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Biomedical subjects

J Adams

Publications and source records attributed to J Adams.

At least 91 records · Page 5Linked to original sources
PubMed2001

Phase I bioequivalency study of MitoExtra and mitomycin C in patients with solid tumors.

BACKGROUND: This study compares serum pharmacokinetics, urinary excretion patterns, and relative bioequivalencies of single doses of MitoExtra (ME; SuperGen, San Ramon, CA) and mitomycin C (MMC). METHODS: Thirty-five patients were entered into this open-label, single-institution, crossover study with 2 treatment arms. Each patient received alternating courses of ME and MMC as 15 mg/m(2) single intravenous doses via a short intravenous infusion. Patients were sequentially assigned to receive either ME or MMC as their first treatment course. The courses were given in 6-week intervals and could be repeated up to 4 times in patients with responding disease. Pharmacokinetic parameters were analyzed during the first two courses of therapy. RESULTS: The noncompartmental pharmacokinetic analysis conducted on serum and urine data obtained from patients who received both ME and MMC indicates that the kinetic disposition of these two formulations is similar. This is evident when the mean (+/- standard deviation) values of the various pharmacokinetic parameters are compared. There were no significant differences in any of the kinetic parameters obtained between treatments in all patients examined. The statistical evaluation conducted on the 25 patients that completed both arms of the 2-way pharmacokinetic crossover demonstrates that ME is bioequivalent to MMC. Hematologic and nonhematologic toxicities were similar between the two treatments. There were three clinically significant infusion-related complications associated with MMC administration and none associated with ME. CONCLUSIONS: The similar pharmacokinetics of MMC and ME suggest complete release of MMC from the hydroxypropyl-Beta-cyclodextrin carrier contained in the ME formulation. Further studies are needed to define the pharmacodynamics, toxicity, and efficacy of this drug-carrier complex.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed2001

Arm edema in breast cancer patients.

The improvement in the life expectancy of women with breast cancer raises important questions about how to improve the quality of life for women sustaining complications of breast cancer treatment. In particular, attention to common problems, such as arm edema, is of critical importance. We reviewed published breast cancer guidelines and literature identified via MEDLINE(R) searches in an effort to summarize the research literature pertinent to management of breast cancer-related arm edema, including incidence, prevalence, and timing; risk factors; morbidity; prevention; diagnosis; and efficacy of nonpharmacologic and pharmacologic interventions. We found that arm edema is a common complication of breast cancer therapy that can result in substantial functional impairment and psychological morbidity. The risk of arm edema increases when axillary dissection and axillary radiation therapy are used. Recommendations for preventive measures, such as avoidance of trauma, are available, but these measures have not been well studied. Nonpharmacologic treatments, such as massage and exercise, have been shown to be effective therapies for lymphedema, but the effect of pharmacologic interventions remains uncertain. Comparing results across studies is complicated by the fact that the definitions of interventions and measures of outcomes and risk stratification vary substantially among studies. As arm edema becomes more prevalent with the increasing survival of breast cancer patients, further research is needed to evaluate the efficacy of preventive strategies and therapeutic interventions.

Arm↗
PubMed2001

Zenker's diverticulostomy with cricopharyngeal myotomy: the endoscopic approach.

