Review of petroleum toxicity and identifying common endpoints for future research on diluted bitumen toxicity in marine mammals.

Large volumes of conventional crude oil continue to be shipped by sea from production to consumption areas across the globe. In addition, unconventional petroleum products also transverse pelagic habitats; for example, diluted bitumen from Canada's oilsands which is shipped along the Pacific coast to the United States and Asia. Therefore, there is a continuing need to assess the toxicological consequences of chronic and catastrophic petroleum spillage on marine wildlife. Peer-reviewed literature on the toxicity of unconventional petroleum such as diluted bitumen exists for teleost fish, but not for fauna such as marine mammals. In order to inform research needs for unconventional petroleum toxicity we conducted a comprehensive literature review of conventional petroleum toxicity on marine mammals. The common endpoints observed in conventional crude oil exposures and oil spills include hematological injury, modulation of immune function and organ weight, genotoxicity, eye irritation, neurotoxicity, lung disease, adrenal dysfunction, metabolic and clinical abnormalities related to oiling of the pelage, behavioural impacts, decreased reproductive success, mortality, and population-level declines. Based on our findings and the body of literature we accessed, our recommendations for future research include: 1) improved baseline data on PAH and metals exposure in marine mammals, 2) improved pre- and post-spill data on marine mammal populations, 3) the use of surrogate mammalian models for petroleum toxicity testing, and 4) the need for empirical data on the toxicity of unconventional petroleum to marine mammals.

Effects of fat supplementation on plasma glucose, insulin and fatty acid analysis in ponies maintained on a forage-based diet.

The objective of this study was to observe how fat incorporated into an equine forage-based diet through supplementation altered levels of plasma glucose, insulin and fatty acids. Five Shetland/Hackney cross pony mares were fed alfalfa pellet diets top dressed with commercially available vegetable oil (blend of soya bean, canola and corn oils) at 0%, 5%, 10% or 15% of diet. Ponies were randomly assigned one of four diets to start, with a 14-day adjustment period between transitioning to another one of the four diets. Ponies were gradually adapted to the new diet within the 14-day period before a five-day trial period. Each pony received all four diets by the end of the study. Each trial was a five-day period with a three-day sample collection. Blood samples for each collection week were taken 0, 30, 60, 90, 120, 150, 180, 210, 240 and 270 min and at 5, 6, 7, 8, 9 and 10 hr post-feeding. Excess fat did not impact plasma glucose (p > .1), nor did it affect blood plasma insulin concentration. While there was no time alteration found for plasma fatty acid concentration (p > .1), C14:0 increased when ponies were fed 0% fat and C18:2 decreased when ponies were fed 0% fat. Plasma fatty acids (% of total FA) were higher in C18:0, C18:1, C18:2 and C20:1 in the added fat diets (p < .1). These findings suggest the amounts reported in this study of fat supplementation on a forage-based diet did influence the fatty acid analysis within the pony, but did not negatively impact blood glucose and insulin concentrations.

Systematic analysis of missed colorectal cancer cases and common pitfalls in diagnosis.

BACKGROUND: Missed colorectal cancer on endoscopic or radiological investigations may delay diagnosis and impact outcome. This study audits incidence of previous investigations in patients with colorectal cancer, considers outcome in 'missed' cancer cases and examines the diagnostic pathway in the derived case series to identify common pitfalls in diagnosis. METHODS: Patients diagnosed with colorectal cancer in 2011 at a single National Health Service (NHS) Trust were reviewed. Incidence of endoscopic and radiological investigations in the 3 years preceding diagnosis and outcome data were collected. Cases of prior investigation not leading to diagnosis were considered 'missed' cancers and survival compared with 'detected' cases. The diagnostic pathway in each 'missed' case was reviewed. RESULTS: 395 colorectal cancer cases were studied. Eighteen (4.6%) patients underwent previous investigation including colonoscopy (n=4), flexible sigmoidoscopy (n=5), barium enema (n=5) and diagnostic abdominal CT scan (n=12), median 708 days prior to diagnosis. Previous investigation predicted reduced overall and disease-free survival (HR 2.07, p=0.04 and HR 2.66, p<0.0001), after age and gender adjustment. Ten different categories termed 'pitfalls' were derived from analysis of the diagnostic pathway. These included CT scanning for abdominal pain without further investigation (n=7), rectosigmoid cancer following a previous diagnosis of diverticular disease (n=4) and incomplete diagnostic investigations without adequate follow-up (n=3). CONCLUSIONS: A proportion of patients diagnosed with colorectal cancer have previously been investigated for gastrointestinal symptoms and survival appears reduced in these patients. Regular audit and analysis of previous investigations can identify common pitfalls in diagnosis, which should be used to inform training and improve practice.

