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Biomedical subjects

W W Lovell

Publications and source records attributed to W W Lovell.

At least 19 recordsLinked to original sources
PubMed2000

Comparison of an in vitro cellular phototoxicity model against controlled clinical trials of fluoroquinolone skin phototoxicity.

Many therapeutic drugs induce phototoxic skin responses following exposure to solar or artificial ultraviolet radiation sources. Several in vitro model systems have been developed to predict drug phototoxicity but none have been conducted in parallel with controlled clinical phototoxicity studies on systemically administered pharmaceuticals. The in vitro phototoxicity of eight fluoroquinolone (FQ) antibiotics (ciprofloxacin, grepafloxacin, lomefloxacin, norfloxacin, ofloxacin, trovafloxacin, BAYy3118, moxifloxacin) was determined by exposing Chinese hamster fibroblasts to UVA radiation. Cell damage was quantified with standard MTT or neutral red assays and an in vitro phototoxic index calculated (PI(vit)=% cell viability with UVA alone /% cell viability with UVA+FQ) for each endpoint. Clinical photosensitizing ability of the eight systemically administered FQ was investigated using double-blind, placebo and positive controlled, clinical skin phototesting of normal subjects. Minimal erythema doses at 365+/-30nm were determined before and after 6-7 days of FQ ingestion and PI(clin) (minimal erythema dose without FQ/minimal erythema dose with FQ) calculated. Linear regression analysis of PI(vit) vs PI(clin) gave correlations of up to 0.893. Principal components analysis of PI(vit), daily dose, plasma levels and photophysical (absorption) properties of the eight FQ showed that phototoxic (arbitrarily defined as PI(clin)> or =2) and non-phototoxic (PI(clin)<2) FQ could be completely discriminated using these parameters, and that the in vitro models were able to rank the relative phototoxic potential of the eight FQ.

Animals↗
PubMed2000

Photobinding of ketoprofen in vitro and ex vivo.

Ketoprofen (KP), a non-steroidal anti-inflammatory drug of the 2-aryl propionic class, has been shown to produce photoallergic side effects as well as cutaneous photosensitizing properties that induce other phototoxic effects. In the present study we investigated photobinding of ketoprofen to both human serum albumin (HSA), a model protein, and to ex vivo pig skin and its photodegradation. Results demonstrate that photoadduct formation and photodegradation progressively increased with irradiation time where they reach a maximum. Maximum photobinding to the viable layer of the epidermis was about 7-8% of the initial radiolabelled KP added, in the region of 15-30 min UV irradiation. These results were comparable to in vitro results that were seen with photobinding of KP to HSA; in this case, the quantity of covalently bound material was approximately 10% of the initial, after a maximum of 18 min irradiation. It was found by HPLC analysis that the KP decrease is accompanied by an increase of the corresponding photoproduct, decarboxylated ketoprofen (DKP). The yield of DKP reaches a maximum at around 15 min. DKP appears to play an important role in vitro and ex vivo, being the major photoproduct and responsible for the photobinding process. Using micro-autoradiographical techniques we investigated the penetration and distribution of ketoprofen in ex vivo pig skin in greater detail. It was apparent that percutaneous absorption was taking place and that most of the ketoprofen was predominately localised in fibroblasts in the papillary dermis. No other specific localisation within the skin architecture was identified. Although there were differences in the quantities of bound ketoprofen within the different layers of the skin, these levels did not appear to correlate with irradiation time.

Albumins↗
PubMed2000

Photobinding of carprofen to protein.

Carprofen is a non-steroidal antiinflammatory drug with marked photosensitising properties. In order to elucidate the mechanisms underlying the phenomenon of drug-protein photobinding, mixtures of the drug and human serum albumin were irradiated under different experimental conditions. After irradiation and subsequent gel-filtration chromatography of the photomixture, the eluting protein fraction was analysed by means of fluorescence spectroscopy. The formation of drug-protein photoadducts could be evidenced by the characteristic emission properties of the carbazole chromophore. The photobinding of the drug to human serum albumin appears to involve the formation of aryl radicals resulting from carbon-halogen photocleavage. This mechanistic interpretation is supported by the observed variations in the intensity of the fluorescence spectra, which can be correlated with the lower quantum yield emission of chlorocarbazoles as compared to non-halogenated analogues. The results from laser flash photolysis studies are also in agreement with this proposal.

Absorption↗
PubMed1992

Phototoxicity testing in guinea-pigs.

