Biomedical subjects
Publications and source records attributed to S Barnard.
Splenogonadal fusion is a rare congenital abnormality. In this case report, the diagnosis of splenogonadal fusion was made after the removal of an abnormal mass at 'routine' left herniotomy. A cautious approach at surgery resulted in no apparent damage to the testicle. A short review of the literature is included.
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Children with sickle cell disease were immunized with either 2 doses of 7-valent pneumococcal conjugate vaccine followed by 1 dose of 23-valent pneumococcal polysaccharide vaccine or a single dose of 23-valent vaccine. Functional antibodies to 7 vaccine serotypes were measured by a flow cytometric opsonophagocytic assay (OPA) and compared with IgG anticapsular polysaccharide antibody concentrations measured by ELISA. Moderate correlations were found between OPA and ELISA antibody titers for all 7 serotypes (r values, 0.41-0.70; P<.001 for all serotypes). After immunization with 23-valent vaccine, geometric mean antibody titers by OPA were significantly higher in the combined schedule group for 5 of 7 vaccine serotypes but were significantly higher for only 2 of 7 serotypes as measured by ELISA. The ability of OPA to show a greater differential response to the 2 immunization schedules used in this study suggests that it may be useful in the evaluation of immunization regimens involving pneumococcal conjugate vaccines.
BACKGROUND: Several innovative approaches have been introduced in the surgical treatment of acute type A aortic dissection. This study examines the effects of these new techniques on the early and late outcomes of patients with this disease. METHODS: The records of patients who had surgery for acute type A aortic dissection during an 18 year interval were reviewed. There were 109 patients: 81 men and 28 women, with a mean age of 57 years, range 23 to 80. Most patients were acutely ill and 15 were in shock at the time of surgery. Operations were performed under cardiopulmonary bypass with femoral artery and right atrial cannulation. In 55 patients, the aorta was clamped and retrograde femoral perfusion was used throughout the procedure (group I). In 54 patients, no clamp was used; under circulatory arrest the primary tear was resected whether in the ascending aorta or transverse arch, and antegrade cardiopulmonary bypass was started after completion of the distal anastomosis (group II). Postoperative computed tomographic or magnetic resonance scans were completed annually. RESULTS: There were 16 operative deaths (15%): 11 (20%) in group I, and 5 (9.2%) in group II (p = 0.10). There were 10 strokes: 8 (14.5%) in group I and 2 (3.7%) in group II (p = 0.05). After a mean follow-up time of 59 +/- 45 months for group I, 31 (56%) patients were alive, and after a mean follow-up time of 45 +/- 26 months for group II, 44 (81%) patients were alive. The actuarial survival of group II was higher than group I, but the difference was not significant (p = 0.09). Postoperatively, a patent false lumen was found in 91% of group I patients and in 59% of group II (p = 0.01). CONCLUSIONS: This study suggests that avoidance of aortic clamping, resection of the primary tear in the ascending aorta or transverse arch, and antegrade perfusion after completion of the distal anastomosis improve the early and late outcomes of surgery for acute type A aortic dissection.
OBJECTIVE: To assess the accuracy and reproducibility of a digital image analyser and the human eye, in measuring radiographic dimensions. DESIGN: We experimentally compared radiographic measurement using either an image analyser system or the human eye with digital caliper. BACKGROUND: The assessment of total hip arthroplasty wear from radiographs relies on both the accuracy of radiographic images and the accuracy of radiographic measurement. METHODS: Radiographs were taken of a slip gauge (30+/-0.00036 mm) and slip gauge with a femoral stem. The projected dimensions of the radiographic images were calculated by trigonometry. The radiographic dimensions were then measured by blinded observers using both techniques. RESULTS: For a single radiograph, the human eye was accurate to 0.26 mm and reproducible to +/-0.1 mm. In comparison the digital image analyser system was accurate to 0.01 mm with a reproducibility of +/-0.08 mm. In an arthroplasty model, where the dimensions of an object were corrected for magnification by the known dimensions of a femoral head, the human eye was accurate to 0.19 mm, whereas the image analyser system was accurate to 0.04 mm. CONCLUSIONS: The digital image analysis system is up to 20 times more accurate than the human eye, and in an arthroplasty model the accuracy of measurement increases four-fold. We believe such image analysis may allow more accurate and reproducible measurement of wear from standard follow-up radiographs.
