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Biomedical subjects

J A Evans

Publications and source records attributed to J A Evans.

At least 19 recordsLinked to original sources

Low lumbar spine bone mineral density in both male and female endurance runners.

There have been many reports of low bone mineral density (BMD) in female endurance runners. Although there have been several reports of low BMD in male runners, it is unclear how comparable the problem is to that in females. We compared BMD between male and female endurance runners and with a reference population. One hundred and nine endurance runners (65 females, 44 males) aged 19-50 years participated and had been training regularly for at least 3 years (32-187.2 km week(-1)) in events from 3 km to the marathon. BMD was measured at the lumbar spine (L2-L4) and hip by DXA. A questionnaire assessed training and menstrual status. Lumbar spine T scores were similar in male and female runners (-0.8 (0.8) versus -0.8 (0.7); f = 0.015; P = 0.904) as were total hip T scores (0.6 (7.9) versus 0.5 (9.2); f = 0.192; P = 0.662). The proportion of male runners with low lumbar spine BMD (<-1.0) (n = 16 from 44) compared to that of females (n = 27 from 65) (P = 0.675). Males had lower spine T scores than eumenorrhoeic females (-0.8 (0.7) versus -0.4 (0.7); f = 5.169; P = 0.03). There were moderate negative correlations between weekly running distance and lumbar spine BMD in males and females (r(2) = 0.267; 0.189; P < 0.001), independent of menstrual status in females (r(2) = 0.192; P < 0.001). Lumbar spine but not hip T scores were greater in runners who participated in resistance training at least twice-a-week (male: -0.4 versus -1.1; female: -0.5 versus -1.1; P < 0.01). Using multiple regression, running distance (-) and BMI (+) together best predicted lumbar spine T scores (r(2) = 0.402; P < 0.01) in females. Although weak, BMI (+) best predicted hip T scores (r(2) = 0.167; P < 0.05). In males, running distance and training years (-) together best predicted lumbar spine T scores (r(2) = 0.400; P < 0.01). Training years (-) best predicted hip T scores (r(2) = 0.361; P < 0.01). To conclude, our findings suggest that male runners face the same bone threat at the spine, as female runners. Further research in male athletes is required. Incorporation of regular resistance training into an athlete's training programme may be a useful preventative strategy.

Absorptiometry, Photon↗

Membrane electroporation theories: a review.

Electroporation, the transient increase in the permeability of cell membranes when exposed to a high electric field, is an established in vitro technique and is used to introduce DNA or other molecules into cells. When the trans-membrane voltage induced by an external electric field exceeds a certain threshold (normally 0.2-1 V), a rearrangement of the molecular structure of the membrane occurs, leading to pore formation in the membrane and a considerable increase in the cell membrane permeability to ions, molecules and even macromolecules. This phenomenon is, potentially, the basis for many in vivo applications such as electrochemotherapy and gene therapy, but still lacks a comprehensive theoretical basis. This article reviews the state of current electroporation theories and briefly considers current and potential applications in biology and medicine.

Animals↗

Pre-treatment with chloroquine and parasite chloroquine resistance in Ghanaian children with severe malaria.

BACKGROUND: Self-medication with anti-malarial drugs is widespread, and chloroquine (CQ) resistance is increasing. The effect of these factors on the incidence and presentation of severe malaria is uncertain. AIM: To investigate subtype of severe malaria, duration of illness, previous CQ treatment and prevalence of Plasmodium falciparum CQ-resistance markers among children presenting with severe malaria to a teaching hospital in Ghana. DESIGN: Prospective clinical study. METHODS: Consecutive patients (n = 189) presenting with severe malaria were examined clinically, and blood was taken for routine haematology and malaria films. Plasma and blood cells were stored and subsequently analysed by ELISA for CQ levels (n = 168) and by PCR and restriction digest for P. falciparum chloroquine resistance transporter gene (pfcrt) mutations (n = 139). RESULTS: Of 47 presenting with cerebral malaria, 21 had severe anaemia and 13 respiratory distress (RDS). Twenty-nine had prostration or RDS alone, 41 severe anaemia with prostration or RDS, and 72 severe anaemia not associated with coma, prostration or RDS. Of the patients studied, 77% had CQ in their plasma, and 88% were carrying P. falciparum with a CQ-resistance genotype. Significant associations were found (i) between the CQ-resistance genotype of parasites and plasma CQ levels, (ii) between the presence of CQ in plasma and the reported duration of illness, and (iii) between the reported duration of illness and the occurrence of severe but otherwise uncomplicated anaemia. DISCUSSION: There was extensive prior CQ use in our patients presenting with severe malaria, and a high prevalence of parasites with the CQ-resistance genotype. CQ resistance in P. falciparum may contribute to the development of severe but otherwise uncomplicated anaemia in this setting.

