Systematic reviews: the case for rigorous methods and rigorous reporting.
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Communication↗
Biomedical subjects
D Cook
Publications and source records attributed to D Cook.
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↗
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↗
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↗
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↗
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↗
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↗
What postmodernism can do for psychoanalysis: a guide to the postmodern vision.
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Humans↗
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↗
Saliva test screening for HIV infection: Author's reply to comment on the accuracy of a saliva test for HIV antibody.
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HIV Antibodies↗
Aerosol deposition in infants with cystic fibrosis.
Twenty asymptomatic infants with cystic fibrosis (CF) were studied to determine the amount of radiolabeled aerosol [99m technetium diethylenetriamine penta acetic acid (Tc99m DTPA)] deposited in the respiratory system and its distribution. Aerosols were generated by jet nebulization systems that were used in the wards and the laboratory. Subjects were studied in three groups: group A (n = 10) was sedated with chloral hydrate; children inhaled an aerosol of 7.7 microns mass median diameter (MMD); group B (n = 5) was not sedated, using the same nebulization system (same aerosol particle size as group A); and group C (n = 5) was not sedated; these children inhaled an aerosol with an MMD of 3.6 microns. Normal saline plus 4 mCi of Tc99m bound to DTPA was added to each nebulizer. A closed system was used to collect the expired aerosol. Radioactivity in each infant and in the equipment was measured with a gamma camera on completion of nebulization. In groups A and B, the percentages of the total dose deposited in the lung were 0.97 +/- 0.35% and 0.76 +/- 0.36%, respectively. In group C, 2.0 +/- 0.71% was deposited in the lung (P < 0.01). Deposition in the nose, mouth, and pharynx was least in group C (P < 0.01). In groups A and B, the intrathoracic deposition occurred predominantly in the trachea and main bronchi, whereas in group C, significantly more aerosol was deposited in the lung region. There was marked inter-subject variability in the percentage of aerosol deposition within the three groups. There was no correlation between percentage of aerosol deposited in the respiratory system and age, height, or weight. Sedation did not have a significant effect on deposition of aerosol in infants. This study indicates that only a small proportion of nebulized solution is deposited in the lungs of infants and that this proportion is influenced by the particle size of the aerosol. The smaller particle size (3.6 microns MMD) was deposited in the lung better than large particles.
Aerosols↗
Does treatment with L-thyroxine influence health status in middle-aged and older adults with subclinical hypothyroidism?
OBJECTIVE: To determine if health-related quality of life (HRQL) in patients of middle age and older with elevated thyroid-stimulating hormone (TSH) and normal total thyroid hormone levels-subclinical hypothyroidism-improves with L-thyroxine replacement therapy. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Outpatient clinic. PATIENTS: Thirty-seven patients with subclinical hypothyroidism, most with symptoms consistent with hypothyroidism, over 55 years of age. INTERVENTIONS: Placebo or L-thyroxine replacement therapy to achieve normal TSH level. MEASUREMENTS AND MAIN RESULTS: Disease-specific and general HRQL, cognitive function, bone mineral density, lipid levels. The mean daily dose of L-thyroxine replacement in the active group was 68 +/- 21 micrograms. TSH decreased by 8.6 mIU/L (95% confidence interval [CI] 4.1 to 13.1) and T4 increased by 27.9 nmol/L (95% CI 14.8 to 41.2). There was a statistically significant improvement in a composite psychometric memory score in treated versus control patients; all other outcomes showed similar findings in the two groups. Although confidence intervals for most measures did not exclude an important improvement in HRQL with thyroid replacement, no measure of symptoms or HRQL either showed clinically important trends in favor of treatment, or approached conventional levels of statistical significance. CONCLUSIONS: In middle-aged and older patients with elevated TSH and normal T4, it may not be harmful to follow biochemical and clinical status even in the presence of nonspecific symptoms potentially associated with hypothyroidism.
Aged↗
Does volume of clinical experience affect performance of clinical clerks on surgery exit examinations?
