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Biomedical subjects

C Chandler

Publications and source records attributed to C Chandler.

At least 37 records · Page 2Linked to original sources
PubMed2000

Intestinal ischemia and the gut-liver axis: an in vitro model.

BACKGROUND: Sustained intestinal ischemic injury often leads to shock and multiorgan failure, mediated in part by a cytokine cascade. Animal models have also identified a central role of Kupffer cells in amplification of cytokines following intestinal ischemia. To better understand this gut-liver axis, we developed an in vitro model. MATERIALS AND METHODS: Kupffer cells were isolated from rat livers by arabinogalactan gradient ultracentrifugation and adherence purification. Cells were grown in RPMI medium in 5% CO(2). Rat intestinal epithelial cells, IEC-6, were cultured under normoxic or anoxic (90% N(2), 10% CO(2)) conditions for 2, 12, and 24 h. Kupffer cells were then grown in the conditioned medium of the IEC-6 cultures. After 24 h, the medium was replaced with fresh medium. This final Kupffer cell supernatant was tested for tumor necrosis factor alpha and interleukin-6 production by ELISA. Trypan blue exclusion was performed to assess cell viability. RESULTS: Intestinal and Kupffer cells remained viable during the experimental time. Production of both tumor necrosis factor alpha and interleukin-6 by Kupffer cells increased with increasing ischemia time of the intestinal cells. CONCLUSIONS: Consistent with animal studies of intestinal ischemia, this study found an increase in cytokine production by Kupffer cells following hypoxia of intestinal cells. This in vitro model offers a new tool to study the expression of cytokines, proteins, and messengers involved in the cascade of events that follow intestinal ischemia.

Animals↗
PubMed2000

Provider gender preference in obstetrics and gynecology: a military population.

OBJECTIVE: This study evaluates patient reasons and preferences for gender selection of their obstetrician-gynecologist. METHODS: A written survey was given to patients attending a military obstetrics and gynecology clinic (N = 203). Mean age was 36 years, with 69% of patients between 20 and 40 years. Caucasian (52%) and African American (34%) were the most common races. RESULTS: Overall, 52% of patients preferred a female practitioner, 4% preferred males, and gender did not matter for 44%. Experience and reputation were the most important factors in 93% of all patient provider selections. Only 10% of patients felt that gender was the most important factor, and 35% ranked gender as one of the top two factors. CONCLUSION: Although a majority of our study population preferred female obstetrician-gynecologist providers, experience and reputation were more frequently cited than gender as the most important factors in selecting a provider. Patients felt that female physicians understand their problems better.

Adolescent↗
PubMed1999

Prevalence of back, neck and shoulder problems in the inner city: implications for the provision of physiotherapy services in primary healthcare.

BACKGROUND AND PURPOSE: More general practitioners are offering physiotherapy services within primary healthcare; however, this provision may result in increased demand. Resource allocation, based on previous patterns of consultation for musculoskeletal conditions, may be inadequate since the need for treatment in the community may not have been met in the past. Therefore the aim of this study was to determine the prevalence of back, neck and shoulder problems that had restricted normal activity for more than one week during the last year and which health professionals (if any) patients had consulted about their symptoms. METHOD: A postal survey of 2400 adult patients selected at random from four general practices in Newcastle upon Tyne (600 from each practice). RESULTS: A total of 1546 questionnaires were returned, a 64% response rate. Overall, 40% of respondants reported having at least one back, neck and/or shoulder problem. Back problems were most common (30%), followed by those with neck (21%) and shoulder (20%) problems. Approximately one-third of those with problems consulted no one, a further third consulted a general practitioner and only one in six consulted a physiotherapist. CONCLUSIONS: There is a high prevalence of substantial back, neck and shoulder problems in the community and thus a wider provision of physiotherapy services within primary healthcare may be required to manage the considerable levels of potentially unmet need.

Adolescent↗
PubMed1999

Spontaneous ambulatory activity as a quantifiable outcome measure for rheumatoid arthritis.

