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Biomedical subjects

D Cook

Publications and source records attributed to D Cook.

At least 73 records · Page 4Linked to original sources
PubMed1998

The mechanism by which aminoglycoside antibiotics cause vasodilation of canine cerebral arteries.

The effects of aminoglycoside antibiotics were examined in canine cerebral arteries and in cultured cerebrovascular smooth muscle cells stimulated with oxyhemoglobin (OxyHb), a blood constituent which has been implicated in the pathogenesis of cerebrovascular spasm. In cerebral arterial rings precontracted with OxyHb (10 microM), the aminoglycosides caused a concentration-dependent decrease in isometric tension. The EC50s for the relaxation were 0.46+/-0.1 mM (n=6), 0.53+/-0.08 mM (n=12), 1.6+/-0.3 mM (n=7) and 3.9+/-0.5 mM (n=5) for neomycin, gentamicin, streptomycin and kanamycin, respectively. This order of potency corresponds approximately to the number of positive charges in the molecules. The aminoglycosides also inhibited the contractions to prostaglandin F2alpha (1 microM) and depolarizing concentrations of potassium chloride (60 mM). The order of potency was neomycin > gentamicin > streptomycin > kanamycin. The relaxation was maintained in vascular preparations denuded of endothelium. Neomycin (5 mM) abolished the Ca2+-independent contraction to PGF2alpha. In Fura-2-loaded cerebrovascular smooth muscle cells, OxyHb (1 microM) significantly enhanced the concentration of intracellular calcium ([Ca2+]i) by 330%. The administration of neomycin, gentamicin, kanamycin and streptomycin in concentrations corresponding to the EC50 from contractility studies, reduced the effects of OxyHb on [Ca2+]i by about 50% to 221+/-35 nM (n=7), 270+/-31 nM (n=7), 229+/-33 nM (n = 6) and 240+/-6 nM (n = 5), respectively. These results suggests that the effects of the aminoglycosides on the OxyHb-induced contraction and the long-term increase in [Ca2+]i, may arise from several effects, including inhibition of PLC, protection of calcium extrusion mechanisms, and interference with the process of [Ca2+]i accumulation.

Animals↗
PubMed1998

Screening for atrial fibrillation in primary care.

OBJECTIVE: To investigate a population of elderly people for atrial fibrillation and to determine how many of the cases identified might benefit from treatment with anticoagulants. METHODS: From a practice of four primary care physicians, 1422 patients aged 65 years and over were identified, of whom 1207 (85% of the total population) underwent electrocardiographic screening to detect the presence of atrial fibrillation. Patients with the arrhythmia were further evaluated by echocardiography and interview, to stratify their risk of stroke based on echocardiographic and clinical risk factors, their perceived risk from anticoagulation, and their attitude towards this treatment. Their primary care physician was also interviewed to determine the factors influencing the prescription of anticoagulants. RESULTS: The arrhythmia occurred in 65 patients (5.4% overall), its prevalence increasing markedly with age (2.3% in 65 to 69 years age group; 8.1% in those over 85). Warfarin was being prescribed to 21.4% of these patients, although the findings of the study indicate that a further 20% were eligible for this treatment. Symptoms suggestive of cardiac failure were common (32.1%) and coexisting pathology was often identified by cardiac ultrasound in these patients (left ventricular hypertrophy, 32.1%; impaired left ventricular contractility, 21.4%; left atrial dilation, 80.4%; mitral annular calcification, 42.9%; mitral stenosis, 7.1%; mitral regurgitation, 48.2%; aortic stenosis, 8.9%). In all but one case, the decision to anticoagulate was based on the clinical rather than the echocardiographic findings. CONCLUSIONS: Individual risk-benefit assessment in elderly patients with atrial fibrillation suggests that almost half (41.4%) are eligible for full anticoagulation with warfarin, whereas presently only one fifth are receiving this treatment. The decision to anticoagulate can be made on clinical grounds in most cases. If these results are confirmed, a doubling of the current number of patients taking anticoagulants can be anticipated.

