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Biomedical subjects

J Phillips

Publications and source records attributed to J Phillips.

At least 37 records · Page 2Linked to original sources
PubMed2002

Acute cholecystitis--room for improvement?

AIMS: A recent survey of UK general surgeons showed that almost 90% prefer to manage patients with acute cholecystitis by initial conservative management and delayed cholecystectomy (DC). The aim of this study was to assess the effectiveness of this management policy in a large university hospital. PATIENTS AND METHODS: All patients admitted with acute cholecystitis between January 1997 and June 1999 who went on to have a cholecystectomy were identified. Patients were required to have right upper quadrant pain for > 12 h, a raised white cell count and findings consistent with acute cholecystitis on ultrasound to be included in the study. RESULTS: 109 patients were admitted with acute cholecystitis (76 female, 33 male) with a median age of 62 years (range, 22-88 years). Conservative management failed in 16 patients (14.7%) who underwent emergency cholecystectomy due to continuing symptoms (9), empyema (4) and peritonitis (3). Symptoms settled in 93 patients and delayed cholecystectomy was performed without further problems in 66 (60.6%). 27 patients were re-admitted with further symptoms before their elective surgery and, of these, 3 were admitted for a third time before surgical intervention. Ten of the 30 re-admission episodes (33%) occurred within 3 weeks of discharge but 15 (56%) occurred more than 2 months after discharge. Elective surgery was undertaken at a median of 10 weeks post-discharge with 67% of operations occurring within 3 months. Mean total hospital stay (days) +/- SEM, for the three groups were: emergency surgery group, 10.21 +/- 0.85; uncomplicated DC group, 12.48 +/- 0.37; re-admitted group, 14.75 +/- 0.71. CONCLUSIONS: The policy of conservative management and DC was successful in 60.6% of cases but 14.7% of patients required emergency surgery and 24.8% were re-admitted prior to elective surgery with a resultant increase in total hospital stay. Performing elective surgery within 2 months of discharge in all cases would have reduced the re-admission rate by 56% and this along with the increased use of early cholecystectomy during the first admission are areas where the treatment of acute cholecystitis could be significantly improved.

Acute Disease↗
PubMed2001

Retrospective analysis of mortalities associated with medication errors.

The types, causes, contributing factors, and patient demographics of fatal medication errors were reviewed. Case reports of medication errors from hospitals, ambulatory care settings, and patients' homes that were entered in FDA's Adverse Event Reporting System during 1993-98 were the source of information on fatal medication errors. Each report was classified using predefined criteria and a taxonomy developed by the National Coordinating Council for Medication Error Reporting and Prevention. The types, causes, contributing factors, and patient demographics were identified, and the causality of each case was assessed to prevent future fatalities. The data indicated 5,366 medication error reports. Fifty-nine reports were excluded and classified as duplicate reports or intentional overdoses. Of the remaining medication error reports, 68.2% resulted in serious patient outcomes and 9.8% were fatal. Of the 469 fatal medication error reports, 48.6% occurred in patients over 60 years. The most common types of errors resulting in patient death involved administering an improper dose (40.9%), administering the wrong drug (16%), and using the wrong route of administration (9.5%). The most common causes of errors were performance and knowledge deficits (44%) and communication errors (15.8%). Fatal medication errors accounted for approximately 10% of medication errors reported to FDA and were most frequently the result of improper dosing of the intended drug and administration of an incorrect drug. A review of case reports of medication errors from 1993 to 1998 yielded information on the most frequent causes of and contributing factors involved in fatal medication errors.

Adolescent↗
PubMed2001

Neuronal hypertrophy in the neocortex of patients with temporal lobe epilepsy.