OBJECTIVE: To validate the objective monitoring of ambulatory activity as an outcome measure for rheumatoid arthritis (RA). METHODS: We have compared ambulatory activity to a range of currently favoured outcome measures, ranging from subjective opinions to X-ray damage, in a population of 93 RA sufferers. RESULTS: Correlations were stronger with measures of joint damage and disability, and less strong with measures of disease activity. Sensitivity to change was good. Three different interventions were compared for the quantity of the response, and the results agree with clinical experience, with steroid injection of the knee and use of non-steroidal anti-inflammatory drugs (NSAIDs) having a similar response and the provision of surgical shoes producing a more modest increase in ambulation. CONCLUSION: The measurement of ambulatory activity has validity for RA assessment. It provides different but related data to the currently used measures. It is objective, relevant, quantifiable and of unlimited scale. It could be used to quantify interventions aimed at increasing ambulation, in carefully constructed studies.

Arthritis, Rheumatoid↗
PubMed1998

Direct injection of 90Y MoAbs into glioma tumor resection cavities leads to limited diffusion of the radioimmunoconjugates into normal brain parenchyma: a model to estimate absorbed radiation dose.

PURPOSE: Previously we have demonstrated that radioimmunoconjugates can be injected into glioma resection cavities to deliver a boost of radiation to the cavity edge with little toxicity to the normal brain. In the mathematical models we have previously published to assist in the development of this strategy we assumed that antibody remains associated with the cavity edge and no diffusion occurs. However, moderate diffusion might be beneficial while, if this were excessive, it would decrease the therapeutic index markedly. METHODS AND MATERIALS: Selected individuals with relapsed malignant glioma underwent further surgical debulking; 90Y MoAb radioimmunotherapy; and open biopsy to determine the extent to which the conjugate diffuses from the cavity edge. Samples from these patients were taken in radial tracts and the corrected activity in each sample was plotted against distance from the cavity wall to determine appropriate diffusion constants. RESULTS: Our data indicates that diffusion of radioimmunoconjugate from the edge of a glioma resection cavity appears to be an exponential process. The mean Ro for each patients data set ranged from 0.48-0.63 (overall mean 0.6) cm. A dosimetric model was developed that translates these measurements into estimates of radiation dose. Applying the clinical data to this model indicates that, in each patient, the peak dose is delivered 0.16-0.18 cm below the cavity margin, and the mean dose at 2 cm deep is 5.3% (4.4-5.8%) of the peak. CONCLUSION: The model described can be used to translate diffusion constants measured by any method into estimates of absorbed radiation dose. Assuming similar diffusion kinetics, it can also be used to predict the dose deposited if alternative radionuclides are linked to MoAb, although the effect of dose rate should also be considered. In the future, it may be possible to manipulate diffusion by using either different antibodies or antibody fragments for intracavity radioimmunotherapy. Before this can be done, however, further data are needed and a noninvasive approach to measuring diffusion would clearly be optimal.

Antibodies, Monoclonal↗
PubMed1998

Dose escalation with repeated intrathecal injections of 131I-labelled MAbs for the treatment of central nervous system malignancies.

We have previously demonstrated a 33% response rate in patients with primitive neurectodermal tumours after the direct injection of 131I-monoclonal antibodies (MAbs) into the cerebrospinal fluid (CSF). Dose-limiting toxicity is myelosuppression due to the passage of the radioimmunoconjugate from the CSF to the blood compartment. This occurs at doses of 2220 MBq of 131I-MAb and above, although this is not seen in all patients studied and appears to be related to the degree of prior therapy received. Rather than attempting to improve the efficacy of this approach to the treatment of disseminated disease within the CSF compartment by dose escalation and haemopoietic rescue, we have explored the possibility of repeatedly administering the radioimmunoconjugate. Eight patients were recruited to the study, two of whom received two and six of whom received three injections of 131I-MAb. After repeated administration of 131I-MAb pharmacokinetic data revealed that, with one exception, the radioimmunoconjugate cleared from the CSF compartment with similar kinetics, while its residence time in the blood decreased with each injection. This was due to the development of an anti-mouse Ig response in the blood. Clearance of 131I-MAb from the ventricular CSF appears to be independent of the presence of an anti-mouse Ig response in this compartment. The differential clearance of the radioimmunoconjugate from the ventricular CSF and from the blood results in a marked increase in the therapeutic index that can be achieved. Up to 5920 MBq of 131I-MAb was administered as the third injection of radioimmunoconjugate and combined doses of up to 12,500 MBq were given without either haematological or neurological toxicity. These data illustrate that dose escalation and thus an increase in the dose rate delivered to tumour cells within the CSF is possible if ways are found to reduce the residence time of the radioimmunoconjugate in the blood compartment. Suggestions as to how this can best be achieved are reviewed in detail.