BACKGROUND: Controversy persists over the educational value of student clerkship clinical activities. METHODS: Students (109) from the class of 1995 recorded their clinical experiences in a logbook during their surgical clerkship at one of four affiliated teaching hospitals. The influence of clinical experience on examination scores and on correlations between prerotation and postrotation examination performance was determined. RESULTS: Between sites, marked variation in clinical experience was observed but postrotation scores were similar. High-volume experience in emergency admissions and feedback was associated with better objective structured clinical examination (OSCE) performance, but high-volume outpatient clinic experience was associated with less satisfactory OSCE performance. Correlations between prerotation examination performance and the OSCE was increased by feedback on emergency and elective admissions, in a positive and negative direction, respectively. CONCLUSIONS: These data show that surgical clerks' clinical skills were enhanced by an increased volume of some but not all clinical experiences and that feedback does not necessarily enhance performance. These data suggest that both the volume of clinical experience and the quality of feedback should be carefully monitored by surgical clerkship directors.
Alberta↗
Cadaveric kidney transplantation under prophylactic polyclonal antibody immunosuppression with anti-lymphoblast globulin versus anti-thymocyte globulin.
OBJECTIVES: This retrospective study was undertaken to evaluate and compare the clinical and immunologic outcomes following prophylactic induction treatment with Minnesota anti-lymphoblast globulin (MALG) and Upjohn anti-thymocyte globulin (ATGAM) in cadaver renal transplantation. METHODS: From 1990 to 1994, 63 patients with renal transplants from cadavers received MALG and 77 patients received ATGAM for induction treatment. Most pretransplant parameters were equivalent in both groups. There was no significant difference in the total dose and mean duration of MALG/ATGAM administration. The post-transplant outcome in these groups was compared. RESULTS: There was no difference between the MALG and ATGAM groups with respect to the overall number of rejection episodes, median days to rejection, or the number of steroid-resistant rejection episodes. However, MALG-treated patients experienced a greater number of rejections in the first 60 days postoperatively (P = 0.06). There was no difference in the nadir serum creatinine level in the first 20 postoperative days in the two groups; however, it took fewer days to reach the nadir in the ATGAM group (P = 0.03). The incidence of delayed graft function was higher in the MALG group than in the ATGAM group (38% versus 31%) but not statistically significant. Graft survival at 12 and 24 months was comparable in both groups. However, patient survival was superior at 12 and 24 months in ATGAM-treated transplant recipients (P = 0.03). The mean serum creatinine at 6, 12, and 24 months was similar in both the MALG and ATGAM groups. The mean fall and recovery of CD3, CD4, and CD8 T-lymphocyte subsets while on MALG/ATGAM were similar in both groups. The incidence of infectious complications was greater in the MALG group. CONCLUSIONS: MALG and ATGAM have comparable clinical immunosuppressive effects. Patients receiving ATGAM experienced fewer rejections in the first 2 months, fewer infections, and better survival.
Antilymphocyte Serum↗
Gene structure and differential regulation of the Rhizobium-induced peroxidase gene rip1.
Primary expression of the Rhizobium meliloti-induced peroxidase gene rip1 occurs prior to nodule morphogenesis, specifically at the site of impending rhizobial infection (D. Cook, D. Dreyer, D. Bonnet, M. Howell, E. Nony, K. VandenBosch [1995] Plant Cell 7: 43-55). We examined the distribution and structure of rip1 transcript throughout nodule development. We determined that expression of rip1 in root tips is correlated with the competence of this zone for symbiotic association, whereas after rhizobial infection rip1 transcript is specifically associated with the zone of nodule development, including nascent nodule primordia. rip1 transcripts are characterized by multiple polyadenylation sites distributed within 200 to 400 bp of the translation stop site, and a single major transcription initiation site in close proximity to the rip1 open reading frame. Thus, rip1 expression is likely to be mediated through effects on a single transcription unit. Immediately 5' of the rip1 transcription unit DNA sequence analysis identified a 377-bp DNA element containing extensive repeat structure that is widely distributed in the Medicago truncatula genome.
Base Sequence↗
Targeting gamma interferon to tumor cells by a genetically engineered fusion protein secreted from myeloma cells.