BACKGROUND: The gold standard for the surgical treatment of Zenker's diverticulum is diverticulectomy and cricopharyngeal myotomy by an external approach. Unfortunately, many of the patients who present with this entity are elderly and have significant comorbidities that increase operative risk. Traditional minimally invasive approaches have not met with widespread success. However, by combining the exposure afforded by the otolaryngologist's newer bivalved operating laryngoscopes with the operative techniques made possible by the general surgeon's laparoscopic instrumentation and staplers, it is possible to achieve reliable and safe endoscopic outpatient management of this disease entity, with resumption of a normal diet on the same day. METHODS: We reviewed the physiologic basis, instrumentation, and technical considerations for this endoscopic procedure. We also documented our operative experience with 21 patients treated over an 18-month period. RESULTS: Successful minimally invasive management of Zenker's diverticulum was possible in 18 of 21 patients. In two patients, anatomic limitations of mouth and neck anatomy precluded exposure of the diverticulum; in another patient, the diverticulum was too small. Small operative perforations of the apex of the diverticulum occurred in three cases. Two of these perforations were repaired primarily with minimally invasive techniques; in the other case, treatment consisted of observation alone. In all but this last patient, oral diet was resumed on the day of the operation. Eleven of the patients were discharged from the hospital on the same day; the remaining patients went home the following morning. CONCLUSIONS: With proper patient selection, minimally invasive management of Zenker's diverticulum is a safe and effective surgical technique that allows for outpatient management of the majority of patients who present with this disease.

Cricoid Cartilage↗
PubMed2001

Proteasome inhibition in cancer: development of PS-341.

The 26S proteasome regulates protein turnover in eukaryotic cells. This is relevant in human cancer because the cell cycle, tumor growth, and survival are governed by a large repertoire of intracellular proteins that are regulated by the ubiquitin-mediated proteasome degradative pathway. In the development of new antitumor agents whose mechanisms are distinct from currently available therapies, we have discovered a potent, selective inhibitor of the proteasome: PS-341, a dipeptide boronic acid. Compared with normal cells, cancer cells--and specifically myeloma--treated with PS-341 are differentially sensitive to proteasome inhibition and apoptosis. A unique feature of PS-341 involves the inhibition of nuclear factor (NF)-kappaB activation through stabilization of the inhibitor protein IkappaB. Myeloma cells depend on NF-kappaB-mediated transcription of cytokine growth factor interleukin-6, angiogenesis through vascular endothelial growth factor, and the cell adhesion molecule VCAM-1 for adherence of the plasma cells to the stromal tissue in bone marrow. At low nanomolar concentrations, PS-341 is highly effective in abrogating the transcription of these genes, which are under the direct regulation of NF-kappaB. Moreover, PS-341 appears to synergize with dexamethasone in myeloma cell culture, which may prove to be of additional benefit clinically. The safety profile in phase I trials of PS-341 in patients with cancer appears encouraging. Because proteasome inhibition with PS-341 results in potent antitumor activity in vitro, PS-341 may offer a promising new approach to treating otherwise fatal malignancy.

Animals↗
PubMed2001

Primary care as intersecting social worlds.

An enhanced role for primary health care (PHC) is currently a matter of political priority in the UK. This higher profile is drawing attention to a range of unresolved challenges and issues, relating to both the structure and content of provision, which currently permeate the system. Running in parallel with this is a recognition that: to date, PHC has been under-researched; that, as a result, our understanding of it is frequently poor; and that, as a consequence, fresh perspectives are needed in order to effectively research this uncertain, evolving and increasingly important healthcare sector. In this paper we argue that social worlds theory (SWT) provides, albeit in a suitably modified form, an ideal conceptual framework for the analysis of contemporary primary care. SWT is an approach which assumes complexity and constant evolution, and its core concepts are directed towards unravelling the consequences of encounters between different interest groups--something which is of particular utility at this time given the increasing attention to user participation, and an ongoing questioning of established patterns of professional authority. It is an approach which has rarely been employed empirically, even beyond medicine. In order to illustrate the wide relevance of the approach, we discuss how it can facilitate research at all levels of PHC: i.e., in relation to aspects of medical practice (the case of medically unexplained symptoms); shifts in service organisation (changing professional roles and the introduction of policy reforms); and issues which straddle both organisation and content (the increasing use of complementary medicine in primary care). In each case the approach is able to embrace the complexity of situations characterised by the intersection of professional and lay social worlds and is able to provide the conceptual tools through which resultant processes can be tracked and investigated.

