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Biomedical subjects

S M Lewis

Publications and source records attributed to S M Lewis.

At least 37 records · Page 2Linked to original sources
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

Measurement of total RBC volume relative to lean body mass for diagnosis of polycythemia.

An elevated total RBC volume (TRCV) in milliliters per kilogram of body weight has been an essential criterion for determining whether a person is polycythemic. This may be misleading in obese subjects as the TRCV per kilogram of fat is only one-tenth that of the TRCV of the lean body mass (LBM). Various formulas based on surface area have been used to account for this difference, but they are not always reliable. Direct measurement of TRCV per kilogram of lean body mass was obtained originally in studies in which body composition was determined by the combined body density and total body water measurement method. This is impractical as a routine procedure, but simple-to-use instruments are now available for direct measurement of a person's body composition and percentage of fat by impedance technology. Thus, the TRCV can be obtained by a direct measurement that discounts the effects of fat, and a graph has been designed to normalize the TRCV to milliliters per kilogram of LBM. The TRCV for men and women has been established as 36 mL/kg LBM; when it is more than 43 mL/kg LBM, a diagnosis of polychthemia can be made with confidence.

Body Composition↗
PubMed1999

Gamma-irradiation directly affects the formation of coding joints in SCID cell lines.

SCID mice have a defect in the catalytic subunit of the DNA-dependent protein kinase, causing increased sensitivity to ionizing radiation in all tissues and severely limiting the development of B and T cell lineages. SCID T and B cell precursors are unable to undergo normal V(D)J recombination: coding joint and signal joint products are less frequently formed and often will exhibit abnormal structural features. Paradoxically, irradiation of newborn SCID mice effects a limited rescue of T cell development. It is not known whether irradiation has a direct impact on the process of V(D)J joining, or whether irradiation of the thymus allows the outgrowth of rare recombinants. To investigate this issue, we sought to demonstrate an irradiation effect ex vivo. Here we have been able to reproducibly detect low-frequency coding joint products with V(D)J recombination reporter plasmids introduced into SCID cell lines. Exposure of B and T lineage cells to 100 cGy of gamma irradiation made no significant difference with respect to the number of coding joint and signal joint recombination products. However, in the absence of irradiation, the coding joints produced in SCID cells had high levels of P nucleotide insertion. With irradiation, markedly fewer P insertions were seen. The effect on coding joint structure is evident in a transient assay, in cultured cells, establishing that irradiation has an immediate impact on the process of V(D)J recombination. A specific proposal for how the DNA-dependent protein kinase catalytic subunit influences the opening of hairpin DNA intermediates during coding joint formation in V(D)J recombination is presented.

Animals↗
PubMed1999

The effect of dietary fat on malondialdehyde concentrations in Fischer 344 rats.

The effects of dietary fat and age on the level of malondialdehyde (MDA), a product of lipid peroxidation, were investigated in cerebellum, kidney, and liver tissues of female Fischer 344 rats. Groups of rats were fed diets containing various levels of corn oil (3, 5, 10, 15, or 20%), starting at 57 days of age, for a duration of 2, 10, or 20 weeks. High fat diets are thought to promote tumor formation, diabetes, and cardiovascular diseases via induction of oxidation stress, and this can begin early in the lifespan. However, it was observed that rats chronically consuming 3 and 5% corn oil diets yielded significantly higher levels of MDA, as analyzed by high-performance liquid chromatography, compared with those fed higher fat diets. After 20 weeks of feeding, the concentration of MDA in each of the three organs studied showed no significant differences among rats consuming diets containing 10, 15, or 20% corn oil. The levels of MDA were highest in the cerebellum, followed by kidney, and lowest in liver. Over the 20-week feeding period, a decrease in MDA level in both cerebellum and liver was observed.

Aging↗
PubMed1999

Functional characterization of B lymphocytes generated in vitro from embryonic stem cells.

