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Biomedical subjects

John Lewis

Publications and source records attributed to John Lewis.

At least 19 recordsLinked to original sources
PubMed2006

Piezoelectric ink jet processing of materials for medical and biological applications.

Many advanced medical and biological devices require microscale patterning of cells, proteins, and other biological materials. This article describes the use of piezoelectric ink jet processing in the fabrication of biosensors, cell-based assays, and other microscale medical devices. A microelectromechanical system-based piezoelectric transducer was used to develop uniform fluid flow through nozzles and to prepare well-defined microscale patterns of proteins, monofunctional acrylate ester, sinapinic acid, deoxyribonucleic acid (DNA), and DNA scaffolds on relevant substrates. Our results demonstrate that piezoelectric ink jet deposition is a powerful non-contact, non-destructive additive process for developing biosensors, cell culture systems, and other devices for medical and biological applications.

Animals↗
PubMed2006

Medical errors: understanding the parent's perspective.

Health care practitioners who advocate for full and open disclosure of medical errors often are met with opposition from legal advisors, insurance providers, hospital leadership, and colleagues. Although some progress has been made, a culture of fear around blame and retribution persists and continues to stymie the progression toward open discussion and disclosure of adverse events. The following case discussion addresses some common obstacles to disclosure of medical errors and reversals the potential for positive outcomes for patients and their families, hospital staff, and the health care system when those challenges are overcome.

Child↗
PubMed2005

Identification of sex hormone-binding globulin in the human hypothalamus.

Gonadal steroids are known to influence hypothalamic functions through both genomic and non-genomic pathways. Sex hormone-binding globulin (SHBG) may act by a non-genomic mechanism independent of classical steroid receptors. Here we describe the immunocytochemical mapping of SHBG-containing neurons and nerve fibers in the human hypothalamus and infundibulum. Mass spectrometry and Western blot analysis were also used to characterize the biochemical characteristics of SHBG in the hypothalamus and cerebrospinal fluid (CSF) of humans. SHBG-immunoreactive neurons were observed in the supraoptic nucleus, the suprachiasmatic nucleus, the bed nucleus of the stria terminalis, paraventricular nucleus, arcuate nucleus, the perifornical region and the medial preoptic area in human brains. There were SHBG-immunoreactive axons in the median eminence and the infundibulum. A partial colocalization with oxytocin could be observed in the posterior pituitary lobe in consecutive semithin sections. We also found strong immunoreactivity for SHBG in epithelial cells of the choroid plexus and in a portion of the ependymal cells lining the third ventricle. Mass spectrometry showed that affinity-purified SHBG from the hypothalamus and choroid plexus is structurally similar to the SHBG identified in the CSF. The multiple localizations of SHBG suggest neurohypophyseal and neuroendocrine functions. The biochemical data suggest that CSF SHBG is of brain rather than blood origin.

Aged↗
PubMed2005

Subgroup analyses in randomized clinical trials: statistical and regulatory issues.

Recently, two CPMP Points to Consider, one on adjustment for baseline covariates and the other on multiplicity issues in clinical trials, have included recommendations on the use of subgroup analysis for regulatory purposes. However, despite their regular use and regulatory attention, the validity and nature of subgroup analyses are still frequently questioned. This article provides guidance on when subgroup analyses can be done, when they should be done, and their interpretation. The validity of common regulatory claims based on subgroup analyses is then discussed.

Data Interpretation, Statistical↗
PubMed2004

Do aposematism and Batesian mimicry require bright colours? A test, using European viper markings.

Predator avoidance of noxious prey, aposematism and defensive mimicry are normally associated with bright, contrasting patterns and colours. However, noxious prey may be unable to evolve conspicuous coloration because of other selective constraints, such as the need to be inconspicuous to their own prey or to specialist predators. Many venomous snakes, particularly most vipers, display patterns that are apparently cryptic, but nevertheless highly characteristic, and appear to be mimicked by other, non-venomous snakes. However, predator avoidance of viper patterns has never been demonstrated experimentally. Here, the analysis of 813 avian attacks on 12,636 Plasticine snake models in the field shows that models bearing the characteristic zigzag band of the adder (Vipera berus) are attacked significantly less frequently than plain models. This suggests that predator avoidance of inconspicuously but characteristically patterned noxious prey is possible. Our findings emphasize the importance of mimicry in the ecological and morphological diversification of advanced snakes.