Colonic Diseases, Functional↗
PubMed2001

Effects of clodronate on vertebral fracture risk in osteoporosis: a 1-year interim analysis.

The aim of this study was to determine whether clodronate reduced the incidence of vertebral fractures in patients with osteoporosis. We report here the interim analysis after 1 year of a 3-year double-blind placebo-controlled study. The objectives of the interim analysis were to determine whether there was a trend in fracture frequency and to examine the effects of clodronate on bone mineral density (BMD). Patients with densitometrically proven osteoporosis (T-score <-2.5 and <-3 for women and men, respectively) or with at least one prevalent vertebral fracture were recruited to a 3-year double-blind, controlled study. Patients were randomized to three strata, namely women with postmenopausal osteoporosis (stratum I, n = 483), women with secondary osteoporosis (II, n = 110), and men with osteoporosis of any causation (III, n = 84). They received either clodronate 800 mg daily by mouth or an identical placebo, and all patients received a calcium supplement of 500 mg daily. BMD was measured at six monthly intervals, and lateral spine radiographs for vertebral morphometry were obtained at baseline and 1 year. Treatment with clodronate was associated with a significant increase in BMD at the spine of 3.2 +/- 0.3% (p < 0.0001 vs. baseline) compared with a nonsignificant change of 0.5 +/- 0.3% in the placebo group (p < 0.0001 between treatments). At the hip, clodronate was associated with a significant increase in total hip BMD of 1.3 +/- 0.3% (p = 0.018 vs. baseline) compared with a small decrease of 0.4 +/- 0.3% in the placebo group (p = 0.027 for the difference between treatment groups). The mean changes at the spine and hip were similar in all three strata. Incident vertebral fractures were observed in 27 patients at 1 year in the placebo group (9.0%) and in 14 patients receiving clodronate (4.9%) (relative risk 0.54; 95% CI 0.29-1.02; p = 0.07). A trend was observed in all treatment strata. Treatment was well tolerated, with no significant adverse events attributable to clodronate treatment. We conclude that clodronate 800 mg daily is effective in preventing bone loss, and at 1 year, there is a trend consistent with antifracture efficacy in patients with established osteoporosis regardless of causation.

Bone Density↗
PubMed2001

Mandatory admission after isolated mild closed head injury in children: is it necessary?

BACKGROUND/PURPOSE: Children with closed head injuries diagnosed as concussion alone or concussion with brief loss of consciousness are admitted routinely for observation despite a normal central nervous system finding, negative computed tomography (CT) scan, and a Glasgow Coma Score (GCS) of 15. Recent studies have questioned the necessity of such an admission. The purpose of this study was to review a large pediatric database and study the length of stay as well as any required procedures or complications in these children. The hypothesis was that routine admission is unnecessary in this population. METHODS: The National Pediatric Trauma Registry-Phase II was reviewed for the period from October 1988 to January 1996. Entry criteria included age less than 18 and an isolated closed head injury after blunt trauma with an admission GCS of 15. Variables studied included age, gender, mechanism of injury, length of stay, procedures, and outcome. RESULTS: A total of 1,033 children met criteria for this study. The average age was 8.3 years. Males predominated at 61.9%. Falls, sports, and motor vehicle crashes were the most common mechanisms of injury. The average length of stay was 1.19 days, and 60 children were not admitted. A total of 583 children had no procedures performed, whereas 386 received a CT scan, and 148 had x-rays. None required neurosurgical intervention, and all were discharged alive. CONCLUSION: These findings indicate that routine admission may not be necessary for children with isolated mild closed head injuries with a negative CT scan and a normal neurologic finding and allows for a prospective randomized trial to confirm this.

Child↗
PubMed2001

Nurses' use of professional distancing in the appropriation of CAM: a text analysis.