The photoirritant potential of topically applied chemicals was studied using guinea-pigs. Solutions of test chemicals were applied to the skin, and after 30 min the animals were irradiated with near-ultraviolet radiation. Skin reactions were assessed subjectively between 3 and 72 hr after the start of treatment. Acridine and anthracene caused immediate photoirritation, whereas reaction to 8-methoxy-psoralen (8-MOP) was delayed; acridine was weakly active compared with the strong photoirritancy of anthracene and 8-MOP. Ethanol and a mixture of dimethylacetamide-acetone-ethanol (DAE) were satisfactory solvents, and a time interval of 15 to 30 min between application and irradiation was optimal. It is concluded that animal tests should not be recommended if ingredients have negligible absorption of sunlight. The safety hazard of ingredients absorbing near-ultraviolet and visible radiation may be assessed by laboratory animal procedures to satisfy governmental regulations. The use of guinea-pigs allows the study to act as a preliminary test for the selection of non-photoirritant concentrations for photoallergy testing and reduction of animal numbers. The risk to consumers of photoactive products may be properly assessed by human studies.

Acridines↗
PubMed1991

The identification of photoallergic potential in the local lymph node assay.

Guinea pig test methods are the most commonly used and reliable of predictive models for contact photoallergenicity of chemicals. The murine local lymph node assay (LLNA) has been developed recently as an alternative method for the identification of skin-sensitizing chemicals. Sensitization potential is measured from an assessment of the proliferation of lymphocytes in lymph nodes draining the site of exposure to the test chemical. This work investigates the activity of 6 widely reported photoactive chemicals in a modified LLNA (a photo-LLNA). The photoallergens tetrachlorosalicylanilide and fentichlor elicited positive ultraviolet radiation (UV)-dependent proliferative responses that were greater than their positive UV-independent responses, suggesting that they are both contact and photoallergic in the mouse. The lack of a proliferative response to 6-methylcoumarin and the absence of a reproducible response to musk ambrette suggest that the assay is insufficiently sensitive to identify weak photoallergic potential. Positive UV-dependent responses to acridine and anthracene, both photoirritants, cast doubt on the specificity of the photo-LLNA. Positive LLNA responses to these chemicals may be due to skin protein modification, based on evidence from the in vitro photo-chemical protein-binding assay. These results demonstrate that the photo-LLNA is able to detect at least moderate photoallergic potential.

Acridines↗
PubMed1991

Ankle arthrodesis in children.

The indications, surgical technique, and long-term functional results for ankle arthrodesis differ between children and adults. In children, the reasons for performing a tibiotalar fusion include pain, most commonly from traumatic and septic arthritis, and instability from congenital anomalies or paralytic disorders. The most appropriate procedure is Chuinard's fusion, which achieves a tibiotalar fusion without causing a growth arrest of the distal tibial growth plate. In the long term, young patients with ankle arthrodesis function very well with minimal pain or disability. Stressful activities such as hill climbing, stair climbing, and running may be restricted or require compensatory movements.

Ankle Joint↗
PubMed1990

Dose-response study of ultraviolet radiation for induction of photoallergy to tetrachlorosalicylanilide in guinea pigs.

The dose of ultraviolet light (UV) required to induce photoallergy to tetrachlorosalicylanilide (T4CS) in guinea pigs was studied. A simple induction technique consisting of only one treatment with adjuvant, chemical and UV was used. The concentration of T4CS, which was administered either topically or intradermally, was low to reduce self-screening of UV by the chemical. Doses of UVA from fluorescent blacklamps ranged from 0.4 to 300 kJ/m2. All animals were challenged with topically applied T4CS and 40 kJ/m2 UV. The results showed that incidence of photoallergy increased with increasing dose of UV and reached a plateau between 4.5-45 kJ/m2 following intradermal T4CS and 4-120 kJ/m2 following topical T4CS. The studies demonstrated for the first time decreased response following larger induction doses of UV; photoallergy was not induced by the largest induction dose of 300 kJ/m2. Attenuation of UVB during induction did not affect the decrease. The lack of response may be attributable to further photochemical reactions of a T4CS-protein conjugate with loss of antigenic properties, or to immune suppression initiated by either UVA or an interaction of T4CS and UVA.

Allergens↗
PubMed1989

The cavovarus foot deformity. Etiology and management.

