Biomedical subjects

M Clancy

Publications and source records attributed to M Clancy.

At least 37 records · Page 2Linked to original sources

PubMed2000

Phase I trial of twice-weekly intravenous interleukin 12 in patients with metastatic renal cell cancer or malignant melanoma: ability to maintain IFN-gamma induction is associated with clinical response.

The aim of this study was to examine the tolerability, antitumor activity, and biological effects of a new schedule of i.v. recombinant human interleukin 12 (rhIL-12). Twenty-eight patients were enrolled in a Phase I trial in which rhIL-12 was administered twice weekly as an i.v. bolus for 6 weeks. Stable or responding patients were eligible to receive additional 6-week cycles until there was no evidence of disease or until tumor progression. Patient cohorts were treated with escalating doses of rhIL-12 (30-700 ng/kg). The maximum tolerated dose (MTD) was 500 ng/kg, with dose-limiting toxicities consisting of elevated hepatic transaminases and cytopenias. At the MTD (n = 14), there was one partial response occurring after 6 cycles of rhIL-12 in a patient with renal cell cancer. Two additional renal cell cancer patients treated at the MTD had prolonged disease stabilization, with one of these exhibiting tumor regression after 8 cycles of rhIL-12. IFN-gamma, IL-15, and IL-18 were induced in patients treated with rhIL-12. Whereas IFN-gamma and IL-15 induction were attenuated midway through the first cycle in patients with disease progression, those patients with tumor regression or prolonged disease stabilization were able to maintain IFN-gamma, IL-15, and IL-18 induction. The down-modulation of IFN-gamma induction during rhIL-12 treatment did not relate to IL-10 production or alterations in rhIL-12 bioavailability but was associated with an acquired defect in lymphocyte IFN-gamma production in response to IL-12, IL-2, or IL-15. This defect could be partially overcome in vitro through combined stimulation with IL-12 plus IL-2. These findings show that the chronic administration of twice-weekly i.v. rhIL-12 is well-tolerated, stimulates the production of IL-12 costimulatory cytokines and IFN-gamma, and can induce delayed tumor regression. Strategies aimed at maintaining IFN-gamma induction, such as the addition of IL-2, may further augment the response rate to this schedule of rhIL-12.

Adult↗

PubMed1999

The portable laboratory: an evaluation of the accuracy and reproducibility of i-STAT.

The i-STAT point-of-care testing analyser, which utilizes single-use multisensor cartridges, was evaluated. Two cartridges were assessed: the 6+ and the G3+, which provide results for urea, glucose, sodium, potassium, chloride, haematocrit, pH, PCO2, PO2 and various calculated parameters. The results for all analytes agreed well with the analysers in routine use in the laboratory. The reproducibility was comparable even when analysis was carried out by a nurse with only 5 min training. The system was found to be reliable, easy to use and required no maintenance (only a 2-min daily check of the electronics). These features, together with portability and the storage capacity for results, make the i-STAT suitable for point-of-care use, particularly in critical care units.

Clinical Chemistry Tests↗

PubMed1998

Point of care testing: randomised controlled trial of clinical outcome.

OBJECTIVES: To describe the proportion of patients attending an accident and emergency department for whom blood analysis at the point of care brought about a change in management; to measure the extent to which point of care testing resulted in differences in clinical outcome for these patients when compared with patients whose samples were tested by the hospital laboratory. DESIGN: Open, single centre, randomised controlled trial. Blood samples were randomly allocated to point of care testing or testing by the hospital's central laboratory. SETTING: The accident and emergency department of the Bristol Royal Infirmary, a large teaching hospital which cares for an inner city population. SUBJECTS: Representative sample of patients who attended the department between April 1996 and April 1997 and who required blood tests. Data collection was structured in 8 hour blocks so that all hours of the day and all days of the week were equally represented. MAIN OUTCOME MEASURES: The proportion of patients for whom point of care testing brought about a change in treatment in which timing was considered to be critical to clinical outcome. Mortality, the length of stay in hospital, admission rate, the amount of time spent waiting for results of blood tests, the amount of time taken to decide on management plans, and the amount of time patients spent in the department were compared between patients whose samples were tested at the point of care and those whose samples were sent to the laboratory. RESULTS: Samples were obtained from 1728 patients. Changes in management in which timing was considered to be critical occurred in 59 out of 859 (6.9%, 95% confidence interval 5.3% to 8.8%) patients in the point of care arm of the trial. Decisions were made 74 minutes earlier (68 min to 80 min, P < 0.0001) when point of care testing was used for haematological tests as compared to central laboratory testing, 86 minutes earlier (80 min to 92 min, P < 0.0001) for biochemical tests, and 21 minutes earlier (-3 min to 44 min, P = 0.09) for analyses of arterial blood gases. There were no differences between the groups in the amount of time spent in the department, length of stay in hospital, admission rates, or mortality. CONCLUSION: Point of care testing reduced the time taken to make decisions on patient management that were dependent on the results of blood tests. It also brought about faster changes in treatment for which timing was considered to be critical in about 7% of patients. These changes did not affect clinical outcome or the amount of time patients spent in the department.