Opsonophagocytosis is the primary mechanism for clearance of pneumococci from the host, and the measurement of opsonophagocytic antibodies appears to correlate with vaccine-induced protection. We developed a semiautomated flow cytometric opsonophagocytosis assay using HL-60 granulocytes as effector cells and nonviable 5, 6-carboxyfluorescein, succinimidyl ester-labeled Streptococcus pneumoniae (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) as bacterial targets. The flow cytometric opsonophagocytosis assay was highly reproducible (for 87% of repetitive assays the titers were within 1 dilution of the median titer) and serotype specific, with >/=97% inhibition of opsonophagocytic titer by addition of homologous serotype-specific polysaccharide. In general, opsonophagocytic titers were not significantly inhibited by the presence of either heterologous pneumococcal polysaccharide or penicillin in the serum. The flow cytometric assay could reproducibly measure functional antibody activity in prevaccination (n = 28) and postvaccination (n = 36) serum specimens from healthy adult volunteers vaccinated with the 23-valent pneumococcal polysaccharide vaccine. When compared with a standardized manual viable opsonophagocytic assay, a high correlation (r = 0.89; P </= 0.01) was found between the two assays for the seven serotypes tested. The flow cytometric assay is rapid ( approximately 4 h) with high throughput ( approximately 50 serum samples per day per technician) and provides a reproducible measurement of serotype-specific functional antibodies, making it a highly suitable assay for the evaluation of the immune responses elicited by pneumococcal vaccines.
Streptococcus pneumoniae undergoes spontaneous phase variation between a transparent and an opaque colony phenotype, the latter being more virulent in a murine model of sepsis. Opaque pneumococci have previously been shown to express lower amounts of C polysaccharide (cell wall teichoic acid) and in this study were shown to have a higher content of capsular polysaccharide by immunoelectron microscopy. This report then examined the relationship between expression of these two cell surface carbohydrate structures and their relative contribution to the increased virulence of opaque variants. Comparison of genetically related strains showed that the differential content of capsular polysaccharide did not affect the amount of teichoic acid as measured by a capture enzyme-linked immunosorbent assay (ELISA). In contrast, when the teichoic acid structure was altered by replacing choline in the growth medium with structural analogs, the quantity of capsular polysaccharide as measured by a capture ELISA was decreased, demonstrating a linkage in the expression of the two surface carbohydrate structures. A standardized assay was used to assess the relative contribution of cell surface carbohydrates to opsonophagocytosis. The opaque variants required 1.2- to 30-fold more immune human serum to achieve 50% opsonophagocytic killing than did related transparent variants (types 6B and 9V). The opsonophagocytic titer was proportional to the quantity of capsular polysaccharide rather than teichoic acid. The major factor in binding of the opsonin, C-reactive protein (CRP), was also the amount of capsular polysaccharide rather than the teichoic acid ligand. Only for the transparent variant (type 6B), which bound more CRP, was there enhanced opsonophagocytic killing in the presence of this serum protein. Increased expression of capsular polysaccharide, therefore, appeared to be the major factor in the decreased opsonophagocytic killing of opaque pneumococci.
We describe a six-channel, all-solid-state, miniaturized fluorescence sensor array for the precise determination of blood analytes for medical diagnostic purposes. The device features superblue LEDs as light sources, GRIN optics, and photodiodes, assembled according to pigtailing procedures (Bruno, A. E.; et al. Trends Anal. Chem. 1994, 13, 190-198). The numerical aperture of the fluorescence optics is 0.46, rendering a collection efficiency of 2.4%. The performance of this instrument has been evaluated in terms of dynamic response, linearity, channel reproducibility, reversibility, long-term drifts, photobleaching of indicator, cross-talk, ionic strength, and selectivity in pH measurements. The responses of the pH sensing membranes were optimized in the physiological range. Responses are linear with typical values of approximately 1.5 V/pH units, with limits of decision of 24 mV, which corresponds to pH resolutions of 0.03 pH unit. Under continuous illumination, using calibration buffers, the sensors display nonstatistical differences within 2 standard deviations over a period of 6 h, and it is shown that, under discontinuous illumination, the membranes can be used in more than 2000 measurements without need of calibration, in contrast to electrochemical sensors which require periodic calibration. After selecting the appropriate combination of LEDs, excitation and emission filters, and sensing membranes, the instrument was used to determine the concentrations of various critical blood analytes in buffer solutions in the various channels. Similar measurements in untreated blood reproduce the reported results.
