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Biomedical subjects

R A Clark

Publications and source records attributed to R A Clark.

At least 181 records · Page 10Linked to original sources

Basics of cutaneous wound repair.

BACKGROUND: Cutaneous wound repair consists of multiple integrated networks of cell-matrix-cytokine interactions. It is generally believed that a better understanding of these networks will lead to improved care of cutaneous wounds, whether freshly made by the surgeon's scalpel or previously existing and not healing secondary to underlying abnormalities. OBJECTIVE: This review is intended to update the readership in some of the salient aspects of wound repair networks. METHODS: To facilitate the review of multiple integrated networks, cutaneous wound repair was arbitrarily divided into three phases: inflammation, tissue regeneration including re-epithelialization and granulation tissue formation, and tissue reorganization. RESULTS: Throughout the entire process of wound repair it is clear that cells produce or alter various cytokines and extracellular matrix. The cytokines and matrix in turn alter the behavior of the producer cells (autocrine response) or neighbor cells (paracrine response). CONCLUSION: The dynamic reciprocity among cells, cytokines, and matrix material helps explain how integrated wound healing networks are sequential as well as tightly controlled.

Animals↗

Bronchodilator reversibility to low and high doses of terbutaline and ipratropium bromide in patients with chronic obstructive pulmonary disease.

BACKGROUND: There is uncertainty regarding the use of monotherapy or combination therapy with beta 2 agonists and anticholinergic drugs in patients with chronic obstructive pulmonary disease (COPD). The measurement of forced expiratory volume in one second (FEV1) or relaxed vital capacity (RVC) in the assessment of reversibility in these patients has also caused considerable debate. METHODS: Twenty seven patients with COPD were evaluated on two occasions. Patients received the following treatments in sequence: (sequence 1) low dose terbutaline 500 micrograms, high dose terbutaline 5000 micrograms, low dose ipratropium 40 micrograms, high dose ipratropium 200 micrograms; (sequence 2) low dose ipratropium 40 micrograms, high dose ipratropium 200 micrograms, low dose terbutaline 500 micrograms, high dose terbutaline 5000 micrograms. RVC, FEV1 and FVC were measured at baseline and 30 minutes after successive treatments. RESULTS: Values for FEV1 at baseline on the first and second study days were not significantly different: 0.90 (0.87-0.93) 1 v 0.90 (0.87-0.93) 1. Likewise, baseline values for RVC and FVC were not different. The number of patients showing a greater than 330 ml overall improvement in RVC was 20 of 27 for sequence 1 and 22 of 27 for sequence 2; similar trends were observed for FEV1 and FVC. For all three parameters there was a significant difference between mean responses to low and high doses of terbutaline when the latter was given as the first drug in sequence 1. When ipratropium was given first in sequence 2 there was, however, no significant improvement with high dose terbutaline over and above the response to low dose terbutaline. The latter effect was more noticeable with RVC than with either FEV1 or FVC. The total bronchodilator response at the end of each sequence was similar whether ipratropium was given first or second. CONCLUSIONS: The measurement of RVC, FEV1, and FVC were equally effective at picking up those patients who had a significant overall bronchodilator response to combined therapy with inhaled beta 2 agonist and anticholinergic medication. There was no significant benefit of adding a higher dose of terbutaline when ipratropium bromide had been given previously, particularly when using RVC as the parameter of response.

Administration, Inhalation↗

Oxidants from neutrophil myeloperoxidase do not enhance elastase-induced emphysema in the hamster.

Alpha-1-protease inhibitor is susceptible to oxidative impairment by the neutrophil myeloperoxidase (MPO) system. The purpose of this study was to assess the effect of the MPO oxidant system on elastase-induced emphysema in the hamster. Intratracheal instillation of 200 micrograms of human neutrophil elastase (HNE) induced a significant secretory cell metaplasia (SCM) and airspace enlargement [23% increase in mean linear intercept (MLI) as compared with control values]. Instillation of MPO system components [0.6 international units (U) of MPO, 5.5 U of glucose oxidase and glucose (0.02 M)] along with 200 micrograms HNE failed to enhance the severity of the SCM or emphysema induced by HNE alone. A second experiment was carried out using 50 micrograms of porcine pancreatic elastase (PPE) to induce emphysema. PPE produced a significant 45% increase in MLI, but the MPO system combined with PPE failed to enhance the emphysema induced by PPE alone. The MPO system alone had no measurable effect on airspace size or SCM. In vitro studies showed that PPE was partially inactivated by the MPO system; a 56% loss of elastolytic activity occurred during a 6-min incubation of PPE with the MPO system. This may explain why the MPO system did not exacerbate PPE-induced injury, but it does not explain the lack of enhancement for HNE. A 6-minute incubation of HNE with the MPO system resulted in a nonsignificant 10% decrease of elastolytic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

An audit of hospital discharge letters in patients admitted with acute asthma. Tayside Asthma Audit Group.