Despite the depth of interest in complementary and alternative medicines (CAM) within the nursing community, the intersection between nurses, nursing and CAM has largely avoided sociological analysis. This paper presents findings from one part of an ongoing exploratory study of how nurses present and interpret the apparent affinity of their profession with CAM. A text analysis of papers published from within the nursing community on CAM was conducted. Within the broad area of professional identity, differentiation and development, two dominant themes emerged from the analysis. Firstly, the use of professional distancing to underpin the legitimacy of the nursing/CAM axis; and second, the potential offered by the relationship for a reconstruction of lines of professional authority. As one dimension of the way in which nursing's intersection with CAM is being constructed and perpetuated, the relationship with medicine appears to be of significance and requires further attention.

Attitude of Health Personnel↗
PubMed2001

Clinical guidelines for the use of the prone position in acute respiratory distress syndrome.

The mortality associated with acute respiratory distress syndrome (ARDS) remains high. It has been suggested that use of the prone position may improve survival. However, approaches to the use of the position are often haphazard. The development of clinical guidelines indicating the need for the prone position in ARDS and the process by which the manoeuvre may be performed were thought to be important for two reasons. Primarily, we sought to improve oxygenation through the use of the prone position whilst promoting patient safety. Secondly, we wished to standardize our approach to the use of the prone position and make recommendations for practice so that its use was no longer seen as a last resort in the management of ARDS. The process associated with the development of clinical guidelines is first described. This is followed by presentation of the clinical guidelines. Included in these are the criteria and discussion which indicate consideration of the prone position, potential exclusion criteria, pre-turn considerations, the turning technique, monitoring the effectiveness of the prone position, passive movements and limb positioning and, finally, documentation of the problems associated with use of the prone position. The paper concludes with discussion concerning the potential for future research in this area.

Algorithms↗
PubMed2001

Direct integrative practice, time constraints and reactive strategy: an examination of GP therapists' perceptions of their complementary medicine.

There has been a movement towards integrating complementary and alternative medicine (CAM) into the NHS and a growing number of general practitioners (GPs) are personally practising CAM to treat their NHS patients (direct integrative practice). While research has begun to examine DIP, time constraints and related issues--of importance not only to practitioners but also to those purchasing and planning health care--have not yet received in depth attention. In response this paper examines GP therapists' experiences of the clinical reality of their DIP. The analysis reveals how a lack of time is perceived by GP therapists as a serious constraint upon their CAM practice and also how they employ a number of strategies in an attempt to overcome such difficulties.

Attitude of Health Personnel↗
PubMed2001

Predicting patient visits to an urgent care clinic using calendar variables.

OBJECTIVE: To develop a prediction equation for the number of patients seeking urgent care. METHODS: In the first phase, daily patient volume from February 1998 to January 1999 was matched with calendar and weather variables, and stepwise linear regression analysis was performed. This model was used to match staffing to patient volume. The effects were measured through patient complaint and "left without being seen" rates. The second phase was undertaken to develop a model to account for the continual yearly increase in patient volume. For this phase daily patient volume from February 1998 to April 2000 was used; the patient volume from May 2000 to July 2000 was used as a validation set. RESULTS: First-phase prediction equation was: daily patient volume = 66.2 + 11.1 January + 4.56 winter + 47.2 Monday + 37.3 Tuesday + 35.6 Wednesday + 28.2 Thursday + 24.2 Friday + 7.96 Saturday + 10.1 day after a holiday. This equation accounted for 75.2% of daily patient volume (p<0.01). Inclusion of significant weather variables only minimally improved the predictive ability (r(2) = 0.786). The second-phase final model was: daily patient volume = 57.2 + 0.035 Newdate + 52.0 Monday + 44. 2 Tuesday + 39.2 Wednesday + 30.2 Thursday + 26.5 Friday + 10.9 Saturday + 12.2 February + 3.9 March, which accounted for 72.7% of the daily variation (p<0.01). The model predicted the patient volume in the validation set within +/-11%. When the first-phase model was used to predict patient volume and thus staffing, the percentage of patients who left without being seen decreased by 18. 5% and the number of patient complaints dropped by 30%. CONCLUSIONS: Use of a prediction equation allowed for improved accuracy in staffing patterns with associated improvement in measures of patient satisfaction.