Prebiotic Oligosaccharides: Comparative Evaluation Using In Vitro Cultures of Infants' Fecal Microbiomes.

The objective of this study was to systematically assess the bifidogenic effect of three commonly used prebiotic products using in vitro cultures of infant fecal samples. Fresh stool samples collected from six term infants, each exclusively fed human milk (n = 3) or infant formula (n = 3), at 28 days of age were used as inocula. The following prebiotic products were added at concentrations applicable to infant formula: Vivinal GOS 15 (containing 28.5% galacto-oligosaccharide [GOS]) at 7.2 g/liter, Beneo HP (99.5% long-chain inulin [IN]) at 0.8 g/liter, Beneo Synergy 1 (enriched oligofructose and inulin [OF-IN]) at 4 g/liter, and a combination of Vivinal GOS 15 (7.2 g/liter) and Beneo HP (0.8 g/liter) (GOS-IN). The growth of total bacteria, Bifidobacterium, Bacteroides, Bifidobacterium longum, and Escherichia coli was quantified using specific quantitative PCR (qPCR). Bifidobacterium was also enumerated on selective Beerens agar plates, with representative colonies identified by sequencing of their 16S rRNA genes. Volatile fatty acids (VFA) and pH in the cultures were also determined. Irrespective of the feeding methods, the GOS product, either alone or in combination with Beneo HP, resulted in substantially higher growth of total bifidobacteria, and much of this growth was attributed to growth of B. longum. Beneo Synergy 1 also increased the abundance of total bifidobacteria and B. longum. Corresponding to the increases in these two bacterial groups, acetic acid concentrations were higher, while there was a trend of lower E. coli levels and pH. The lower pH and higher acetic acid concentration might be directly responsible for the lower E. coli population. At the concentrations studied, the GOS product was more bifidogenic and potent in inhibiting E. coli than the other products tested. These results suggest that supplementation of infant formula with GOS may increase intestinal bifidobacteria and benefit infant health.

Replacing a suite of commercial pectinases with a single enzyme, pectate lyase B, in Saccharomyces cerevisiae fermentations of cull peaches.

Fermentation of pectin-rich biomass with low concentrations of polysaccharides requires some treatment of the pectin, but does not need complete degradation of the polysaccharide to reach maximum ethanol yields. Cull peaches, whole rotten fruits that are not suitable for sale, contain high concentrations of glucose (27.7% dw) and fructose (29.3% dw) and low amounts of cellulose (2.8% dw), hemicellulose (4.5% dw) and pectin (5.6% dw). Amounts of commercial saccharification enzymes, cellulase and cellobiase can be significantly decreased and commercial pectinase mixtures can be replaced completely with a single enzyme, pectate lyase (PelB), while maintaining ethanol yields above 90% of the theoretical maximum. PelB does not completely degrade pectin; it only releases short chain oligogalacturonides. However, the activity of PelB is sufficient for the fermentation process, and its addition to fermentations without commercial pectinase increases ethanol production by ~12%.

New magnetic phase diagram of (Sr,Ca)2RuO4.

High-T(c) cuprates, iron pnictides, organic BEDT and TMTSF, alkali-doped C(60), and heavy-fermion systems have superconducting states adjacent to competing states exhibiting static antiferromagnetic or spin density wave order. This feature has promoted pictures for their superconducting pairing mediated by spin fluctuations. Sr(2)RuO(4) is another unconventional superconductor which almost certainly has a p-wave pairing. The absence of known signatures of static magnetism in the Sr-rich side of the (Ca, Sr) substitution space, however, has led to a prevailing view that the superconducting state in Sr(2)RuO(4) emerges from a surrounding Fermi-liquid metallic state. Using muon spin relaxation and magnetic susceptibility measurements, we demonstrate here that (Sr,Ca)(2)RuO(4) has a ground state with static magnetic order over nearly the entire range of (Ca, Sr) substitution, with spin-glass behaviour in Sr(1.5)Ca(0.5)RuO(4) and Ca(1.5)Sr(0.5)RuO(4). The resulting new magnetic phase diagram establishes the proximity of superconductivity in Sr(2)RuO(4) to competing static magnetic order.