Animals↗

Discrepancies in upper and lower limb patterning in split hand foot malformation.

Discrepancies in upper and lower limb patterning in split hand foot malformation. Split hand foot malformation (SHFM) is genetically heterogeneous with five loci mapped to date. Highly variable in presentation, it can occur as an isolated finding or with other anomalies. The genetic heterogeneity and clinical variability make genetic counselling of SHFM families challenging. By establishing genotype/phenotype correlations, one can provide insight into responsible developmental genes and help to direct mapping efforts and target genetic testing, ultimately providing more accurate information for family members. Preaxial involvement of the upper extremities was a significant discriminating limb-specific variable in our analysis of genetically mapped SHFM cases. This finding, which was originally identified through descriptive epidemiology, was subsequently confirmed by discriminant function analysis (p < 0.0001) to be a significant locus discriminator. Preaxial involvement of the upper extremities was most commonly seen at the SHFM3 locus mapped to chromosome 10q24 (OMIM 600095) and consisted of proximally placed thumbs and/or triphalangeal thumbs (TPT), preaxial polydactyly and/or absence of the first ray. These patients' feet, however, tended to show a classical central longitudinal deficiency without a significant preaxial component. This article discusses this discrepant clefting pattern between the upper and lower extremities and proposes potential mechanisms.

Abnormalities, Multiple↗

Split hand foot malformation (SHFM).

The nomenclature describing the phenotype of missing central rays in the hand and/or foot in the genetics and surgical literature is heterogeneous and confusing. Split hand/foot malformation (SHFM) is the most common term for this phenotype in the genetics community; however, other names such as the offensive 'lobster-claw malformation' and the non-specific 'ectrodactyly' are still utilized to describe this malformation. In this article, we briefly review the nomenclature associated with SHFM and its classifications.

Foot Deformities, Congenital↗

High mortality of infant bacteraemia clinically indistinguishable from severe malaria.

BACKGROUND: Early recognition of children at highest risk of dying and the targeting of appropriate drug therapy are vital to the improvement of paediatric care in developing countries. This will rely upon the development of simple clinically-based algorithms and treatment guidelines. AIM: To determine the role of bacteraemia in children presenting with clinical signs and symptoms of severe malaria. DESIGN: Retrospective analysis of blood culture results following prospective data collection. METHODS: We studied 251 children presenting with symptoms and signs of severe malaria to a tertiary referral centre in Ghana. Blood was taken for malaria blood films, bacterial culture and haemograms. RESULTS: On the basis of clinical signs alone, malaria-film-positive (n = 182) and -negative (n = 69) patients were indistinguishable. Some 40% of film-negative patients were bacteraemic, vs. 12% of film-positive patients. Severe malaria and bacteraemia were not positively associated. Film-negative bacteraemic patients had a mortality of 39%, primarily affecting the age group <30 months. DISCUSSION: Infants presenting with symptoms and signs of severe malaria but a negative malaria film require immediate antibiotic treatment.

Age Distribution↗

Photoperiod differentially modulates photic and nonphotic phase response curves of hamsters.

Circadian pacemakers respond to light pulses with phase adjustments that allow for daily synchronization to 24-h light-dark cycles. In Syrian hamsters, Mesocricetus auratus, light-induced phase shifts are larger after entrainment to short daylengths (e.g., 10 h light:14 h dark) vs. long daylengths (e.g., 14 h light:10 h dark). The present study assessed whether photoperiodic modulation of phase resetting magnitude extends to nonphotic perturbations of the circadian rhythm and, if so, whether the relationship parallels that of photic responses. Male Syrian hamsters, entrained for 31 days to either short or long daylengths, were transferred to novel wheel running cages for 2 h at times spanning the entire circadian cycle. Phase shifts induced by this stimulus varied with the circadian time of exposure, but the amplitude of the resulting phase response curve was not markedly influenced by photoperiod. Previously reported photoperiodic effects on photic phase resetting were verified under the current paradigm using 15-min light pulses. Photoperiodic modulation of phase resetting magnitude is input specific and may reflect alterations in the transmission of photic stimuli.

