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Biomedical subjects

A Perera

Publications and source records attributed to A Perera.

At least 19 recordsLinked to original sources

Ciprofloxacin implants for bone infection. In vitro-in vivo characterization.

To elucidate the antibiotic release mechanism from implants composed of calcium phosphates (hydroxyapatite [HAP] and tricalcium phosphate [TCP]), 30 kDa poly(DL-lactide) (PLA-30) and ciprofloxacin (CFX), nine formulations were prepared. In vitro results show that the release rate decreased as compression load and PLA/phosphates ratio increased. In contrast, a slower percent release rate was observed with higher drug loading. Swelling-erosion-disintegration of the implants was observed during the release assays, due to CFX swelling. Two CFX implant formulations were selected for implantation in the femur of rabbits, according to in vitro results. The implant drug loads tested were 10% and 40% of CFX. The in vivo results showed that the antibiotic concentrations achieved throughout the femur were higher for 4 weeks than the minimum inhibitory concentrations (MIC) against the most common of the pathogens that cause osteomyelitis. The CFX-10% implant was considered the best formulation as CFX was totally released within 6 weeks, and therapeutic bone levels were achieved, and the histological and radiographic analyses showed the osteoconductive properties of the materials. All these results showed that CFX release is limited by its solubility, and the erosion-disintegration and bone ingrowth into the implants enhanced the antibiotic release.

Animals↗

In vitro-in vivo characterization of gentamicin bone implants.

A gentamicin carrier system composed of calcium phosphates, poly(DL-lactide) (PLA) and gentamicin was developed and characterized in vitro and in vivo for use in the prevention and treatment of bone infection. Four formulations were prepared according to an experimental design based on the Hadamard matrix. The technological variables included in the design were: gentamicin loading with respect to the implant weight, weight average molecular weight (M(w)) of the PLA as a compound of the matrix and the presence or absence of a PLA coating of 200 kDa. The variable to be optimized in vitro was the gentamicin release level during the first week. According to this goal, the selected formulation was F-D which was composed of 80% phosphates (25% hydroxyapatite, HAP and 75% tricalcium phosphate, TCP), 20% PLA (M(w), 30 kDa) and 3.5% gentamicin sulfate (GS) and was coated with PLA (M(w), 200 kDa). To elucidate the in vitro release mechanism of this implant, another implant lot (F-X) uncoated, but with identical matrix composition, was prepared. Results showed that the PLA coating delay the gentamicin release, indicating that part of the antibiotic released from the matrix diffuses through the polymer coating film. The selected formulation was tested in the femur of rabbits and showed a faster release rate in vivo than in vitro. This is due to a greater degree of PLA degradation, changes in the phosphate blend, and bone tissue invading the implant. Gentamicin concentration in the areas of the bone closest to the implant was higher than the minimum inhibitory concentration (MIC) against Staphylococcus aureus.

Animals↗

Entropy-driven demixing in spherocylinder binary mixtures.

The stability of binary fluid mixtures, with respect to a demixing transition, is examined within the framework of the geometrical approximation of the direct correlation for hard nonspherical particles. In this theory, the direct correlation function is essentially written in terms of the geometrical properties of the individual molecules, and those of the overlap region between two different molecules, taken at fixed separation and orientations. Within the present theory, the demixing spinodal line in the (rho(1),rho(2)) concentration plane is obtained analytically, and shown to be a quadratic function of the total packing fraction and the compositions. The theory is applied herein to binary mixtures of hard spherocylinders in the isotropic phase. Isotropic fluid-fluid demixing can be predicted for a large variety of sizes and aspect ratios, and the necessary condition for entropic demixing is a sufficiently large thickness difference between the two particles that belong to each of the fluids in the mixture. As the theory reduces exactly to the Percus-Yevick approximation for a hard sphere mixture, accordingly it will not predict fluid-fluid demixing for this particular case. Demixing is also forbidden in two other cases; for a mixture of spherocylinders and small spheres, and for mixtures of equally thin spherocylinders. The influence and competition of an ordering instability on the demixing is also examined. The ordering of a fluid will always be displaced toward higher packing fractions by the addition of a nonordering fluid, and in some cases the entropic demixing can dominate the entire fluid range. Although the present theory merges exactly with the correct Onsager limit, it is shown that, for intermediate cases, the results can be significantly different from predictions of Onsager type approaches. These discrepancies are analyzed in particular for the needle plus spherocylinder mixture. Finally, in view of the nature of the theory, it is conjectured that the predicted demixing densities values are rather upper bounds to what should be expected.

Journal Article↗

In vivo-in vitro study of biodegradable and osteointegrable gentamicin bone implants.

