Specimen collection, storage, and transmission to the laboratory for hematological tests.
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Blood Specimen Collection↗
Biomedical subjects
S M Lewis
Publications and source records attributed to S M Lewis.
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↗
Validity of the haemoglobin colour scale in blood donor screening.
BACKGROUND AND OBJECTIVES: The haemoglobin colour scale (HCS) has been developed as a simple, reliable and inexpensive clinical device for diagnosing anaemia and estimating its severity when laboratory-based haemoglobinometry is not available. The purpose of this study was to assess its validity for screening blood donors for anaemia. MATERIAL AND METHODS: The HCS was tested at five blood transfusion centres on a total of 2801 donors. Blood was obtained by skin puncture as part of the routine procedure at the donor sessions. HCS readings were compared with screening by the copper sulphate method, which was in routine use in the centres, and with haemoglobin (Hb) measurements by means of calibrated HemoCue haemoglobinometers. HCS readings were considered as normal when the readings were > or = 12 g/dl. RESULTS: Analysis of the paired results showed that the HCS had an accuracy of 97.5% in distinguishing subjects with normal Hb from those below the acceptable limit, when checked against the HemoCue. The HCS was more reliable than the copper-sulphate specific-gravity method, yielding 3.7% false readings compared with 6.1% false readings, respectively. When discrimination was set at 12 g/dl with the HemoCue, the HCS gave an incorrect reading in 2.4% of donors. The majority of these false results (44 donors; 1.58%) were caused by the HCS indicating rejection of the donor (i.e. Hb < 12 g/dl) when the correct Hb was higher, whilst in 23 donors (0.82%) the HCS incorrectly indicated a normal Hb; however, in all but four of these donors the correct Hb values were 11.0-11.9 g/dl, and none were below 10 g/dl. CONCLUSION: The operators were able to master the HCS technique after a few minutes of practice, and all found the test to be user friendly and easy to read. The HCS is proposed as a replacement for the copper sulphate method for blood transfusion donor selection.
Adult↗
Acute abdomen during adjuvant chemotherapy: superior mesenteric artery thrombosis associated with CMF chemotherapy.
We report a case of superior mesenteric artery thrombosis in a 57-year-old woman undergoing chemotherapy for T1N1M0, breast cancer. Although cancer itself is associated with an increased risk of thrombotic events, treatment with chemotherapy and/or tamoxifen in breast cancer patients increases this risk. Most cases reported are of venous thromboembolism; arterial events are rare.
Abdomen, Acute↗
Urgent coronary bypass surgery for failed percutaneous coronary intervention in the stent era: Is backup still necessary?
BACKGROUND: Current practice guidelines for performance of percutaneous coronary intervention (PCI) in the United States mandate availability of on-site surgical backup. With the decreasing frequency of urgent coronary bypass surgery (UCABG) with newer technologies, it is unclear whether such backup continues to be necessary. METHODS: A database of 5655 consecutive patients undergoing PCI at a single center between August 1, 1992, and December 31, 1997, was analyzed. Outcomes were determined as well as clinical, lesion, and procedural characteristics of patients during 4 time periods preceding and during use of coronary stenting. RESULTS: Frequency of UCABG for failed PCI decreased from 2.2% to 0.6% in the most recent time period (P <.01) with no change in incidence of in-hospital death or myocardial infarction. Incidence of stenting progressively increased to 72% in the latest period. Patients requiring UCABG had a higher prevalence of acute coronary syndromes (95%) and type B lesions (79%), but these characteristics were also common in patients who did not undergo UCABG. Although coronary stents were available during the last 3 periods studied, only 30% of UCABG patients had lesions or complications amenable to stenting, and stenting attempts in these patients were all unsuccessful. Despite stenting and use of perfusion balloons and intra-aortic balloon pumps, only 40% of patients having UCABG were stable and pain free on transfer to the operating room. CONCLUSIONS: Although use of UCABG for a failed PCI is currently very low, there are no satisfactory predictors, patients requiring UCABG are frequently clinically unstable, and availability of stenting does not reliably eliminate the need for UCABG or result in a decrease in mortality. This small group of patients continues to require readily available surgical standby.
