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Biomedical subjects

L M Harris

Publications and source records attributed to L M Harris.

At least 19 recordsLinked to original sources

Fermentation characterization and flux analysis of recombinant strains of Clostridium acetobutylicum with an inactivated solR gene.

The effect of solR inactivation on the metabolism of Clostridium acetobutylicum was examined using fermentation characterization and metabolic flux analysis. The solR-inactivated strain (SolRH) of this study had a higher rate of glucose utilization and produced higher solvent concentrations (by 25%, 14%, and 81%, respectively, for butanol, acetone, and ethanol) compared to the wild type. Strain SolRH(pTAAD), carrying a plasmid-encoded copy of the bifunctional alcohol/aldehyde dehydrogenase gene (aad) used in butanol production, produced even higher concentrations of solvents (by 21%, 45%, and 62%, respectively, for butanol, acetone, and ethanol) than strain SolRH. Clarithromycin used for strain SolRH maintenance during SolRH(pTAAD) fermentations did not alter product formation; however, tetracycline used for pTAAD maintenance resulted in 90% lower solvent production.

Acetone↗

Evaluation of a screening protocol to exclude the diagnosis of deep venous thrombosis among emergency department patients.

OBJECTIVE: The purpose of this study was to evaluate the efficacy and cost effectiveness of a deep venous thrombosis (DVT) screening protocol incorporating DVT pretest probability (PTP), selective D-dimer assay, and venous duplex imaging (VDI) to exclude the diagnosis of DVT among emergency department (ED) patients. METHODS: A prospective study of all patients evaluated in the ED for suspected DVT during 1 year was undertaken. Patients were classified into PTP risk category by ED physicians before VDI. Correlation studies were completed using VDI as the gold standard. Charges associated with the protocol were calculated. RESULTS: One hundred fourteen patients were included. The incidence of DVT was 9.6% (11). Thirty-six (55%) patients were classified as high risk, 23 (35%) as moderate, and 7 (10%) as low risk. All patients diagnosed with DVT were in the high-risk group (incidence, 16.7%). The sensitivity and negative predictive value were both 100% when PTP and D-dimer were used, but fell to 80% and 95%, respectively, when only D-dimer was considered. The true negative rates were 23% and 37%, respectively. Based on this study, we propose the following screening: for high-risk patients, use direct VDI (no D-dimer); for low-risk or moderate-risk patients, obtain D-dimer, and if it is positive, use VDI, and if it is negative, no further action is required. The average charge associated with the protocol was 170.50 dollars as opposed to 202.00 dollars for global VDI. CONCLUSION: A screening protocol using PTP along with selective D-dimer and VDI to exclude the diagnosis of DVT among ED patients is efficacious and cost efficient. This screening approach establishes criteria to satisfy billing requirements, can eliminate unnecessary VDI in 23% of ED referrals, and can reduce charges by 16%.

Adult↗

Balloon angioplasty for arteriovenous graft stenosis.

PURPOSE: To retrospectively review the long-term outcome as well as the cost effectiveness of thrombolytic therapy and balloon angioplasty (TBA) versus surgical thrombectomy and balloon angioplasty (SBA) in the treatment of prosthetic dialysis access grafts. METHODS: Between February 1996 and February 1999, 63 hemodialysis patients (35 women; mean age 62.2 years) were treated for 105 thromboses in 6-mm polytetrafluoroethylene straight or loop bridge arteriovenous grafts. Choice of treatment was at the discretion of the surgeon or interventional radiologist: either Fogarty balloon thrombectomy followed by balloon dilation of the venous anastomotic stenosis or urokinase thrombolysis followed by angioplasty. RESULTS: Forty-eight SBAs and 55 TBAs were performed in 63 patients without complications. The primary patency rates in the entire cohort were 34%, 29%, and 17% at 1, 2, and 3 months, respectively. Primary patency after TBA was 29%, 18%, and 11%, and that for SBA, 45%, 45%, and 33% over the same time intervals. The mean graft survival was 10 days for TBA versus 31 days for SBA. Repeat angioplasty performed in 23 grafts produced secondary patency rates of 52% at 1 month, 34% at 3 months, and 5% at 5 months. The Medicare reimbursement for both treatments was identical ($1638 for TBA and $1670 for SBA). CONCLUSIONS: The poor patency rate and high cost of TBA and SBA suggests that these procedures should not be routinely used for salvage of thrombosed arteriovenous grafts with outflow stenosis. Patch angioplasty or creation of simultaneous temporary and new permanent accesses may be a more cost-effective approach in these patients.

