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Biomedical subjects

L Foster

Publications and source records attributed to L Foster.

At least 19 recordsLinked to original sources

Botulinum toxin A and chronic low back pain: a randomized, double-blind study.

OBJECTIVES: To investigate the efficacy of botulinum toxin A in chronic low back pain and associated disabilities. METHODS: Thirty-one consecutive patients with chronic low back pain who met the inclusion criteria were studied: 15 received 200 units of botulinum toxin type A, 40 units/site at five lumbar paravertebral levels on the side of maximum discomfort, and 16 received normal saline. Each patient's baseline level of pain and degree of disability was documented using the visual analogue scale (VAS) and the Oswestry Low Back Pain Questionnaire (OLBPQ). The authors reevaluated the patients at 3 and 8 weeks (visual analogue scale) and at 8 weeks (OLBPQ). RESULTS: At 3 weeks, 11 of 15 patients who received botulinum toxin (73.3%) had >50% pain relief vs four of 16 (25%) in the saline group (p = 0.012). At 8 weeks, nine of 15 (60%) in the botulinum toxin group and two of 16 (12.5%) in the saline group had relief (p = 0.009). Repeat OLBPQ at 8 weeks showed improvement in 10 of 15 (66.7%) in the botulinum toxin group vs three of 16 (18.8%) in the saline group (p = 0.011). No patient experienced side effects. CONCLUSION: Paravertebral administration of botulinum toxin A in patients with chronic low back pain relieved pain and improved function at 3 and 8 weeks after treatment.

Adult↗

The bifunctional Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2) protein is necessary for amebic growth and survival and requires an intact C-terminal domain for both alcohol dahydrogenase and acetaldehyde dehydrogenase activity.

The intestinal protozoan pathogen Entamoeba histolytica lacks mitochondria and derives energy from the fermentation of glucose to ethanol with pyruvate, acetyl enzyme Co-A, and acetaldehyde as intermediates. A key enzyme in this pathway may be the 97-kDa bifunctional E. histolytica alcohol dehydrogenase 2 (EhADH2), which possesses both alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase activity (ALDH). EhADH2 appears to be a fusion protein, with separate N-terminal ALDH and C-terminal ADH domains. Here, we demonstrate that EhADH2 expression is required for E. histolytica growth and survival. We find that a mutant EhADH2 enzyme containing the C-terminal 453 amino acids of EhADH2 has ADH activity but lacks ALDH activity. However, a mutant consisting of the N-terminal half of EhADH2 possessed no ADH or ALDH activity. Alteration of a single histidine to arginine in the putative active site of the ADH domain eliminates both ADH and ALDH activity, and this mutant EhADH2 can serve as a dominant negative, eliminating both ADH and ALDH activity when co-expressed with wild-type EhADH2 in Escherichia coli. These data indicate that EhADH2 enzyme is required for E. histolytica growth and survival and that the C-terminal ADH domain of the enzyme functions as a separate entity. However, ALDH activity requires residues in both the N- and C-terminal halves of the molecule.

Alcohol Dehydrogenase↗

Human resources. Getting even.

A trust where a third of the workforce is a member of ethnic minority groups has set up a programme to enhance career advancement for this group. The programme aims to celebrate the achievements of ethnic minority staff and give them greater visibility within the organisation. Mentoring programmes and learning sets have been established with the support of senior.

Career Mobility↗

Helicobacter pylori-selective antibacterials based on inhibition of pyrimidine biosynthesis.

We report the discovery of a class of pyrazole-based compounds that are potent inhibitors of the dihydroorotate dehydrogenase of Helicobacter pylori but that do not inhibit the cognate enzymes from Gram-positive bacteria or humans. In culture these compounds inhibit the growth of H. pylori selectively, showing no effect on other Gram-negative or Gram-positive bacteria or human cell lines. These compounds represent the first examples of H. pylori-specific antibacterial agents. Cellular activity within this structural class appears to be due to dihydroorotate dehydrogenase inhibition. Minor structural changes that abrogate in vitro inhibition of the enzyme likewise eliminate cellular activity. Furthermore, the minimum inhibitory concentrations of these compounds increase upon addition of orotate to the culture medium in a concentration-dependent manner, consistent with dihydroorotate dehydrogenase inhibition as the mechanism of cellular inhibition. The data presented here suggest that targeted inhibition of de novo pyrimidine biosynthesis may be a valuable mechanism for the development of antimicrobial agents selective for H. pylori.

