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Biomedical subjects

M S Phillips

Publications and source records attributed to M S Phillips.

At least 37 records · Page 2Linked to original sources
PubMed1994

Using pharmacist clinical intervention data for quality improvement of medication use and physician assessment.

BACKGROUND: Patient-specific intervention data are often used for drug usage evaluation (DUE), but their use in physician assessment is less often discussed. In response to the quality assurance department's request, the pharmacy department at the Medical College of Georgia (Augusta) developed a database and a reporting system that supports quality assessment of the medical staff, identifies housestaff education needs, and directs efforts for improvement in medication use. THE REPORTING SYSTEM: In 1991 the comprehensive, concurrent screening of drug therapy by pharmacists formed the foundation of the hospital's DUE program. Each month information from the pharmacy database is sorted with use of a spreadsheet software program to generate medical department-level reports and for use in physician reappointment. Identified performance deficiencies can be used to educate individual prescribers and to develop educational programs for the department or specialty areas. Feedback from the medical staff assessment is useful for pharmacist education, such as identifying newly reported indications and dosage regimens. RESULTS: During the first six months after all pharmacists began participating in the reporting program, a mean of 224 interventions were recorded monthly. For the period January through June 1994, 400-550 interventions were recorded monthly. System improvements in medication during the first year of implementation included hospitalwide guidelines for parenteral potassium and phosphate dosing and administration and a renewed focus on patient allergies. CONCLUSION: Emphasis for use of intervention data has shifted from identifying "problem" persons to improving performance by identifying topics for corrective education and redesigning systems to promote positive patient outcomes.

Adverse Drug Reaction Reporting Systems↗
PubMed1994

The substitution of Arg for Gly2433 in the human skeletal muscle ryanodine receptor is associated with malignant hyperthermia.

Single strand conformational polymorphism analysis was used to screen exons 43 and 44 in the skeletal muscle ryanodine receptor gene from 17 positively diagnosed members of families in which chromosome 19-linked malignant hyperthermia (MH) was segregating. A polymorphism in two unrelated individuals was found to result from the substitution of A for G7297, leading to the substitution of Arg for Gly2433. This mutation is adjacent to a mutation (Arg2434 to His) previously linked to MH and central core disease (Y. Zhang et al., Nature Genet. 1993, 5, 46-50). Subsequent screening showed the presence of the mutation in four of 106 MH families tested and its absence from about 1000 other chromosomes. The mutation was present in all six individuals in four families who had had an MH reaction, in two obligate carriers and in 10 individuals diagnosed as MH susceptible by the caffeine/halothane contracture test (CHCT). The mutation was present in an individual with a normal response to the CHCT and was absent in three individuals with a positive CHCT response. These discrepancies would be consistent with inaccuracies in the CHCT and/or with segregation of a second MH allele within two of the four affected families.

Arginine↗
PubMed1994

Ribosomal spacer length variability in the large raspberry aphid, Amphorophora idaei (Aphidinae: macrosiphini).

The large raspberry aphid, Amphorophora idaei, has several biotypes described by their abilities to overcome plant resistance genes. Bioassays of field populations showed a strong shift towards A1 resistance-breaking biotypes since the 1960s. RFLP analysis of the rDNA cistron was used to study variation found within and between standard clones of three A. idaei biotypes and twenty-nine field populations collected over 3 years. Probing genomic DNA with the ribosomal DNA probe pBG 35 produced consistent differences in RFLPs between standard clones of biotypes. However, analysis of field populations gave more complex RFLP patterns that were not biotype-specific, unlike characteristic intergenic spacer (IGS) patterns reported for Schizaphis graminum biotypes. All but one sample collected from separate fields showed considerable genetic diversity within populations, attributed to alate migrations of parthenogenetic females in summer and males in autumn.

Animals↗
PubMed1993

A cosmid and yeast artificial chromosome contig containing the complete ryanodine receptor (RYR1) gene.