To study molecular events involved in B lymphocyte development and V(D)J rearrangement, we have established an efficient system for the differentiation of embryonic stem (ES) cells into mature Ig-secreting B lymphocytes. Here, we show that B lineage cells generated in vitro from ES cells are functionally analogous to normal fetal liver-derived or bone marrow-derived B lineage cells at three important developmental stages: first, they respond to Flt-3 ligand during an early lymphopoietic progenitor stage; second, they become targets for Abelson murine leukemia virus (A-MuLV) infection at a pre-B cell stage; third, they secrete Ig upon stimulation with lipopolysaccharide at a mature mitogen-responsive stage. Moreover, the ES cell-derived A-MuLV-transformed pre-B (EAB) cells are phenotypically and functionally indistinguishable from standard A-MuLV-transformed pre-B cells derived from infection of mouse fetal liver or bone marrow. Notably, EAB cells possess functional V(D)J recombinase activity. In particular, the generation of A-MuLV transformants from ES cells will provide an advantageous system to investigate genetic modifications that will help to elucidate molecular mechanisms in V(D)J recombination and in A-MuLV-mediated transformation.

Abelson murine leukemia virus↗
PubMed1999

Palindromy is eliminated through a structure-specific recombination process in rodent cells.

Higher eukaryotes are proficient at remodeling palindromic DNA. As shown here, a fully palindromic 15.4 kb circular DNA can be introduced into rodent cells with the novel result that the molecule is reproducibly and site-specifically converted to a monomeric circle. The dimer-to-monomer conversion has not been described previously, and in particular is undetectable in Escherichia coli. Comparative DNA sequence analyses of the new junctions found within the monomer circles suggest that the resolution process involves formation of hairpin DNA structures followed by the introduction of single-strand nicks near their termini. By extension, hairpin nicking combined with non-homologous end-joining may be important as a general mechanism for the main-tenance of genomic stability in mammalian cells. It is suggested that the absence of a comparable strategy for coping with palindrome-induced structure in E.coli and other unicellular organisms underlies a fundamental difference in DNA sequence organiz-ation in the genomes of prokaryotes versus higher eukaryotes.

Animals↗
PubMed1999

Stenting for in-stent restenosis: A long-term clinical follow-up.

We studied the feasibility, safety, and short- and long-term outcomes of treating coronary in-stent restenosis with primary restenting. Thirty-one patients (32 lesions) were treated. Eleven patients had adjunctive rotational atherectomy. Clinical follow-up was obtained in all 31 patients at a mean of 9.1 +/- 5.5 months by direct phone contact with the patients, medical records, and subsequent hospitalization for recurrent symptoms and/or revascularization. There were no cardiac deaths or myocardial infarctions. In native vessels (26 patients), repeat target lesion revascularization was required in eight patients (31%); two other patients (7.7%) had angina and were treated medically. All vein graft lesions had recurrent restenosis. Significant predictors of recurrent clinical events were lesions in vein grafts, multivessel disease, and use of higher poststent deployment inflation pressures. Primary restenting for in-stent restenosis in native vessels is a safe approach with good short-term outcome. Recurrent restenosis remains a problem, as it does with other devices, particularly in vein graft lesions and in patients with multivessel disease. Restenting for in-stent restenosis should probably be used selectively. Cathet. Cardiovasc. Intervent. 48:143-148, 1999.

Aged↗
PubMed1999

Choice and stimulus-response compatibility affect duration of response selection.

In general, for movements to visual targets, response times increase with the number of possible response choices. However, this rule only seems to hold when an incompatibility exists between the stimulus and response, and is absent when stimulus and response are highly compatible (e.g., when reaching toward the location of the stimulus). Stimulus-response (S-R) compatibility can be manipulated either at the level of stimulus and response characteristics, or at the level of the mapping between elements of the stimulus and response sets. The current study was undertaken to determine the extent of the interaction between choice and each of these two levels of S-R compatibility. Subjects used a joystick to move a cursor in response to two, four or eight possible cues, with S-R compatibility manipulated along two dimensions (type of stimulus, and mapping between stimulus and response sets) in separate blocks of trials. Choice effects were absent when S-R relationships were highly compatible, moderate when incompatible in either of the two dimensions, and greatest when incompatible in both dimensions. These results indicate that choice affects response selection at each stage in the decoding of S-R relationships. Similar but smaller effects were seen for trials in which the stimulus was the same as that presented in the immediately preceding trial, suggesting that repeated stimulus-response transformations are faster and more efficient due to the priming effects of previous trials.

Adult↗