The underlying cause of neocortical involvement in temporal lobe epilepsy (TLE) remains a fundamental and unanswered question. Magnetic resonance imaging has shown a significant loss in temporal lobe volume, and it has been proposed that neocortical circuits are disturbed functionally because neurons are lost. The present study used design-based stereology to estimate the volume and cell number of Brodmann's area 38, a region commonly resected in anterior temporal lobectomy. Studies were conducted on the neocortex of patients with or without hippocampal sclerosis (HS). Results provide the surprising finding that TLE patients have significant atrophy of neocortical gray matter but no loss of neurons. Neurons are also significantly larger, dendritic trees appear sparser, and spine density is noticeably reduced in TLE specimens compared with controls. The increase in neuronal density we found in TLE patients is therefore attributable to large neurons occupying a much smaller volume than in normal brain. Neurons in the underlying white matter are also increased in size but, in contrast to other reports, are not significantly elevated in number or density. Neuronal hypertrophy affects HS and non-HS brains similarly. The reduction in neuropil and its associated elements therefore appears to be a primary feature of TLE, which is not secondary to cell loss. In both gray and white matter, neuronal hypertrophy means more perikaryal surface area is exposed for synaptic contacts and emerges as a hallmark of this disease.

Adolescent↗
PubMed2001

Enzyme-replacement therapy in mucopolysaccharidosis I.

BACKGROUND: Mucopolysaccharidosis I is a lysosomal storage disease caused by a deficiency of the enzyme alpha-L-iduronidase. We evaluated the effect of enzyme-replacement therapy with recombinant human alpha-L-iduronidase in patients with this disorder. METHODS: We treated 10 patients with mucopolysaccharidosis I (age, 5 to 22 years) with recombinant human alpha-L-iduronidase at a dose of 125,000 U per kilogram of body weight given intravenously once weekly for 52 weeks. The patients were evaluated at base line and at 6, 12, 26, and 52 weeks by detailed clinical examinations, magnetic resonance imaging of the abdomen and brain, echocardiography, range-of-motion measurements, polysomnography, clinical laboratory evaluations, measurements of leukocyte alpha-L-iduronidase activity, and urinary glycosaminoglycan excretion. RESULTS: Hepatosplenomegaly decreased significantly in all patients, and the size of the liver was normal for body weight and age in eight patients by 26 weeks. The rate of growth in height and weight increased by a mean of 85 and 131 percent, respectively, in the six prepubertal patients. The mean maximal range of motion of shoulder flexion and elbow extension increased significantly. The number of episodes of apnea and hypopnea during sleep decreased 61 percent. New York Heart Association functional class improved by one or two classes in all patients. Urinary glycosaminoglycan excretion decreased after 3 to 4 weeks of treatment; the mean reduction was 63 percent of base-line values. Five patients had transient urticaria during infusions. Serum antibodies to alpha-L-iduronidase were detected in four patients. CONCLUSIONS: In patients with mucopolysaccharidosis I, treatment with recombinant human alpha-L-iduronidase reduces lysosomal storage in the liver and ameliorates some clinical manifestations of the disease.

Adolescent↗
PubMed2001

Thoracolumbar immobilization for trauma patients with torso gunshot wounds: is it necessary?

BACKGROUND: Previous studies have suggested that patients transported by emergency medical services (EMS) following major trauma had a longer injury-to-treatment interval and a higher mortality rate than their non-EMS-transported counterparts. HYPOTHESIS: There is little actual benefit of thoracolumbar immobilization for patients with torso gunshot wounds (GSW). DESIGN: Retrospective analysis of prospectively gathered data from the Maryland Institute for Emergency Medical Service Systems State Trauma Registry from July 1, 1995, through June 30, 1998. SETTINGS: All designated trauma centers in Maryland. PATIENTS: All patients with torso GSW. MAIN OUTCOME MEASURES: (1) A patient was considered to have benefited from immobilization if he or she had less than complete neurologic deficits in the presence of an unstable vertebral column, as shown by the need for operative stabilization of the vertebral column; (2) mortality. RESULTS: There were 1000 patients with torso GSW. Among them, 141 patients (14.1%) had vertebral column and/or spinal cord injuries. Two patients (0.2%) (95% confidence interval, -0.077% to 0.48%) required operative vertebral column stabilization, while 6 others required other spinal operations for decompression and/or foreign body removal. The presence of vertebral column injury was actually associated with lower mortality (7.1% vs 14.8%, P<.02). CONCLUSIONS: This study suggests that thoracolumbar immobilization is almost never beneficial in patients with torso GSW, and that a higher mortality rate existed among those GSW patients without vertebral column injury vs those with such injuries. The role of formal thoracolumbar immobilization for patients with torso GSW should be reexamined.

Adult↗
PubMed2001

Pathogenesis of fusion deficient recombinant mouse hepatitis viruses.