The ryanodine receptor (RYR1) gene is responsible for some forms of malignant hyperthermia and has been localized to 19q13.1. Central core disease is a genetic myopathy that is genetically linked to RYR1. We have identified an overlapping set of cosmid and YAC clones that spans more than 800 kb and includes the RYR1 gene (approximately 205 kb). Cosmids from this region were identified by screening three chromosome 19 cosmid libraries (11-fold coverage) with six subclones representing the entire RYR1 cDNA. Genomic sequences from positive cosmids were then used as probes to identify additional cosmids. A minimally overlapping set of 23 cosmids was assembled into two contigs on the basis of restriction fragment analysis and hybridization data. Three YAC clones were isolated by screening a human YAC library with selected cosmid inserts. Overlaps among these YACs and the cosmid contigs were determined by hybridizing YAC Alu-PCR products to cosmid DNAs. The YACs bridged the gap between the cosmid contigs and extended the contig on both sides. Fluorescence in situ hybridization experiments positioned the RYR1 contig between GPI, MAG, and D19S191 on the proximal side and D19S190, CYP2A, CYP2F, SNRPA, BCKDHA, and other markers on the distal side. The 800-kb contig of cloned reagents will facilitate the detailed characterization of the RYR1 gene and other loci that may be closely related to central core disease.

Animals↗
PubMed1993

A mutation in the human ryanodine receptor gene associated with central core disease.

Central core disease (CCD) is a morphologically distinct, autosomal dominant myopathy with variable clinical features. A close association with malignant hyperthermia (MH) has been identified. Since MH and CCD genes have been linked to the skeletal muscle ryanodine receptor (RYR1) gene, cDNA sequence analysis was used to search for a causal RYR1 mutation in a CCD individual. The only amino acid substitution found was an Arg2434His mutation, resulting from the substitution of A for G7301. This mutation was linked to CCD with a lod score of 4.8 at a recombinant fraction of 0.0 in 16 informative meioses in a 130 member family, suggesting a causal relationship to CCD.

Amino Acid Sequence↗
PubMed1992

Malignant hyperthermia.

In humans genetically predisposed to malignant hyperthermia, anesthesia can induce skeletal muscle rigidity, hypermetabolism, and high fever, which, if not immediately reversed, can lead to tissue damage or death. The corresponding condition in swine leads to stress-induced deaths and devalued meat products. Abnormalities in the Ca2+ release channel of skeletal muscle sarcoplasmic reticulum (the ryanodine receptor) have been implicated in the cause of both the porcine and human syndromes by physiological and biochemical studies and genetic linkage analysis. In swine, a single founder mutation in the ryanodine receptor gene (RYR1) can account for all cases of malignant hyperthermia in all breeds, but a series of different RYR1 mutations are likely to be uncovered in human families with MH. Moreover, lack of linkage between malignant hyperthermia and RYR1 in some families indicates a heterogeneous genetic basis for the human syndrome.

Animals↗
PubMed1992

Refinement of diagnostic assays for a probable causal mutation for porcine and human malignant hyperthermia.

The substitutions of T for C1843 in the porcine ryanodine receptor (RYR1) gene, which deletes a HinPI restriction endonuclease site and creates a HgiAI site, and of T for C1840 in human RYR1, which deletes a RsaI site, lead to Cys for Arg substitutions in the ryanodine receptors and are probable causal mutations for malignant hyperthermia (MH). To improve the restriction endonuclease assay of these sites, thereby providing an accurate, reliable diagnosis for MH, introns flanking the exon containing the mutation were sequenced, permitting identification and PCR amplification of a 659-bp porcine gene sequence that contains both constant and variant HgiAI sites and a 922-bp human gene sequence that contains both constant and variant RsaI sites. As a result, these PCR-amplified sequences contain constant internal controls for the reliable differentiation by restriction endonuclease digestion of normal, heterozygous, and MH genotypes.

