon with many interacting variables.

Adult↗
PubMed1996

The Canadian Organ Replacement Register.

The analyses presented in this chapter are a subset of the yearly audit of organ donation and transplantation in Canada published in the CORR Annual Report. They represent the collaborative efforts and the voluntary contributions of many of the transplant physicians, surgeons, nurses and coordinators in Canada. In Canada, organ donation has remained static at approximately 14 per million population. Despite many local and provincial as well as corporate initiatives, this rate is approximately half the current rate in many regions of the U.S.A. and Spain. The modest increases in transplant activity represent an increase in the use of living donors, reassessment of the traditional donor risk factors (including age) and expansion of the potential donors for each organ. Analysis of the renal transplant activity has determined that the likelihood of being transplanted during the first year on the list was less than 40%. A graft loss rate of 4% per year after the first year was observed for a cadaveric kidney, compared with graft loss rates of 3% and 2% per year for living-related and living-unrelated donor kidneys, respectively. Cox regressional analysis identified that the major determinants of patient survival were the transplant year, the region where the transplant was performed, the presence of diabetes, the recipient's age, and whether the kidney was from a living donor. Liver transplantation has increased each year at the transplant centers in Vancouver, Edmonton, London, Toronto, Montreal, and Halifax. Patient and graft survival rates have improved since 1985 and the most significant determinant of patient survival following transplantation was the patient's medical status at the time of transplantation. Living-related liver donor transplant programs have begun in London and Toronto. Pancreas transplantation remains limited across Canada, but with the development of new pancreas programs in Toronto and Halifax, an increase in the availability of this therapy for Type 1 diabetics is anticipated. Heart transplantation has recovered from a decline in 1991-1992 to approximately 6 hearts per million population. There has been a trend towards better one- and 3-year patient survival rates since 1985. With the development of a lung transplantation program in Winnipeg, lung transplantation has increased. This likely reflects increased utilization of the available donor lungs. A particular increase in double-lung transplants was noted.

Adolescent↗
PubMed1995

The value of information generated by long-term toxicity studies in the dog for the nonclinical safety assessment of pharmaceutical compounds.

Data on 117 pharmaceutical compounds in the CMR toxicology database have been analyzed to determine what new toxicological information was provided by the dog in chronic (6 months or longer) toxicity testing. For more than half of the 117 compounds, all salient effects in the dog were seen for the first time within 3 months. For just under one-third of the compounds, any effects that occurred for the first time beyond 3 months in the dog were also seen in studies in the rat. Only 13 of the 117 compounds showed new and possibly important effects in the chronic study. No particular therapeutic class nor any other single circumstance was implicated in these 13 cases. Types of late-onset findings in the dog occurring with more than 1 compound included nonspecific effects or hypertrophic/hyperplastic changes. There may be several reasons, pragmatic as well as scientific, why it can sometimes be desirable to carry out chronic repeat-dose studies of 6 months or longer in the dog. However, the results of this retrospective evaluation have demonstrated that in the large majority of cases analyzed, long-term toxicity studies in the dog provide relatively little qualitatively new toxicological information not already gained from a short-term (3 month) study in the dog in conjunction with short- and long-term studies in the rat.

Animals↗
PubMed1994

New chemical entity output of the international pharmaceutical industry from 1970 to 1992.

A database has been established that contains confidential information, together with publicly available data, on various aspects of the development of 1106 new chemical entities and biological compounds (including products of biotechnology) first marketed as medicines since 1970 on one or more of 20 major international markets. These data have been used to examine the performance of the European, U.S., and Japanese pharmaceutical industries by examining the numbers and types of new medicines reaching the marketplace from 1970 to 1992 and the companies responsible for introducing them. Although the European marketing companies dominate in total numbers first marketed over this period, there has been a significant decline in their annual output. In contrast, the Japanese companies have shown a significant increase in the number of new compounds marketed annually. However, European marketing companies remain the most successful in terms of sales because they are responsible for first marketing approximately 50% of the top 50 products by international sales in 1992. The main therapeutic areas of output by all three regions have remained relatively unchanged over the 23-year period: cardiovascular system (21%), nervous system (18%), and anti-infectives (16%). This article provides insight into the changing status of the international pharmaceutical industry over the last 23 years in terms of output from research and development.

