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Biomedical subjects

M A Potter

Publications and source records attributed to M A Potter.

At least 19 recordsLinked to original sources
PubMed2002

Treatment of hemophilia B in mice with nonautologous somatic gene therapeutics.

The implantation of nonautologous cells encapsulated in immunoprotective microcapsules provides an alternative nonviral method for gene therapy. This strategy was successful in reversing the disease phenotypes of dwarfism and a lysosomal storage disease, mucopolysaccharidosis VII, in murine models. In this article we implanted transgenic hemophilic B mice with microcapsules enclosing factor IX-secreting C2C12 myoblasts to study the clinical potential of this approach in the treatment of hemophilia. Treated mice showed increased plasma factor IX levels as high as 28 ng of human factor IX per milliliter of plasma and decreased activated thromboplastin times (reduced by 20% to 29%). However, the level of factor IX decreased to baseline levels by day 7, coinciding with emergence of anti-human factor IX antibody, the titer of which increased greater than 10-fold by day 28. Monoclonal anti-CD4 antibodies were used to deplete CD4+ T cells to suppress the immune response against the recombinant factor IX. In the treated hemophilic mice, the anti-factor IX antibody response was totally suppressed to beyond day 28 accompanied by a significant decrease in activated thromboplastin time compared with that seen in untreated hemophilic mice. When the microcapsules were recovered from the intraperitoneal cavity after 38 days of implantation, the encapsulated cells continued to secrete factor IX at preimplantation levels, but both cell viability and microcapsule mechanical stability were reduced. Hence although the polymer chemistry of the microcapsules and cell viability may need to be improved for long-term delivery, nonautologous gene therapy with microencapsulated cells has been shown to be effective, at least for the short-term, in alleviating the hemophilic hemostatic anomaly. Coadministration of an immunosuppressant is effective in inhibiting antibody development against the delivered factor IX and should be considered for recipients at risk of inhibitor development.

Animals↗
PubMed2001

Randomized comparison of a strategy of predischarge coronary angiography versus exercise testing in low-risk patients in a chest pain unit: in-hospital and long-term outcomes.

OBJECTIVES: This randomized trial compared a strategy of predischarge coronary angiography (CA) with exercise treadmill testing (ETT) in low-risk patients in the chest pain unit (CPU) to reduce repeat emergency department (ED) visits and to identify additional coronary artery disease (CAD). BACKGROUND: Patients with chest pain and normal electrocardiograms (ECGs) have a low likelihood of CAD and a favorable prognosis, but they often seek repeat evaluations in EDs. Remaining uncertainty regarding their symptoms and diagnosis may cause much of this recidivism. METHODS: A total of 248 patients with no ischemic ECG changes triaged to a CPU were randomized to CA (n = 123) or ETT (n = 125). All patients had a probability of myocardial infarction < or =7% according to the Goldman algorithm, no biochemical evidence of infarction, the ability to exercise and no previous documented CAD. Patients were followed up for > or =1 year and surveyed regarding their chest pain self-perception and utility of the index evaluation. RESULTS: Coronary angiography showed disease (> or =50% stenosis) in 19% and ETT was positive in 7% of the patients (p = 0.01). During follow-up (374+/-61 days), patients with a negative CA had fewer returns to the ED (10% vs. 30%, p = 0.0008) and hospital admissions (3% vs. 16%, p = 0.003), compared with patients with a negative/nondiagnostic ETT. The latter group was more likely to consider their pain as cardiac-related (15% vs. 7%), to be unsure about its etiology (38% vs. 26%) and to judge their evaluation as not useful (39% vs. 15%) (p < 0.01 for all comparisons). CONCLUSIONS: In low-risk patients in the CPU, a strategy of CA detects more CAD than ETT, reduces long-term ED and hospital utilization and yields better patient satisfaction and understanding of their condition.

Adult↗
PubMed2001

Proctalgia fugax.

Proctalgia fugax is a benign, self-limiting pain experienced in the perineum. It is common, but most sufferers do not seek medical advice. The aetiology is unclear, but a variation of irritable bowel syndrome, pelvic floor myalgia, and internal anal sphincter spasm have all been suggested. A careful history can elicit the characteristic history, and simple reassurance is often all that is necessary. For persistent symptoms, therapies that induce internal anal sphincter relaxation are of value.