Improved hyperthermia treatment control using SAR/temperature simulation and PRFS magnetic resonance thermal imaging.

PURPOSE: This article explores the feasibility of using coupled electromagnetic and thermodynamic simulations to improve planning and control of hyperthermia treatments for cancer. The study investigates the usefulness of preplanning to improve heat localisation in tumour targets in treatments monitored with PRFS-based magnetic resonance thermal imaging (MRTI). METHODS: Heating capabilities of a cylindrical radiofrequency (RF) mini-annular phased array (MAPA) applicator were investigated with electromagnetic and thermal simulations of SAR in homogeneous phantom models and two human leg sarcomas. High frequency structure simulator (HFSS) (Ansoft) was used for electromagnetic simulations and SAR patterns were coupled into EPhysics (Ansoft) for thermal modelling with temperature-dependent variable perfusion. Simulations were accelerated by integrating tumour-specific anatomy into a pre-gridded whole body tissue model. To validate this treatment planning approach, simulations were compared with MR thermal images in both homogenous phantoms and heterogeneous tumours. RESULTS: SAR simulations demonstrated excellent agreement with temperature rise distributions obtained with MR thermal imaging in homogeneous phantoms and clinical treatments of large soft-tissue sarcomas. The results demonstrate feasibility of preplanning appropriate relative phases of antennas for localising heat in tumour. CONCLUSIONS: Advances in the accuracy of computer simulation and non-invasive thermometry via MR thermal imaging have provided powerful new tools for optimisation of clinical hyperthermia treatments. Simulations agree well with MR thermal images in both homogeneous tissue models and patients with lower leg tumours. This work demonstrates that better quality hyperthermia treatments should be possible when simplified hybrid model simulations are performed routinely as part of the clinical pretreatment plan.

[Does the thumb have two phalanges or three? Development of ideas since Aristotle]. / Le pouce a-t-il deux ou trois phalanges ? Evolution des idées depuis Aristote.

Many controversies mark the long road of the history of anatomy. The hand is not exempt of them. Even Galen's clear thinking, founded on the strict determinism between the structure of an organ and its function, and based on animal dissection, was criticized. In view of the structural complexity of the hand, we will limit our study to one of the most symptomatic conceptual disagreements: whether the human thumb has two or three phalanges, according to whether we include the first metacarpus, or if the thumb's first phalanx is considered as the initial element. According to the latter theory, there is a missing element in the first digital row, and this missing element is the metacarpus. This theory is ancient and its evolution throughout history is discussed in our study. Finally, we explain the origin and bases of the reasoning that led us to suggest the word 'metaphalanx' to designate the first metacarpus.

Single dose topical corticosteroid inhibits IL-5 and IL-13 in nasal lavage following grass pollen challenge.

BACKGROUND: Nasal lavage is a noninvasive method of obtaining inflammatory exudates following nasal allergen challenge (NAC), and permits cells and released mediators to be evaluated. OBJECTIVE: To determine the effects of a single dose of topical steroid on eosinophils and levels of chemokines and cytokines in nasal lavage fluid following NAC in patients with allergic rhinitis. METHODS: Patients with grass pollen seasonal allergic rhinitis (n = 32) out of the allergy season received either nasal budesonide (100 microg per nostril) or matched placebo before allergen challenge in a double blind two-way crossover design. A semi-automated mixed bead array system was employed to measure multiple chemokines and cytokines in small volumes (50 microl) of nasal lavage supernatants. RESULTS: Following NAC there was a rapid onset of nasal symptoms together with nasal eosinophilia, and the appearance of IL-5 and IL-13 in lavages between 4 and 8 h. Elevated levels of eotaxin, RANTES, IL-8 and MCP-1 were also detected following allergen challenge. A single dose of nasal budesonide caused a decrease in symptoms (P < 0.05) and nasal eosinophils (P < 0.05) with selective abrogation of IL-5 and IL-13 responses (P < 0.05), but a lack of effect on levels of eotaxin, RANTES, IL-8 and MCP-1. CONCLUSION: This study suggests that a single dose of nasal steroid has the capacity to selectively abolish IL-5 and IL-13 responses following NAC. This model should be convenient for testing novel anti-inflammatory and immunoregulatory agents intended for the treatment of allergic rhinitis.

Topical corticosteroid inhibits interleukin-4, -5 and -13 in nasal secretions following allergen challenge.