Three implants composed of phosphate (25% hydroxyapatite, 75% tricalcium phosphate), 20% poly(DL-lactide) (DL-PLA; weight-average molecular weight (Mw), 30 kD) and 3% gentamicin sulphate (GS) were assayed in vitro and in vivo to study their release profiles as potential drug delivery systems to prevent or treat osteomyelitis. To prolong GS release, some implants were coated with poly(lactide-co-glycolide) (PLGA; Mw, 100 kD; I-PLGA) or DL-PLA (Mw, 200 kD; I-PLA). GS levels were measured in bone, kidney and blood after implantation into the femur of rats. The release profiles show a burst in the first few days, followed by a slower release rate. After I-PLA implantation, bone antibiotic concentrations higher than the minimum bactericidal concentration were maintained for 4 weeks. A linear correlation between in vitro and in vivo GS release was found to continue until complete drug release. Histological and radiological analysis showed that the implants were well tolerated and gradual new bone formation was observed.

Absorbable Implants↗

Prevalence of skin diseases in suburban Sri Lanka.

BACKGROUND: In Sri Lanka the only available measures of disease frequency related to skin disorders are from hospital-based clinic studies. They reflect only the patterns of clinic attendance, and the actual prevalence of skin diseases in the community is unknown. The main objective of this study was to determine the prevalence of skin diseases in a selected area. METHODS: A household survey based on health interviews and clinical examination was conducted over a period of 4 months. 418 households were selected for modified cluster sampling from predetermined areas in Piliyandala. RESULTS: There were 1806 people residing in the 418 households surveyed. 894 cases were identified, of which 34 people could not be traced for clinical examination. 33 households did not have anyone with a skin lesion. The prevalence of skin disease was 47.6%. Fungal infections, followed by dermatitis, were found to be the commonest problems. There was only one case of leprosy. Psoriasis was found to be of low prevalence. CONCLUSIONS: The overall prevalence of skin disease was high in the community that we surveyed. There were marked differences between community prevalence and hospital dermatology clinic attendance data for a number of skin diseases.

Adolescent↗

Integral equation theory for fluids ordered by an external field: separable interactions.

The structural and thermodynamical properties of classical fluids orientationally ordered by an external field are investigated by means of integral equation theories. A general theoretical framework for handling these theories is developed and detailed for the particular case of separable interactions between fluid particles. This approach is then illustrated for the case of two (off lattice) models: the ferromagnetic Heisenberg model and a simple liquid crystal model, for which the numerical solution of integral equations such as the Percus-Yevick, the hypernetted chain, and the reference hypernetted chain closure equations are presented and compared with Monte Carlo simulation results and the analytical solution of the mean spherical approximation. The zero-field case is also examined, and the spontaneous ordering is analyzed in detail, mainly in what concerns the appearance of infinite wavelength singularity in the Ornstein-Zernike equation and the relation with the one-body closure equations and the long range orientational ordering that occurs. In particular, it is shown that the Wertheim one-body closure equation appears as a sum rule compatible with the Ornstein-Zernike equation. The relation between the elastic constant and the long range tail of the pair correlation function is made explicit. In particular, the long range behavior of the various terms in the expansion of the pair correlation function is depicted. The numerical investigation of the two models shows that it is not possible to discriminate between the four integral equations, as to which one would be the most accurate in all cases. The general trends in the thermodynamical and structural properties seem to indicate that the Percus-Yevick approximation is generally better in the strong ordering case, whereas the reference hypernetted chain approximation might be better suited to the study of the isotropic phase and the low ordering regimes.

Journal Article↗

99mTc-labeled antihuman epidermal growth factor receptor antibody in patients with tumors of epithelial origin: Part III. Clinical trials safety and diagnostic efficacy.

UNLABELLED: Monoclonal antibody (moAb) ior egf/r3 is an IgG2a that recognizes the epidermal growth factor receptor (EGF-R). The aim of this study was to evaluate the diagnostic efficacy of the 99mTc-labeled moAb ior egf/r3 for the detection of epithelial-derived tumors, their metastases and recurrences. METHODS: One hundred forty-eight adult patients (51 women, 97 men; mean age 53 +/- 13 y) who were suspected of having cancer of epithelial origin were administered 3 mg/50 mCi (1.85 GBq) 99mTc-labeled moAb ior egf/r3 by intravenous bolus injection. Planar anterior and posterior images of the lesion sites and suspected metastases were acquired at 2, 4, 6 and 24 h after injection, and SPECT images were scanned at 5 h postinjection, using a 360 degrees circular orbit with 64 images. The backprojection method was used for image reconstruction with a Hamming-Hann filter. RESULTS: Labeling efficiency was always greater than 98.5% +/- 2.1 %. No adverse reactions or side effects were observed. Results of the biopsy specimens showed that 85.1% (126/148) of the patients had tumors of epithelial origin, 14.2% (21/148) were negative and 0.7% (1/148) had non-Hodgkin's lymphoma. The sensitivity rate by organ was as follows: brain (8/8, 100%), digestive tract (10/11, 90.9%), head and neck (17/23, 73.9%), lung (52/62, 83.9%) and breast (16/18, 88.9%). Overall sensitivity, specificity, accuracy, and positive and negative predictive values of the immunoscintigraphic imaging were 84.2% (106/126), 100.0% (22/22), 86.5% (128/148), 100% (106/106) and 52.4% (22/42), respectively. New metastases not identified previously by other diagnostic methods were detected in the 50% of the patients. CONCLUSION: Immunoscintigraphy with 99mTc-labeled moAb ior egf/r3 could be a useful procedure for the diagnosis and follow-up of the patients with tumors of epithelial origin.