Angioplasty, Balloon↗

Characterization of recombinant strains of the Clostridium acetobutylicum butyrate kinase inactivation mutant: need for new phenomenological models for solventogenesis and butanol inhibition?

Two metabolic engineering tools, namely gene inactivation and gene overexpression, were employed to examine the effects of two genetic modifications on the fermentation characteristics of Clostridium acetobutylicum. Inactivation of the butyrate kinase gene (buk) was examined using strain PJC4BK, while the combined effect of buk inactivation and overexpression of the aad gene-encoding the alcohol aldehyde dehydrogense (AAD) used in butanol formation-was examined using strain PJC4BK(pTAAD). The two strains were characterized in controlled pH > or = 5.0 fermentations, and by a recently enhanced method of metabolic flux analysis. Strain PJC4BK was previously genetically characterized, and fermentation experiments at pH > or = 5.5 demonstrated good, but not exceptional, solvent-production capabilities. Here, we show that this strain is a solvent superproducer in pH > or = 5.0 fermentations producing 225 mM (16.7 g/L) of butanol, 76 mM of acetone (4.4 g/L), and 57 mM (2.6 g/L) of ethanol. Strain PJC4BK(pTAAD) produced similar amounts of butanol and acetone but 98 mM (4.5 g/L) of ethanol. Both strains overcame the 180 mM (13 g/L) butanol toxicity limit, without any selection for butanol tolerance. Work with strain PJC4BK(pTAAD) is the first reported use of dual antibiotic selection in C. acetobutylicum. One antibiotic was used for selection of strain PJC4BK while the second antibiotic selected for the pTAAD presence. Overexpression of aad from pTAAD resulted in increased ethanol production but did not increase butanol titers, thus indicating that AAD did not limit butanol production under these fermentation conditions. Metabolic flux analysis showed a decrease in butyrate formation fluxes by up to 75% and an increase in acetate formation fluxes of up to 100% during early growth. The mean specific butanol and ethanol formation fluxes increased significantly in these recombinant strains, up to 300% and 400%, respectively. Onset of solvent production occurred during the exponential-growth phase when the culture optical density was very low and when total and undissociated butyric acid levels were <1 mM. Butyrate levels were low throughout all fermentations, never exceeding 20 mM. Thus, threshold butyrate concentrations are not necessary for solvent production in these stains, suggesting the need for a new phenomenological model to explain solvent formation.

1-Butanol↗

The relationship between inflated personal responsibility and exaggerated danger expectancies in obsessive-compulsive concerns.

The association between responsibility for a negative outcome, perceived severity of the outcome and perceived likelihood of the outcome was examined in a sample of 70 undergraduate students. Participants were asked to rate the likelihood and severity of 10 negative outcomes, five related to contamination and five related to checking. Thirty-eight participants completed a version of the questionnaire that presented the subject as responsible for the action that may lead to a negative outcome ('personally responsible' group). The remaining 32 completed a version of the questionnaire that presented someone else performing the actions that may lead to a negative outcome ('other responsible' group). Significant differences emerged between the personally responsible and other responsible groups for severity of outcome ratings but not for likelihood of outcome ratings. Specifically, for both washing and checking concerns, participants in the personally responsible group rated the severity of the potential negative outcome as greater than did those in the other responsible group. The results support the claimed general tendency for individuals to regard an outcome as more aversive if they are personally responsible for that outcome, rather than someone else being responsible. The results suggest that, in general, increasing perceptions of personal responsibility will increase cost or severity estimates in subjective danger calculations, and that responsibility may influence OCD phenomena in this way. Finally, the results suggest that attempts to manipulate responsibility in the laboratory may be confounded by necessarily impacting on cost estimates, and therefore on danger expectancies.

Adolescent↗

Intravenous leiomyomatosis with cardiac extension: tumor thrombectomy through an abdominal approach.