Databases, Factual↗
PubMed1994

Intracerebral propagation of interictal activity in partial epilepsy: implications for source localisation.

The hypothesis that focal scalp EEG and MEG interictal epileptiform activity can be modelled by single dipoles or by a limited number of dipoles was examined. The time course and spatial distribution of interictal activity recorded simultaneously by surface electrodes and by electrodes next to mesial temporal structures in 12 patients being assessed for epilepsy surgery have been studied to estimate the degree of confinement of neural activity present during interictal paroxysms, and the degree to which volume conduction and neural propagation take part in the diffusion of interictal activity. Also, intrapatient topographical correlations of ictal onset zone and deep interictal activity have been studied. Correlations between the amplitudes of deep and surface recordings, together with previous reports on the amplitude of scalp signals produced by artificially implanted dipoles suggest that the ratio of deep to surface activity recorded during interictal epileptiform activity on the scalp is around 1:2000. This implies that most such activity recorded on the scalp does not arise from volume conduction from deep structures but is generated in the underlying neocortex. Also, time delays of up to 220 ms recorded between interictal paroxysms at different recording sites show that interictal epileptiform activity can propagate neuronally within several milliseconds to relatively remote cortex. Large areas of archicortex and neocortex can then be simultaneously or sequentially active via three possible mechanisms: (1) by fast association fibres directly, (2) by fast association fibres that trigger local phenomena which in turn give rise to sharp/slow waves or spikes, and (3) propagation along the neocortex. The low ratio of deep-to-surface signal on the scalp and the simultaneous activation of large neocortical areas can yield spurious equivalent dipoles localised in deeper structures. Frequent interictal spike activities can also take place independently in areas other than the ictal onset zone and their interictal propagation to the surface is independent of their capacity to trigger seizures. It is concluded that: (1) the deep-to-surface ratios of electromagnetic fields from deep sources are extremely low on the scalp; (2) single dipoles or a limited number of dipoles are not adequate for surgical assessment; (3) the correct localisation of the onset of interictal activity does not necessarily imply the onset of seizures in the region or in the same hemisphere. It is suggested that, until volume conduction and neurophysiological propagation can be distinguished, semiempirical correlations between symptomatology, surgical outcome, and detailed presurgical modeling of the neocortical projection patterns by combined MEG, EEG, and MRI could be more fruitful than source localization with unrealistic source models.

Adult↗
PubMed1994

Psychiatric disorders of opioid addicts entering treatment: preliminary data.

Psychiatric disorders have become an increasing concern in the treatment of substance abusers. The introduction of the Human Immunodeficiency Virus (HIV) into this population has further complicated treatment. This study examines the prevalence of psychiatric disorders in an opioid dependent population maintained on methadone. Results from this preliminary analysis show high rates of psychiatric disorders in this population. Additionally, needle sharing behavior appears to be increased in patients with a diagnosis of dysthymia. These findings have direct implications for aggressive screening and treatment of psychiatric disorders in methadone maintenance clinics.

Adult↗
PubMed1992

An international appraisal of the minimum duration of chronic animal toxicity studies.

1. There are international differences in regulatory guidelines for the appropriate duration of chronic, two species repeat-dose animal tests for new medicines intended for long-term use in man, ranging from 6 months in Europe to 12 months in Japan and the USA. 2. An adequate data base is necessary to support any challenge to the scientific rationale behind regulatory guidelines with regard to the design, duration and relevance of toxicity tests of new medicines. 3. The Centre for Medicines Research has established an international toxicology data base which has been expanded to enable a comparison of data obtained within 6 months, with information from longer periods, for 154 studies. 4. Although new findings were revealed after 6 months for 9/75 cases for which pathology data are available at 6 and 12 months or longer, and 21/80 with data at 1 or 3 (but not 6 months) and 12 months or longer, in no instance did these influence the decision to drop or further develop the compounds in question. 5. These data suggest that a 6-month period of dosing is all that is routinely required for evaluating the chronic toxic (excluding carcinogenic) potential of a new chemical entity intended for therapeutic use.