Age Factors↗
PubMed1998

Development of a health-related quality-of-life questionnaire (PCOSQ) for women with polycystic ovary syndrome (PCOS).

OBJECTIVE: To develop a self-administered questionnaire for measuring health-related quality of life (HRQL) in women with polycystic ovary syndrome (PCOS). METHODS: We identified a pool of 182 items potentially relevant to women with PCOS through semistructured interviews with PCOS patients, a survey of health professionals who worked closely with PCOS women, and a literature review. One hundred women with PCOS completed a questionnaire in which they told us whether the 182 items were relevant to them and, if so, how important the issue was in their daily lives. We included items endorsed by at least 50% of women in the analysis plus additional items considered crucial by clinicians and an important subgroup of patients in a factor analysis. We chose items for the final questionnaire taking into account both item impact (the frequency and importance of the items) and the results of the factor analysis. RESULTS: Over 50% of the women with PCOS labelled 47 items as important to them. Clinicians chose 5 additional items from the infertility domain, 4 of which were identified as important by women who were younger, less educated, married, and African-American. The Cattell's Scree plot from a factor analysis of these 51 items suggested 5 factors that made intuitive sense: emotions, body hair, weight, infertility, and menstrual problems. We chose the highest impact items from these 5 domains to construct a final questionnaire, the Polycystic Ovary Syndrome Questionnaire (PCOSQ), which includes a total of 26 items and takes 10-15 minutes to complete. CONCLUSIONS: We have used established principles to construct a questionnaire that promises to be useful in measuring health-related quality of life. The questionnaire should be tested prior to, or concurrent with, its use in randomized trials of new treatment approaches.

Adult↗
PubMed1998

Octreotide as primary therapy for acromegaly.

The effects of octreotide (up to 5 yr) as primary treatment in 26 patients with acromegaly were compared with those in 81 patients with acromegaly who received octreotide as secondary or adjunctive therapy after previous surgery and/or pituitary radiation. These patients were part of a multicenter study that took place between 1989-1995. The study was divided into 3 phases beginning with a 1-month placebo-controlled treatment period followed by a 1-month washout period. In the second phase, patients were randomized to treatment with either 100 or 250 micrograms octreotide, sc, every 8 h for 6 months. Octreotide was then discontinued for 1 month and reinitiated at the lower dose for a total mean treatment duration of 39 months. The dose was titrated by each investigator to improve each patient's individual response, which included improvement in symptoms and signs of acromegaly as well as reduction of GH and insulin-like growth factor I (IGF-I) into the normal range. In the second phase of the study, in which patients were randomized to either 100 or 250 micrograms octreotide, three times daily, mean integrated GH and IGF-I concentrations after 3 and 6 months were equivalent in the primary and secondary treatment groups. During long term open label treatment, mean GH fell from 32.7 +/- 5.2 to 6.0 +/- 1.7 micrograms/L 2 h after octreotide injection in the primary therapy group and remained suppressed for a mean period of 24 months (range, 3-60 months). The mean final daily dose was 777 micrograms. In the patients receiving secondary treatment, mean GH fell from 30.2 +/- 7.6 to 5.6 +/- 1.1 micrograms/L after 3 months and remained suppressed for the remainder of the study (average dose, 635 micrograms daily). Mean IGF-I concentrations fell from 5.2 +/- 0.5 x 10(3) U/L (primary treatment group) and 4.7 +/- 0.4 x 10(3) U/L (secondary treatment group) to a mean of 2.2 +/- 0.3 x 10(3) U/L in both groups after 3 months of open label treatment and remained suppressed. IGF-I was reduced into the normal range during at least half of the study visits in 68% of the primary treatment group and in 62% of the secondary treatment group. Patients whose GH levels fell to at least 2 SD below the baseline mean GH were considered responders. There was no significant difference in the percentage of responders in the primary and secondary treatment groups (70% vs. 61%), nor was there a statistical difference in the mean GH concentrations between the groups. Symptoms of headache, increased perspiration, fatigue, and joint pain were reported at baseline by 46%, 73%, 69%, and 85%, respectively, of patients in the primary therapy group and improved during 3 yr of octreotide treatment in 50-100%. Similarly, these acromegaly-related symptoms were reported by 62%, 58%, 78%, and 60% of patients in the secondary therapy group, and improvement was noted in 62-88%. Pituitary magnetic resonance imaging scans were available in 13 of 26 patients in the primary treatment group before and after 6 months of octreotide treatment. Tumor shrinkage was observed in 6 of 13 patients, with reduction in tumor volume greater than 25% in only 3. Of 6 patients with documented tumor shrinkage, IGF-I was reduced into the normal range in 4 patients. Of the 7 remaining patients in whom tumor shrinkage was less than 10%, IGF-I was reduced into the normal range in 4 patients. Of the 7 remaining patients in whom tumor shrinkage was less than 10%, IGF-I was reduced into the normal range in 5 patients. The degree of tumor shrinkage did not correlate with the percent reduction in IGF-I or GH. In summary, octreotide was equally effective in 26 previously untreated acromegalic patients (primary treatment group) and 81 patients previously treated with either surgery or pituitary radiation (secondary treatment group). These observations call into question the current practice of surgical resection of all newly diagnosed GH-secreting pituitary adenomas regardless of the likelihood of cure. (AB

