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Biomedical subjects

S M Lewis

Publications and source records attributed to S M Lewis.

At least 19 recordsLinked to original sources

Neutrophils in development of multiple organ failure in sepsis.

Multiple organ failure is a major threat to the survival of patients with sepsis and systemic inflammation. In the UK and in the USA, mortality rates are currently comparable with and projected to exceed those from myocardial infarction. The immune system combats microbial infections but, in severe sepsis, its untoward activity seems to contribute to organ dysfunction. In this Review we propose that an inappropriate activation and positioning of neutrophils within the microvasculature contributes to the pathological manifestations of multiple organ failure. We further suggest that targeting neutrophils and their interactions with blood vessel walls could be a worthwhile therapeutic strategy for sepsis.

Humans↗

Measurement of haemoglobin as a screening test in general practice.

OBJECTIVE: To assess the validity of using the measurement of haemoglobin as a primary screen test at point-of-care in general practice. METHODS: 1100 consecutive full blood counts carried out at Hammersmith Hospital haematology laboratory on blood samples sent by the general practitioners in the area were reviewed. Where haemoglobin was in the normal range all the parameters of a full blood count were checked and a blood film was screened in order to identify any abnormal features occurring in the absence of anaemia. RESULTS: Haemoglobin was normal in 81% of the samples, and in 81% of this set none of the blood count components showed any abnormal features (i.e. outside two standard deviations of normal reference range). The remaining 19% of cases included 32 with iron deficiency, 26 with high MCV, 84 with leucocyte abnormalities (neutrophilia, neutropenia, lymphocytosis, eosinophilia, monocytosis) and 19 with platelet counts either too high or too low. The predictive value of a normal full blood count from a normal haemoglobin was 0.81. However, when the limits of normal reference values were set at three standard deviations only 7% of the cases showed abnormal features and the predictive value of normality from a normal haemoglobin increased to 0.92. CONCLUSION: There are now simple and suitable devices available for measuring haemoglobin at point-of-care, away from a laboratory. This provides a useful screening test in general practice as a full blood count would, as a rule, be required only in the small proportion of cases where anaemia is detected or the patient's history and/or clinical signs specifically indicate the need for this further investigation. This approach should contribute to more efficient, convenient and economical practice without compromising clinical management.

Blood Cell Count↗

Haemoglobinometry in general practice.

Haemoglobinometry as a primary point-of-care test is well established. This study was undertaken to assess whether haemoglobinometry by itself provides an adequate haematological screening procedure in general practice. In a series of 500 sequential blood counts received by the central hospital laboratory from local doctors, 405 (81%) had a normal haemoglobin. Full blood counts on these samples showed 15% with one or more blood count parameters outside 2SD of normal reference values, including increased MCV, low MCV with low MCH and MCHC, leucocytosis with neutrophilia, a few cases with neutropenia, lymphopenia, monocytosis or eosinophilia. When the limits were set at 3SD, these abnormalities were found in only 7.6% of the cases. Calculation of test utility gave a positive predictive value of 0.83, a negative predictive value of 0.85, with a likelihood ratio of 14.3 and an overall diagnostic reliability of 84%. It was concluded that haemoglobin alone is a valuable primary screening test and a full blood count is required only when anaemia is present or when the patient's history and clinical signs indicate the need for such further investigation. Using this protocol it is unlikely that any serious error will be made in diagnosing a clinically significant condition; the main limitation is failure to diagnose pre-anaemic iron deficiency.

Anemia↗

International Council for Standardization in Haematology (ICSH) recommendations for "surrogate reference" method for the packed cell volume.

The spun packed cell volume (PCV, hematocrit) is a key measurement on which are based hematology instrument calibration, reference range determination, and assignment of values to calibrators/controls. In 2001, the International Council for Standardization in Haematology (ICSH) recommended a Reference PCV method, which is fully traceable to the ICSH reference hemoglobin method. Because of its complexity, however, this method is impractical for occasional use in routine laboratories and is therefore intended primarily for use by manufacturers of capillary microhematocrit tubes, liquid calibrators, and multichannel analyzers. In response to the need for a simpler method--accessible to all routine laboratories--the ICSH offers this "Surrogate Reference" PCV procedure. It is traceable to the original ICSH Reference PCV method and is based on spun PCVs obtained using borosilicate capillary tubes with an already-known relationship to this reference procedure. This ICSH "Surrogate Reference" PCV method is substantially simpler, thus putting it within the reach of most routine hematology laboratories.