Animals↗
PubMed1991

An ASSEMBLER routine for on-line graphic display and averaging of data acquired on a personal microcomputer.

An ASSEMBLER routine is described for data acquisition and "on-line" averaging, artefact rejection and graphic display of data on a personal microcomputer (IBM compatible). The user determines the number of input channels, sampling frequency, number of samples, input range, stimulation frequency (epoch frequency) and the number of epochs to be acquired and averaged. Data from each epoch are scanned in search of saturating artefacts and will be added to previous epochs if none is found. Data are then graphically displayed as voltage versus time before acquiring next epoch. Display options can be defined by the user at run time by means of the keyboard and include: display of last epoch, display of the average, storage screen and refreshing screen after every epoch. High data transfer rates and program speed allows for high stimulation rates in the presence of on line graphic display. The computer then behaves as a multichannel digital oscilloscope with access to large memory buffers, disk storage, high averaging capabilities, artefact rejection and wide potential for data analysis. Its applications to the recording of magnetic and electric evoked responses are illustrated. The program is available from the authors.

Computer Graphics↗
PubMed1991

The need for a control animal pathology database: an international survey.

1. The sensitivity of long-term toxicity tests is impaired due to the 'background noise' of spontaneous lesions which are unrelated to treatment. 2. The need for a comprehensive source of computerized information concerning the occurrence and incidence of spontaneous lesions in control animals has been highlighted by initiatives in Europe and the USA. It is, however, essential to identify the potential users, and the type of information required for such a database to be of value. 3. This information has been acquired following an international survey of the pharmaceutical industry in Europe, Japan and the USA, including responses from 48 toxicologists and toxicopathologists representing 38 company groups. 4. Thirty-eight respondents indicated that they would use a historical control database that was regularly updated with the majority of respondents suggesting that they currently use external sources (Breeder's data, the literature, other companies) occasionally to acquire information on control animal pathology data. 5. The majority (94%) of the respondents indicated that a control animal database should contain information on both neoplastic and non-neoplastic lesions for use in evaluating long-term studies, in particular carcinogenicity studies. 6. The survey confirms the need for a historical control animal pathology database wider then those currently available.

Animals↗
PubMed1990

Harmonization of guidelines for toxicity testing of pharmaceuticals by 1992.

In the past there has been considerable disagreement between various regulatory authorities regarding the type and design of animal tests that should be required before a new medicine can be used ethically and safely in the clinic. However, regulatory variations have largely been removed within politically and geographically similar regions (e.g., the U.S.A., the European Community, the Nordic countries) and there now appears to be a consensus regarding the value of harmonizing international requirements. In order to assist the process of harmonization, a detailed table of preclinical toxicity requirements in the U.S.A., Canada, Japan, and the European Community for each test (acute, subacute, chronic, carcinogenicity, mutagenicity, reproduction) has been compiled. This has been circulated to the relevant regulatory authorities to ensure that it accurately reflects current requirements. The major differences between authorities were found to be the duration of chronic, repeated-dose tests and the design of reproduction studies. International pharmaceutical companies were asked to complete a questionnaire, indicating how they design their preclinical testing program to comply with varying regulatory requirements. Most of the respondent companies indicated that chronic tests of longer than 6 months were conducted solely to comply with some regulatory requirements. Many companies repeat reproduction studies in order to comply with Japanese requirements. This emphasizes the need to harmonize these guidelines and discussions are currently underway to attempt to develop protocols acceptable to the FDA, the EC, and the Japanese Ministry of Health and Welfare.

Animals↗
PubMed1989

Distribution of rabbit mucosal glycoprotein throughout urinary tract.