Adaptation, Physiological↗
PubMed2004

Stable isotope-enriched selenite and selenate tracers for human metabolic studies: a fast and accurate method for their preparation from elemental selenium and their identification and quantification using hydride generation atomic absorption spectrometry.

Stable isotope tracers are safe and nutritionally relevant tools for the investigation of mineral metabolism in man. Increased research into the functional role of selenium has resulted in a need for well-characterised, isotopically enriched solutions of the element in order to determine the nutritional relevance of selenium fortification of foods. A simple method for the conversion of isotopically enriched elemental selenium (2.5-10 mg) into selenite and selenate, and their accurate characterisation and quantification is described. Analysis of selenite and selenate tracers using continuous-flow hydride generation-atomic absorption spectrometry technique was based on the specificity of the selenium hydride reaction and allowed their precise (RSD<2.5%) and accurate determination in aqueous solutions. The detection and determination limits were at 0.13 and 0.36 microg Se/l, respectively. Isotopically enriched elemental selenium was converted into selenite and selenate by a nitric acid and a combined nitric acid/hydrogen peroxide oxidation, respectively. The conversion was quantitative (>95%) and specific for both inorganic selenocompounds. Selenite and selenate labels were stable in 0.1 mol/l nitric acid for at least 18 months, i.e. making them ideally suitable for use in long-term metabolic studies. An overview of data relating to the absorption and retention of selenium by humans obtained using the two, well-characterised, tracers is presented and indicates that selenite and selenate are equally well retained in adult men and infants, despite differences in their absorption and urinary excretion characteristics.

Humans↗
PubMed2004

Genetic testing for enzymes of drug metabolism: does it have clinical utility for pain medicine at the present time? A structured review.

STUDY DESIGN: This is a structured review of genomic (genetic) testing for enzymes of drug metabolism. OBJECTIVES: Recently, industry began offering genomic testing for enzymes of drug metabolism. As such, the objective of this review was to determine if genomic testing for enzymes of drug metabolism has any imminent clinical relevance for the practice of pain medicine. METHODS: Relevant references relating to pharmacogenetics, pharmacogenomics, and the metabolizing of drugs used in pain medicine by cytochrome P-450 enzymes were located and reviewed in detail. The P-450 enzymes that metabolize each drug and whether that drug had been identified as being subject to a clinical consequence of a genetic polymorphism of the P-450 enzyme involved in its metabolism were placed into tabular form. RESULTS OF DATA SYNTHESIS: 1) For a large number of drugs, we do not yet know which cytochrome P-450 enzymes are involved in their metabolism; 2) For a large number of drugs, the consequences of a P-450 genetic polymorphism have yet to be determined; 3) Genetic polymorphism can lead to important potential clinical consequences for some opioids, anticonvulsants (phenytoin), benzodiazepines (diazepam), muscle relaxants (succinylcholine), antidepressants (imipramine, nortriptyline, venlafaxine), typical neuroleptics, alcohol, antihypertensives (propranolol, timolol), local anesthetics (procainamide), L-dopa, nicotine, and warfarin. Based on these results, factors for and against using genomic testing were reviewed. CONCLUSIONS/RECOMMENDATIONS: It was concluded that genomic testing for enzymes of drug metabolism has significant potential for improving the efficacy of drug treatment and reducing adverse drug reactions. Recommendations for when such testing would be useful are outlined.

Analgesics↗
PubMed2004

Do the second-generation "atypical neuroleptics" have analgesic properties? A structured evidence-based review.