Animals↗

A new method for characterizing carotid plaque: multiple cross-sectional view echomorphology.

PURPOSE: This study compares the ability of computer-derived B-mode ultrasound gray-scale measurements from a single longitudinal view (SLV) versus multiple cross-sectional views (MCSV) to differentiate symptomatic from asymptomatic carotid plaque causing more than 70% stenosis. METHOD: Seventy-four internal carotid artery (ICA) stenoses (70%-99%; 33 asymptomatic, 41 symptomatic within 3 months) were imaged to obtain the "best" SLV and five to eight MCSV images at 5 mm intervals from the carotid bifurcation. Digitized sonograms were computerized and normalized to the gray scale median (GSM) of blood (0) and vessel adventitia (200). Plaque GSM was determined for each frame (image analysis, MATLAB 5.3). General risk factors for stroke and plaque echogenicity (SLV GSM; minimum MCSV GSM; cross-sectional axial heterogeneity (highest minus lowest MCSV GSM) were determined for each group. RESULTS: Risk factors for stroke were similar in both groups, as was mean SLV GSM: symptomatic, 34 (95% confidence interval [CI], 24.8-43.0), asymptomatic, 43 (CI, 32.6-53.2); P =.1. Minimum MCSV GSM was lower for symptomatic plaque: 7 (CI, 4.2-9.8] vs 18.3 (CI, 12.2-24.5); P =.002. Greater axial GSM heterogeneity was present in symptomatic plaque: 34.5 (CI, 27.2-41.9) vs 16 (CI, 11.0-20.8); P =.0001. CONCLUSIONS: MCSV cross-sectional imaging that enables objective assessment of regional plaque echolucency and heterogeneity is more sensitive than SLV sonography for differentiating symptomatic from asymptomatic plaque.

Aged↗

Total body water measurement using bioelectrical impedance analysis, isotope dilution and total body potassium: a scoring system to facilitate intercomparison.

OBJECTIVES: (1) To develop a scale that is useful in evaluating the accuracy of multifrequency bioelectrical impedance analysis (MF-BIA) in the assessment of body water volumes against the accepted gold standard measurements based on isotope-dilution and total body potassium (TBK). (2) To perform a pilot test of the scale. DESIGN: A scale was developed to evaluate the accuracy of MF-BIA in the assessment of body water volumes. Questions were obtained from reading the scientific literature and discussions involving the four authors. Three of these and two additional independent readers pre-tested the scale. A weighting was identified for each question and a pilot test with a sample of 10 articles (different to those used for the questionnaire performance) was conducted. A further validation was carried out with a second set of 20 articles and two additional independent readers. RESULTS: The kappa statistic expressing the level of agreement between pairs of the first three authors using this scale with 10 articles, was 0.3, 0.4 and 0.6 after the first attempt. A second evaluation after specific changes improved the agreement to 0.8, 0.6 and 0.8. The mean score for 10 articles was 252+/-36 points from a total score of 400 (63+/-9%). The evaluation with the second set of 20 articles resulted in a kappa of 0.7 from two pairs of authors. The evaluation with two additional reviewers resulted in a kappa=0.7. CONCLUSION: A tool has been developed to assess the accuracy of the MF-BIA technique and to identify methodological components, plan future studies and critically evaluate data in this area. It is likely that this tool may also be used to assess the accuracy of single frequency studies.

Body Water↗

Application of (1)H- and (19)F-NMR spectroscopy in the investigation of the urinary and biliary excretion of 3,5-, 2,4-ditrifluoromethylbenzoic and pentafluorobenzoic acids in rat.