Angioplasty, Balloon, Coronary↗
Leucodepletion and the interaction of polymorphonuclear cells with endothelium in systemic inflammatory response syndrome.
The abnormal interaction of polymorphonuclear cells (PMNs) with blood vessel walls is considered to underlie the multiple organ failure of systemic inflammatory response syndrome (SIRS). This consideration is supported by the present finding that PMNs from patients with SIRS are activated, as assessed by an increased distribution of cells bearing CD64, enhanced expression of CD11b and decreased expression of CD62L, and are highly adhesive to endothelial monolayers. Passage of SIRS blood through leucodepletion filters in a laboratory-designed extracorporeal circuit resulted in a marked depletion of PMNs. Of the PMNs that remained in the blood, far fewer cells bound to cultured endothelial cells in comparison with PMNs prior to leucofiltration. We propose that leucofiltration of SIRS blood will limit the number of PMNs available for binding to blood vessel walls and, hence, reduce the pathological manifestations associated with this disorder.
Case-Control Studies↗
Effect of varying dietary fat levels on rat growth and oxidative DNA damage.
Dietary fat has previously been shown to have somewhat complicated relationships to levels of oxidative stress in rats. In this study, we examined the effects of five different dietary fat intakes on levels of oxidative DNA damage in rats. Animals fed diets containing 3%, 5%, 10%, or 15% corn oil had body weights that were similar after 20 weeks. Animals fed a 20% fat diet, however, had significantly higher mean body weight than any other group. Levels of 5-hydroxymethyl-2'-deoxyuridine, one marker of oxidative DNA damage, had different relationships to dietary fat in blood and mammary gland. In blood, levels increased with dietary fat levels, and the highest levels were observed with the 20% fat diet (65% higher levels than with the 3% fat diet). In mammary gland, a plateau-type effect was observed, with maximal levels of oxidative DNA damage being obtained using 10% fat (representing a 68% increase relative to the 3% fat diet). This could be a result of induction of compensatory mechanisms in response to a high-fat diet in mammary gland but not in the short-lived nucleated blood cells. Oxidative DNA damage levels in blood thus appear to be a marker of dietary fat intake. In mammary gland, however, levels of DNA damage are consistent with previously observed promotional effects of dietary fat on mammary gland tumorigenesis at lower levels of fat intake with little or no incremental promoting effects at higher levels of fat intake.
Animals↗
Evolution of the recombination signal sequences in the Ig heavy-chain variable region locus of mammals.
The Ig and T cell receptor (TCR) loci have an exceptionally dynamic evolutionary history, but the mechanisms responsible remain a subject of speculation. Ig and TCR genes are unique in vertebrates in that they are assembled from V, D, and J segments by site-specific recombination in developing lymphocytes. Here we examine the extent to which the V(D)J recombination in germline cells may have been responsible for remodeling Ig and TCR loci in mammals by asking whether gene segments have evolved as a unit, or whether, instead, recombination signal sequences (RSSs) and coding sequences have different phylogenies. Four distinct types of RSS have been defined in the human Ig heavy-chain variable region (Vh) locus, namely H1, H2, H3, and H5, and no other RSS type has been detected in other mammalian species. There is a well-supported discrepancy between the evolutionary history of the RSSs as compared with the Vh coding sequences: the RSS type H2 of one Vh gene segment has clearly become replaced by a RSS type H3 during mammalian evolution, between 115 and 65 million years ago. Two general models might explain the RSS swap: the first involves an unequal crossing over, and the second implicates germline activation of V(D)J recombination. The Vh-H2/RSS-H3 recombination product has likely been selected during the evolution of mammals because it provides better V(D)J recombination efficiency.
Base Sequence↗
Training health workers to assess anaemia with the WHO haemoglobin colour scale.