Adult↗

PubMed1998

A two-part phase I trial of high-dose interleukin 2 in combination with soluble (Chinese hamster ovary) interleukin 1 receptor.

Our purpose was to determine the maximum tolerated dose and toxicity associated with soluble Chinese hamster ovary [s(CHO)] recombinant human interleukin (IL) 1 receptor (IL-1R; Immunex, Seattle, WA) administration in humans and to determine the effective biological dose and/or maximum tolerated dose of the s(CHO) IL-1R in combination with high-dose IL-2 as determined by reduction in IL-2 toxicity and modulation of its biological effects. Twenty-seven patients with metastatic cancer were treated with escalating doses of s(CHO) IL-1R at 1, 1, 5, 10, 20, 40, and 55 mg/m2 i.v. on days -6 (except cohort 2), 1, and 15 and IL-2 at doses of 300,000 IU/kg (cohort 1) and 600,000 IU/kg (cohorts 2-7) i.v. every 8 h on days 1-5 and 15-19. No toxicity directly attributable to s(CHO) IL-1R was observed. The median number of IL-2 doses was 23. Hypotension and neurotoxicity were the major dose-limiting toxicities for the IL-2/s(CHO) IL-1R combination. Of the 24 patients treated with full-dose IL-2, there were six responses, three complete and three partial (response rate, 25%). Three patients developed thyroid dysfunction, and all 3 responding melanoma patients exhibited vitiligo. The t1/2 of s(CHO) IL-1R alone was 24-30 h and was not significantly altered by coadministration with IL-2. Whole-blood functional assays indicated that sufficient s(CHO) IL-1R was present in the circulation at top dose levels to inhibit the in vitro effects of IL-1beta on IL-8 induction; however, no effect on IL-2-induced IL-8 induction, or on the IL-1beta- or IL-2-induced tumor necrosis factor production, was observed. Suppression of IL-2-mediated tumor necrosis factor alpha and IL-6 induction in vivo during the first 24 h after IL-2 administration was observed, and the neutrophil chemotactic defect normally seen with IL-2 was not observed. IL-1R antagonist induction far exceeded that seen previously with IL-2 alone. No inhibition of either serum C-reactive protein induction or enhanced urinary nitrate excretion and no consistent effect on IL-2-related changes in peripheral blood mononuclear cell phenotype or endothelial adhesion molecule expression were seen. The coadministration of s(CHO) IL-1R produced no apparent reduction in IL-2 clinical toxicity manifested by either the ability to administer more IL-2 than anticipated or a reduction in the toxicity associated with a given amount of IL-2. Therefore, no effective biological dose could be identified for the s(CHO) IL-1R.

Adult↗

PubMed1997

Mental health. Careering around.

An orientation exercise provided a structured, supervised induction for practice based community psychiatric nurses. The exercise also provided community perspectives on need. The same process could be used for other new primary healthcare workers.

Career Mobility↗

PubMed1997

Discontinuation of cervical spine immobilisation in unconscious patients with trauma in intensive care units--telephone survey of practice in south and west region.