1. The metabolism and excretion of 2,4-, 3,5-ditrifluoromethyl- and pentafluorobenzoic acids were studied in the bile-cannulated rat using (1)H- and (19)F-NMR spectroscopy following intraperitoneal administration at 50 mg kg(-1). 2. Pentafluorobenzoic acid was excreted in the urine entirely unchanged. No detectable compound or metabolites were eliminated in the bile. A total of 63.5 +/- 6.7% of the dose was recovered in the 24-h collection period. 3. In the case of 2,4-ditrifluromethyl benzoic acid, 83.9 +/- 5.2% of the dose was recovered in the 24h after administration, with about 52% being excreted in the urine and 32% in the bile. The majority of the material present in the urine was unchanged parent compound. In bile, some 60% of the compound-related material excreted was present as transacylated ester glucuronide conjugates. 4. For 3,5-ditrifluoromethylbenzoic acid, 49.6 +/- 5.3% of the dose was recovered in the 24-h collection period, with about 22% being excreted in the urine and 28% in the bile. The material excreted in both the urine and bile was a mixture of the parent acid and transacylated ester glucuronides. 5. Urinary excretion in bile-cannulated animals was similar to that found in studies using non-cannulated animals dosed at 100mg kg(-1).

Animals↗

Genomic DNA hybridizes with the same rate constant on the QCM biosensor as in homogeneous solution.

Hybridization rates of sheared, genomic E. coli DNA in 0.14 M, pH 6.7 phosphate buffer at 65 degrees C were determined by: (1) observing the rate of absorbance decrease at 260 nm due to self-hybridization in solution; and (2) measurement of the rate of mass increase caused by hybridization between DNA in solution and DNA photografted to polystyrene. The latter measurement was done using a quartz crystal microbalance (QCM). In both the spectrophotometric and QCM experiments the probe was identical to the target, as both were taken from the same sample of sheared E. coli DNA. In the QCM measurements, viscoelastic effects were made negligible by drying the biopolymer layer on the QCM's surface before taking the frequency readings. Our purpose was to explore the effect of immobilizing DNA on its hybridization rate constant. A second-order constant of 2.32 +/- 0.09 x 10(-6) ml microg(-1) s(-1), n = 14, for hybridization in solution was obtained spectrophotometrically, while the QCM experiment gave a constant of 2.2 +/- 0.3 x 10(-6) ml microg(-1) s(-1), n = 6. These values are not statistically different. The reaction half-lives for the spectrophotometric and QCM experiments were 6.5 h and 13 min, respectively. The shorter half-life on the QCM can be explained solely by the much greater reactant concentration in the QCM experiment. About 25% of the DNA was inactivated by the attachment reaction. After correcting for this, the surface-attached DNA hybridized with the same rate constant as DNA free in solution. Therefore, it is concluded that, in these specific experiments with genomic DNA, the immobilized regions must have been short compared to the length of the molecules. The data demonstrate the high hybridization rate obtainable when nucleic acids are hybridized in a thin-film, micro-volume reaction on a non-porous surface.

Biosensing Techniques↗

Severe acro-renal-uterine-mandibular syndrome.

Although limb and renal defects occur together in a variety of patterns of multiple malformations, familial cases of acro-renal disorders are rare. In 1980, Halal et al. ¿Am J Med Genet 5:277-284 described two sisters with unusual limb deficiencies, renal anomalies, and mandibular hypoplasia and termed this condition acro-renal-mandibular syndrome. A girl reported earlier by Fitch and Lachance ¿1972; Can Med Assoc J 107:653-656 had similarly limb and renal findings, but an apparently normal jaw. We document three sibs with unusual limb deficiencies, renal agenesis, uterine anomalies in the two females, and orofacial defects, who clearly have a similar but more severe type of acrorenal disorder, apparently inherited as an autosomal recessive condition. The sibs with limb deficiencies and renal agenesis reported by Hennekam et al. ¿1994; Am J Med Genet 53:102-107 appear to be additional cases of this very rare disorder, the pathogenesis of which may be related to abnormal epithelial-mesenchymal interactions.

Abnormalities, Multiple↗

Rapid SLT gene detection on polyethylene-coacrylic acid film without molecular labels or surface-fouling agents.

