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Biomedical subjects

M Wallace

Publications and source records attributed to M Wallace.

At least 73 records · Page 4Linked to original sources

A comparison of two dosing regimens of succimer in children with chronic lead poisoning.

There is limited information defining the optimal dosing regimen of succimer in the treatment of children with chronic lead poisoning. It is typically administered as a five day course of high dose therapy (1,050 mg/m2/day) followed by 14 days of low dose therapy (700 mg/m2/day). This study compared the effect on blood lead concentrations (BPb) of treatment with this standard regimen and an alternate regimen consisting of two courses of high dose therapy separated by one week. There were significant reductions in the mean BPb in both the standard (n = 7) and alternate (n = 4) treatment groups but there was not a significant difference between the groups. In the standard group, the BPb decreased from 33 +/- 4 to 27 +/- 6 mcg/dL. The BPb decreased from 33 +/- 6 to 23 +/- 4 mcg/dL in those treated with alternate therapy. This study suggests that two short courses of high dose therapy may be an acceptable alternative to standard succimer therapy. Because of the small size of this study, other studies are warranted.

Chelating Agents↗

Identification of a 6 base pair insertion in West Highland White Terriers with erythrocyte pyruvate kinase deficiency.

OBJECTIVE: To define the disease-causing mutation in West Highland White Terriers (WHWT) with erythrocyte pyruvate kinase (R-PK) deficiency and to design a genetic test capable of recognizing affected (homozygous) and carrier (heterozygous) dogs. ANIMALS: 3 anemic WHWT littermates and 1 unaffected littermate; 16 dogs from the same kennel, including 4 unrelated, phenotypically normal dogs (control dogs), and 12 for which PK activity was not known; 2 PK-deficient Basenjis; 2 PK-deficient Beagles; 4 unaffected English Springer Spaniels; and 1 mixed-breed dog. PROCEDURES: cDNA was cloned and sequenced, and cDNA sequences were compared with the published sequence for canine R-PK cDNA to identify the putative disease-causing mutation. Genomic DNA spanning the affected region was cloned and sequenced to verify the mutation. Subsequently, polymerase chain reaction primers were designed to amplify the section of the gene containing the mutation from DNA in blood or buccal swab samples. Gel electrophoresis allowed assignment of genotypes on the basis of allele separation. RESULTS: 4 single base polymorphisms attributable to sequencing errors in the published sequence were identified, along with a 6 base pair (bp) insertion in exon 10 that was recognized as a putative disease-causing mutation. An identical insertion was found in genomic DNA. Amplification of genomic DNA yielded a 117 bp product for genotypically normal dogs and a 123 bp product for WHWT homozygous for PK deficiency. Carriers had 1 copy of each allele and variable heteroduplex structures. CONCLUSIONS AND CLINICAL RELEVANCE: A 6 bp insertion in the C domain of R-PK was identified in WHWT with PK deficiency. Affected and carrier dogs could be distinguished with a genetic test.

Animals↗

Rapid simultaneous comparison system for subjective grading scales grading scales for facial paralysis.

OBJECTIVE: The senior authors developed a computer-assisted rapid, simultaneous comparison system for nine international grading scales for facial paralysis. The purpose of this study is to present the system and to compare the agreement of hand-performed House-Brackmann and Sunnybrook scales, two frequently used scales herein taken as the concurrent criterion test standards, with those like scales done simultaneously in the computed system. STUDY DESIGN: The study design was a prospective concurrent criterion validity study. Test-retest reliability and interobserver agreement were assessed using the kappa statistic (k) for ordinal data and the intraclass correlation coefficient (ICC) for semidimensional data. SETTING: The study was conducted at a university practice. PATIENTS: Ten consecutive consenting subjects with varying degrees of facial paralysis were studied. INTERVENTION: Each subject was measured, in random order, twice by each method by each of two independent observers. MAIN OUTCOME MEASURES: House-Brackmann score, Sunnybrook score, and like-scale scores done simultaneously in the computed system were measured. RESULTS: Agreement between the computed system and hand-performed criterion standards was equal to each scale compared against itself; for the House-Brackmann, agreement was moderate (k = 0.554); for the Sunnybrook, agreement was excellent (ICC = 0.976). CONCLUSIONS: The computed system has the advantage of allowing an examiner to view a rapid, simultaneous display of multiple grading scale scores at a keystroke from one clinical assessment input, obviating the labor of repeating measures by hand.