In this study we have demonstrated that recombinant viruses carrying the amino acid mutations Q1067H, Q1094H, and L1114R were unable to induce fusion at neutral pH, replicated more efficiently in L2 cells, and that infection was delayed by ammonium chloride. These results suggest that the R120/R121 recombinants most likely use the endosomal pathway to enter cells. In this sense they are similar to the pH-dependent MHV-4 variant OBLV60. We were able to observe an attenuated virulence in vivo, despite the fact that our R120/R121 recombinants replicated to comparable (IC) or higher (IN) titers than the S4R29 recombinant in the brain. Preliminary results showed that the level of inflammation observed in infected mice is consistent with the attenuated virulence, but they cannot be explained by the high titers of replication.

Animals↗
PubMed2001

Adenosine-enhanced ischemic preconditioning modulates necrosis and apoptosis: effects of stunning and ischemia-reperfusion.

BACKGROUND: Adenosine-enhanced ischemic preconditioning extends the protection of ischemic preconditioning by both significantly decreasing infarct size and significantly enhancing postischemic functional recovery. METHODS: The effects of adenosine-enhanced ischemic preconditioning on necrosis and apoptosis were investigated in the sheep heart using models of stunning (15 minutes regional ischemia, 120 minutes reperfusion) and ischemia-reperfusion (30 and 60 minutes regional ischemia, 120 minutes reperfusion). Ischemic preconditioned hearts received 5 minutes regional ischemia, 5 minutes reperfusion before ischemia. Adenosine-enhanced ischemic preconditioned hearts received a 10 mmol/L adenosine bolus (10 mL) through the left atrium coincident with ischemic preconditioning. Adenosine hearts received a 10 mmol/L bolus (10 mL) of adenosine. Regional ischemic hearts received no pretreatment. RESULTS: Minimal apoptosis (< 45 per 3,000 myocytes) was observed in the stunning models but was significantly increased with ischemia-reperfusion in regional ischemic hearts after 30 minutes (p < 0.05 versus ischemic preconditioning, adenosine, or adenosine-enhanced ischemic preconditioning) and in adenosine and ischemic preconditioned hearts after 60 minutes ischemia (p < 0.05 versus adenosine-enhanced ischemic preconditioning). DNA laddering was apparent after 60 minutes ischemia in regional ischemia, adenosine, and ischemic preconditioning but not in adenosine-enhanced ischemic preconditioned hearts. CONCLUSIONS: Adenosine-enhanced ischemic preconditioning significantly ameliorates necrosis and apoptosis in the regional ischemic blood-perfused heart.

Adenosine↗
PubMed2001

Development of a neurobehavioral battery for children exposed to neurotoxic chemicals.

In recent years there has been heightened concern over the potential impact of environmental exposures on neurological function in children. Children are thought to be especially vulnerable to neurotoxic effects due to a number offactors including play behavior, differences in metabolism, and the development state of the brain. Performance tests from the computerized Behavioral Assessment and Research System (BARS) and other non-computerized tests have been combined to develop a brief battery that assesses multiple neurobehavioral functions in preschool children aged 4-6. Tests were selected to assess a variety of cognitive functions including attention, memory, motor speed and coordination and other executive functions. The battery has also been translated into Spanish and developed for use with Latino populations. Four to six-year-old children are particularly challenging because of the shorter attention span and lower motivation to complete an extended test session. When testing this group it is important to maintain the motivation of the child throughout the entire session in order to obtain accurate performance measures. A series of sequential pilot studies were used to select and develop appropriate methods and parameters for the tests in the battery. Although English-speaking children were able to complete the initial battery with minimal difficulties, several difficulties were encountered when the tests were administered to a Latino population. Cultural differences made some material inappropriate for testing due to unfamiliarity with the material, and in some cases items in a test had more than one correct translation which made administration difficult.

Child↗
PubMed2001

Keratinocytes suppress TRP-1 expression and reduce cell number of co-cultured melanocytes - implications for grafting of patients with vitiligo.