Humans↗
PubMed2001

Training readiness of public health agencies: a framework for assessment.

The Healthy People 2010 Objectives and the Taskforce on Public Health Workforce Development both have recognized the important roles of state and local agencies in the education and training of their employees. This article describes an initial step in the development of a tool to assess agencies' training readiness using five factors derived from learning organization theory. These factors (resources, policies, learning culture, programs, and leadership) offer a useful framework for further development of a tool to assess training program readiness.

Education, Continuing↗
PubMed2000

Cardiac troponin T in chest pain unit patients without ischemic electrocardiographic changes: angiographic correlates and long-term clinical outcomes.

OBJECTIVES: We prospectively evaluated the relation between cardiac troponin T (cTnT) level, the presence and severity of coronary artery disease (CAD) and long-term prognosis in patients with chest pain but no ischemic electrocardiographic (ECG) changes who had short-term observation. BACKGROUND: Cardiac TnT is a powerful predictor of future myocardial infarction (MI) and death in patients with ECG evidence of an acute coronary syndrome. However, for patients with chest pain with normal ECGs, it has not been determined whether cTnT elevation is predictive of CAD and a poor long-term prognosis. METHODS: In 414 consecutive patients with no ischemic ECG changes who were triaged to a chest pain unit, cTnT and creatine kinase, MB fraction (CK-MB) were evaluated > or = 10 h after symptom onset. Patients with adverse cardiac events, including death, MI, unstable angina and heart failure were followed for as long as one year. RESULTS: A positive (>0.1 ng/ml) cTnT test was detected in 37 patients (8.9%). Coronary artery disease was found in 90% of 30 cTnT-positive patients versus 23% of 144 cTnT-negative patients who underwent angiography (p < 0.001), with multivessel disease in 63% versus 13% (p < 0.001). The cTnT-positive patients had a significantly (p < 0.05) higher percent diameter stenosis and a greater frequency of calcified, complex and occlusive lesions. Follow-up was available in 405 patients (98%). By one year, 59 patients (14.6%) had adverse cardiac events. The cumulative adverse event rate was 32.4% in cTnT-positive patients versus 12.8% in cTnT-negative patients (p = 0.001). After adjustment for baseline clinical characteristics, positive cTnT was a stronger predictor of events (chi-square = 23.56, p = 0.0003) than positive CK-MB (>5 ng/ml) (chi-square = 21.08, p = 0.0008). In a model including both biochemical markers, CK-MB added no predictive information as compared with cTnT alone (chi-square = 23.57, p = 0.0006). CONCLUSIONS: In a group of patients with chest pain anticipated to have a low prevalence of CAD and a good prognosis, cTnT identifies a subgroup with a high prevalence of extensive and complex CAD and increased risk for long-term adverse outcomes.

Cardiology Service, Hospital↗
PubMed2000

Cooperative coevolution: an architecture for evolving coadapted subcomponents.

To successfully apply evolutionary algorithms to the solution of increasingly complex problems, we must develop effective techniques for evolving solutions in the form of interacting coadapted subcomponents. One of the major difficulties is finding computational extensions to our current evolutionary paradigms that will enable such subcomponents to "emerge" rather than being hand designed. In this paper, we describe an architecture for evolving such subcomponents as a collection of cooperating species. Given a simple string-matching task, we show that evolutionary pressure to increase the overall fitness of the ecosystem can provide the needed stimulus for the emergence of an appropriate number of interdependent subcomponents that cover multiple niches, evolve to an appropriate level of generality, and adapt as the number and roles of their fellow subcomponents change over time. We then explore these issues within the context of a more complicated domain through a case study involving the evolution of artificial neural networks.

Adaptation, Physiological↗
PubMed2000

Needs assessment and a model agenda for training the public health workforce.

OBJECTIVES: A training needs assessment project tested the use of "universal" competencies for establishing a model training agenda for the public health workforce. METHODS: Agency supervisors selected competencies for training priorities. Regional and national public health leaders used these selections to design the model training agenda. RESULTS: The competencies given high priority by supervisors varied among state and local agencies and included some not within the universal set. The model training agenda reflected supervisors' priorities as well as leaders' perspectives. CONCLUSIONS: The universal competencies provide a useful starting point, but not necessarily an exclusive framework, for assessing and meeting the training needs of the public health workforce.