Acromegaly↗
PubMed1998

Clinical evaluation of a new in-line continuous blood gas monitor.

Two methodologies for obtaining accurate blood gas and electrolyte values during cardiopulmonary bypass (CPB) are traditional laboratory analyzers, which use an electrochemical technology, and continuous in-line monitoring systems, which use a fluorometric and/or spectrophotometric technology. The purpose of the present study was to evaluate the accuracy of a new continuous in-line monitor, the 3M CDI Blood Parameter Monitoring System 500, which provides continuous in-line measurements of pH, PCO2, PO2, potassium (K+), oxygen saturation, hematocrit, hemoglobin, and temperature, during partial or complete CPB. Study parameters included arterial pH, PCO2, PO2, and K+ values. Overall performance was analyzed by calculating the mean difference (expressed as the bias) between the CDI system 500 and the laboratory analyzer for each parameter. The accuracy of the arterial pH, PCO2, and K+ values provided by the CDI system 500 was then evaluated using target values established in the acceptable performance standards for laboratory analyzers from the Clinical Laboratory Improvement Act of 1988 (CLIA '88). The accuracy of the PO2 value provided by the CDI system 500 was evaluated using a target value of +/- 10% of the reference, or laboratory analyzer, value. A prospective multi-center trial was conducted following Institutional Review Board approval. A total of 75 cases was included in the analyses, with over 200 data points from 4 clinical locations. Results for pH, PCO2, and K+ were within the target values established by CLIA '88. pH bias was 0.00 +/- 0.02 pH units. PCO2 bias was -0.3 +/- 3.3 mm Hg. K+ bias was approximately +0.12 +/- 0.31 mmole/l. Results for PO2 were within 10% of the reference value. PO2 bias was 7.5 +/- 13.8 mm Hg. The results of this clinical trial show that the CDI System 500 continuous in-line monitoring system provides values that meet the accuracy standards for laboratory analyzers for arterial pH, PCO2, PO2, and K+.

Bias↗
PubMed1998

Evidence-based critical care medicine: a potential tool for change.

This issue of New Horizons is about change. While our traditional apprenticeship model of physician training has served us well, adaptation is required for the new millennium. Among several sectoral trends in medicine, two are particularly relevant for intensivists: a) the information explosion and b) increased accountability to society regarding effective, efficient, compassionate, and culturally sensitive care. Evidence-based medicine (EBM) (or any other single initiative, for that matter) is not going to address all of tomorrow's challenges. However, EBM does help by enhancing clinical informatics and critical appraisal skills so that clinicians are better able to keep up with the growing literature, and decide whether, and if so, this literature applies to individual patients. In addition, EBM can help to highlight the determinants of clinical decisions, which may include contributions of caregiver knowledge, patient pathophysiology, research evidence, patient and societal values, and increasingly, costs. While EBM is best practiced at the individual level, its application to other aspects of health care is growing.