Intravenous leiomyomatosis is an uncommon vascular tumor that may be seen with potentially life-threatening symptoms resulting from intracardiac extension. This tumor is frequently misdiagnosed and treated without appropriate preoperative imaging and planning, which at times leads to inadequate treatment and incomplete resections. The appropriate therapy is complete excision of the tumor. We describe a patient who was treated with a new approach involving a single-stage operation without the need for median sternotomy, cardiopulmonary bypass graft, or hypothermic arrest by resection of the tumor from the point of attachment in the abdominal portion of the inferior vena cava.

Female↗

Metabolic flux analysis elucidates the importance of the acid-formation pathways in regulating solvent production by Clostridium acetobutylicum.

Metabolic flux analysis was used to investigate the roles of the acid formation pathways in Clostridium acetobutylicum. The acid formation pathways were revealed to serve different roles in wildtype fermentations than previously expected. Specifically, enzymes known to catalyze butyrate formation were found to uptake butyrate without concomitant production of acetone. This role was further corroborated by flux analysis of a recombinant strain overexpressing the butyrate formation enzymes. Analysis of wildtype fermentation data also revealed an important role for the acetate formation enzymes, namely the cycling of carbon between acetate and acetylCoA during the stationary phase. Next, metabolic flux analysis was used to compare the patterns of activity in two butyrate kinase deficient strains of C. acetobutylicum. The strain developed by gene inactivation, PJC4BK, exhibited a shift in acid formation fluxes toward acetate while the strain developed by antisense RNA strategies, 824(pRD4), did not exhibit such a shift. However, both strains exhibited altered solvent formation patterns. PJC4BK exhibited a strong transient enhancement of solvent formation fluxes. In contrast, 824(pRD4) exhibited relatively lower levels of solvent formation fluxes, although fluxes were sustained over a longer period of time.

Acetic Acid↗

Isolated iliac artery aneurysms in patients with or without previous abdominal aortic aneurysm repair.

BACKGROUND: Isolated iliac artery aneurysms (IAA) in patients with or without previous abdominal aortic aneurysm (AAA) repair are rare. We wanted to compare the presentation, distribution, treatment, outcome and patterns of subsequent aneurysm formation in these patients. METHODS: We retrospectively reviewed patients with isolated IAA over a 10-year period. Patients with primary isolated IAA (group 1) were compared with patients who presented with IAA after previous AAA repair (group 2). RESULTS: There were 23 patients in each group. Demographics and comorbidities were similar. No aneurysms were detected outside of the iliac system in group 1; 22% of patients in group 2 had other aneurysms. The mean time after AAA repair to IAA diagnosis was 8.8 +/- 3.2 years for operated on patients. The in-hospital mortality was 0% for elective cases and 50% for emergency cases for both groups. Three patients in group 2 (13%) developed new aneurysms during follow-up, whereas the only new aneurysm in group 1 was a contralateral IAA. CONCLUSIONS: Patients with new IAA after AAA repair have a greater tendency to develop further aneurysms in other sites, synchronously or metachronously. The time to detection of new IAA after AAA repair is at least 5 years in most cases. In both groups, a quarter to a third of patients present with rupture, with a resultant mortality of 30% to 50%, whereas those operated on electively have minimal morbidity and almost no mortality.

Aged↗

Evidence for fear of restriction and fear of suffocation as components of claustrophobia.

Recent investigations of the aetiology and treatment of specific phobias have focused on clarifying the concerns underlying phobic anxiety. It has been proposed that claustrophobic fear is comprised of separable confinement and suffocation components. This paper presents data from 78 general medical outpatients undergoing magnetic resonance imaging (MRI) scans in two major teaching hospitals. The findings support the two factor structure of claustrophobia, in that exposure to confinement reduced confinement subscale scores, but did not influence suffocation scores.

Adult↗

Mood and prospective memory.

This study considered the relationship between mood states, prospective memory, and retrospective memory among a non-clinical sample of undergraduate students. Multiple regression analyses with simultaneous entry of variables were undertaken to examine the unique contributions of the alternate memory test and the emotional states to memory test performance. As expected, retrospective free recall performance and anxiety made unique and significant contributions to performance on the prospective memory task. However, only prospective memory performance emerged as a significant predictor of retrospective free recall. It is suggested that none of the mood measures emerged as a significant predictor of retrospective memory performance because they do not account for unique variance. In contrast, the relationship between anxiety and prospective memory appears to be due to factors uniquely associated with anxiety, and unrelated to depression.