Adult↗

Localization of the 26S proteasome during mitosis and meiosis in fission yeast.

The 26S proteasome is a large multisubunit complex involved in degrading both cytoplasmic and nuclear proteins. We have investigated the localization of this complex in the fission yeast, Schizosaccharomyces pombe. Immunofluorescence microscopy shows a striking localization pattern whereby the proteasome is found predominantly at the nuclear periphery, both in interphase and throughout mitosis. Electron microscopic analysis revealed a concentration of label near the inner side of the nuclear envelope. The localization of green fluorescent protein (GFP)-tagged 26S proteasomes was analyzed in live cells during mitosis and meiosis. Throughout mitosis the proteasome remained predominantly at the nuclear periphery. During meiosis the proteasome was found to undergo dramatic changes in its localization. Throughout the first meiotic division, the signal is more dispersed over the nucleus. During meiosis II, there was a dramatic re-localization, and the signal became restricted to the area between the separating DNA until the end of meiosis when the signal dispersed before returning to the nuclear periphery during spore formation. These findings strongly imply that the nuclear periphery is a major site of protein degradation in fission yeast both in interphase and throughout mitosis. Furthermore they raise interesting questions as to the spatial organization of protein degradation during meiosis.

Base Sequence↗

The Pad1+ gene encodes a subunit of the 26 S proteasome in fission yeast.

We have isolated a fission yeast mutant, mts5-1, in a screen for mutations that confer both methyl 2-benzimidazolecarbamate resistance (MBCR) and temperature sensitivity (ts) on Schizosaccharomyces pombe. This screen has previously isolated mutations in the 26 S proteasome subunits Mts2, Mts3, and Mts4. We show that the mutation in the mts5-1 strain occurs in the pad1(+) gene. pad1(+) was originally isolated on a multicopy plasmid that was capable of conferring staurosporine resistance on a wild type strain. mts5-1/pad1-1 has a similar phenotype to 26 S proteasome mutants previously isolated in the same screen and we show that Pad1 interacts genetically with two of these subunits, Mts3 and Mts4. In this study we describe the identification of Pad1 as a subunit of the 26 S proteasome in fission yeast.

Amino Acid Sequence↗

The effects of interleukin-15 on human gammadelta T cell responses to Plasmodium falciparum in vitro.

We observed that the gammadelta T cell subset expands when human peripheral blood mononuclear cells (PBMC) from malaria-naive donors are cultured with Plasmodium falciparum lysate in the presence of IL-2 or IL-15, cytokines that utilize two common IL-2 receptor subunits. IL-15 induced the expansion of the gammadelta T cell subset at all levels tested, whereas IL-2 was not stimulatory at high levels. Flow cytometric analysis of apoptosis using the TUNEL assay indicated that the percentage and absolute number of gammadelta T cells undergoing apoptosis were greater in cultures stimulated with antigen and IL-2 than in cultures stimulated with either antigen and IL-15 or control erythrocyte lysate and IL-2. The ability of IL-15 to enhance gammadelta T cell function was also assessed; the results suggest that IL-15 can function with IL-2 to enhance the capacity of gammadelta T cells to inhibit parasite replication. Together these data indicate that IL-2 and IL-15, which both bind to IL-2Rbeta and IL-2R(gamma)c, enhance gammadelta T cell function, but they appear to have different effects on proliferation and survival.

Animals↗

Pioneering the 12-hour shift in Australia--implementation and limitations.

Twelve-hour shift rostering offers an alternative to the traditional 8- and 10-hour shifts usually worked in Australian nursing practice. This paper outlines the implementation process involved in introducing 12-hour shifts in a Melbourne hospital intensive care unit. The process was instigated by the nursing staff. After extensive consultation with the union and hospital management, a roster pattern of two 12-hour days, followed by 12-hour night shifts then days off, was introduced. Independent researchers were engaged to evaluate the impact of the 12-hour shifts on staff well-being and work performance. Effects on staff retention, sick leave and inservice education were examined. The researchers found that well-being and work performance were minimally affected by the 12-hour shift roster, while staff retention and sick leave were unaffected. Further, the pattern of 12-hour shifts, which was democratically implemented, was preferred by the nursing staff and did not diminish their well-being and work performance.