A pilot study for grafting of patients with vitiligo using cultured epithelial autografts containing melanocytes gave disappointing clinical results, with pigmentation achieved in only one out of five patients. Irrespective of the fate of melanocytes grafted back onto the patients, we experienced problems in identifying melanocytes within these well-integrated keratinocyte sheets. This led us to explore the fate of these cells within these sheets in vitro and to seek to improve their number and function within the sheets. We report that the introduction of a fibroblast feeder layer can improve melanocyte number within melanocyte/keratinocyte co-cultures initially, but at very high keratinocyte density, there is a marked loss of melanocytes (as detected by staining for S100). Additionally, we found that keratinocytes not only down-regulate melanocyte number, but also pigmentary function; thus, it was possible to identify melanocytes that were S100 positive but tyrosinase-related protein-1 (TRP-1) negative in confluent well-integrated keratinocyte sheets. In summary, our data suggest that keratinocytes at high density initially suppress melanocyte pigmentation (as evidenced by a lack of TRP-1 expression) and then cause a physical loss of melanocytes. The introduction of a fibroblast feeder layer can help maintain melanocyte number while keratinocytes are subconfluent, but fails to oppose the inhibitory influence of the keratinocytes on melanocyte TRP-1 expression.

Adult↗
PubMed2001

Patients' aims for epilepsy surgery: desires beyond seizure freedom.

PURPOSE: To evaluate prospectively patient's aims for epilepsy surgery as previously outlined theoretically by Taylor et al. (Epilepsia 1997;3:625-30). METHODS: Ninety-three consecutive patients were interviewed by a psychiatrist as part of their evaluation for epilepsy surgery. Open-ended questions about the patient were asked, and carers' aims or ambitions for change as a result of putative relief of seizures were elicited. The interviewer aimed to obtain a maximum of five aims for later follow-up purposes. These questions were part of an extensive psychiatric interview that is described. RESULTS: The aims of 69 patients or carers were analyzed. The 204 statements of aims were grouped into 59 categories initially. The five most frequently cited constituted 50% of all the aims listed. These aims were desire for work, driving of motor vehicles, independence, socializing, and freedom from drugs. The patients rarely identified a desire for improvement in cognitive functioning as an aim for epilepsy surgery. A final analysis into six categories showed that changes in social process predominated, even over changes in personal behavior. CONCLUSIONS: The social and personal aims to accompany relief of epilepsy identified by patients are consistent with the literature on psychosocial adjustment to epilepsy.

Adaptation, Psychological↗
PubMed2001

Comparison of EMLA cream versus placebo in children receiving distraction therapy for venepuncture.

UNLABELLED: Eutectic mixture of local anaesthetics (EMLA) cream is used routinely as a local anaesthetic prior to venepuncture in children. Despite this, however, a significant proportion of children will still be distressed. Cognitive-behavioural interventions, such as distraction by breathing and blowing exercises, have been used and found to be helpful as alternative coping strategies. There is, however, a paucity of data regarding effectiveness. We have evaluated the efficacy of distraction therapy as a coping strategy before and during venepuncture, and in these children evaluated the need for EMLA using a prospective, randomized, double-blind, placebo-controlled clinical trial. Twenty-eight children attending for venepuncture were recruited, median age 6 y (range 4-8 y), and randomly allocated to receive either EMLA or a placebo cream. All were given distraction therapy prior to and during the procedure by a play specialist. Venepuncture was carried out by one investigator. A modified paediatric pain assessment chart was used for objective pain score at the end of the procedure. After one exclusion, the treatment group (17 children) and the placebo group (10 children) were similar: median age of 6 and 7 y (range 4-8), median baseline and post-procedure heart rate and oxygen saturation. The median (interquartile range) for total pain score in the treatment group was 1 (0 to 4.5) and in the control group 1 (0 to 2.3). There was no significant difference in pain score between the two groups (Mann-Whitney test, p = 0.7). The 95% confidence interval for the difference in pain score was -1.0 to +3.0. CONCLUSIONS: The low pain score in both groups suggests the effectiveness of distraction therapy, although factors such as skill of the operator and previous experience of the patient group are of relevance. There was no significant difference in the pain score between the EMLA and placebo groups, suggesting that in this age group if carefully selected children receive distraction during venepuncture EMLA may not be necessary.

Adolescent↗
PubMed2001

Manufacture and quality control of CAMPATH-1 antibodies for clinical trials.