The cavovarus foot is a complex deformity of the forefoot and hindfoot, frequently of neuropathologic etiology. A progressive spinal or peripheral neuromuscular disorder must be excluded by a thorough clinical evaluation. With the failure of nonoperative modalities, surgical options depend on patient age, etiology of the deformity, and the constellation and flexibility of the defects observed. If the hindfoot varus is flexible, correction of the cavus and forefoot pronation through extensive plantar release and metatarsal osteotomies is reliable. The underlying muscle imbalance must be addressed through tendon transfers to prevent further progression. In the young child, a rigid hindfoot varus will often be corrected by a radical plantar-medial release, but the more mature foot may require midtarsal osteotomy and calcaneal osteotomy or triple arthrodesis. The surgery is usually staged to provide correction of deformity and stabilization of the hindfoot prior to tendo Achilles lengthening or tendon transfer. Arthrodesis of a previously well-corrected foot is common due to progression of the neurologic deficit or failure to achieve muscular balance. The claw toe deformity also must be corrected by tendon transfer, osteotomy, and arthrodesis for reasons of both comfort and function.

Foot Deformities↗
PubMed1987

Induction of photoallergy in guinea-pigs by injection of photoallergen-protein conjugates.

Photoconjugates were prepared by ultraviolet irradiation of guinea-pig albumin (GPA) with the photoallergens tetrachlorosalicylanilide (T4CS) and fentichlor. Injections of T4CS-GPA induced photoallergy to T4CS in 11 of 12 guinea-pigs whereas injections of fentichlor-GPA induced photoallergy in 5 of 12 guinea-pigs. Thus the fentichlor-GPA photoconjugate, which contained a molar ratio of hapten to protein 3 times higher than the corresponding T4CS conjugate, produced a significantly lower response. The results demonstrate the importance of protein conjugate formation in the induction of photoallergy, i.e. the role of carrier protein in contact sensitivity. The high potency of the T4CS-GPA photoconjugate in inducing photoallergy suggests that albumin may have a special role as a carrier protein in T4CS photoallergy.

Albumins↗
PubMed1983

Modified Hoke-Miller flatfoot procedure.

Within a relatively limited follow-up study of ten patients, the modified Hoke-Miller flatfoot operation proved effective both in removing symptoms and changing the architecture of the foot.

Adolescent↗
PubMed1982

Congenital pseudarthrosis of the tibia. A long-term follow-up study.

A review of 36 cases of congenital pseudarthrosis of the tibia revealed that at long-term follow-up, patients tended to fall into three groups: (1) those who show the typical radiographic and physical findings of congenital pseudarthrosis of the tibia, fracture before eight years of age and progress of pseudarthrosis; these cases tended to proceed to a poor end-result, regardless of the form of treatment; (2) those who did not show the typical prefracture stage but fractured after the eight years of age responded well to grafting procedures and had minimal shortening and satisfactory results at long-term follow-up; and (3) those patients who presented with a prefracture stage tibia but were braced and never fractured, and had a satisfactory end-result.

Adolescent↗
PubMed1981

Congenital elevation of the scapula. Surgical correction by the Woodward procedure.

We reviewed the cases of eleven patients with congenital elevation of the scapula who were treated by the Woodward procedure. A discussion of the characteristic findings, associated congenital anomalies, indications for operation, and surgical techniques, and a review of the literature, also are presented. The average postoperative increase in combined shoulder abduction in the eleven patients was 29 degrees. However, if preoperative abduction was less than 120 degrees (five patients), the average increase in motion was 50 degrees. The average scapular lowering was 1.6 centimeters. The cosmetic results were rated as excellent or good in 82 per cent of the patients. It is significant, however, that in more than 60 per cent of the patients unsightly surgical scars developed. The importance of the often-underemphasized rotational component of Sprengel's deformity is stressed, as well as the importance of the meticulous surgical technique and attention to detail that are essential for the best results.

Adolescent↗
PubMed1980

Thompson Arthrodesis of the hip in children.

Between 1966 and 1975, we performed a fusion of the hip by the Thompson method in fifteen children with non-tuberculous, non-paralytic conditions. An attempt was made to position the hip in 30 degrees of flexion, neutral rotation, and neutral abduction. Fourteen patients were followed for an average of 4.5 years (range, one to ten years) postoperatively. A fibrous pseudarthrosis developed in one patient. The remainder had solid arthrodeses. None had delayed union. At follow-up, all patients were free of pain and had returned to normal activities. There was no significant increase in adduction with growth.

Adolescent↗