BACKGROUND: Cytokines and chemokines produced by allergen-reactive T-helper type 2 (Th2) cells may be pivotal to the pathophysiology of allergic disorders. OBJECTIVE: This study was performed to assess the effect of 7 days of topical corticosteroid on nasal allergen challenge (NAC) in terms of eosinophils, cytokines and chemokines obtained by nasal lavage and filter paper methods. METHODS: Patients with grass pollen seasonal-allergic rhinitis (n = 13) out of season received nasal challenge following matched placebo (twice daily into each nostril for 7 days) and fluticasone propionate (100 microg twice daily into each nostril for 7 days). Chemokine and cytokine levels were analysed using a sensitive automated bead immunoassay system at intervals up to 8 h after NAC. RESULTS: Levels of cytokines and chemokines from filter paper were generally higher than from nasal lavage. Fluticasone propionate caused a reduction in symptoms, total leukocyte counts and eosinophils, and abrogation of IL-4, IL-5, IL-6 and IL-13 responses in the filter paper taken in the late phase (P < 0.05 for IL-4 and IL-13, P < 0.01 for IL-5 and IL-6). Levels of chemokines (eotaxin, RANTES, MCP-1, MIP-1alpha, IL-8 and IP-10) were also reduced in the late phase (P < 0.01 at 8 h). However, levels of IL-2, IL-3, IL-7, IL-12 (p40 and p70), -15, TNF-alpha, IFN-gamma and GM-CSF were not affected. CONCLUSION: Fluticasone propionate has selective inhibitory effects on Th2 cytokine synthesis following nasal challenge, while also decreasing release of chemokines, but not affecting levels of Th1 cytokines.

Nematode neuropeptide receptors and their development as anthelmintic screens.

This review addresses the potential use of neuropeptide receptors for the discovery of anthelmintic agents, and particularly for the identification of non-peptide ligands. It outlines which nematode neuropeptides are known and have been characterized, the published information on drug discovery around these targets, information about existing high- and low-throughput screening systems and finally the likely safety of neuropeptide mimetics.

Targeting angiogenic processes by combination rofecoxib and ionizing radiation.

Tumor growth and angiogenesis are interdependent. Cyclooxygenase (COX) catalyzes the synthesis of prostaglandins from arachidonic acid. Nonsteroidal antiinflammatory drugs (NSAIDs) inhibit COX-mediated synthesis of prostaglandins. COX-1 is constitutively expressed in a wide range of tissues, whereas COX-2 is cytokine inducible. Enhanced COX-2 expression has been attributed a key role in the development of inflammation and related processes observed in pathologically altered disease states. Two specific COX-2 inhibitors, namely rofecoxib (Vioxx) and celecoxib (Celebrex), both oral agents and U.S. Food and Drug Administration approved, have been shown preclinically and clinically to have efficacy comparable to that of NSAIDs for relief of pain and inflammation in osteoarthritis, with decreased risk of gastrointestinal damage. Little is known about how angiogenesis is affected by the combination of rofecoxib and radiation. We have evaluated the combination of rofecoxib, at various concentrations, and radiation on cytokine-induced angiogenesis in vitro. We have found that rofecoxib inhibited endothelial cell proliferation, migration, and tube formation (differentiation) at clinically relevant doses. In combination with radiation, inhibition of endothelial cell function further increased twofold. The combination of rofecoxib and radiation suggests a complementary strategy with clinical ramifications to target angiogenesis-dependent malignancies.

The mechanisms of parasite clearance after antimalarial treatment of Plasmodium falciparum malaria.

Studies were conducted to determine how malaria parasites are cleared from the blood after antimalarial treatment. Neither artesunate nor quinine decreased parasitized red cell deformability or increased antibody binding. In acute falciparum malaria, ring-infected erythrocyte surface antigen (RESA) was observed in erythrocytes without malaria parasites (RESA-red blood cell [RBC]), indicating prior parasitization. In uncomplicated malaria, RESA-RBC numbers increased significantly (P=.002) within 24 h of starting artesunate but rose much more slowly (7 days) after quinine treatment. In severe malaria, RESA-RBC increased significantly (P=. 001) within hours of starting artesunate but not with quinine treatment (P=.43). RESA-RBCs were not produced after drug treatment of malaria parasite cultures in vitro. Rapid malaria parasite clearance after treatment with artemisinin derivatives results mainly from the extraction of drug-affected parasites from host erythrocytes-presumably by the spleen. This explains why the fall in hematocrit after treatment of hyperparasitemia is often less than that predicted from loss of parasitized cells.