OBJECTIVE: To study how the cervical spine is assessed before discontinuation of cervical spine immobilisation in unconscious trauma patients in intensive care units. DESIGN: Telephone interview of consultants responsible for adult intensive care units. SETTING: All 25 intensive care units in the South and West region that admit victims of major trauma. MAIN OUTCOME MEASURES: The clinical and radiological basis on which the decision is made to stop cervical spine immobilisation in unconscious patients with trauma. RESULTS: In 19 units cervical spine immobilisation was stopped in unconscious patients on the basis of radiology alone, and six units combined radiology with clinical examination after the patient had regained consciousness. Sixteen units relied on a normal lateral radiological view of the cervical spine alone, five required a normal lateral and anteroposterior view, and four required a normal lateral, anteroposterior, and open mouth peg view. CONCLUSIONS: There are inconsistencies in the clinical and radiological approach to assessing the cervical spine in unconscious patients with trauma before the removal of immobilisation precautions. There is an overreliance on the lateral cervical spine view alone, which has been shown to be insensitive in this setting.

Adult↗

PubMed1997

Implementation of the Ottawa Ankle Rules by nurses working in an accident and emergency department.

OBJECTIVE: To assess whether accident and emergency (A&E) nurses using the Ottawa Ankle Rules could detect all ankle fractures. DESIGN: Prospective observational study. SETTING: A&E department of a university teaching hospital. SUBJECTS: All patients who presented with ankle injuries who were initially assessed by a nurse taught the Ottawa Ankle Rules. OUTCOME MEASURES: (1) The numbers of patients referred by the nurse for ankle radiography; (2) of these, the number with ankle fractures; (3) of those not sent for radiography initially by the nurse, the number who subsequently had x rays (ordered by the doctor) and had a fracture; (4) of those having no x rays, the number who reattended later. RESULTS: 324 patients were eligible; 238 had x rays at the request of the nurse (73%); 48 of these (20%) were diagnosed as having a fracture. Of those 86 patients not sent for radiography by the nurse, 19 subsequently had x ray examinations at the request of a doctor and no fracture was detected. Of the 67 not sent for radiography, none returned within the subsequent eight weeks. CONCLUSIONS: Nurses can apply the Ottawa Ankle Rules safely without missing acute fractures; that is, of those who were not sent for radiography by nurses, none subsequently reattended the A&E department or the trauma service of the Bristol Royal Infirmary during the following two months.

Ankle Injuries↗

PubMed1996

Computerised tomography and acute traumatic head injury: time for change?

The aim was to reconsider the "Guidelines for initial management of head injury in adults"--particularly with respect to the indications for computerised tomographic (CT) scanning--suggested by "a group of neurosurgeons" over a decade ago and still followed in some accident and emergency (A&E) departments. These recommendations are placed in the context of more recent research and the increased number of A&E departments with on-site rapid access to a CT scanner but without a resident neurosurgical facility. A case can be made for an updated policy with more liberal indications for CT scanning of acutely head injured adults in peripheral A&E departments. However, calculating the cost-efficiency of more frequent use of what is now a common but relatively expensive resource would remain a challenge.

Acute Disease↗

PubMed1994

De novo synthesis of an intron by the maize transposable element Dissociation.

The mechanisms by which introns are gained or lost in the evolution of eukaryotic genes remain poorly understood. The discovery that transposable elements sometimes alter RNA splicing to allow partial or imperfect removal of the element from the primary transcripts suggests that transposons are a potential and continuing source of new introns. To date, splicing events that precisely restore the wild-type RNA sequence at the site of insertion have not been detected. Here we describe alternative RNA splicing patterns that result in precise removal of a Dissociation (Ds) insertion and one copy of its eight-nucleotide host site duplication from an exon sequence of the maize shrunken2-mutabe1 (sh2-m1) mutant. In one case, perfect splicing of Ds was associated with aberrant splicing of an intron located 32 bp upstream of the insertion site. The second transcript type was indistinguishable from wild-type mRNA, indicating that Ds was spliced like a normal intron in about 2% of the sh2-m1 transcripts. Our results suggest that the transposition of Ds into sh2 in 1968, in effect, marked the creation of a new intron in a modern eukaryotic gene. The possibility of precise intron formation by a transposable element demonstrated here may be a general phenomenon of intron formation, since consensus intron splice sites can be explained by insertions that duplicate host sequences upon integration. A model is presented.

Alleles↗

PubMed1994

Determination and comparison of heat exchange efficiency of four commercially available blood cardioplegia sets.