Affect↗

Molecular epidemiologic evaluation of transmissibility and virulence of Mycobacterium tuberculosis.

Discovery of genotypic markers associated with increased transmissibility in Mycobacterium tuberculosis would represent an important step in advancing mycobacterial virulence studies. M. tuberculosis strains may be classified into one of three genotypes on the basis of the presence of specific nucleotide substitutions in codon 463 of the katG gene (katG-463) and codon 95 of the gyrA gene (gyrA-95). It has previously been reported that two of these three genotypes are associated with increased IS6110-based clustering, a potential proxy of virulence. We designed a case-control analysis of U.S.-born patients with tuberculosis in San Francisco, Calif., between 1991 and 1997 to investigate associations between katG-463 and gyrA-95 genotypes and epidemiologically determined measures of strain-specific infectivity and pathogenicity and IS6110-based clustering status. We used a new class of molecular probes called molecular beacons to genotype the isolates rapidly. Infectivity was defined as the propensity of isolates to cause tuberculin skin test conversions among named contacts, and pathogenicity was defined as their propensity to cause active disease among named contacts. The molecular beacon assay was a simple and reproducible method for the detection of known single nucleotide polymorphisms in large numbers of clinical M. tuberculosis isolates. The results showed that no genotype of the katG-463- and gyrA-95-based classification system was associated with increased infectivity and pathogenicity or with increased IS6110-based clustering in San Francisco during the study period. We speculate that molecular epidemiologic studies investigating clinically relevant outcomes may contribute to the knowledge of the significance of laboratory-derived virulence factors in the propagation of tuberculosis in human communities.

AIDS-Related Opportunistic Infections↗

The convergent validity of the Phobia Origins Questionnaire (POQ): a review of the evidence.

The Phobic Origins Questionnaire (POQ) [Ost, L.-G. & Hugdahl, K. (1981). Acquisition of phobias and anxiety response patterns in clinical patients. Behaviour Research and Therapy, 19, 439-447.] is the most commonly cited instrument for determining the origins of phobic anxiety and data obtained using this instrument strongly support the role of conditioning in the acquisition of fear reactions. The construct validity of the POQ in assessing episodes of conditioning has been questioned [e.g. Menzies, R. G. & Clarke, J. C. (1994). Retrospective studies of the origins of phobias: a review. Anxiety, Stress and Coping, 7, 305-318.] This paper examined the convergent validity of the POQ by comparing origins' classifications based on the POQ to classifications based on alternative instruments. The convergent validity of the POQ was found to be extremely poor. The POQ was consistently associated with a much greater likelihood of classifying the origin of fear reactions as due to direct conditioning episodes than was found using alternative instruments. The findings question the usefulness of the POQ in examining the origins of phobic anxiety.

Conditioning, Psychological↗

Premature peripheral vascular disease: clinical profile and abnormal lipid peroxidation.

The aim of this study was to determine any biochemical differences between early-onset peripheral vascular disease and typical onset atherosclerosis, and age-matched controls. A subset of patients present at a young age ( < 50 years) with peripheral vascular disease which pursues an aggressive course. As lipid oxidation seems important in atherosclerosis, total lipid peroxides, oxidized subfractions, and Trolox equivalent antioxidant capacity (TEAC) were studied in patients with premature peripheral vascular disease. Charts were reviewed of patients operated on for vascular occlusive disease over a 5-year period. Patients with early-onset peripheral vascular disease (group I) were evaluated for biochemical abnormalities and compared with typical onset atherosclerotics (group II) and age-matched controls (group III). Sixteen patients with early-onset peripheral vascular disease underwent biochemical evaluation. Conventional lipid profiles did not differ statistically from those of age-matched controls, except for mild elevations in LDL and VLDL in patients with vascular occlusive disease (207 and 195 mg/dl in groups I and 11 versus 157 mg/dl in group III). Total oxidative potential was significantly elevated (P = 0.006) 3.04, 2.15 and 2.04 nmol/ml in groups I, II and III, respectively. Levels of oxidized LDL and VLDL were even more significantly elevated (P = 0.0009) for premature peripheral vascular disease, (1.2, 0.58 and 0.47 nmol/ml in groups I-II). TEAC values did not differ significantly between groups (0.83, 0.82, 0.82 nmol/ml) and did not correlate with total lipid peroxide values for individual patients. In conclusion, lipid peroxides were significantly elevated in patients with premature peripheral vascular disease, the most marked changes being seen in oxidized LDL and VLDL subfractions. Lipid peroxides were elevated when standard lipid profiles were only mildly abnormal. The poor long-term prognosis in these patients suggests the need for aggressive evaluation and treatment of lipid abnormalities.