WHO recommends that all pregnant women be screened for anaemia. In rural Africa this is often done by clinical examination which is known to have variable reliability. The recently developed WHO Haemoglobin Colour Scale may be the answer to this problem as it is simple and reliable. This study examines the training procedure recommended by WHO for the Haemoglobin Colour Scale when resources are very limited. We trained 7 laboratory technicians from the Medical Research Council Laboratories Hospital, Fajara, The Gambia and 13 Community Health Nurses (CHNs) from North Bank Division East, a rural area in The Gambia, to use the Colour Scale. The CHNs used the Scale to estimate haemoglobins on all new bookings to the antenatal clinics for a period of one month and recorded how they were managed. At the end of the study period they completed a qualitative questionnaire about the scale. Both groups of trainees were successfully trained although the WHO protocol for training was impossible to follow due to resource limitations. Eight of the 13 trained CHNs used the scale in practice and recorded 307 estimations with a mean haemoglobin of 9.1 g/dl. The results were normally distributed. Six of the 9 patients with Hb readings of < 4 g/dl were managed correctly. In response to the questionnaire the CHNs thought the scale was cheap, easy and quick to use and as good as the haemoglobinometer they had used previously. The main criticism was that it was not robust enough. The development of a low-technology, cheap, simple and reliable method for measuring haemoglobin is a welcome development. However, a simpler training procedure and a standard way of measuring observer performance are necessary.
Anemia↗
Postcleavage sequence specificity in V(D)J recombination.
Unintended DNA rearrangements in a differentiating lymphocyte can have severe, oncogenic consequences, but the mechanisms for avoiding pathogenic outcomes in V(D)J recombination are not well understood. The first level at which fidelity is instituted is in discrimination by the recombination proteins between authentic and inauthentic recombination signal sequences. Nevertheless, this discrimination is not absolute and cannot fully eliminate targeting errors. To learn more about the basis of specificity during V(D)J recombination, we have investigated whether it is possible for the recombination machinery to detect an inaccurately targeted sequence subsequent to cleavage. These studies indicate that even postcleavage steps in V(D)J recombination are sequence specific and that noncanonical sequences will not efficiently support the resolution of recombination intermediates in vivo. Accordingly, interventions after a mistargeting event conceivably occur at a late stage in the joining process and the likelihood may well be crucial to enforcing fidelity during antigen receptor gene rearrangement.
Animals↗
Clinical use of WHO haemoglobin colour scale: validation and critique.
AIM: The World Health Organisation (WHO) haemoglobin colour scale has been developed as a simple, inexpensive clinical device for diagnosing anaemia when laboratory based haemoglobinometry is not available. In an initial validation study at several health centres, scale readings were compared with measurements of haemoglobin by the laboratory. This showed the scale to have 90% sensitivity and 70% specificity in identifying whether anaemia was present or not. In addition, when present, the degree of anaemia was correctly classified in clinical terms as moderate, pronounced, or severe, with an overall sensitivity of 60% and specificity of 88%. Errors were mainly marginal--that is, between two adjacent categories--but there were also some major discrepancies, such as a blood with a haemoglobin of 6-7 g/dl being read as normal or vice versa. Because this would compromise the scale's reliability in practice, this study was undertaken to identify the cause of the discrepancies and to reassess the performance of the scale. METHODS: Venous blood samples were collected into potassium EDTA from patients attending selected clinics at three South African hospitals with good laboratory facilities. A prototype of the device was used unsupervised by nursing staff, doctors, and phlebotomists, who were told to follow the printed instructions. The blood specimens were then immediately sent to the laboratory where haemoglobin was measured by standardised automated blood cell counters. Any discrepancies > 1 g/dl were recorded and the tests were repeated by the same operators under supervision of the investigators. RESULTS: Almost all the errors that occurred resulted from the incorrect use of the device, namely: inadequate or excessive blood, reading the results too soon or too late (beyond the limit of two minutes), poor lighting, or holding the scale at the wrong angle. The accuracy improved dramatically when the tests were repeated under supervision and these faults were avoided: 95% of readings were within 1 g/dl of the reference measurements, and 97% within 1.5 g/dl. Anaemia screening showed 96% sensitivity and 86% specificity. Clinical judgement of pallor was frequently wrong, whereas the scale gave the correct diagnosis in more than 97% of cases. CONCLUSION: The study confirmed the usefulness and reliability of the scale and its advantage over clinical signs for the diagnosis of anaemia, thus providing a clinically reliable near patient method in the absence of a laboratory. The instructions are easy to follow but must be strictly adhered to.
Anemia↗