STUDY DESIGN: This is a structured, evidence-based review of all available studies on the potential effectiveness of the atypical neuroleptics for the treatment of pain (analgesia). To determine what evidence, if any, exists for, or against, the effectiveness of the atypical neuroleptics for analgesia. SUMMARY OF BACKGROUND DATA: There has been significant controversy over whether the conventional neuroleptics (non-atypicals) have analgesic properties. A recent review (Patt et al. 1994) did conclude that the evidence for effectiveness was sparse, except for methotrimeprazine. However, that review did not include a new class of neuroleptics: the atypicals such as olazapine, risperidone, quetiapine, etc. METHODS: A computer and manual search for studies relating to the atypicals and their analgesic effectiveness produced 10 studies/reports. These were reviewed in detail, and information relating to the above problem was abstracted and placed into tabular form. Each report was also categorized by the type of study it represented according to the guidelines developed by the Agency for Health Care Policy and Research (AHCPR). The strength and consistency of the evidence represented by the 10 studies were then categorized according to the AHCPR guidelines. Conclusions of this review were based on these results. RESULTS OF DATA SYNTHESIS: Of the 10 studies/reports, four were characterized by AHCPR guidelines as Type II (experimental), two were Type III (quasiexperimental), two were Type IV (nonexperimental), and two were Type V (case reports). Of these studies/reports, 90% indicated that the atypicals did have an analgesic effect. The overall strength and consistency of this evidence using the AHCPR guidelines was, therefore, categorized as B (generally consistent from Type II, Type III, and Type IV studies). CONCLUSIONS: Based on the above results, it was concluded that the reviewed data were generally consistent, suggesting that some of the atypicals may have an analgesic effect. There were, however, few double-blind, placebo-controlled studies, and many of the reports/studies had less than 50 patients. As such, this question requires further research.

Analgesics↗
PubMed2003

Do the proposed cervicogenic headache diagnostic criteria demonstrate specificity in terms of separating cervicogenic headache from migraine?

Diagnostic criteria for cervicogenic headache (CH) have been proposed. These criteria are controversial in that they appear to overlap or include characteristics that usually are attributed to migraine headache (MH). Whether these criteria are specific enough to separate CH patients from MH patients remains to be controversial. The literature on this issue is reviewed. In addition, the authors report the results of a study attempting to build a model of variables typically associated with CH or MH, which would identify patients with CH. A significant model could not be built that did not include MH symptoms. As such, it has been concluded that it is unlikely that the criteria for CH will have the specificity required to separate CH patients from MH patients.

Adult↗
PubMed2003

Pilot randomized double blind placebo-controlled study of dexamphetamine for cocaine dependence.

AIMS: To establish the feasibility of conducting a placebo-controlled clinical trial of dexamphetamine replacement therapy for cocaine dependence and to obtain preliminary data. DESIGN: Double-blind randomized placebo-controlled trial. PARTICIPANTS: Thirty cocaine-dependent injecting drug users. INTERVENTION: Subjects were assigned randomly to receive 60 mg/day dexamphetamine (n = 16) or placebo (n = 14) for 14 weeks. MEASUREMENTS: Immunoassay and mass spectrometric techniques were used to identify cocaine metabolites in urine. Subjects were screened using the Composite International Diagnostic Interview and DSM-IV. The Opiate Treatment Index, Brief Symptom Inventory, Severity of Dependence Scale and visual analogue craving scales were used to collect pre- and post-self-report data. FINDINGS: Treatment retention was equivalent between groups; however, outcomes favoured the treatment group with no improvements observed in the placebo control group. The proportion of cocaine-positive urine samples detected in the treatment group declined from 94% to 56% compared to no change in the placebo group (79% positive). While the improvements were not significant between groups, within-group analysis revealed that the treatment group reduced self-reported cocaine use (P = 0.02), reduced criminal activity (P = 0.04), reduced cravings (P < 0.01) and reduced severity of cocaine dependence (P < 0.01) with no within-group improvements found in the placebo group. CONCLUSIONS: A definitive evaluation of the utility of dexamphetamine in the management of cocaine dependence is feasible and warranted.

Adult↗
PubMed2003

Is pain fatiguing? A structured evidence-based review.