Critical Care↗
PubMed1997

Hemolytic uremic syndrome following taipan envenomation with response to plasmapheresis.

We report a case of hemolytic uremic syndrome (HUS) in a 33 year old male who was bitten by a taipan, with apparent massive envenomation. The microangiopathic hemolytic anemia (MAHA) and thrombocytopenic aspects of his HUS appeared to respond to plasmapheresis, but his anuric renal failure persisted. He also had prolonged severe muscular paralysis which gradually began to resolve over the course of two weeks. At this point he suffered a cardiac arrest sustaining severe and subsequently fatal hypoxic brain injury. This case raises the possibility that the taipan venom may have induced HUS by damaging the renal endothelium. His cardiac arrest was not apparently related to his HUS.

Adult↗
PubMed1997

Diagnostic accuracy of a rural live video telepathology system.

Accuracy of diagnoses rendered using a live video telepathology network was assessed for permanent sections of surgical pathology specimens. To determine accuracy, telepathology diagnoses were compared with those obtained by directly viewing the glass slide using a standard microscope. A total of 294 cases were read via both telepathology and glass slide by attending pathologists at a tertiary care medical center. Overall accuracy was defined as exact concordance between diagnoses. Clinically insignificant differences in diagnoses were excluded to determine clinically significant accuracy. For the 285 cases with complete data, the overall accuracy for telepathology was 0.912 (95% confidence interval [CI], 0.872-0.941), whereas the overall accuracy for glass slide readings was 0.968 (95% CI, 0.939-0.985). This difference is statistically significant (p = 0.009). When focusing on clinically significant discrepancies, where the difference in diagnosis might affect therapeutic decisions, the video accuracy was only slightly less than the glass slide accuracy (0.965 [95% CI, 0.934-0.982] vs. 0.982 [95% CI, 0.957-0.994], respectively), but this difference is not statistically significant (p = 0.302). Most of the cases with clinically significant differences involved lesions with inherently high interobserver variation. Certainty of diagnosis did not differ between video and glass slide readings (p = 0.911), but there was an association between certainty of diagnosis and diagnostic accuracy for video (p = 0.003 for clinically significant accuracies). Based on these findings, we recommend when using this telepathology system that only preliminary diagnoses should be given in the following situations: for diagnostic areas with known high interobserver variability; when the consultant has any degree of uncertainty about the presence or absence of the lesion in question; and when there is insufficient experience using telepathology as a diagnostic medium.

Crohn Disease↗
PubMed1997

Central venous catheter replacement strategies: a systematic review of the literature.

OBJECTIVE: To evaluate the effect of guidewire exchange and new-site replacement strategies on the frequency of catheter colonization and infection, catheter-related bacteremia, and mechanical complications in critically ill patients. DATA SOURCES: We searched for published and unpublished research by means of MEDLINE and Science Citation Index, manual searching of Index Medicus, citation review of relevant primary and review articles, review of personal files, and contact with primary investigators. STUDY SELECTION: From a pool of 151 randomized, controlled trials on central venous catheter management, we identified 12 relevant randomized trials of catheter replacement over a guidewire or at a new site. DATA EXTRACTION: In duplicate and independently, we abstracted data on the population, intervention, outcome, and methodologic quality. DATA SYNTHESIS: As compared with new-site replacement, guidewire exchange is associated with a trend toward a higher rate of catheter colonization (relative risk 1.26, 95% confidence interval 0.87 to 1.84), regardless of whether patients had a suspected infection. Guidewire exchange is also associated with trends toward a higher rate of catheter exit-site infection (relative risk 1.52, 95% confidence interval 0.34 to 6.73) and catheter-related bacteremia (relative risk 1.72, 95% confidence interval 0.89 to 3.33). However, guidewire exchange is associated with fewer mechanical complications (relative risk 0.48, 95% confidence interval 0.12 to 1.91) relative to new-site replacement. Exchanging catheters over guidewires or at new sites every 3 days is not beneficial in reducing infections, compared with catheter replacement on an as-needed basis. CONCLUSIONS: Guidewire exchange of central venous catheters may be associated with a greater risk of catheter-related infection but fewer mechanical complications than new-site replacement. More studies on scheduled vs. as-needed replacement strategies using both techniques are warranted. If guidewire exchange is used, meticulous aseptic technique is necessary.