Alterations in endocrine responses in male Sprague-Dawley rats following oral administration of methyl tert-butyl ether.

Methyl tert-butyl ether (MTBE) is an oxygenated fuel additive used to decrease carbon monoxide emissions during combustion. MTBE is a nongenotoxic chemical that induces Leydig cell tumors (LCT) in male rats. The mechanism of MTBE-induced LCT is not known; however, LCT induced by other nongenotoxic chemicals have been associated with the disruption of the hypothalamus-pituitary-testicular (HPT) axis. The objective of this study was to determine whether MTBE functions as an endocrine-active compound by affecting levels of specific hormones involved in the maintenance of the HPT axis. Nine-week-old male Sprague-Dawley rats were administered MTBE by gavage at 0, 250, 500, 1000, or 1500 mg MTBE/kg/day for 15 or 28 consecutive days and sacrificed 1 h following the last dose. Relative testis weights were increased only in high-dose animals treated for 28 days, and no testicular lesions were observed at any dose level. Adrenal gland, liver, and kidney weights were also increased. Histologic changes included protein droplet nephropathy of the kidney and centrilobular hypertrophy of the liver. Interstitial fluid and serum testosterone levels as well as serum prolactin levels were decreased only in animals treated with 1500 mg MTBE/kg/day for 15 days. At 28 days, serum triiodothyronine (T3) was significantly decreased at 1000 and 1500 mg MTBE/kg/day compared to control animals, and a decrease in serum luteinizing hormone and dihydrotestosterone was observed at 1500 mg MTBE/kg/day. These results indicate that MTBE causes mild perturbations in T3 and prolactin; however, the changes in testosterone and LH levels did not fit the pattern caused by known Leydig cell tumorigens.

Topical treatment of interdigital tinea pedis: terbinafine compared with clotrimazole.

A multicentre, prospective, randomized, double-blind, parallel group study was undertaken to compare the efficacy and tolerability of topical terbinafine with topical clotrimazole in the treatment of interdigital tinea pedis. Patients were randomized to receive either terbinafine 1% cream twice daily for 1 week, followed by a similar placebo cream for 5 weeks, or clotrimazole 1% cream twice daily for 4 weeks. Outcome measures were: (i) mycological cure (negative culture); (ii) effective treatment (negative culture plus a symptom score of 2 or less out of a maximum score of 18); and (iii) complete cure (negative culture and a symptom score of 0); measured at 1, 4, 8 and 12 weeks after the commencement of the study. One hundred and four of the 217 patients randomized had a culture-confirmed dermatophyte infection at baseline. In these patients, 84.6% in the terbinafine group were culture negative after 1 week, compared with only 55.8% in the clotrimazole group. Both agents were well tolerated. The study showed that terbinafine achieves mycological cure more rapidly than clotrimazole. This may result in improved compliance and better control over transmission of infection.

Non-thiol 3-aminomethylbenzamide inhibitors of farnesyl-protein transferase.

The design and syntheses of non-thiol inhibitors of farnesyl-protein transferase are described. Substitutions on an imidazolylmethyl-AMBA-methionine template gave a highly potent and cell-active inhibitor.

Oral niacin prevents photocarcinogenesis and photoimmunosuppression in mice.

Topical nicotinamide (niacinamide) has demonstrable preventive activity against photocarcinogenesis in mice. To better understand how this vitamin prevents ultraviolet (UV) carcinogenesis, we tested systemic administration of another form of the vitamin, niacin, and its capacity to elevate cutaneous nicotinamide-adenine dinucleotide (NAD) content as well as to decrease photoimmunosuppression and photocarcinogenesis. BALB/cAnNTacfBR mice were fed the AIN-76A diet supplemented with 0%, 0.1%, 0.5%, or 1.0% niacin throughout the experiment. UV irradiation consisted of five 30-minute exposures per week to banks of six FS40 Westinghouse sunlamps for 22 weeks in the carcinogenesis experiments, yielding a total cumulative dose of approximately 1.41 x 10(6) Jm-2 of UV-B radiation. Dietary supplementation with 0.1%, 0.5%, or 1.0% niacin reduced the control incidence of skin cancer from 68% to 60%, 48%, and 28%, respectively, at 26.5 weeks after the first UV treatment. Two potential mechanisms by which niacin prevents tumor formation were identified. Photoimmunosuppression, critical for photocarcinogenesis, is measured by a passive transfer assay. Syngeneic, antigenic tumor challenges grew to an average of 91.6 +/- 19.7, 79.8 +/- 11.5, 41.9 +/- 11.7, or 13.2 +/- 4.1 mm2 in naive recipients of splenocytes from UV-irradiated mice treated with 0%, 0.1%, 0.5%, or 1.0% niacin supplementation, respectively, demonstrating niacin prevention of immunosuppression. Niacin supplementation elevated skin NAD content, which is known to modulate the function of DNA strand scission surveillance proteins p53 and poly(ADP-ribose) polymerase, two proteins critical in cellular responses to UV-induced DNA damage. These results clearly demonstrate a dose-dependent preventive effect of oral niacin on photocarcinogenesis and photoimmunosuppression and establish the capacity of oral niacin to elevate skin NAD levels.