The management of patients following discharge with acute asthma is dependent on effective communication with general practitioners. A retrospective audit was therefore performed on copies kept of 81 typed discharge letters with a diagnosis of acute asthma between March and October 1991. A subset of 42 interim (handwritten) letters were also audited where case notes could be retrieved. Details on clinic follow up were also obtained from the case notes (n = 42). In the typed letter documentation of severity and treatment of the acute attack was accurate in most cases. Information concerning a precipitating factor was provided in 54% of cases and a smoking history in 57%. Deficiencies were found in specifying inhaler delivery devices (40% recorded), and whether inhaler technique had been formally assessed whilst in hospital (17%). Drug prescribing on discharge was as follows: oral steroid (69%), inhaled steroids (77%), inhaled B2-agonists (92%), theophylline slow release (38%), salbutamol controlled release (20%), and antibiotics (30%). The implementation of a self-management plan and domiciliary peak flow was mentioned in 66% of the letters. The interim letter was generally poor in particular for mention if discharge peak flow (2%), clinic follow-up (64%) and prednisolone regime (61%). Mean +/- s.d. time for clinic follow-up (n = 42) was 4.7 +/- 1.7 weeks (range 1-13 weeks) with 24% non-attendance. Thus, improvements in discharge letters are clearly required for optimum continuity of care in the community.

Acute Disease↗

Biology of dermal wound repair.

Dermal wound repair events can be temporally, albeit arbitrarily, grouped into inflammation, granulation tissue formation, and tissue remodeling. These phases are not mutually exclusive but rather overlap in time. This review follows the chronology of dermal wound repair, that is, inflammation, granulation tissue formation, and tissue remodeling.

Biology↗

Integrins.

Explore the source record for details and available documents.

Cytokines↗

New agents for controlling emesis with cancer chemotherapy.

Over the past decade, marked progress in support techniques has been made in patients with cancer. In addition to improvement in pain and infection control, the ability to control chemotherapy-induced nausea and vomiting has improved greatly. Studies have demonstrated that serotonin type 3 receptors play an important role in mediating this side-effect. Several new agents, with excellent efficacy and few side effects have now been developed and are available clinically. Results of trials with these agents, and with newer investigative approaches are discussed.

Antineoplastic Agents↗

Reductive detoxification as a mechanism of fungal resistance to singlet oxygen-generating photosensitizers.

Fungi that are resistant or sensitive to the singlet oxygen-generating toxin cercosporin were assayed for their ability to detoxify it by reduction. Cercosporin reduction was assayed microscopically by using bandpass filters to differentiate between fluorescence emission from cercosporin and reduced cercosporin. Hyphae of the resistant Cercospora and Alternaria species emitted a green fluorescence, indicative of reduced cercosporin. Hyphae of nonviable cultures and of cercosporin-sensitive fungi did not reduce cercosporin. Sensitive fungi occasionally reduced cercosporin when incubated with reducing agents that protect against cercosporin toxicity. Cercosporin could not be efficiently photoreduced in the absence of the fungus. Cercospora species were also resistant to eosin Y but were sensitive to rose bengal. Microscopic observation demonstrated that Cercospora species were not capable of reducing rose bengal but were capable of reducing eosin Y. These observations were supported by in vitro electrochemical measurements that revealed the following order with respect to ease of reduction: cercosporin >> eosin Y > rose bengal. The formal redox potential (E 0') of cercosporin at pH 7.5 was found to be -0.14 V vs. the normal hydrogen electrode. We conclude that Cercospora species protect themselves against cercosporin by the reduction and detoxification of the toxin molecule.

Aspergillus flavus↗

Oral ondansetron for the control of delayed emesis after cisplatin. Report of a phase II study and a review of completed trials to manage delayed emesis.

BACKGROUND: Despite excellent control of vomiting during the initial 24 hours after chemotherapy with combination antiemetics, most patients who receive cisplatin at doses of 120 mg/m2 experience delayed emesis 24-120 hours after chemotherapy. METHODS: Twenty patients receiving cisplatin (greater than or equal to 100 mg/m2) as initial chemotherapy were entered into this Phase II trial to test the effectiveness of oral ondansetron, a specific serotonin receptor (5-HT3) antagonist, in controlling delayed emesis. All patients received intravenous metoclopramide, dexamethasone, and lorazepam for the control of acute emesis 0-24 hours after receiving cisplatin. They then received ondansetron 16 mg orally three times a day for 4 days. RESULTS: Fifteen percent of those who were treated with oral ondansetron had complete control of delayed emesis during the entire 4-day period (95% confidence interval, 3-38%). No serious adverse events occurred. CONCLUSIONS: At the dose and schedule tested, oral ondansetron did not appear to control delayed emesis. Previous trials of programs to lessen this complication suggest that both metoclopramide and dexamethasone are effective in lessening delayed vomiting and that the combination of these drugs is more effective than placebo. Although in one trial ondansetron appeared to control delayed emesis in patients who received cisplatin at doses of 50-120 mg/m2, it was not superior to either placebo or metoclopramide in two randomized studies. Additional testing of the 5-HT3 antagonists, both alone and in combination, will be needed to establish their role in the management of this condition.

Administration, Oral↗

Mammography screening credit card and compliance.