STUDY DESIGN: This is a structured, evidence-based review of all available studies on the coexistence of fatigue and pain. OBJECTIVES: To determine what evidence, if any, exists for or against the existence of an association between fatigue and pain and a potential etiological relationship between pain and fatigue. SUMMARY OF BACKGROUND DATA: Pain physicians have noted fatigue as a frequent complaint in chronic pain patients (CPPs), and previous studies have reported the association of fatigue and pain. METHODS: Computer and manual literature searches for studies relating to fatigue and pain produced 23 reports. These references were reviewed in detail, and information relating to the above problems was abstracted and placed into tabular form. Each report was also categorized for the type of study it represented according to the guidelines developed by the Agency for Health Care Policy and Research (AHCPR). In addition, a list of 15 quality criteria was utilized in order to measure the quality of each study. Each study was categorized for each criterion as positive, (criterion filled), negative (criterion not filled), or not applicable independently by two of the authors. A percent quality score was obtained for each study by counting the total number of positives obtained, dividing by 15 minus the total number of not applicable, and multiplying by 100. Only studies having a quality score of 75% or greater were utilized to formulate the conclusions of this review. The strength and consistency of the evidence represented by the remaining studies was then categorized according to the AHCPR guidelines. Conclusions of this review were based on those results. RESULTS OF DATA SYNTHESIS: Of the 23 reports, 17 had quality scores of 75% or greater. Of these 17 reports, 94.1% indicated that there was an association between fatigue and pain. In addition, 100% of a subgroup of 13 reports (all with quality scores of 75% or greater) indicated that there may be an etiological relationship between pain and fatigue. The overall strength and consistency of this evidence according to AHCPR guidelines was therefore categorized as A (highly consistent findings from multiple studies). CONCLUSIONS: Based on the above results, it was concluded that there is an association between fatigue and pain and that there may be an etiological relationship between pain and fatigue. Pain physicians and other pain treatment professionals should be aware of the high prevalence of fatigue in pain patients. In addition, future research might investigate possible mechanisms for the relationship between pain and fatigue.

Chronic Disease↗
PubMed2003

A structured evidence-based review on the meaning of nonorganic physical signs: Waddell signs.

STUDY DESIGN: This is a structured, evidence-based review of all available studies addressing the concept of nonorganic findings: Waddell signs (WSs). OBJECTIVES: To determine what evidence, if any, exists for the various interpretations for the presence of WSs on physical examination. SUMMARY OF BACKGROUND DATA: WSs are a group of eight physical findings divided into five categories, the presence of which has been alleged at times to have the following interpretations: Malingering/secondary gain, hysteria, psychological distress, magnified presentation, abnormal illness behavior, abnormal pain behavior, and somatic amplification. At the present time, there is, therefore, significant confusion as to what these findings mean. METHODS: A computer and manual literature search produced 61 studies and case series reports relating to WSs. These references were reviewed in detail, sorted, and placed into tabular form according to the following subject areas: 1) Reliability (test-retest); 2) Reliability (inter-rater); 3) Reliability (factor analysis); 4) Validity, psychological distress; 5) Validity, correlation Minnesota Multiphasic Pain Inventory (MMPI); 6) Validity, correlation abnormal illness behavior; 7) Validity, other behaviors; 8) Validity, as a nonorganic phenomenon; 9) Validity, correlation pain drawing; 10) Validity, functional performance; 11) Validity, treatment outcome; 12) Validity, predicting surgical treatment outcome; 13) Validity, return to work outcome; 14) Validity, secondary gain correlation; and 15) Validity, pain correlation. Each study in each topic area was classified according to the type of study it represented according to the type of evidence guidelines developed by the Agency for Health Care Policy and Research (AHCPR). In addition, a list of 14 study quality criteria was used to measure the quality of each study. Each study was categorized for each criterion as positive, (criterion filled), negative (criterion not filled), or not applicable independently by two of the authors. A percent quality score was obtained for each study by counting the total number of positives obtained, dividing by 14 minus the total number of not applicables, and multiplying by 100. Only studies having a quality score of 75% or greater were used to formulate the conclusions of this review. The strength and consistency of the evidence represented by the remaining studies in each topic area (above) was then categorized according to the strength and consistency AHCPR guidelines. Conclusions of this review for each topic area are based on these results. RESULTS OF DATA SYNTHESIS: Of the 61 studies, four had quality scores below 75% and were not used to generate the results of this review. According to the AHCPR guidelines for strength and consistency of the reviewed data, the following results were obtained: 1) There was consistent evidence for WSs being associated with decreased functional performance, poor nonsurgical treatment outcome, and greater levels of pain; 2) There was generally consistent evidence for WSs not being associated with psychological distress, abnormal illness behavior, or secondary gain; 3) There was also generally consistent evidence that WSs are an organic phenomenon and that they cannot be used to discriminate organic from nonorganic problems; 4) There was inconsistent evidence that WSs do demonstrate inter-rater reliability, do not correlate with the neurotic triad of the MMPI, are associated with poorer surgical treatment outcome, and are associated with nonreturn to work; 5) There was little or no evidence that WSs demonstrate test-retest reliability, or reliable factors, and are associated with self-esteem problems, catastrophizing, or the nonorganic pain drawing. CONCLUSIONS: Based on the above results, the following conclusions were made: 1) WSs do not correlate with psychological distress; 2) WSs do not discriminate organic from nonorganic problems; 3) WSs may represent an organic phenomenon; 4) WSs are associated with poorer treatment outcome; 5) WSs are associated with greater pain levels; 6) WSs are not associated with secondary gain; and 7) As a group, WS studies demonstrate some methodological problems.