Amino Acid Sequence↗

The impact of different response alternatives on responders' reporting of health-related behaviour in a postal survey.

Previous experimental research in other topic areas has shown that the choice of response alternatives can influence respondents' reporting of the frequency of vaguely defined events and that the set of response alternatives is treated as information in the interpretation of the question. The aim of this study was to examine whether such affects would occur in the context of respondents reporting of health-related events using high and medium frequency closed format response categories, which might be used interchangeably by researchers. The study consisted of a postal survey of n = 518 patients aged > or = 18 years randomly selected from the patient list of a diabetes centre and who were equally and randomly allocated to one of three conditions (Condition A: high frequency response alternatives/horizontal orientation; condition B: medium frequency response alternatives/horizontal orientations; condition C: high frequency response alternatives/vertical orientation). Testing for the effect of response alternatives for the combined responses of five vaguely defined questions between conditions A and B was chi 2 = 5.5, p = 0.019, for the difference in proportions, indicating that overall, those respondents presented with response alternatives discriminating at medium frequency, reported significantly fewer target events than those presented with high frequency response alternatives. Testing for the effect of orientation of the combined question responses between conditions A and C, differences in proportions between conditions, did not reach statistical significance (p > 0.05). Findings from this and previous studies indicate that response alternatives provide information on the interpretation of vaguely defined questionnaire items and that their choice should not be left to intuition alone when designing questionnaire items.

Adult↗

A comparison of hydrofibre and alginate dressings on open acute surgical wounds.

This study aimed to compare the performance of a hydrofibre (Aquacel) and an alginate (Sorbsan) dressing on acute surgical wounds left to heal by secondary intention. A total of 100 patients were prospectively randomised pre-operatively to receive either the hydrofibre or the alginate dressing. Dressing performance was measured at operation, at 24 hours and seven days. Parameters measured included ease of: application and removal of the first dressing; re-application on the first postoperative day; and removal and re-application one week postoperatively. The hydrofibre dressing received higher scores for all of these categories. Patients in this group also experienced less pain (mild or none) on removal of the first dressing and at one week. However, these results did not achieve statistical significance, and should be seen as a trend. Nevertheless, the authors recommend the use of hydrofibre dressings on open acute surgical wounds.

Acute Disease↗

Isolation and species typing of Lyme borreliosis spirochaetes from UK patients with erythema migrans.

Skin biopsies taken from UK cases of erythema migrans rash were cultured for Borrelia burgdorferi sensu lato. Reverse line blotting was used to type the infecting genospecies in PCR-positive cultures and biopsies. B. garinii or B. afzelii was identified in 56% (5/9) of biopsies/cultures tested. All patients were tested by conventional serology. PCR confirmed infection in two patients where serological testing failed to detect antibody.

Bacterial Typing Techniques↗

Self-reported body-rocking and other habits in college students.

A brief survey of eight motor habits, including body-rocking, was administered to two large samples of college undergraduates. A subsample was retested to establish survey reliability and validity. Those indicating engagement in body-rocking were interviewed about their body-rocking. Two psychopathology instruments were administered. The general prevalence of self-described body-rocking was higher than expected, and there were positive correlations among the eight habits. Body-rocking was usually related to negative affect and usually reported to begin during the school years and later. Many individuals said other family members engaged in body-rocking. Psychopathology assessments indicated higher levels of general distress and higher prevalence of Generalized Anxiety Disorder in this subsample compared with a group not reporting body-rocking.

Anxiety Disorders↗

Two neuronal cell lines expressing the myelin basic protein gene display differences in their in vitro survival and in their response to glia.