Bacteremia↗
PubMed1997

Pigmented squamous cell carcinoma with dendritic melanocytes.

A 79-year-old man presented with a pigmented nodule on the right ear which, on epiluminescence microscopy, demonstrated a diffuse grey-blue colour. Skin biopsy revealed an irregularly acanthotic epidermis with lobular clusters of atypical keratinocytes that projected into the dermis in the pattern of an invasive squamous cell carcinoma. Numerous dendritic melanocytes were present throughout the lesion. Although the close relationship between the highly dendritic intra-epidermal melanocytes and the atypical keratinocytes raised the issue of whether this tumour represented a malignant melanoacanthoma, the authors considered the lesion to be better classified as an unusual variant of pigmented squamous cell carcinoma.

Aged↗
PubMed1997

Characterisation of ACTH peptides in human skin and their activation of the melanocortin-1 receptor.

Alpha-Melanocyte-stimulating hormone (alpha-MSH) is a proopiomelanocortin (POMC)-derived peptide, which is produced in the pituitary and at other sites including the skin. It has numerous effects and in the skin has a pigmentary action through the activation of the melanocortin-1 (MC-1) receptor, which is expressed by melanocytes. Recent evidence suggests that the related POMC peptides such as adrenocorticotrophin (ACTH), which is the precursor of alpha-MSH, is also an agonist at the MC-1 receptor. By using immunocytochemistry, we confirmed the presence of alpha-MSH in human skin where staining was evident in keratinocytes and especially strong in melanocytes and possibly Langerhans cells. ACTH was also present and tended to show the strongest reaction in differentiated keratinocytes. Immunostaining was also observed for the prohormone convertases, PC1 and PC2, which are involved in the formation of ACTH and its cleavage to alpha-MSH, respectively. The amounts of immunoreactive ACTH exceeded those of alpha-MSH. Using HPLC we identified for the first time the presence of ACTH1-39, ACTH1-17, ACTH1-10, acetylated ACTH1-10, alpha-MSH, and desacetyl alpha-MSH in epidermis and in cultured keratinocytes. The ability of these peptides to activate the human MC-1 receptor was examined in HEK 293 cells that had been transfected with the receptor. All peptides increased adenylate cyclase in these cells with the following order of potency: ACTH1-17 > alpha-MSH > ACTH1-39 > desacetyl alpha-MSH > acetylated ACTH1-10 > ACTH1-10. ACTH1-17 also increased the dendricity and melanin content of cultured human melanocytes indicating that the peptide was able to activate MC-1 receptors when present in their normal location. However, as found with alpha-MSH, not all cultures were responsive and, as we have previously suggested, we suspect that this was the result of changes at the MC-1 receptor. Nevertheless, it would appear that ACTH peptides can serve as natural ligands of the MC-1 receptor on human melanocytes and their presence in the skin suggests that, together with alpha-MSH, they may have a role in the regulation of human melanocytes.

Adrenocorticotropic Hormone↗
PubMed1997

The relation between nutrition and nosocomial pneumonia: randomized trials in critically ill patients.