Curriculum↗
PubMed1999

Review--the use of immunosuppressive agents to prevent neutralizing antibodies against a transgene product.

A potential obstacle to successful gene therapy for some patients is the in vivo production of neutralizing antibodies against the recombinant therapeutic product delivered. This is a problem inherent to all gene therapy methods, regardless of the vector used to deliver the protein. This clinical situation can be mimicked in animal models by delivering a foreign protein (i.e., a human protein) to the animal to provoke anti-human protein antibody production. The efficacy of different immunosuppressive treatments to inhibit the development of neutralizing antibodies can then be investigated. The immunosuppressive agents examined here include drugs (e.g., cyclophosphamide, FK506), cytokines (e.g., interferon-gamma, interleukin-12), and monoclonal antibodies (e.g., anti-CD4, anti-gp39, CTLA4-Ig). It has been found that a high level of antibody suppression is necessary to allow prolonged delivery of a foreign protein. Immunosuppressive agents capable of this high level of suppression will be important adjuncts to prevent treatment failures in situations where patients are at risk of developing neutralizing antibodies.

Animals↗
PubMed1999

Prealbumin measurement as a screening tool for protein calorie malnutrition in emergency hospital admissions: a pilot study.

OBJECTIVE: To examine the effectiveness of prealbumin measurement as a routine diagnostic test for protein calorie malnutrition (PCM) in emergency admissions. DESIGN: Cohort study. SETTING: Canadian tertiary care hospital. PATIENTS: A total of 147 consecutive patients admitted through the emergency department, excluding psychiatric admissions, for whom a serum sample was sent to the chemistry laboratory. OUTCOME MEASURES: (1) Albumin and prealbumin levels to diagnose PCM; (2) length of stay (LOS), in-hospital mortality, and nutritional supplementation in patients with PCM; and (3) cost analysis of using prealbumin level as an admission screening test for PCM. RESULTS: Twenty-four per cent of the patients had at least mild PCM (prealbumin level < 160 mg/L). Albumin level (< 35 g/L) had a sensitivity of 50% and specificity of 95% in identifying PCM. The mean LOS in the patients with PCM was 16 (standard deviation 18) days, compared with 8 (SD 12) days in the patients without PCM (p < 0.0002). The in-hospital mortality rate was 17% in patients with PCM compared with 4% in patients without PCM (p < 0.02). Only 42% of patients with PCM received nutritional supplementation. Cost analysis of screening with prealbumin level projected a saving of $414 per patient screened. CONCLUSIONS: PCM is underdiagnosed in current clinical practice and is associated with an increased LOS and mortality rate. Prealbumin is a biochemical marker that could be used as a cost-effective screening test to identify patients with PCM who may benefit from nutritional supplementation.

Adolescent↗
PubMed1999

Diagnostic delay in colorectal cancer.

Recent guidelines recommend early diagnosis of colorectal cancer. Little data exists for comparison or to set standards. The aims of this study were to calculate the time to diagnosis for colorectal cancer from first hospital attendance and to identify any remedial factors felt to contribute to an undue delay in diagnosis. A one year retrospective audit was undertaken in a specialist teaching hospital. There were 59 patients and the median time to diagnosis was 17 days after first hospital consultation (mean 52 days). Some 34% had to wait more than one month for diagnosis. Incomplete examination or initial referral to a non-surgical specialty appeared to contribute to delay. Greater awareness of guidelines across the breadth of hospital specialties may reduce time to diagnosis.

Aged↗
PubMed1998

Suppression of immunological response against a transgene product delivered from microencapsulated cells.