Acute Disease↗
PubMed2003

Medico-legal rounds: medico-legal issues and alleged breaches of "standards of medical care" in opioid rotation to methadone: a case report.

OBJECTIVES: The objectives of this medico-legal case report were the following: 1) To present an example of a medico-legal problem that developed as a result of a decision to rotate a chronic pain patient (CPP) to methadone in order to taper the CPP from oxycodone; 2) To present both the plaintiff's and defendant's expert witnesses' opinions as to if and where the care of that patient fell below the "standard of medical care;" and 3) Based on these opinions, to develop some recommendations on how, in the future, pain medicine physicians and other physicians should proceed, in order to avoid allegations of breach of "standards of care" when using methadone. METHODS: This is a case report of a CPP treated at a regional hospital pain clinic. Methadone rotation was used in order to taper the CPP from oxycodone because of addictive disease. RESULTS: During the rotation process, the CPP expired. This had medico-legal consequences. Expert witnesses differed as to whether methadone caused the death. CONCLUSION: Pain physicians should proceed with caution in using methadone for opioid rotation.

Adult↗
PubMed2003

Is the location of nondermatomal sensory abnormalities (NDSAs) related to pain location?

OBJECTIVES: Nondermatomal sensory abnormalities (NDSAs) are alleged to be nonorganic physical findings, where one finds diminished sensation to light touch, pinprick, and, sometimes, other modalities fitting a "nondermatomal pattern." The presence of NDSAs has historically been classified as a conversion symptom. We wished to determine if, in chronic pain patients (CPPs), NDSA location was associated with pain location. METHODS: The setting was a multidisciplinary pain facility. Patients included in the study were those CPPs who, on physical examination by two independent examiners, were found to have NDSAs. NDSA location and pain location were recorded for each CPP. Chi-square analyses (Fisher exact tests) and Kappa statistics were used to test for a relationship between NDSA location and pain location in three patient groups: Pain, upper body only; pain, lower body only; and pain, both lower and upper body. RESULTS: Of 283 consecutive CPPs, 74 were found to have NDSAs, by both examiners, and to fulfill the inclusion criteria of this study. The relationship between NDSA location and pain location was found to be significant (Fisher exact test) for all three patient subsets: Upper body P < 0.05, lower body P < 0.0001, and upper and lower body P < 0.000001. Similarly, the relationship between NDSA location and pain location was found to be statistically significant for all three patient subsets using the Kappa statistic. CONCLUSIONS: The findings of this study suggest that NDSA location is associated with perceived pain location. This finding has implications for whether the presence of NDSAs is considered a conversion symptom.

Adult↗