Intradermal testing for food and chemical sensitivities: a double-blind controlled study.

BACKGROUND: Confirming adverse reactions to foods and chemicals is fundamental in providing a basis for diagnosis and treatment of patients with reported environmental sensitivities. Provocation-neutralization testing is widely used in this respect but has not been thoroughly evaluated, therefore remaining a controversial and unproven technique. OBJECTIVE: This study investigated the validity of intradermal testing for evaluation of reported adverse reactions to a variety of incidents within the patient population at the Nova Scotia Environmental Health Centre. METHODS: A total of 132 people who were referred to the Nova Scotia Environmental Health Centre, a dedicated government-funded research and treatment facility for suspected environmental sensitivities, were tested by the technique of provocation-neutralization by the guidelines set out by the American Academy of Environmental Medicine. A panel of 13 foods, 9 chemicals, and 4 placebos (normal saline solution) was evaluated in a double-blind, randomized study. Symptoms and skin reactions were recorded, and response rates were determined for all substances, including saline solution injections. RESULTS: Seventy percent of the patients reported symptoms to 1 or more of the 4 saline solution injections. In comparison, 15% of patients experienced a skin reaction (wheal) to 1 or more injections of saline solution. Only 5% of individuals experienced a wheal to more than 1 saline solution injection, although 40% of the patients reported symptoms to more than 1 saline injection. Patients who experienced 1 or more reactions (wheal or symptoms) to saline solution were more reactive to injected allergens, on average reacting to 67% of active substances. Patients who experienced no reaction to the saline solution did experience a reaction to 48% of injected substances on average. Reaction by symptoms to foods, chemicals, and normal saline solution showed a random pattern, although wheal reactions showed a distinct pattern. Subsequent observations have indicated that experiencing no reaction to previous saline solution injections does not accurately predict response to saline solution in later testing. Some individuals who did not experience a reaction to saline solution in an initial screening later experienced a reaction to saline solution during further testing. CONCLUSIONS: Provocation of symptoms in usual testing conditions is not a useful tool for discriminating between reactions to saline solution and reactions to specific chemicals or foods. Skin response alone may be a more reliable indicator and will require cross-validation with other tests, such as oral and inhalation challenges and comparison with a control population. Heightened sensitivity and chaotic responses may be a feature of chemical sensitivity. Meanwhile, the results of provocation-neutralization testing, using symptoms alone as an indicator of neutralization, should not be used as a basis for clinical intervention.

Comparison of one week of oral terbinafine (250 mg/day) with four weeks of treatment with clotrimazole 1% cream in interdigital tinea pedis.

Treatment of interdigital tinea pedis often involves long-term therapy with topically applied preparations. Effective oral preparations, such as the allylamine terbinafine (Lamisil), taken over a shorter period, could provide a useful therapeutic alternative. A total of 269 patients from five centres with clinically diagnosed interdigital tinea pedis were entered into this double-blind, randomized, double-dummy, parallel-group study comparing oral terbinafine 250 mg once daily for 1 week with 1% clotrimazole (Canesten) cream applied twice daily for 4 weeks. Of these, 137 patients were evaluable for efficacy (confirmed dermatophyte infection by microscopy and culture): 63 terbinafine and 74 clotrimazole. At week 4, the mycological cure rates (negative culture at week 1 and negative results on microscopy and culture at week 4 onwards) were very similar (71% for clotrimazole and 72% for terbinafine). There was a faster response rate in the terbinafine group with respect to signs and symptoms at week 1. Both treatments were equally well tolerated; adverse events occurred equally in the two groups. In conclusion, oral terbinafine in a single daily dose of 250 mg for 1 week is as effective and as well tolerated as 1% clotrimazole cream applied twice daily for 4 weeks in the treatment of interdigital tinea pedis.