Blood Specimen Collection↗

Assessment and significance of 24-h energy intake patterns among young and aged non-affluent southern US women.

Energy intake patterns that may impact health status among non-affluent southern U.S. women from small urban communities have not been evaluated extensively. Usual intake estimates are confounded by factors such as validity of intake methods and socioeconomic status. Typical 24-h energy intakes were reported by Caucasian (CA, n=149) and African-American (AA, n=110) women; at 43% of this sub-population, AA women are appropriately and proportionately represented. Daily energy intake was examined for these non-pregnant females, 24 to 93 y of age, to define typical energy, carbohydrate, protein, and fat intake. Study groups were: 24-29 y, 30-39 y, 40-49 y, 50-59 y, 60-69 y, 70-79 y, and 80-93 y. Statistical comparisons of nutrient variables by age were made by least squares means between groups. Body mass index (BMI) calculations accounted for differences in height and relative body mass. Both races reported similar energy intakes and significant (P<0.05) decreases with age were noted. Energy intakes were 15-40% below recommended levels, similar to reported values; senior lunch programs ameliorated declines among some women >60 y. More daily calories (52-62%) were provided by carbohydrates, followed by fat (26-35%) and protein (14-17%) findings in close agreement with health recommendations. Time-of-day intake patterns suggest women >59 y consume larger noon meals. BMI for AA women was greater (P<0.05) than that of CA women between 30-59 y. At 24-29 y, AA women had lowest BMI values; BMI decreases occurred in CA women after 80 y. These factors may impact the health of non-affluent southern AA and CA women, particularly the elderly who may require guidance for diet planning and intake intervention programs.

Adult↗

Assessment of antioxidant nutrient intake of a population of southern US African-American and Caucasian women of various ages when compared to dietary reference intakes.

Antioxidant nutrient intervention strategies to ameliorate negative health factors are of notable research interest. Central to the thesis that antioxidant nutrients improve biological defense systems and provide health benefits is an accurate indication of daily antioxidant nutrient intake. Little information is available concerning these nutrient intakes among non-affluent women of the southern U.S. This study examines the 24-h intake of vitamins: A, E, C, -carotene, a-tocopherol, riboflavin, and minerals: zinc, selenium, copper, manganese, iron, and molybdenum among 259 Caucasian (CA) and African-American (AA) women from small urban communities. Women were non-pregnant females, 19-93 y of age. Statistical comparisons of nutrient intake were made by least squares means within age groups. Intakes were compared to various Dietary Reference Intakes including Recommended Daily Allowance (RDA) and Estimated Average Requirement (EAR) values as established by the U.S. National Research Council. Numerous dietary deficiencies in important antioxidant nutrients associated with metabolic antioxidant systems were identified. Few race-related differences were detected. Intake of vitamin A was generally within recommended levels while vitamin E intake was below the EAR. The vitamin precursors, -carotene and a-tocopherol, were significantly (P<0.05) below customary intakes at all ages. More than 60% of this population reported dietary copper, zinc, and selenium intakes below recommended levels. A lack of race differences for most nutrient intakes suggests similar socioeconomic or endogeneous regional factors. All women in this population reported dietary intakes of antioxidant vitamins and minerals below recommended values, conditions that could contribute to subsequent health risks unless nutrient-dense food choices and antioxidant supplementation are considered in their overall nutritional support.

Adult↗

Restructuring of international council for standardization in haematology (ICSH) in Asia.