The mucin layer covering the transitional epithelium of the bladder is thought to be an anti-adherence substance for bacteria. We describe the use of an immunoperoxidase staining technique to demonstrate the presence of glycoprotein lining the urothelium of both the upper and lower urinary tracts of the rabbit. Antisera against this glycoprotein (GP1) were raised in Swiss-Webster mice. The genitourinary tracts of male and female NZW rabbits were removed and sequentially treated with mouse anti-GP1 sera, biotin-labelled anti-mouse IgG, and an avidin-biotinylated horseradish peroxidase complex. The results demonstrated that an antigenically similar (or identical) glycoprotein covers the distal renal tubules and urothelium of the renal pelvis, ureters, bladder, and urethra, suggesting that it may function as an antibacterial defense mechanism throughout the urinary tract.

Animals↗
PubMed1989

Novel medicines marketed in the UK (1960-87).

1. A total of six hundred and eighty three new chemical entities (NCEs), were marketed in the UK between 1960 and 1987. The number of NCEs introduced annually onto the UK market declined to an average of 20 per year in 1964 and subsequently to only 7 in 1985. 2. Average development times have increased fourfold since 1960 to a peak value of 13 years in 1984. The concomitant decline in effective patent life has resulted in a mean effective patent life of less than 10 years since the mid 1960s and no more than 6 years since the early 1980s, except for the cohort marketed in 1987. 3. The largest contribution to total development time was made by the clinical phase. For NCEs marketed in the mid 1960s it was 3.3 years increasing to a peak of almost 8 years in the early 1980s, and representing on average two-thirds of research and development time. 4. Between 1960 and the early 1970s total development time for central nervous system (CNS) agents, cardiovascular products and anti-infectives had doubled to 9, 8 and 7.3 years respectively. By the 1980s it was averaging 13 years for CNS agents and was 54% and 28% longer than for anti-infectives and cardiovascular compounds respectively.

Drug Industry↗
PubMed1989

Erosion number and area progression in the wrists and hands of rheumatoid patients: a quantitative microfocal radiographic study.

Microfocal radiography has been used to evaluate the relation between erosion number and erosion area in the hands and wrists of 51 patients with early to moderately advanced rheumatoid arthritis. The hands of these patients showed different patterns of erosion progression, in terms of the relation between changes in number and area, and included those showing a decrease in one or both of the erosion parameters. The mean number of erosions in the group increased between the first and second visits. By the third visit (a mean of 48 months from the onset of symptoms) the mean number of erosions in the wrist and hand of the group had approached a constant value of 75 erosions. Over the same period the mean erosion area of the group continued to increase. Measurement of changes in erosion area is a more sensitive indicator of erosion progression than erosion number, both within the group and in individual patients.

Arthritis, Rheumatoid↗
PubMed1989

Properties of isolated nonciliated bronchiolar cells from mouse lung.

Nonciliated bronchiolar cells (Clara cells) are thought to provide important respiratory secretions in the small airways and to have other metabolic functions. In mice, nonciliated bronchiolar cells have been the subject of special investigation because tumors of these cells can be specifically induced by chemical carcinogens. A method for isolating nonciliated bronchiolar cells from mice has been reported. However, we have developed a method to isolate these cells from the lungs of BDF1 mice with approximately 80% purity. Cells were identified by electron microscopy, nitroblue tetrazolium dye reduction in the presence of NADPH, immunocytochemical staining of cytochrome P450 isozymes, and mitochondrial staining with rhodamine 123. The isolated cells were examined in culture for synthesis and secretion of proteins and phospholipids. Protein synthesis and secretion were examined in cells labeled with [34S]methionine for 16 h. Fresh medium was added to washed cells and the cells were incubated for an additional 3h. The secreted proteins were precipitated with 10% trichloroacetic acid. Molecular weights of the most prominent radiolabeled secreted proteins were 6, 36, 43, and 45 kDa. Phospholipid synthesis and secretion were examined in cells labeled with [14C]acetate and 32P. Less than 1% of the radioactive lipids was found in the medium, and secretion of lipid was not stimulated by terbutaline or tetradecanoylphorbol acetate compounds, which stimulate phospholipid secretion by type II cells. These data support the hypothesis that nonciliated bronchiolar cells synthesize and secrete proteins but do not secrete phospholipids in any appreciable amount.

Animals↗