Adult↗

Screening for asymptomatic deep vein thrombosis in surgical intensive care patients.

PURPOSE: To identify the presence of occult deep vein thrombosis (DVT) in surgical intensive care unit (SICU) patients and to avoid unnecessary screening, we reviewed our experience with routine duplex screening for DVT in SICU patients. METHODS: Over a 24-month period, all patients who were admitted to an SICU with an anticipated length of stay greater than 36 hours were studied to determine the prevalence of risk factors for asymptomatic proximal DVT. Risk factors, demographics, and operative data were collected and analyzed with multilinear regression, t tests and chi 2 analysis. RESULTS: There was a 7.5% prevalence of major DVT in the 294 patients studied. APACHE II scores (14.5 +/- 6.24 vs 10.3 +/- 3.15; p < 0.0001) and emergent procedures (45.5% vs 23.2%; p > 0.0344) were associated with DVT by multifactorial analysis. Age was significant by univariate analysis. An algorithm based on the presence of any one of the three risk factors identified (APACHE II score 12 or more; emergent procedures; or age 65 or greater) could be used to limit screening by 30% while achieving a 95.5% sensitivity for identification of proximal DVT. CONCLUSION: Absence of all three risk factors indicates a very low risk for DVT (1.1%). Screening of SICU patients is indicated because of a high prevalence of asymptomatic disease. Patients who have proximal DVT require active therapy and not prophylaxis. Costs and resources may be contained by using the above risk factors as a filter for duplex screening.

APACHE↗

Small bowel obstruction secondary to enterolith impaction complicating jejunal diverticulitis.

A case of small bowel obstruction secondary to enterolith impaction in the presence of jejunal diverticular disease is described. Only 27 cases of small bowel obstruction by enterolith expelled from small bowel diverticula have been reported in the literature. The reported incidence of jejunal diverticulosis in the general population ranges from 0.02 to 7.1%. Most patients are asymptomatic, but 10% develop complications requiring surgical intervention. Surgical treatment is an enterotomy and stone extraction or manually crushing and milking the stone distally into the colon. Small bowel resection and anastomosis or laparoscopic-assisted small bowel resection are indicated for the treatment of diverticulitis, bowel perforation, or multiple diverticuli. Jejunal diverticular disease should be considered in the differential diagnosis of mechanical small bowel obstruction without an obvious cause, especially in the elderly population.

Age Factors↗

Health science graduates: preparation for the workplace.

The research reported in this article was undertaken to assess the perceptions of health science graduates in the fields of health information management, occupational therapy, orthoptics, physiotherapy, and speech pathology regarding their perceptions of the adequacy of undergraduate preparation in meeting the demands of a changing health care environment. An instrument was devised for use by graduates on the basis of the skills and workplace behaviours specified by experienced practitioners in the above fields as necessary in newly recruited graduates. A total of 527 health science graduates completed the 52 item instrument. The statistical analyses indicated that 11 factors define the adequacy of graduates' preparation for the workplace. Health science graduates perceived themselves to have been more thoroughly prepared on certain workplace dimensions than on others. Specifically, graduates perceived themselves to be ill-equipped on dimensions concerned with workplace management, knowledge of the health industry, and coping in the workplace. Graduates also perceived themselves to be inadequately prepared in terms of communicating with clients, health professionals, and the general public. The strengths of their courses were perceived to be in completing essential tasks, having confidence in the clinical role, in ethical practice, in pursuit and application of knowledge, and having a realistic expectation of the workplace role. The results are discussed in terms of the need to address curriculum changes.

Adult↗