Animals↗

Reliable and easy identification of bacterial acute respiratory infections of childhood.

OBJECTIVES: To identify the causative bacteria in childhood acute respiratory infections (ARI) and to determine the usefulness of pus cell counts in differentiating between pathogenic and commensal bacteria, cultured from nasopharyngeal aspirates. DESIGN: Case control prospective study. SETTING: Outpatients' department and the paediatric unit at General Hospital, Colombo South. SUBJECTS: 200 children under 5 years with cough and difficulty in breathing for less than one week who had no history of antibiotic therapy for the current illness, and 50 healthy controls matched for age and sex. RESULTS: 56.5% of cases had bacterial infections. Branhamella catarrhalis (25%), Haemophilus influenzae (12.5%) and Streptococcus pneumoniae (10.5%) were the major pathogens identified. Pus cell counts were found to be significantly higher in cases than in controls (X2 58.28 df = 1 p < 0.001), and the pathogens were more often associated with pus cell counts of more than 10/field. CONCLUSIONS: 56.5% of children with ARI had bacterial infections. B catarrhalis seems to play a major role in childhood ARI. Examination of nasopharyngeal aspirates is a useful way to identify pathogens, provided microscopic examination for pus cells is performed together with culture.

Acute Disease↗

[Antibody radiolabeling with technetium-99m].

Nowadays, labelled polyclonal and monoclonal antibodies are widely used for immunoscintigraphic diagnosis of different diseases. Technetium-99m is often considered to be the label of choice for radioimmunodiagnosis for reasons of cost, availability and imaging properties, in spite of its relatively short physical half-life (6.01 h). The existing labelling methods may be classified into two types: direct approaches, in which disulphide bridges within are reduced to generate endogenous sulfhydryl groups able to efficiently bind technetium due to their strong chelating capacity and indirect methods, in which an exogenous chelator is covalently attached to the protein to serve as the binding site. All these procedures have their advantages and drawbacks. There is no consensus among the authors about which of the methods is the best. The employed approach depends on the particular situation. The aim of the present work is to show an update about the available procedures for 99mTc-labelling of antibodies and its fragments.

Antibodies↗

Renal 99Tc(m)-DMSA SPET and planar imaging: are they really the same?

Previous studies have suggested that more defects are detected on SPET than on planar DMSA images. The aim of this study was to evaluate differences between planar and SPET imaging. Sixty-four kidneys from pyelonephritic patients were studied using both techniques. An automated algorithm for reorientation and centring of the SPET images was used to minimize inter-observer variability. Reduced uptake and contour defects showed different localization on planar and SPET imaging. Coincidence of defects on both types of image was low. We also noted a dependence on defect frequency content for detectability. Image contrast played a noticeable role in the detection of defects. Differences in contrast between SPET and planar images may be responsible for the variable success in the detection of defects. Contour defects are seen more frequently on tomographic slices, whereas reduced uptake defects are seen more frequently on planar images. A difference is also noted between the cortical and calyceal zones for differently contrasted lesions. SPET and planar DMSA images can potentially provide a different diagnosis of renal lesions.

Adult↗

High resolution 1H NMR investigations of the reactivities of alpha-keto acid anions with hydrogen peroxide.

The chemical reactivity of various alpha-keto acid anions (beta-hydroxypyruvate, beta-phenylpyruvate, 2-ketobutyrate and 2-ketoglutarate) with hydrogen peroxide (H2O2) was investigated at physiological pH (7.4) and a temperature of 25 degrees C. The initial concentration of the alpha-keto acid anions was kept constant at 1.00 mM whilst that of added H2O2 was varied from 0.25 to 1.00 mM, and the rate and extent of these reactions was evaluated using 1H NMR spectroscopy. At all H2O2 concentrations utilised, the order of reactivity of the alpha-keto acid anions was beta-hydroxypyruvate > beta-phenylpyruvate > 2-ketobutyrate > 2-ketoglutarate. The results obtained are in agreement with a proposed mechanism for these reactions, involving nucleophilic attack of the mono-deprotonated peroxide species (HO2-) at the C-2 carbonyl group carbon centre. The antioxidant capacity of such alpha-keto acids is discussed in terms of their potential use as therapeutic agents in clinical conditions where H2O2 has been shown to play a critical role in the disease process, i.e., those involving 'oxidative stress'.

Butyrates↗

Febrile ulceronecrotic Mucha-Habermann disease: a case report and review of the literature.

A 32-year-old male with febrile ulceronecrotic Mucha-Habermann disease (FUMHD) responsive to methotrexate is reported. This is a severe variant of pityriasis lichenoides et varioliformis acuta characterized by the acute onset of a widespread ulceronecrotic cutaneous eruption together with high fever and systemic involvement. To our knowledge, only 13 patients with FUMHD have been reported to date.

Adult↗