The commercially available copolymer of 10 mol% acrylic acid and polyethylene is easily formed into a nonfluorescing, non-polynucleotide-adsorbing film. The film has surface carboxylate functions whose concentration can be increased by heating to 80 degrees C in 30% NaOH. The carboxylate groups will react at pH approximately 7 with commercially available, oligo-DNA, 2-8 ng/microl, that has been synthesized with a C(12)-alkylamino tail on the 5'-end. The reaction is mediated with water-soluble carbodiimide reagent and is assumed to result in a primary amide bond between the polymer film and the modified oligo-DNA. The tethered oligo-DNA retains its hybridization activity, and its surface concentration is sufficient to permit qualitative, labelless detection of hybridized target by fluorescence after brief staining with ethidium bromide. The film is used to detect Shiga-like toxin gene II (SLT-II) from Escherichia coli O157:H7 after asymmetric, capillary, PCR amplification, and a 4-h hybridization. Captured target may be removed from the film using distilled water, after which the film can be used again without noticeable loss of activity. The method provides relatively rapid detection of PCR amplimers without having to use molecular labels, or surface-fouling agents.

Acrylates↗

The interactive Web-based histology atlas system.

Molecular pathways and mechanisms underlying human cancer are frequently investigated in animal models. Studies to identify and dissect molecular pathways include the discovery of genes and their subsequent analysis in transgenic and 'knock-out' mice. A critical aspect in such investigations is the evaluation of organ integrity and histology upon the alteration or inactivation of specific genes. Results from such studies are usually published in scientific journals. However, due to print space and costs the display of large high quality images is limited. Furthermore, the printed media does not permit an easy comparison of histological images published in different journals and different years. The Internet provides a tool for the timely and inexpensive dissemination of scientific data to the research community. However, its potential for the analysis of histological images has not been explored. Here we present a web-based interactive histology atlas (http://histology.nih.gov) that permits the retrieval of annotated, high-resolution histology images via the Internet. This histology atlas also takes advantage of the interactive nature of the Internet to support the communication between different research groups. As an outline forum this atlas provides the framework to evaluate and understand cancer pathology, and to develop a consensus between veterinary and human pathologists.

Animals↗

Osteonecrosis of the knee after arthroscopic surgery for meniscal tears and chondral lesions.

PURPOSE: Avascular necrosis of the knee following arthroscopic surgery has been described. The purpose of this article is to report a large series of patients who developed avascular necrosis after arthroscopy of the knee in an effort to delineate casual factors and results of treatment. TYPE OF STUDY: Case series. METHODS AND MATERIALS: The charts, radiographs, and magnetic resonance imaging (MRI) scans of patients who developed osteonecrosis (ON) of the knee after routine arthroscopic surgery were reviewed. Only those patients with no evidence of ON on preoperative MRI performed 6 weeks or longer after symptom onset and who postoperatively developed ON confirmed by repeat MRI and/or by pathological testing (specimens obtained at subsequent total knee arthroplasty) were included in the study. Seven patients with average age of 60 years (range, 41 to 79 years) met these inclusion criteria. RESULTS: The lesions noted at arthroscopy included 4 medial meniscus tears, 3 lateral meniscal tears, 6 chondromalacia of the medial femoral condyle, 2 chondromalacia of the medial tibial plateau, 1 chondromalacia of the lateral femoral condyle, 1 chondromalacia of the lateral tibial plateau, and 2 chondromalacia of the patella. The location of postarthroscopy ON correlated geographically with pre-existing pathology. All 7 patients had meniscal and/or chondral lesions addressed surgically in the compartment that subsequently developed ON. Six of the 7 patients had an adjacent ipsilateral meniscus tear treated with partial meniscectomy (4 medial, 2 lateral). In addition, of the 4 patients who developed ON of the medial femoral condyle, all had overlying chondromalacia, 3 of whom were treated with arthroscopic chondroplasty. Of the 2 patients with lateral meniscal tears, 1 developed ON of the lateral femoral condyle and the other developed ON of the lateral tibial plateau. Three patients went on to require total knee arthroplasty, and 2 high tibial osteotomy. One patient's ON resolved and another patient was lost to follow-up. CONCLUSION: ON should be considered in patients who have worsening symptoms after arthroscopy of the knee. These findings suggest a possible relationship between arthroscopic treatment of chondral and meniscal lesions and later appearance of ON in some patients. The role of arthroscopy in the development of ON needs to be further studied. Those at risk are elderly patients with chondral and meniscus lesions.

Adult↗