A potential obstacle to successful gene therapy for some patients is the in vivo production of neutralizing antibodies against the recombinant therapeutic product delivered. To mimic this clinical situation, we implanted microencapsulated recombinant cells producing human growth hormone into C57B1/6 mice to provoke antihuman growth hormone antibody production. We then investigated the efficacy of different immunosuppressive treatments to inhibit the development of neutralizing antibodies. The experimental mice were treated with either an immunosuppressive drug (FK506 or cyclophosphamide), a cytokine (interferon-gamma [IFN-gamma] or interleukin-12 [IL-12], or a monoclonal antibody (anti-CD4, anti-gp39, or CTLA4-Ig). Serum human growth hormone and mouse anti-human growth hormone antibody levels were measured by enzyme-linked immunosorbent assay (ELISA) for 4 weeks. There were three patterns of response noted among the seven treatment groups. First, the mice receiving IFN-gamma, IL-12, anti-gp39, or CTLA4-Ig were similar to the untreated controls-no suppression of anti-hGH antibodies and no improvement in delivery of hGH. Next, the mice receiving FK506 or cyclosphosphamide showed > or = 90% suppression of antibodies but also no improvement in product delivery. Last, the mice receiving anti-CD4 showed almost complete antibody suppression over 1 month postimplantation. Furthermore, only anti-CD4 permitted a sustained level of human growth hormone delivery to day 28, in contrast to the controls whose human growth hormone delivery was undetectable by day 14 postimplantation. Hence, the use of anti-CD4 inhibited formation of neutralizing antibodies against a recombinant gene product delivered in vivo, and allowed prolonged delivery of a foreign protein. Its role as adjunct treatment for appropriate patients receiving gene therapy should be examined further.

Animals↗
PubMed1998

A prospective controlled study of the association of Streptococcus bovis with colorectal carcinoma.

AIM: To investigate the ability of Streptococcus bovis to colonise colorectal cancers. PATIENTS: 19 patients with colorectal cancer and 23 controls without malignancy. SETTING: University teaching hospital. METHODS: Prospective study comparing unselected patients with known colorectal cancer with age and sex matched controls. Carcinoma tissue from patients with colorectal cancer and normal colonic mucosa, stool, and blood from both patients and control subjects were cultured. RESULTS: In contrast to published data, the faecal carriage rate was similar in cancer (11%) and control groups (13%). CONCLUSIONS: Faecal colonisation by Str bovis in colorectal cancer patients is lower than previously reported and does not differ significantly from controls.

Adenocarcinoma↗
PubMed1998

Diagnostic accuracy, angiographic correlates and long-term risk stratification with the troponin T ultra sensitive Rapid Assay in chest pain patients at low risk for acute myocardial infarction.

AIMS: This prospective study of acute chest pain patients clinically at low risk for a myocardial infarction was designed to: determine the diagnostic accuracy of a cardiac troponin T (cTnT) ultra sensitive Rapid Assay (RAII) compared with the quantitative cTnT assay; evaluate the association of a positive RAII with the presence and severity of coronary artery disease (CAD); and determine the ability of the RAII result to predict adverse events during long-term follow-up. METHODS AND RESULTS: A total of 199 patients referred for chest pain, without ST segment elevation on presenting ECG, underwent RAII, quantitative cTnT, CK and CK-MB tests drawn simultaneously > or = 10 h after symptom onset. An abnormal value for cTnT was defined as >0.1 ng.mL(-1). The presence and extent of CAD was recorded in patients undergoing angiography. Adverse events, including cardiac death, non-fatal infarction, and readmission for unstable angina or heart failure, were assessed long-term. An abnormal RAII was found in 41 (20-6%) patients. The RAII sensitivity for detecting abnormal quantitative cTnT levels was 100%, specificity 96.3% (158/164) and overall concordance 97.5%. Although the presenting ECG was normal or non-specific in 95%, ST depression or T wave inversion occurred in 17% of RAII-positive versus 2%, RAII-negative patients (P=0.004). Of RAII-positive patients who underwent angiography (79%), 87% had CAD and 60% had multivessel disease. Kaplan Meier event-free survival curves showed early separation and continued to modestly diverge for patients with positive and negative RAII (69% versus 90% one-year event-free survival, P=0.002). CONCLUSION: In a chest pain population anticipated to have a low prevalence of acute coronary syndromes and a good prognosis, the RAII is a quick and reliable test. It provides an important initial opportunity to identify patients with a high prevalence of CAD and increased incidence of future cardiac events.

Adult↗