Animals↗
PubMed1992

The role of the skeletal muscle ryanodine receptor gene in malignant hyperthermia.

Malignant hyperthermia (MH) is an inherited, potentially lethal condition in which sustained muscle contracture with attendant hypermetabolism and hyperthermia is triggered in humans, heterozygous for the gene defect, by inhalational anaesthetics and skeletal muscle relaxants, and in pigs, homozygous for the defect, by stress. Because muscle contracture could result from a defective Ca2+ release channel, we have focussed our attention on the linkage of MH to defects in the gene (RYR1) encoding the skeletal muscle Ca2+ release channel. We have cloned and sequenced human RYR1 cDNA and found restriction fragment length polymorphisms (RFLPs) in the human gene. We also localized RYR1 to human chromosome 19q13.1. Studies of the cosegregation of MH with these RFLPs established RYR1/MH linkage on human chromosome 19q13.1 (lod score of 4.2; recombinant fraction 0.0). We then sequenced MH and normal porcine RYR1 cDNAs. Mutation of C1843 to T, leading to substitution of Cys for Arg615, was the sole amino acid change noted between MH and normal animals. Linkage of this mutation to MH was established in a study of 338 informative meioses (lod score of 102; recombinant fraction 0.0). We identified the corresponding mutation in 1 of 35 human MH families studied and found cosegregation of the mutation and MH. The combination of a high lod score with crossing of a species barrier supports the causal nature of this mutation. Future studies are aimed at finding the major human MH mutations and establishing assays for their accurate diagnosis.

Amino Acid Sequence↗
PubMed1991

Patients who reoffend while on warrants of the Lieutenant-Governor.

Occasionally, psychiatric patients detained in institutions against their will or residing in the community under legal restraints elope and commit serious offenses. The authors looked at the frequency with which this occurred with patients on warrants of the Lieutenant-Governor in Ontario. Using the files of the Ontario Lieutenant-Governor's Board of Review, they examined the records and isolated such recorded incidents over a 16 year period. In spite of the limitations identified by the authors, their findings indicate a lower than expected occurrence. As well, they point to the risk management implications of certain diagnostic groups being treated in a less than secure setting.

Adult↗
PubMed1991

Collaborating with physicians in the drug-usage evaluation process.

The Joint Commission requires that DUE be performed by the medical staff with pharmacy department participation. To gain physician acceptance of the DUE process, it must be promoted as a means of ensuring quality care and improved patient outcomes, employing an educational rather than punitive approach. Peer interaction is the ideal method to enforce and reenforce desired practices. The pharmacy department can play a major role in ensuring appropriate prescribing practices by reporting information, serving as an educational resource, facilitating physician participation, and overseeing the DUE process.

Drug Utilization↗
PubMed1990

Quality assurance through adverse drug reaction reporting: improving hypnotic prescribing.

While adverse drug reactions (ADRs) contribute to excessive health care costs through increased patient morbidity and mortality, most hospital ADR reporting programs are ineffective in documenting the adverse reactions to drugs that occur in their institutions. Furthermore, the ADR reporting programs have an untapped potential as a quality assurance (QA) tool; ADR reports provide a means of identifying potential problems in patient care. If 10-20% of hospitalized patients develop adverse effects while taking medications and over 50% of the iatrogenic events are avoidable, educational strategies and prospective monitoring could reduce this significant cause of patient morbidity. At Memorial Hospital (Ormond Beach, FL), routine QA screening detected a potential problem with the use of Halcion (triazolam). A plan of action, which included a drug use evaluation (DUE), educational efforts, and hypnotic prescribing guidelines was developed to address and resolve the concerns raised by initial ADR reports.

Confusion↗
PubMed1989

Exercise responses in patients treated for pulmonary tuberculosis by thoracoplasty.