Attitude of Health Personnel↗

Indiana Youth Access Project: a model for responding to the HIV risk behaviors of gay, lesbian, and bisexual youth in the heartland.

The Indiana Youth Access Project (IYAP) is supported by the Special Projects of National Significance Program, Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) Bureau, Health Resources and Services Administration. The IYAP is a model HIV care program being developed at the Indiana Youth Group, Inc. (IYG) in conjunction with the Indiana State Department of Health and Indiana University. Previous studies indicate that gay, lesbian, and bisexual youth are at increased risk of acquiring HIV because of the stigmatization and social marginalization they experience as a result of their sexual identities. During the course of the first 3 years of the demonstration, the program has served 418 young people, including nine who are HIV infected. The IYAP targets the special needs of this special population by confronting institutional barriers which limit these young people's access to HIV care services, assisting them in building stronger peer support networks, and providing them with professional case management and related services. The model builds upon the successful peer-support program established at IYG by incorporating a unique set of health, mental health, and social case-management services provided by trained professionals. In addition, the program incorporates an extensive peer-counselor training and outreach program which targets street youth and other at-risk young people. The program has provided education and training workshops on the special needs of gay, lesbian, and bisexual youth to thousands of health care, education, and social service professionals both in central Indiana and around the nation.

Acquired Immunodeficiency Syndrome↗

Indications for sinus surgery: how appropriate are the guidelines?

Sinusitis is the most commonly reported chronic disorder in America. More than 75,000 sinus surgical procedures were performed in 1993. Evaluating the appropriateness of procedures is a major focus of health care reform. The American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) collaborated with Value Health Sciences, Inc. (VHS) to develop guidelines for the use of sinus surgery. The clinical utility of these guidelines is presented. Patients undergoing sinus surgery at Barnes Hospital in St. Louis, Missouri, between November 1994 and July 1995 were eligible. Relevant patient information was used to prospectively rate surgery on the nine-point VHS appropriateness scale (1 to 3, inappropriate; 4 to 6, equivocal; 7 to 9, appropriate). Of 55 patients, 37 (67%) had chronic sinusitis, 10 (18%) recurrent sinusitis, five (9%) chronic sinusitis with nasal polyps, and three (6%) sinusitis with moderate to severe asthma; 27 (49%) had previous sinus surgery. Appropriateness ratings ranged from 1 to 9, with nine (16%) procedures rated as inappropriate, 22 (40%) uncertain, and 24 (44%) appropriate. There were no significant differences in the ratings of appropriateness between the group of patients who had undergone previous sinus surgery and the group of patients who had not. Overall, the guidelines were easily applied and clinically pertinent.

Adult↗

CD4+-T-cell and CD20+-B-cell changes predict rapid disease progression after simian-human immunodeficiency virus infection in macaques.

Simian-human immunodeficiency virus 89.6PD (SHIV89.6PD) was pathogenic after intrarectal inoculation of rhesus macaques. Infection was achieved with a minimum of 2,500 tissue culture infectious doses of cell-free virus stock, and there was no evidence for transient viremia in animals receiving subinfectious doses by the intrarectal route. Some animals experienced rapid progression of disease characterized by loss of greater than 90% of circulating CD4+ T cells, sustained decreases in CD20+ B cells, failure to elicit virus-binding antibodies in plasma, and high levels of antigenemia. Slower-progressing animals had moderate but varying losses of CD4+ T cells; showed increases in circulating CD20+ B cells; mounted vigorous responses to antibodies in plasma, including neutralizing antibodies; and had low or undetectable levels of antigenemia. Rapid progression led to death within 30 weeks after intrarectal inoculation. Plasma antigenemia at 2 weeks after inoculation (P < or = 0.002), B- and T-cell losses (P < or = 0.013), and failure to seroconvert (P < or = 0.005) were correlated statistically with rapid progression. Correlations were evident by 2 to 4 weeks after intrarectal SHIV inoculation, indicating that early events in the host-pathogen interaction determined the clinical outcome.

Animals↗