We have generated two conditionally immortalized neuronal cell lines from primary cultures of embryonic day 13 (E13) and postmitotic (postnatal day 0; P0) cortical neurons transformed with the temperature-sensitive SV-40 large-T antigen. Two clonal cell lines (CN1.4 from E13 cultures and SJ3.6 from P0 cultures) were isolated and stable maintained in vitro. Both cell lines expressed a number of neuronal markers such as the neurofilaments, glutamic acid decarboxylase 67, neuron-specific enolase, and the BG21 isoform of the myelin basic protein gene. At 34 degrees C, the CN1.4 cell line had elaborated short processes, whereas the SJ3.6 cell line produced long processes that formed a delicate network. When these cell lines were cultured at 39 degrees C, some of the cellular processes grew longer, adopting a more mature neuronal morphology. Interestingly, at 39 degrees C, the in vitro survival of these cell lines differed significantly. Whereas the survival of CN1.4 cell line was greatly unaffected, SJ3.6 cells died soon after they were cultured at 39 degrees C. The cell death of SJ3.6 cells was accompanied by fragmentation and condensation of DNA in their nuclei, indicative of an apoptotic event. Under these conditions, SJ3.6 showed an upregulation of the p75 receptor. When this cell line was cocultured with oligodendrocytes, astrocytes, or glial conditioned media (GCM), there was a marked increase in survival. In contrast, little effect of glial cells or GCM was observed on the CN1.4 cell line. These lines appear to be useful models to study neuronal-glial interactions in addition to neuronal cell death and the effects of glial factors that promote the survival of neurons.

Animals↗

Assessing outcomes, costs, and benefits of emerging technology for minimally invasive saphenous vein in situ distal arterial bypasses.

BACKGROUND: Instrumentation for a minimally invasive angioscopic in situ peripheral arterial bypass (MIAB) with catheter-directed side-branch occlusion has recently been approved for use. Despite the attractiveness of this approach (2 short incisions), benefits such as lower morbidity and shorter hospitalizations remain undocumented. To justify wide acceptance, minimally invasive surgical techniques must match conventional procedures in durability and cost while enhancing patient comfort. Often such comparisons are difficult during the implementation phase of a new procedure. OBJECTIVE: To compare the outcomes of the MIAB procedures with a concurrent group of patients undergoing conventional in situ bypass procedures. DESIGN: Retrospective review. SETTING: University medical center. PATIENT: The first 20 consecutive MIAB procedures in 19 patients performed between August 1, 1995, and July 31, 1997, were compared with 19 contemporaneous consecutive conventional in situ bypass procedures performed at the same institution. MAIN OUTCOME MEASURES: Operative time, postoperative length of stay, hospital costs, complications, primary assisted and secondary patency, limb salvage, and survival. RESULTS: The patient groups were comparable with respect to age, sex, incidence of smoking, coronary artery disease, hypertension, diabetes, renal failure, cerebrovascular disease, indication, and distal anastomosis level. The median operative time was significantly greater for the MIAB group (6.6 hours vs 5.7 hours; P=.009), and intraoperative completion arteriography more frequently showed retained arteriovenous fistulas in the MIAB group (55% vs 21%; P=.05). The median postoperative length of stay and total cost were 6.5 days and $18,000 for the MIAB group and 8 days and $27,800 for the conventional group (P > or = .05). There were no significant differences in major complications (10% in the MIAB group vs 11% in the conventional group), wound complications (10% vs 11%, respectively), primary assisted patency at 1 year (68%+/-11% vs 78%+/-10%, respectively), secondary patency at 1 year (79%+/-10% vs 88%+/-8%, respectively), limb salvage at 1 year (85%+/-10% vs 94%+/-6%, respectively), or patient survival at 1 year (89%+/-8% vs 61%+/-13%, respectively). CONCLUSION: Patients undergoing the MIAB procedure avoided lengthy vein exposure incisions without sacrificing short-term results. There was a trend toward decreased hospital stay and cost, which may be further realized as the clinical experience broadens. Although longer follow-up and larger cohorts will always be required to define durability, immediate access to outcomes and costs on small numbers of patients facilitates the early assessment of emerging technology.

Adult↗

Community parenteral therapy project: a pilot study.