The construction, synthesis and expression of a genetically engineered bifunctional antibody/cytokine fusion protein is described. To target IFN-tau to tumor cells, recombinant antibody techniques were used to construct a RM4/IFN-tau fusion protein containing the chimeric anti-tumor F(ab')2 (RM4) and the IFN-tau moiety. The recombinant cDNA of IFN-tau was linked to 3 prime end of the chimeric heavy-chain gene fragment (M4) containing the VH, the CH1 and the hinge region to form the fused heavy-chain gene fragment M4-IFN-tau. Transfection of the M4-IFN-tau gene fragment into a myeloma derived cell line VKCK which produced the chimeric light-chain of the same antibody, allowed the transfectant secreting the bifunctional fusion protein RM4/IFN-tau. The RM4/IFN-tau was purified by the affinity chromatography. Our data showed that the RM4/IFN-tau retained the TAG72 antigen-binding reactivity as well as the IFN-tau activity as measured in ELISA, FACS analysis of cell-surface TAG72 expression, immunohistochemical study, and up-regulation of cell-surface expression of CEA, HLA class I and class II antigens. Therefore, the bifunctional fusion protein RM4/IFN-tau may prove to be useful in targeting biological effects of the IFN-tau to tumor cells and in this way to stimulate the immune destruction of tumor cells.
Adenocarcinoma↗
Birth weight and blood pressure: cross sectional and longitudinal relations in childhood.
OBJECTIVE: To examine cross sectional and longitudinal relations between birth weight and blood pressure in childhood. DESIGN: Cross sectional study of primary school children aged 9-11 years, with analysis in relation to previous measurements at 5-7 years in a subgroup. SETTING: 20 primary schools in Guildford and Carlisle. SUBJECTS: 1511 children measured at 9-11 years (response rate 79%), including 549 who had been measured at 5-7 years. MAIN OUTCOME MEASURES: Blood pressure at 9-11 years, change in blood pressure between 5-7 and 9-11 years, birth weight (based on maternal recall), and placental weight (based on birth records). RESULTS: At 9-11 years birth weight was inversely related both to systolic blood pressure (regression coefficient -2.80 mm Hg/kg; 95% confidence interval -3.84 to -1.76) and to diastolic blood pressure (regression coefficient -1.42 mm Hg/kg; -2.14 to -0.70) once current height and body mass index were taken into account. Placental weight was inversely related to blood pressure after adjustment for current height and body mass index but placental ratio (placental weight to birth weight) was unrelated to blood pressure. Between 5-7 and 9-11 years systolic blood pressure rose more rapidly in children of lower birth weight (regression coefficient -1.71 mm Hg/kg; -3.35 to -0.07). This effect seemed to be stronger in girls. CONCLUSIONS: Birth weight rather than placental ratio is the early life factor most importantly related to blood pressure in childhood. The results support the possibility of "amplification" of the relation between birth weight and blood pressure, particularly in girls.
Aging↗
Endoscopic ligation compared with sclerotherapy for treatment of esophageal variceal bleeding. A meta-analysis.
PURPOSE: To compare the effect of endoscopic ligation with that of sclerotherapy in the treatment of patients with bleeding esophageal varices. DATA SOURCES: Strategies to identify published and unpublished research included searches of computerized bibliographic and scientific citations, review of citations in relevant primary articles, searches of services providing information on unpublished studies, contact with primary investigators and the ligation equipment manufacturer, and review of proceedings from pertinent scientific meetings. STUDY SELECTION: From 158 potentially relevant articles, duplicate independent review identified 7 relevant randomized trials that compared endoscopic ligation with sclerotherapy for the treatment of patients with bleeding esophageal varices. DATA ABSTRACTION: Independent, duplicate data abstraction of the population, intervention, outcome, and methodologic quality of the trials was done. DATA SYNTHESIS: Ligation therapy compared with sclerotherapy reduced the rebleeding rate (odds ratio, 0.52 [95% CI, 0.37 to 0.74]), the mortality rate (odds ratio, 0.67 [CI, 0.46 to 0.98]), and the rate of death due to bleeding (odds ratio, 0.49 [CI, 0.24 to 0.996]). Four patients would need to be treated with ligation instead of sclerotherapy to avert one rebleeding episode, and 10 would need to be treated with ligation instead of sclerotherapy to prevent one death. Esophageal strictures occurred less frequently with ligation (odds ratio, 0.10 [CI, 0.03 to 0.29]), but no significant differences were seen between treatments for pulmonary infections or bacterial peritonitis. Additionally, the number of endoscopic treatment sessions required to achieve variceal obliteration was lower with ligation than with sclerotherapy. CONCLUSIONS: On the basis of lower rates of rebleeding, mortality, and complications and the need for fewer endoscopic treatments, ligation should be considered the endoscopic treatment of choice for patients with esophageal variceal bleeding.
Cause of Death↗