Standardization and harmonization in Laboratory testing are a key issue in the midst of globalization era, because most of laboratory testing has been currently achieved with various kinds of automated systems. In the developed countries, automated systems with highly-regulated principles are commonly used in the routine laboratory. However, there are so many undeveloped and developing countries in Asia that diversity of testing levels can be observed in the area. Some laboratories use glass chamber method for blood cell counting, while other laboratory use semi-automated or fully automated analyzers for complete blood count. International standardization on Hematology is focused on the developed system but not for the developing system. Established standardized documents therefore whould not be unsuitable for Asian societies. In the context, International Council for Standardization in Hematology (ICSH) changed its rules to adjust our Asian Societies and ICSH started to restructure the body. International ICSH society is divided into 5 region sub-groups. Asian area is able to possess one new sub-society, ICSH-Asia. Its reconstruction work has been just started with Asain colleagues, and we are now extending the new societies to discuss Asian problems on the quality of hematology testing.

Asia↗

Laboratory practice at the periphery in developing countries.

An effective national health service structure requires a comprehensive programme for primary health care in peripheral and rural areas. This is especially important in under-resourced countries where facilities are sparse, the population is widely dispersed and transport is limited. Haematology has a key role in diagnosis and patient management by selecting tests for their clinical relevance and utility for the specific circumstances, and ensuring their technical reliability when used in health clinics and point-of-care testing. WHO has proposed a basic menu of tests in three categories: (a) tests such as haemoglobin screen which can be performed by nurses, midwives, health-aides or community doctors, (b) tests such as haemoglobinometry, microhaematocrit and microscopic examination of stained preparations which can be performed by a technician or laboratory assistant in a health centre, (c) tests requiring greater technical expertise of a laboratory technician or trained doctor. The peripheral health clinics and district laboratories must be familiar with the guidelines on standardized methods for collecting and storing specimens and transporting them to a regional laboratory or a reference centre. A training syllabus should be provided at the health centres and district laboratories, and this should include on-site instruction from supervisors and access to training manuals and distance-learning material. A co-ordinated programme of quality assurance and standardization of test methods should be established by a reference centre or national health authority with a network which encompasses all laboratories and health clinics undertaking any tests. Each regional laboratory should foster lower level laboratories or clinics within its neighbourhood. Of particular concern is the reliable diagnosis and management of anaemia. WHO reports indicate that 40% of the world population suffer from anaemia, especially affecting pregnant women, and a high proportion of infants and children in developing countries. The Haemoglobin Colour Scale (HCS) was recently developed for WHO as a simple, cheap and portable device which reads haemoglobin within 1 g/dl of the true value. It has been validated in a number of studies and is now manufactured commercially in accordance with WHO specifications under control of a WHO Collaborating Centre. It has an important potential role in the resource-limited environment where anaemia screening presently usually depends on unreliable clinical examination.

Anemia↗

Reasons for higher in-hospital mortality >24 hours after percutaneous transluminal coronary angioplasty in women compared with men.

Women have a higher in-hospital mortality rate than men after percutaneous transluminal coronary angioplasty (PTCA). To determine reasons for this, we analyzed the outcome of PTCA at our institution from 1989 to 1995 for 5,989 patients (2,101 women). Women were older than men (66.8 +/- 10.9 vs 61.0 +/- 11.2 years, respectively; p <0.0001) and more likely to have diabetes mellitus, hypertension, or a history of congestive heart failure than men. In-laboratory complications at the time of PTCA were similar for women and men. During the first 24 hours after PTCA, women were more likely than men to become hypotensive (0.33% vs 0.08%, p = 0.04) and had a higher rate of vascular injury than men (1.6% vs 0.6%, p <0.001). More than 24 hours after the procedure, women had a significantly higher mortality rate (1.2% vs 0.52%, p = 0.017), which was no longer significantly different after adjustment for age (odds ratio 0.72, 95% confidence interval 0.39 to 1.32). Multivariate correlates of death >24 hours after PTCA were age, a prior history of congestive heart failure, vascular injury, and use of thrombolytic agents. Of those dying >24 hours after the procedure, 67% of women suffered a noncardiac-related death compared with only 10% of men (p <0.001). The noncardiac death rate was 0.8% for women and 0.05% for men. These deaths were related to renal failure, vascular complications, bleeding, hypotension, and stroke, especially hemorrhagic stroke. In conclusion, immediate procedural complications at PTCA were similar for women and men; however, mortality was higher for women >24 hours after PTCA and before discharge due to a higher rate of noncardiac death.