An in vitro comparison of the heat exchange properties of the Electromedics D1081A, Sarns MP-4 'Conducer Coil' 165720, Bentley HE-100 and the Shiley BCD Plus 4: 1 blood cardioplegia sets was performed. The efficiency was calculated for each heat exchanger and post-heat exchange blood path temperatures were compared. The calculated efficiency for each heat exchanger is as follows: Electromedics D1081A at 18 l/minute coil water flow (0.95); Sarns MP-4 165720 at 9 l/minute coil water flow (0.93); Bentley HE-100 at 10 l/minute coil water flow (0.91); Shiley BCD Plus at 15 l/minute coil water flow (0.90). Blood path, precoil temperatures for each unit were compared statistically with no differences found (p > 0.05). Blood side, postcoil temperatures were then compared. The average postcoil blood path temperature of the Electromedics D1081A was 1.6 degrees +/- 0.1 degree C, of the Sarns MP-4 165720 it was 2.1 degrees +/- 0.1 degree C, of the Bentley HE-100 it was 2.7 degrees +/- 0.3 degree C, and the Shiley BCD Plus 3.0 degrees +/- 0.4 degree C. The results of this experiment indicate that the average postcoil temperature of the Electromedics D1081A was lower than the Sarns MP-4 165720 (p < 0.05) which was lower than that of the Bentley HE-100 (p < 0.05) and Shiley BCD Plus (p < 0.05). No statistical difference was found between the average postcoil temperature of the Bentley HE-100 and the Shiley BDC Plus.

Blood Physiological Phenomena↗

PubMed1994

The semimembranosus-tibial collateral ligament bursa. Anatomical study and magnetic resonance imaging.

A bursa that was deep to the tibial collateral ligament and adjacent to the semimembranosus tendon was studied in fifty cadaveric knees; a vinyl solution was injected into four of the specimens in order to facilitate a study of the relationship between the bursa and its surrounding structures. The bursa had the shape of an inverted U: the superficial arm was an elliptical pocket that was located between the semimembranosus tendon and the tibial collateral ligament, and the deep arm was a triangular pocket that was located between the semimembranosus tendon and the medial tibial condyle. The bursa measured, on the average, twenty-one millimeters in its greatest anteroposterior dimension and ten millimeters in its greatest superoinferior dimension. Magnetic resonance images were made of two patients, and they showed fluid in the bursa.

Adult↗

PubMed1993

Are there indications for partial rib resection in patients with adolescent idiopathic scoliosis treated with Cotrel-Dubousset instrumentation?

In adolescent idiopathic scoliosis the cosmetically unacceptable rib prominence is one of the main reasons patients seek treatment. Ninety-eight patients were reviewed with Cotrel-Dubousset (CD) instrumentation (average follow-up, 27 months; average preoperative curve, 53 degrees) and 27 patients with Harrington instrumentation and rib resection (average follow-up, 43 months; average preoperative curve, 52 degrees). Of the 98 patients who had CD instrumentation, 15 underwent concomitant rib resection. Of the 83 patients without rib resection, 71 (72%) were rated satisfactory and 12 unsatisfactory by cosmetic criteria based on residual rib deformity. These results were compared to those of 27 patients receiving Harrington rod instrumentation and rib resection, of whom 23 (85%) were rated as satisfactory. All 15 patients with CD and rib resection were rated satisfactory. The CD patients were then redivided into two groups (rib resection indicated or rib resection not indicated) as follows: the 12 unsatisfactory CD patients without rib resection (in whom a rib resection should have been done) were grouped with the 15 CD patients who underwent rib resection, for a total of 27 rib resections indicated, or 28%. This group was compared to the 71 satisfactory CD patients without rib resection (rib resection not indicated). Patients with a rib prominence of > 15 degrees preoperatively had or should have had a rib resection. Patients with a higher chance of needing rib resection included those with a curve severity greater than 60 degrees, curve flexibility less than 20%, a preoperative rib prominence > 10 degrees, or intraoperative curve correction of less than 50%.

Adolescent↗

PubMed1993

A syndrome of dislocated hips and radial heads, carpal coalition, and short stature in Puerto Rican children.