Colorado↗
PubMed2001

Renal transplantation in small children--a comparison between surgical procedures.

OBJECTIVES: Renal transplantation is the therapy of choice for patients with end-stage renal failure. From the surgical point of view, small children remain a challenging patient group. METHODS: We report our experience with 61 consecutive kidney transplantations in small children aged < or =6 years. Outcome and graft survival rates were presented with special reference to the surgical procedure used to perform the renal transplantation. RESULTS: Of the 31 renal grafts, placed into the fossa iliaca (group 1), 8 grafts were lost shortly after transplantation due to a vascular complication (5 venous thromboses and 3 arterial thromboses). Six allografts were lost because of acute rejection. All in all, the 1- and 5-year graft survival rate in this group was 55.8% (p = 0.0106)/51.6% (p = 0.0134), respectively. Thirty grafts were placed retroperitoneally, using the aorta and the distal caval vein to perform end-to-side anastomoses (group 2). One graft was lost because of a venous thrombosis 6 weeks following transplantation, 3 further grafts were lost during the 1st year after transplantation due to acute rejection. The 1- and 5-year graft survival rate in that group was 86.6% (p = 0.0106)/83.3% (p = 0.0134), respectively. Comparing the 1-year graft survival rates of the two patient groups with special reference to vascular complications, we observed a 1-year graft survival rate of 74.2% (group 1) versus 96.6% (group 2; p = 0.026). CONCLUSIONS: Our results on kidney transplantation in small children have considerably improved with the consistent use of the aorta and the distal caval vein to perform vascular anastomoses. The number of vascular complications following renal transplantation decreased, and especially for very small children the retroperitoneal placement of the graft is a safe, feasible surgical procedure that should be performed whenever possible.

Child↗
PubMed2001

Elimination of bleeding associated with urinary catheterization in neonates.

Three cases of hematuria associated with urinary catheterization in infant males in this NICU over a year prompted an investigation by the health care team. The team tracked catheterizations in the unit, conducted a national survey, and did a literature review. Based on their findings, the team revised the unit policy and procedure and evaluated new products. After changes were implemented, the incidence of hematuria--originally at 20.7 percent--dropped to 5.5 percent during the first evaluation period and to zero during a second follow-up period.

Catheters, Indwelling↗
PubMed2001

Respiratory drive during carbachol challenge in allergic sheep.

Diaphragmatic activity is the standard assessment of respiratory neural output but is difficult to measure and cannot be used for long-term clinical monitoring. The tidal breathing minute ventilation (V') and mean inspiratory flow (VT/tI) reflect respiratory drive and can be monitored non-invasively using respiratory inductive plethysmography (RIP). Recent findings indicate that peak inspiratory acceleration (PIA) correlates to diaphragmatic activity during CO2 rebreathing in piglets. The aim of the present study was to assess whether tidal breathing peak inspiratory acceleration reflects respiratory drive during carbachol challenge. Aerosolized carbachol was administered to 15 allergic sheep until pulmonary resistance increased by at least 400%. After threshold dose, slight increases in V' and VT/tI were seen (8 and 5%, respectively; P=NS), while PIA increased by 30% (P<0.05). The change in PIA was closely correlated to changes in V'[bar over] and VT/tI (r=0.73, P<0.01 and r=0.88, P<0.001, respectively). In conclusion, peak inspiratory acceleration reflected respiratory drive during bronchoprovocation. Further, this new measure of drive has the potential to accurately estimate drive in chronic obstructive lung disease where intrinsic positive end expiratory pressure prevents accurate selection of beginning inspiration necessary for computation of, e.g. VT/tI.

Animals↗