Age Distribution↗

Nitric oxide and the control of firefly flashing.

Bioluminescent flashing is essential for firefly reproduction, yet the specific molecular mechanisms that control light production are not well understood. We report that light production by fireflies can be stimulated by nitric oxide (NO) gas in the presence of oxygen and that NO scavengers block bioluminescence induced by the neurotransmitter octopamine. NO synthase is robustly expressed in the firefly lantern in cells interposed between nerve endings and the light-producing photocytes. These results suggest that NO synthesis is a key determinant of flash control in fireflies.

Animals↗

The effect of stimulus-response compatibility on cortical motor activation.

Stimulus-response compatibility (SRC) is a general term describing the relationship between a triggering stimulus and its associated motor response. The relationship between stimulus and response can be manipulated at the level of the set of stimulus and response characteristics (set-level) or at the level of the mapping between the individual elements of the stimulus and response sets (element-level). We used functional magnetic resonance imaging (fMRI) to investigate the effects of SRC on functional activation in cortical motor areas. Using behavioral tasks to separately evaluate set- and element-level compatibility, and their interaction, we measured the volume of functional activation in 11 cortical motor areas, in the anterior frontal cortex, and in the superior temporal lobe. Element-level compatibility effects were associated with significant activation in the pre-supplementary motor area (preSMA), the dorsal (PMd) and ventral (PMv) premotor areas, and the parietal areas (inferior, superior, intraparietal sulcus, precuneus). The activation was lateralized to the right hemisphere for most of the areas. Set-level compatibility effects resulted in significant activation in the inferior frontal gyri, anterior cingulate and cingulate motor areas, the PMd, PMv, preSMA, the parietal areas (inferior, superior, intraparietal sulcus, precuneus), and in the superior temporal lobe. Activation in the majority of these areas was lateralized to the left hemisphere. Finally, there was an interaction between set and element-level compatibility in the middle and superior frontal gyri, in an area co-extensive with the dorsolateral prefrontal cortex, suggesting that this area provided the neural substrate for common processing stages, such as working memory and attention, which are engaged when both levels of SRC are manipulated at once.

Adult↗

The effects of different levels of dietary restriction on aging and survival in the Sprague-Dawley rat: implications for chronic studies.

A study was undertaken to determine the effects of incremental levels of dietary restriction (DR) in rats. Survival, growth, reproductive, and dietary intake (DI) variables were monitored in a chronic study in which male Sprague Dawley (SD) rats (NCTR colony) were fed their ration ad libitum (AL), or DR. The main objectives were to determine if low levels of DR could be used to increase the survival rate of SD rats in the chronic bioassay, and to identify the survival characteristics of a long-lived SD rat strain (NCTR colony). The average life span of AL rats was 115 months. At 104 weeks on study (110 weeks of age), the survival rate for the AL and 10%, 25%, and 40% DR groups was 63.4, 87.5, 87.5, and 97.5%, respectively. The largest increase in survival (24.1%) occurred between AL and 10% DR, indicating that very low levels of DR have a significant effect on survival. Whole-body, liver, prostate, and epididymis weights and body length were decreased by DR, whereas brain weight, testicular weight, and skull length were not altered by DR. Rats from the NCTR colony were found to be ideal for chronic studies because they are much longer-lived than other SD stocks. Although the 104-week survival rate for these SD, non-obese AL rats exceeds the FDA's "Redbook" survival guideline (> 50%) for chronic bioassays, the use of DR is advocated because it reduces individual variability in body weight.

Aging↗

Cardiac surgery report cards: comprehensive review and statistical critique.