Twenty five participants were invited to a workshop looking at the role of research and development in complementary therapies. These participants took part in a modified Delphi study to ascertain a consensus from their broad spectrum of views and see how those views changed over time. Opinions were sought about respondents' perceptions of complementary therapies, the type and scope of research needed, and how such research should be coordinated. The workshop, arranged by the Regional Health Authority, included orthodox and complementary practitioners, purchasers, providers and academics. Questionnaires were administered at the beginning and end of the workshop and 6 months later. The group was small and potentially positively biased, having both pre-existing knowledge and interest in complementary therapies. In consensus, the more mainstream complementary therapies of osteopathy, acupuncture, and homeopathy were perceived to be the most beneficial to patients, and therefore, most likely to be recommended as treatments. These were also felt to be the priority areas for research. For some unknown reason homeopathy had lost its popularity in ranking 6 months later. The respondents agreed that research into complementary therapies was needed and ideally should be collaborative between practitioners, professional bodies, and academics. The workshop appeared to produce some changes in knowledge that were not always maintained over time. It was, however, formative in the decision of the Regional Health Authority to allocate research funding into complementary therapies.
The widely used analgesic paracetamol (P) produces fulminant hepatocellular necrosis in humans when taken in overdose. The toxicity is mediated by drug oxidation and depletion of hepatic glutathione. We have, therefore, explored the effects of fluorine substitution on the hepatotoxicity of P in female CD1 mice. 3-Fluoro-4-hydroxyacetanilide (1FPO), 3,5-difluoro-4-hydroxyacetanilide (2FPO), 2,6-difluoro-4-hydroxyacetanilide (2FPN) and 2,3,5,6-tetrafluoro-4-hydroxyacetanilide (4FP) were synthesized, characterized and investigated for their potential to cause hepatotoxicity in the mouse. Introduction of fluorine into P increases the oxidation potential of the drug. The oxidation potentials of paracetamol and its fluorinated analogues were measured by cyclic voltametry and found to increase in the order P < 1FPO < 2FPO < 2FPN < 4FP. Serum transaminase (ALT) and hepatic glutathione were measured 24 and 6 hr, respectively, after administration of a single dose (2.65 mmol/kg) of each compound to female CD1 mice. There was significant elevation of ALT in mice given P, 1FPO and 2FPO, but not in those which received either 2FPN or 4FP. Hepatic glutathione was reduced significantly by administration of P and IFP, but not after administration of 2FPO, 2FPN or 4FP. Accordingly, glucuronide and sulphate conjugates, but not thioether metabolites, were detected in urine after administration of 14C-labelled 2FPO, 2FPN and 4FP. These data indicate that introduction of fluorine into the 2 and 6 positions increases the oxidation potential of paracetamol which in turn reduces the propensity of the molecule to undergo oxidative bioactivation, and thereby reduces the in vivo toxicity of the molecule.
The physicochemical properties and analgesic action of six fluorinated analogues of 4-hydroxyacetanilide (paracetamol) have been investigated. Fluorine substitution adjacent to the hydroxyl group increased lipophilicity and oxidation potential whilst substitution adjacent to the amide had little effect on lipophilicity but led to a greater increase in oxidation potential. Lack of coplanarity and conjugation of the amide group and aromatic ring was also apparent with the analogues that had fluorine in the 2 and 6 positions. Introduction of fluorine into the amide group of paracetamol increased the lipophilicity 4-fold and also increased the oxidation potential of paracetamol. ED50 values for analgesic activity in the phenylquinone-induced abdominal constriction test on male Swiss White mice showed that ring substitution by fluorine reduced activity, especially at the 2,6-positions. Introduction of fluorine into the amide group enhanced activity significantly. Correlation of the analgesic activity with the physicochemical properties indicated that conjugation (and planarity) of the amide group with the aromatic ring is essential for activity and that ease of oxidation may also be an important factor.
The acoustic brainstem response (ABR) in clinical use is generally elicited by a wide band click stimulus. This gives a well-synchronized response detectable at low sound intensities, but requires tedious biological recalibration which could be largely eliminated by the use of pure tone pip stimuli. We have therefore assessed ABRs in response to pure tone pips at 2 KHz and 4 KHz. This has shown that these tone pips elicit a much poorer response than clicks, having thresholds which are both significantly higher, and more widely distributed. We therefore conclude that wide band clicks remain the most satisfactory stimulus for clinical use.
The case notes of 841 subjects who had had ECochG carried out between January 1972 and December 1980, were examined and the results compared with PTA results in 263 cases in which these were available. ECochG was found to be a good predictor of peripheral hearing as long as its limitations were recognized, and some of these are discussed. BSER, which has similar limitations, was also found to be a good predictor of peripheral hearing, although slightly less sensitive, and sometimes gave additional information on the hearing loss and the clinical state of the patient.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Optical sensors are prepared by immobilizing an indicating layer on the distal end of a fiber optic cable. Dyes, enzymes, and antibodies can all be incorporated into the layer using a variety of immobilization techniques. Much of the present work is devoted to developing novel indicating schemes by combining appropriate recognition schemes into polymeric matrices.