The pilot study reported in this paper was devised to develop and compare service delivery models that would achieve the provision of high quality parenteral therapy care to patients in the Gold Coast District Health Service community. All data were collected on 113 patients for a 12-month period, January to December 1996. The study compared the provision of outreach nursing services and contracted nursing services on measures of satisfaction and cost. The study showed that patient and carers indicated a preference for community care, medical officers advocated the benefits of administering parenteral therapies in the community, general practitioners were interested in managing future community parenteral therapies, and contracted (nurse) service providers endorsed the development of a parenteral therapy resource centre. The findings also revealed considerable potential cost savings in community-based care.

Adult↗

Longitudinal study of the antibody response to recombinant Entamoeba histolytica antigens in patients with amebic liver abscess.

Serology is a critical component in the diagnosis of amebic liver abscess. However, in areas endemic for amebiasis there is a high background level of seropositivity for amebiasis (owing to previous infection with Entamoeba histolytica), which may complicate the interpretation of a positive serologic test result. Recently, we reported that serologic tests based on recombinant E. histolytica antigens might offer improved diagnosis of current invasive amebiasis because they apparently differentiated active infection from past exposure to the parasite. To confirm this finding, we have performed a longitudinal study on 20 patients with amebic liver abscess by examining their seroreactivity over time with recombinant versions of two major E. histolytica proteins, the serine rich E. histolytica protein (SREHP), and the 170-kD subunit of the galactose-specific adhesin. We found that more than 50% of the patients examined had become seronegative by one or both recombinant tests within 180 days of their diagnosis of amebic liver abscess. In the case of the recombinant SREHP-based tests, 12 patients had become seronegative 90 days after presentation. In contrast, all patients remained seropositive by a standard conventional test, an indirect hemagglutination test, at more than six months after presentation. Our study shows that patients lose seroreactivity with the recombinant SREHP or 170-kD antigen-based tests more rapidly than with a conventional serologic test; this may make them useful for the serologic diagnosis of amebiasis in endemic areas.

Animals↗

Induction of heme oxygenase-1 expression in vascular smooth muscle cells. A link to endotoxic shock.

Endotoxic shock is a life-threatening consequence of severe Gram-negative infection characterized by vascular smooth muscle cell relaxation and severe hypotension. The production of nitric oxide (NO), through the inducible NO synthase pathway, has been implicated as a major contributor in this process. We now demonstrate that heme oxygenase (HO), an enzyme that generates carbon monoxide (CO) in the course of heme metabolism, may also be involved in the hemodynamic compromise of endotoxic shock. Inducible HO (HO-1) mRNA levels are dramatically increased in aortic tissue from rats receiving endotoxin, and this increase in vascular HO-1 message is associated with an 8.9-fold increase in HO enzyme activity in vivo. Immunocytochemical staining localizes an increase in HO-1 protein within smooth muscle cells of both large (aorta) and small (arterioles) blood vessels. Furthermore, zinc protoporphyrin IX, an inhibitor of HO activity, abrogates endotoxin-induced hypotension in rats. Studies performed in rat vascular smooth muscle cells in vitro show that the induction of HO-1 mRNA is regulated at the level of gene transcription, and this induction is independent of NO production. Taken together, these studies suggest that the up-regulation of HO-1, and the subsequent production of CO, contributes to the reduction in vascular tone during endotoxic shock.

Animals↗

The application of a cellulose-based fibre dressing in surgical wounds.

In this randomised prospective parallel-group controlled study, a modern cellulose-based fibre dressing was compared with a traditional ribbon gauze and proflavine dressing, used intra- and post-operatively. The study evaluates each treatment for the reduction in pain, improvement in the quality of treatment and patient satisfaction. Forty patients, with wounds left to heal by secondary intention, were studied. The results show several significant advantages for the cellulose-based fibre dressing. Pain levels on removal at the first dressing change were significantly reduced in the cellulose-based fibre dressing group (p = 0.002); the ribbon gauze patients routinely required analgesia before removal of the first dressing. At one week, a significantly greater number of patients in the cellulose-based fibre dressing group stated that they would be happy to have their first dressing change carried out at home without analgesia compared to the ribbon gauze group. This would enable patients to be discharged earlier and could represent a considerable financial saving to the hospital.

Adolescent↗