Public report cards and confidential, collaborative peer education represent distinctly different approaches to cardiac surgery quality assessment and improvement. This review discusses the controversies regarding their methodology and relative effectiveness. Report cards have been the more commonly used approach, typically as a result of state legislation. They are based on the presumption that publication of outcomes effectively motivates providers, and that market forces will reward higher quality. Numerous studies have challenged the validity of these hypotheses. Furthermore, although states with report cards have reported significant decreases in risk-adjusted mortality, it is unclear whether this improvement resulted from public disclosure or, rather, from the development of internal quality programs by hospitals. An additional confounding factor is the nationwide decline in heart surgery mortality, including states without quality monitoring. Finally, report cards may engender negative behaviors such as high-risk case avoidance and "gaming" of the reporting system, especially if individual surgeon results are published. The alternative approach, continuous quality improvement, may provide an opportunity to enhance performance and reduce interprovider variability while avoiding the unintended negative consequences of report cards. This collaborative method, which uses exchange visits between programs and determination of best practice, has been highly effective in northern New England and in the Veterans Affairs Administration. However, despite their potential advantages, quality programs based solely on confidential continuous quality improvement do not address the issue of public accountability. For this reason, some states may continue to mandate report cards. In such instances, it is imperative that appropriate statistical techniques and report formats are used, and that professional organizations simultaneously implement continuous quality improvement programs. The statistical methodology underlying current report cards is flawed, and does not justify the degree of accuracy presented to the public. All existing risk-adjustment methods have substantial inherent imprecision, and this is compounded when the results of such patient-level models are aggregated and used inappropriately to assess provider performance. Specific problems include sample size differences, clustering of observations, multiple comparisons, and failure to account for the random component of interprovider variability. We advocate the use of hierarchical or multilevel statistical models to address these concerns, as well as report formats that emphasize the statistical uncertainty of the results.

Bias↗

Increased distribution and expression of CD64 on blood polymorphonuclear cells from patients with the systemic inflammatory response syndrome (SIRS).

Evidence is growing to suggest that the multiple organ damage of the systemic inflammatory response syndrome (SIRS) arises from the untoward activity of blood polymorphonuclear cells (PMNs), which upon activation acquire the IgG high affinity receptor, CD64. In the current study, flow cytometry was used to assess the prevalence of CD64-bearing PMNs and the intensity of expression of CD64 in whole blood samples from 32 SIRS patients, 11 healthy normal subjects and from eight non-SIRS patients in the intensive care unit (ICU). The percentage of PMNs expressing CD64 was higher in SIRS patients (mean 65%) than in non-SIRS patients (mean 42%; P < 0.02) and in healthy controls (mean 19%; P < 0.001) and was particularly evident in patients with SIRS and sepsis (mean 71%; P < 0.02) as opposed to SIRS alone (mean 55%). There were more CD64 molecules expressed on PMNs from patients with SIRS (median 1331 molecules/cell) in comparison with PMNs from healthy subjects (median 678 molecules/cell; P < 0.01). The highest intensity of CD64 expression was associated with PMNs from patients with both SIRS and sepsis. Functional studies revealed that the supranormal binding of PMNs from patients with SIRS to endothelial monolayers treated with TNFalpha was impeded by anti-CD64 antibodies (mean 24% inhibition; P < 0.01). Monitoring the distribution of CD64+ PMNs and their level of CD64 expression could be of assistance in the rapid discrimination of patients with SIRS from other ICU patients and in the identification of PMNs which are likely to participate in the pathological manifestations of the disease.

Adult↗

Use of a new HemoCue system for measuring haemoglobin at low concentrations.

In many photometers and spectrometers used in routine practice Beer's law (relating absorbance to concentration) fails at low concentrations. A refinement of the HemoCue haemoglobin system (HemoCue AB, Sweden) provides a facility for accurate measurement of haemoglobin at the lower end of the scale. This study confirmed excellent linearity of the photometer response of the HemoCue Plasma/Low Hb photometer to haemoglobin concentration by direct measurement on whole blood samples, thus providing a reliable method when laboratory facilities are limited and where critical patient management may be dictated by the severity of anaemia. Furthermore, measurements on plasma and on samples of urine containing haemoglobin demonstrated the utility of the device for reliable quantification of plasma haemoglobin and haemoglobinuria, thus providing a useful method in investigating moderate or severe intravascular haemolysis. A study of plasma haemoglobin on stored samples of ethylenediamine tetraacetic acid (EDTA) blood showed that a small but measurable degree of lysis occurs after two days at room temperature and after four days when stored at 4 degrees C. This effect on the red cell count will reflect on the reliability of using such blood as a quality control preparation.

Hemoglobins↗