OBJECTIVE: To review the effect of enteral nutrition on nosocomial pneumonia in critically ill patients as summarized in randomized clinical trials. STUDY IDENTIFICATION AND SELECTION: Studies were identified through MEDLINE, SCISEARCH, EMBASE, the Cochrane Library, bibliographies of primary and review articles, and personal files. Through duplicate independent review, we selected randomized trials evaluating approaches to nutrition and their relation to nosocomial pneumonia. DATA ABSTRACTION: In duplicate, independently, we abstracted key data on the design features, population, intervention and outcomes of the studies. RESULTS: We identified four trials of enteral vs total parenteral nutrition, one trial of early enteral nutrition vs delayed enteral nutrition, one trial of gastric vs jejunal tube feeding, one trial of intermittent vs continuous enteral feeding, and three trials evaluating different enteral feeding formulae. Sample sizes were small, pneumonia definitions were variable and blinded outcome assessment was infrequent. Randomized trial evidence is insufficient to draw conclusions about the relation between enteral nutrition and nosocomial pneumonia. CONCLUSIONS: Nutritional interventions in critically ill patients appear to have a modest and inconsistent effect on nosocomial pneumonia. This body of evidence neither supports nor refutes the gastropulmonary route of infection.

Journal Article↗
PubMed1997

Current guidelines on stress ulcer prophylaxis.

Acute uppergastrointestinal bleeding in intensive care unit (ICU) patients may occur due to peptic ulcer disease, adverse drug effects, gastric tube lesions, acute renal failure, liver failure or stress-induced gastric mucosal lesions. Gastric acid hypersecretion can be observed in patients with head trauma or neurosurgical procedures. Gastric mucosal ischaemia due to hypotension and shock is the most important risk factor for stress ulcer bleeding. Preventive strategies aim to reduce gastric acidity (histamine H2 receptor antagonists, antacids), strengthen mucosal defensive mechanisms (sucralfate, antacids, pirenzepine) and normalise gastric mucosal microcirculation (sucralfate, pirenzepine). However, the most important prophylactic measure is an optimised resuscitation and ICU regime aiming to improve oxygenation and microcirculation. All drugs approved for stress ulcer prophylaxis in Europe (H2 antagonists, antacids, pirenzepine, sucralfate) have been shown to be effective in prospective controlled randomised trials. However, due to insufficient clinical data, prostaglandins and omeprazole cannot be recommended for this use. Stress ulcer prophylaxis is indicated only in patients at risk, and not in every ICU patient. The selection of drugs today depends not only on efficacy but also on possible adverse effects and on costs. In this regard, the most cost-effective drug is sucralfate. The clinical relevance of nosocomial pneumonia due to gastric bacterial overgrowth has decreased during the past decade due to several changes in the management of critically ill patients.

Antacids↗
PubMed1996

Wingless inactivates glycogen synthase kinase-3 via an intracellular signalling pathway which involves a protein kinase C.

The Drosophila gene product Wingless (Wg) is a secreted glycoprotein and a member of the Wnt gene family. Genetic analysis of Drosophila epidermal development has defined a putative paracrine Wg signalling pathway involving the zeste-white 3/shaggy (zw3/sgg) gene product. Although putative components of Wg- (and by inference Wnt-) mediated signalling pathways have been identified by genetic analysis, the biochemical significance of most factors remains unproven. Here we show that in mouse 10T1/2 fibroblasts the activity of glycogen synthase kinase-3 (GSK-3), the murine homologue of Zw3/Sgg, is inactivated by Wg. This occurs through a signalling pathway that is distinct from insulin-mediated regulation of GSK-3 in that Wg signalling to GSK-3 is insensitive to wortmannin. Additionally, Wg-induced inactivation of GSK-3 is sensitive to both the protein kinase C (PKC) inhibitor Ro31-8220 and prolonged pre-treatment of 10T1/2 fibroblasts with phorbol ester. These findings provide the first biochemical evidence in support of the genetically defined pathway from Wg to Zw3/Sgg, and suggest a previously uncharacterized role for a PKC upstream of GSK-3/Zw3 during Wnt/Wg signal transduction.

Androstadienes↗