BACKGROUND: CAMPATH-1 Abs have been used for T-cell depletion in stem-cell transplantation since the early 1980s. During that time there has been substantial progress in manufacturing techniques and quality control procedures. This article summarizes the methods used to produce the Abs for clinical use and describes results of quality control tests on representative batches. METHODS: Rat hybridoma and recombinant CHO cells were cultured in hollow-fiber fermentors. Antibodies were purified from the culture supernatant by fractionation with ammonium sulphate, or by column chromatography. Additional steps were added to assure the removal of DNA and viruses. A range of analytical methods was used to characterize the antibodies. Samples were stored frozen at -70 degrees C and re-analyzed many years later to assess the long-term stability. RESULTS: Hollow-fiber fermentors provided a simple and reliable means for antibody production, with yields between 3-10 mg/h and a convenient concentration for further processing (0.6-2.0 mg/mL). All of the CAMPATH-1 Abs (rat IgM, rat IgG2b and human IgG1) could be purified by affinity chromatography on Protein A, but the low pH required for elution caused unacceptable aggregation of the IgM. CAMPATH-1H contained approx. 20% dimeric IgG, which could be removed by size exclusion chromatography. Antibodies were stable for at least 6 years at -70 degrees C, but there was unacceptable aggregation of CAMPATH-1M in one batch stored for 9 years. DISCUSSION: Pilot-scale production of MAbs for clinical studies is feasible in a small academic center, but regulatory requirements now demand that great attention is paid to all aspects of manufacturing and quality assurance. Although the underlying principles of cell culture and protein chemistry remain the same, the level of documentation, validation and quality control has increased greatly over the last 20 years.

Alemtuzumab↗
PubMed2001

Overlapping functions of the yeast oxysterol-binding protein homologues.

The Saccharomyces cerevisiae genome encodes seven homologues of the mammalian oxysterol-binding protein (OSBP), a protein implicated in lipid trafficking and sterol homeostasis. To determine the functions of the yeast OSBP gene family (OSH1-OSH7), we used a combination of genetics, genomics, and sterol lipid analysis to characterize OSH deletion mutants. All 127 combinations and permutations of OSH deletion alleles were constructed. Individual OSH genes were not essential for yeast viability, but the elimination of the entire gene family was lethal. Thus, the family members shared an essential function. In addition, the in vivo depletion of all Osh proteins disrupted sterol homeostasis. Like mutants that affect ergosterol production, the viable combinations of OSH deletion alleles exhibited specific sterol-related defects. Although none of the single OSH deletion mutants was defective for growth, gene expression profiles revealed that each mutant had a characteristic molecular phenotype. Therefore, each gene performed distinct nonessential functions and contributed to a common essential function. Our findings indicated that OSH genes performed a multitude of nonessential roles defined by specific subsets of the genes and that most shared at least one essential role potentially linked to changes in sterol lipid levels.

Alleles↗
PubMed2001

Spreading of the tears after a blink: velocity and stabilization time in healthy eyes.

PURPOSE: To quantify the tear spreading velocity and stabilization time after blinks in healthy patients. METHODS: Video recordings (magnification, x130) were made of the movements of naturally occurring particles in the tear film while patients blinked naturally. After each blink, tear spreading velocity was computed every 40 milliseconds from particle displacements determined from a frame-by-frame analysis of the records. RESULTS: After a blink, tears moved rapidly upward over the cornea. Forty milliseconds after passage of the lid, the velocity was 7.34 +/- 2.73 mm/s (mean +/- standard deviation, n = 20). The time to tear stabilization (i.e., zero velocity) was 1.05 +/- 0.30 seconds. The decay of spreading velocity with time was well described by a logarithmic function for all individual patient data (R2 range, 0.88-0.99; n = 20). We have shown that initial velocity and stabilization time are independent descriptors of tear spreading. Meibomian gland expression markedly reduced initial velocity leaving a normal stabilization time, whereas inhalation of an irritant reduced stabilization time leaving a normal initial velocity. In a patient with Sjögren syndrome, punctal plugs rapidly restored initial velocity and stabilization time from near zero values to normal values. CONCLUSION: We provide normal values for two descriptors of tear spreading, namely initial velocity and time to stabilization. These values can be modified by manipulations that alter tear constituents. Consequently, these descriptors may provide a basis for quantitative, noninvasive tear assessment.

Adolescent↗