BACKGROUND: Screening for breast cancer using mammography has been shown to be effective in reducing mortality from breast cancer. The authors attempted to determine if use of a wallet-size plastic screening "credit" card would increase participants' compliance for subsequent mammograms when compared with traditional methods of increasing compliance. METHODS: Two hundred and twenty consecutive women, ages 40-70 years, undergoing their first screening mammography were recruited and assigned randomly to four groups receiving (1) a reminder plastic credit card (2) reminder credit card with written reminder; (3) appointment card; and (4) verbal recommendation. Return rates of the four groups were determined after 15 months. RESULTS: The return rate for subsequent mammograms was significantly higher for participants (72.4%) using the credit card than for participants (39.8%) exposed to traditional encouragement/reminders (P less than 0.0001). CONCLUSIONS: The credit card was designed to show the participant's screening anniversary, and the durability of the card may have been a factor in increasing the return rate. The use of reminder credit cards may increase compliance for periodic screening examinations for other cancers and other chronic diseases.

Adult↗

Lymphoscintigraphy in malignant melanoma.

The development and rationale for the use of lymphoscintigraphy in the preoperative evaluation of patients with malignant melanoma being considered for elective lymph node dissection is reviewed. This overview is updated by an analysis of 135 patients with early stage malignant melanoma involving the head, neck, shoulders, and trunk at Moffitt Cancer Center and Research Institute at the University of South Florida (Tampa, FL). High discordancy rates (overall, 41%) were seen between drainage patterns predicted from historical anatomical guidelines and those revealed by the lymphoscintigraphic examination. The high discordancy rate was most pronounced in the head (64%) and the neck (73%). Surgical management was changed in 33% of the patients, overall. A preoperative lymphoscintigram is recommended for all patients with melanoma with head, neck, and truncal lesions evaluated for elective lymph node dissection as the lymphatic drainage patterns are often unpredictable and variable.

Decision Making↗

Rapid and sensitive assay for fluconazole which uses gas chromatography with electron capture detection.

Fluconazole, an orally active antifungal agent, has been shown to be clinically beneficial for maintenance therapy of cryptococcal meningitis. A sensitive gas-liquid chromatographic assay with electron capture detection, which required only a single extraction step and precluded any pretreatment of the chromatographic column, was developed for fluconazole. The assay was linear from 0.1 to 20 micrograms/ml, with a correlation coefficient of 0.999. The intraassay and interassay coefficients of variation were less than 9%. The measured values on average were within 8% of the target values. The extraction recoveries ranged from 87 to 106%. Steady-state plasma fluconazole levels (mean +/- standard deviation) in three AIDS patients with cryptococcal meningitis receiving 200 mg of fluconazole per day ranged from 8.95 +/- 1.32 to 11.41 +/- 0.63 micrograms/ml and were within the expected range for this dosing rate, on the basis of previous studies. The ratio of fluconazole concentration in cerebrospinal fluid to fluconazole concentration in plasma in one patient receiving 400 mg/day was 0.73 at steady state and was consistent with published reports.

Chromatography, Gas↗

Economic issues in screening mammography.

The issues surrounding screening mammography present apparent conflicts: conflicting guidelines for screening; an oversupply of facilities, yet inadequate access to mammography for some groups of women; increased medicolegal vulnerability as participation in screening is promoted; disparate results from studies of cost-effectiveness; wide variations in delivery modes and practice patterns of facilities, yet an evolution toward a single set price for mammography by payers for screening. This review does not claim to offer solutions to these conflicts, rather it attempts to carry forward a discussion of the issues. With these conflicts, screening mammography may be only a microcosm of similar economic issues in general health care delivery. Our health care system has room for variety, if access and quality are improved at an affordable cost. Screening for breast cancer with mammography will not reach its full potential to reduce mortality until many of these issues can be resolved.

Cost-Benefit Analysis↗

Diagnosis and treatment of asthma in children: usefulness of a review of medical records.

In order to tackle the problems of underdiagnosis and undertreatment of asthma in childhood general practitioners need to be aware of which children in their practices have or might have asthma. In an effort to identify a cohort of asthmatic or potentially asthmatic children a trained audit facilitator studied all the medical records of children aged between one year and 15 years who were registered with 12 Tayside general practices. From a total of 10,685 medical records the frequency of 'key items' sometimes associated with asthma were as follows: one or more episodes of bronchospasm or wheeze 23.7% of children, persistent cough 23.2%, treatment with anti-asthma therapy in the past 20.0%, exercise induced cough or wheeze 5.2% and history of 'wheezy bronchitis' 4.6%. However, in only 896 children (8.4%) had a formal diagnosis of asthma been made. Of all the children, 5.4% had received a prescription for anti-asthma medication within the past three months. Only 1.2% were taking an inhaled corticosteroid and 1.0% sodium cromoglycate, but many more were taking inhaled bronchodilators (3.1%) and oral bronchodilators (1.7%). The findings suggest that a systematic review of medical records by a trained facilitator can identify those children who could benefit from clinical review. Practices who wish to know which of their children have or might have asthma should consider using medical record review to search for key items associated with asthma.

Adolescent↗