An orthopaedic syndrome that apparently had not been reported previously was identified in twenty-three children. Characteristics shared by all twenty-three children included Hispanic descent, residence in Puerto Rico, bilateral dislocation of the hip, dislocated radial heads, short stature, and other osseous anomalies. Twelve dislocated hips in six patients were not treated. All of these hips were functioning satisfactorily at the time of the review, but only four of the children had reached skeletal maturity. Sixteen hips in eight patients remained reduced after closed reduction. Of these eight patients, the four who were skeletally immature at the time of the review had a satisfactory result, and the four who were skeletally mature had an unsatisfactory result because of discomfort or fibrous ankylosis. Eighteen hips in nine patients were treated with a reduction augmented by some form of operation. All of these hips redislocated. Of the forty-six elbows in the twenty-three children, thirty-three were dislocated, as seen clinically and radiographically; eight were normal, both clinically and radiographically; and there was dysplasia at the radiocapitellar articulation of the remaining five. Twenty of the twenty-three children were found to have carpal coalitions. Fourteen children had scoliosis, and five of them were managed with spinal arthrodesis and correction. Three patients had an anomaly of the cervical spine, with one deformity causing symptoms and signs that were treated with decompression. Eight patients had talipes cavus bilaterally, which was not treated.

Abnormalities, Multiple↗

PubMed1992

Index finger pollicization for congenital aplasia or hypoplasia of the thumb.

Sensation, strength, dexterity, length, and range of motion were evaluated after index finger pollicization in 10 patients (14 hands). Diagnoses included congenital absence of the thumb (10 hands) and hypoplasia (4 hands). Average age at operation was 7 years, and follow-up averaged 9 years. Patients with unilateral pollicization averaged 67% grip strength, 60% lateral pinch, 56% palmar pinch, and 39% three-point pinch as compared with the normal contralateral hand. Manual dexterity averaged 70% efficiency as compared with normal standards defined according to age and sex. However, 55% of the patients, when stressed, used side-to-side pinch. It was noted that in those patients who used side-to-side pinch performance averaged 54% of normal standards, compared with 93% in patients who used tip-to-tip pinch for prehension.

Child↗

PubMed1992

Both-bone forearm fractures in children.

Treatment of both-bone forearm fractures remains a difficult dilemma for the orthopedist. We assessed the results of 33 children treated with closed reduction and a long-arm cast using traction with finger traps in neutral rotation. Patients were grouped according to age and analyzed for residual angulation and range of motion (ROM). Despite some residual angulation and loss of rotation, all patients were fully active with no functional restriction at follow up. For patients 10 years old or younger with less than 30 degrees of post-casting angulation, full ROM and minimal residual angulation on radiograph can be expected. For patients ages 11 to 15 years (the oldest patient in this series was 15), residual angulation is likely and approximately 60% of patients will have residual loss of less than or equal to 30 degrees of rotation. In spite of this, we found no evidence of functional loss at follow up. Our series supports the continued use of closed manipulation as an effective treatment in children with both-bone forearm fractures.

Adolescent↗

PubMed1992

Simultaneous detection of seven drugs of abuse by the Triage panel for drugs of abuse.

This novel, competitive immunoassay simultaneously detects seven drugs of abuse in urine. A urine sample is placed in contact with lyophilized reagents, the reaction mixture is allowed to come to equilibrium (10 min), and then the whole mixture is applied to a solid phase that contains various immobilized antibodies in discrete drug-class-specific zones. After a washing step, the operator visually examines each zone for the presence of a red bar. The method incorporates present threshold concentrations that are independent for each drug. In the absence of drug or in the presence of drug in quantities less than the threshold concentration, no colored bar is visible. Samples containing drug(s) at or above the threshold concentration cause a red bar to appear for the appropriate drug(s). Positive and negative procedural control zones are incorporated into each determination. The performance of the assay methodology matches that of instrumented immunoassay systems.

Antibodies, Monoclonal↗

PubMed1991

Continuous retrograde blood cardioplegia.

We present a technique of myocardial protection using retrograde cold blood cardioplegia. This safe and simple method allows excellent continuous and homogeneous cooling of the heart during the ischemic period in all types of open heart operations.

Cardiac Surgical Procedures↗

PubMed1991

Post-traumatic spinal cord cysts evaluated by magnetic resonance imaging.

In order to determine a more accurate prevalence of post-traumatic spinal cord cysts (PTSCC) in spinal cord injured (SCI) patients, we retrospectively reviewed magnetic resonance scans from symptomatic imaging and asymptomatic SCI patients. We found the incidence of PTSCC to be 51% in our patient population. The only symptom that correlated to the presence of a cyst was spasticity. The cyst develops at the site of injury and appears to be a common sequela of SCI. We believe that conservative treatment is indicated in most patients with a PTSCC.

Adolescent↗