Adolescent↗
PubMed1998

Spontaneous ambulatory activity as a quantifiable outcome measure for osteoarthritis of the knee.

OBJECTIVE: Quantifiable outcome measures for disabling diseases such as osteoarthritis (OA) of the knee are necessary in order to compare the impact of different interventions competing for financial resources. Current subjective and questionnaire data are not satisfactory for such study. In this study, we examine the potential of the direct measurement of ambulatory activity as such a measure. POPULATION: Patients with X-ray evidence of OA of the knee recruited to studies of anti-inflammatory agents (n = 29). Patients with OA of the knee awaiting knee replacement surgery (n = 28). METHODS: Comparison of various standard measures with total energy output data from an activity monitor. RESULTS: Spearman rho correlations of ambulatory energy output (number of steps x average amplitude of steps) correlated with other measures. Correlation with physician's opinion was greater than with patient's opinion (r = 0.4 and 0.2, respectively). There was no correlation with visual analogue pain scale or OA severity index. Correlation with scales of the Nottingham Health Profile questionnaire were not significant either for mobility (r = - 0.15) or for pain (r = - 0.13). There was, however, a significant correlation between poor sleep and increased activity (r = 0.34, P < 0.05). Correlation with Kellgren X-ray grade was significant (r = - 0.45, P = 0.01). Patients recruited to anti-inflammatory studies were 69% more active than those awaiting replacement surgery. CONCLUSION: The monitoring of ambulatory activity shows some construct and discriminant validity, and is worthy of further study.

Energy Metabolism↗
PubMed1998

Safety of completion thyroidectomy for multicentric carcinoma.

The role of completion thyroidectomy after lobectomy for well-differentiated thyroid carcinoma remains controversial. The purpose of the present study is to compare the relative safety of a one-stage versus a two-stage approach in the management of thyroid cancer. Thirty consecutive patients with thyroid carcinoma were studied. In 14 patients, frozen-section diagnosis of carcinoma allowed total thyroidectomy at the initial operation. In 16 patients, carcinoma was found only on permanent section; thus, completion thyroidectomy was undertaken as a second stage. Transient hypocalcemia occurred in one patient in each group (one-stage, 7%; two-stage, 6%). There was one unilateral recurrent nerve paresis in the one-stage group and none in the two-stage group. We conclude that a two-stage procedure is a safe and effective approach for the treatment of thyroid cancer and can be employed in those instances in which the diagnosis of malignancy is insecure at the initial operation.

Adenocarcinoma, Follicular↗
PubMed1998

Ambulatory activity as an objective and quantifiable measure of nonsteroidal therapy.

OBJECTIVE: To quantify any increase in short term spontaneous ambulatory activity resulting from the use of nonsteroidal antiinflammatory drugs (NSAID) in patients with rheumatoid arthritis (RA). METHODS: Double blind placebo controlled crossover study of 8 women with RA using conventional assessments and the Numact activity monitor. RESULTS: Patients' ambulatory activity was 50% greater during NSAID treatment compared to placebo treatment. Effect size calculated at 0.62, suggesting good sensitivity to change. The increased activity occurred late morning. CONCLUSION: Spontaneous ambulatory activity is an objective and relevant measure of disability.

Adult↗
PubMed1997

Pharmacists on a primary care team at a Veterans Affairs medical center.

The role of pharmacists on a primary care team in the VA Chicago Health Care System--Lakeside Division is described. In 1990 the Veterans Affairs Lakeside Medical Center (now called the VA Chicago Health Care System--Lakeside Division) implemented the "Firm" system to improve the quality of patient care. This system split the original primary care clinics into three identical but smaller groups, or Firms. Each Firm provides three types of care: longitudinal care (ongoing care with a primary care physician), interim care (frequent care and close patient monitoring between primary physician visits), and un-scheduled care (acute care for complaints that may require immediate attention). Each Firm has a care team composed of physicians, a pharmacist, nurses, and other health care personnel. The pharmacist assists with interim care and, in conjunction with Firm physicians, is involved in follow-up and monitoring of drug therapy and identification of new problems. Originally it was expected that pharmacists would care for 30-40% of interim care patients, but Firm pharmacists have assisted in providing care to over 50% of these patients (plus 4% of un-scheduled care patients). The pharmacists have received high ratings from the internal medicine resident staff. Pharmacists on multidisciplinary care teams provided primary care to more than half of outpatient veterans in need of health care between regularly scheduled appointments.