Twenty eight subjects (mean age 64 years) who had been treated for tuberculosis by thoracoplasty in the past performed an increasing work rate exercise test, from which maximum oxygen consumption (VO2max), ventilation and heart rate were measured. VO2max was significantly lower than predicted, being 0.75 l/min in 17 subjects, 1.0 l/min in 10, and 1.5 l/min in one. Only one subject achieved a heart rate of 85% of the predicted maximum. The ratio of heart rate to oxygen consumption (HR/VO2) and heart rate at standard interpolated submaximal levels of oxygen uptake at 0.75 l/min (heart rate 0.75) and 1.0 l/min (heart rate 1.0) were normal. VO2max correlated with ventilation at maximal exercise (VE max) (r = 0.87) and FEV1 (r = 0.47). It did not correlate with resting arterial oxygen or carbon dioxide tensions, FEV1, maximum inspiratory pressure, angle of scoliosis, or number of ribs resected. The relation between ventilation and oxygen consumption (VE/VO2) and VE at the submaximal levels of oxygen consumption of 0.75 l/min (VE 0.75) and 1.0 l/min (VE 1.0) were normal. In 10 subjects a plateau of breathing frequency (fmax) was reached, after which the increase in ventilation was achieved by a further increase in tidal volume (VT). These subjects showed significantly lower values for the forced expiratory ratio, VO2max, and VEmax than those with a normal relation between tidal volume and breathing frequency. VEmax was correlated with FEV1 (r = 0.61), FVC (r = 0.46), maximum VT (r = 0.55), change in VT (r = 0.52), fmax (r = 0.56), and change in breathing frequency (r = 0.72). These results indicate that exercise in patients treated for tuberculosis by thoracoplasty is limited by ventilatory capacity and that this is due to a reduction in both dynamic lung volumes and respiratory frequency.

Aged↗
PubMed1988

Pulmonary tissue volume and blood flow as functions of body surface area and age.

We measured pulmonary tissue volume (Vt) and capillary blood flow (Qc) by rebreathing acetylene as the soluble gas in 94 male and 82 female patients with normal healthy lungs. We found that the standard deviation of Vt was a function of Vt and that the standard deviation of Qc was a function of Qc; logarithm transforms were used to prevent this. A significant correlation exists between log Vt and body surface area (BSA) and log Vt and vital capacity (VC). For both sets of regressions older subjects (greater than or equal to 40 years of age) exhibited greater variability about the regression line than younger subjects; therefore the 2 age groups of subjects were analyzed separately for tissue volume. We describe regression equations of log Vt vs. BSA or VC for younger male, younger female, older male, and older female patients. The normal limits by sex and age groups are also included. A significant correlation was found between log Qc, BSA, and age. Thus 2 equations, for male and female patients, are used to predict log Qc based on these 2 covariates.

Adolescent↗
PubMed1988

Anterior segment ischemia after three rectus muscle surgery.

Nine patients underwent simultaneous or staged detachment of the vertical and medial rectus muscles in the treatment of sixth nerve palsy or Duane's retraction syndrome. In five adult patients (34, 35, 41, 45, and 65 years of age), clinically significant anterior segment ischemia developed postoperatively. Known medical risk factors were present in only one case. With the exception of corectopia, there were no apparent sequelae and all involved eyes returned to preoperative visual acuity within 9 weeks of surgery. Anterior segment ischemia may be a frequent complication of strabismus surgery in adult patients when the superior, inferior, and medial rectus muscles are detached from the globe.

Abducens Nerve↗
PubMed1988

Appearances on computed tomography following thoracoplasty for pulmonary tuberculosis.

Thoracic computed tomography was performed in 32 patients who had undergone thoracoplasty as part of their treatment for pulmonary tuberculosis. Pleural thickening and the prevalence of bronchiectasis were more marked in the operated hemithorax. Bullae were more prevalent in the operated hemithorax but the difference was not statistically significant. In all but one patient, scoliosis was present. Illustrative examples are presented to demonstrate the range of appearances following this operation.

Bronchiectasis↗