Chicago↗
PubMed1995

A pilot study of the treatment of patients with recurrent malignant gliomas with intratumoral yttrium-90 radioimmunoconjugates.

A pilot study of the treatment of patients with relapsed malignant gliomas with direct intratumoral injections of yttrium-90 (90Y) radioimmunoconjugates has been completed. Patients were recruited following maximal tumour resection, and received 1-3 injections of 90Y conjugated to a monoclonal antibody designated ERIC-1, which binds the neural cell-adhesion molecule. Data were collected to establish clinical toxicity, pharmacokinetics and radiation doses to the cavity wall and critical body organs. Twenty-three injections were completed in 15 patients, with a mean injected activity of 675 MBq (range 399-921). Early toxicity manifested as cerebral oedema and was readily controlled with dexamethasone. Delayed myelosuppression was observed but no intervention was required. Pharmacokinetic analysis confirmed prolonged retention of isotope in the cavity with correspondingly low activity in the bloodstream. These data were translated into estimates of absorbed radiation dose using the Medical Internal Radiation Dosimetry (MIRD) scheme. Mean doses, and dose rates, to the wall of the cavity, i.e. 'tumour,' were very high in comparison to normal tissue doses, with a further advantage if targeting was achieved.

Adolescent↗
PubMed1994

Energy metabolism in free-living, 'large-eating' and 'small-eating' women: studies using 2H2(18)O.

The doubly-labelled water (2H2(18)O) technique was used to assess the long-term rates of energy expenditure and, after accounting for any changes in body composition, the derived rates of energy intake in weight-stable 'large-eating' (n 6) and 'small-eating' (n 6) women. The self-reported energy intakes (approximately 11.2 v. 5.6 MJ/d) and energy expenditures (approximately 8.5 v. 12.4 MJ/d) for the 'large-eating' and 'small-eating' groups respectively, should not be sustainable without significant body-weight changes. 2H2(18)O-assessed rates of energy expenditure for the 'large-eaters' (approximately 8.5 MJ/d) and 'small-eaters' (approximately 11.3 MJ/d) were in close agreement with the results obtained using 5 d, self-reported activity diaries but the derived rates of energy intake for the 'large-' (approximately 8.5 MJ/d) and 'small-eaters' (approximately 10.8 MJ/d) were markedly different from those obtained using self-reported, weighed food diaries. When two 'small-eaters' were supplied with their self-reported energy intakes (approximately 5 MJ/d) for up to 28 d both subjects lost about 0.75 kg body-weight/week. These results provide no support for the existence of 'metabolically efficient' women in the community.

Adult↗
PubMed1994

Advances in image-directed neurosurgery: preliminary experience with the ISG Viewing Wand compared with the Leksell G frame.

Because of the limited application of frame-based stereotaxy to general neurosurgical procedures, we have carried out a preliminary evaluation of the ISG Viewing Wand, a frameless image-directed surgical system that is based on the rapid reformat and accurate three-dimensional reconstruction capability of parallel processor-based computer technology. We have compared the first 36 cases carried out with the system in the Frenchay Neurosurgery Department with a retrospective analysis of the previous 36 cases carried out using the Leksell G frame. The stereotactic cases were completed over a period of 15 months, representing 2.8% of intracranial procedures. The wand cases were completed in 3 months, 13% of the intracranial practice during that time. The wand was used for 28 supratentorial craniotomies (76%), four infratentorial procedures (11%) and five biopsy procedures (13%). Conventional stereotaxy was not used for posterior fossa or skull base procedures. Supratentorial craniotomy was carried out in nine cases (25%), while the remaining 27 cases involved point source localization within the cranium (75%). The mean preparation time prior to surgery was 65 min for the stereotactic cases and 37 min for the wand cases. We therefore conclude that the indications for frame-based stereotaxy and Viewing Wand use are mutually exclusive. Leksell stereotaxy remains the method of choice for point source localization deep within the cranium. All other procedures requiring an image-directed minimally invasive surgical approach are more appropriately carried out using the Viewing Wand. The system has potential immediate application in supratentorial, skull base and infratentorial tumour surgery, vascular surgery, epilepsy surgery and upper cervical spine surgery.

Brain Mapping↗