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Biomedical subjects

Dominique Blanc

Publications and source records attributed to Dominique Blanc.

11 recordsLinked to original sources

Magnetic resonance imaging correlated with the histopathological effect of Pd-bacteriopheophorbide (Tookad) photodynamic therapy on the normal canine prostate gland.

BACKGROUND AND OBJECTIVE: To determine the optimal magnetic resonance imaging (MRI) methodology to assess photodynamic therapy (PDT)-induced histopathological responses in the prostate. STUDY DESIGN/MATERIALS AND METHODS: Laparotomy was performed in five healthy dogs. Cylindrical diffuser was placed in the prostates to deliver light of 50-300 J/cm at 150 mW/cm and 763 nm to activate IV-injected Tookad (1 mg/kg b.w.). Fast spin echo (FSE) T2-weighted, post-contrast-enhanced T1-(CE-T1) and diffusion weighted images (DWI) were obtained pre- and 2 days, 7 days, and 1 month post-PDT. Radiological-histopathological correlation was performed at 7 days (n = 4) and 1 month (n = 1) after PDT. A qualitative assessment of signal changes and apparent diffusion coefficient (ADC) mapping was performed. RESULTS: At 2 or 7 days post-PDT, there was good spatial correlation between PDT-induced hemorrhagic necrosis and unenhanced regions on CE-T1 images. There was a rapidly and persistently enhancing rim corresponding to edema and inflammation. FSE T2 and DWI showed altered signal but did not clearly define necrosis in all cases. At 1 month, it was hard to correlate MR images to histopathologic changes as they represented a mixture of necrosis and developing fibrosis, which led to a mixed signal intensity and less demarcated contrast enhancement. CONCLUSIONS: At 7 days after PDT, gadolinium DTPA contrast-enhanced MRI is superior to DWI and T2 imaging in assessing the boundary of Tookad PDT-induced tissue necrosis in the normal canine prostate.

Animals↗

Assessing phytophotodermatitis: boy with erythema and blisters on both hands.

Phytophotodermatitis (PPD) is a phototoxic reaction which occurs when the skin comes in contact with a photosensitizer and is subsequently exposed to radiation. PPD is often seen in people handling furocoumarin-containing products, such as agricultural workers, bartenders, florists, and gardeners. It may also be seen in beachgoers, athletes, and children. The pattern of the lesions usually resembles streaks; the hands and mouth are most commonly affected due to eating and handling of the offending furocoumarin-containing agents.

Adolescent↗

Studies of a vascular-acting photosensitizer, Pd-bacteriopheophorbide (Tookad), in normal canine prostate and spontaneous canine prostate cancer.

BACKGROUND AND OBJECTIVES: Photodynamic therapy (PDT) mediated with Tookad (Pd-bacteriopheophorbide, WST09) was investigated pre-clinically as part of a program to develop an alternative modality for treating prostate cancer. STUDY DESIGN/MATERIALS AND METHODS: Spontaneous canine prostate cancer and normal canine prostate were used as the animal models. Interstitial PDT was performed by IV infusion of the photosensitizer and irradiating the prostates with a diode laser (763 nm). The prostates were harvested 1-week post-PDT and subjected to histopathologic examinations. The effects of the drug doses and light doses were studied for one- and two-session PDT. Pharmacokinetics were studied using HPLC assay. The feasibility of using perfusing CT scans for assessing PDT lesions was also evaluated. RESULTS: Tookad is a vascular-acting drug and clears rapidly from the circulation. Tookad-PDT-induced lesions, in both normal and cancerous prostates, were characterized by marked hemorrhagic necrosis. CONCLUSIONS: Tookad-PDT is very effective in ablating prostatic tissue through its vascular effects.

Animals↗

Effects of photodynamic therapy on peripheral nerve: in situ compound-action potentials study in a canine model.

OBJECTIVE: Our aim is to investigate the effects of photodynamic therapy (PDT) on peripheral nerve conductivity. BACKGROUND DATA: Interstitial PDT has been demonstrated as a promising treatment modality for prostate cancer. However, the sensitivity of nerves, in the immediate vicinity of the prostate gland, to PDT procedures has not been studied. This study attempts to establish an in situ canine model to evaluate direct PDT effect on peripheral nerves. METHODS: PDT was performed by irradiating the cutaneous branches of the saphenous nerve at 763 nm with light doses of 50-200 J/cm2 after i.v. infusion of the photosensitizer Tookad (0-2 mg/kg). Evoked compound-action potentials (CAP) were recorded directly from the surface of the saphenous nerve. The latencies to onset and conduction velocities were determined during PDT and 1-week post-PDT. RESULTS: Nerve and surrounding tissue damage corresponded well with drug/light doses. With Tookad doses of 2 mg/kg, treatment with 50 J/cm2 induced little change in saphenous nerve conduction properties. However, treatment with 100 J/cm2 resulted in localized nerve injury and decreases in nerve conduction velocities, and treatment with 200 J/cm2 severely damaged the nerve. CONCLUSIONS: This canine model adequately demonstrates effects of Tookad PDT on peripheral nerves. Direct irradiation of 100-200 J/cm2 can alter nerve conduction and induce nerve damage. Therefore, possible side effects of interstitial PDT on the pelvic plexus need to be investigated in future studies.

Action Potentials↗

Characterization of cell-to-cell signaling-deficient Pseudomonas aeruginosa strains colonizing intubated patients.

Cell-to-cell signaling involving N-acyl-homoserine lactone compounds termed autoinducers (AIs) is instrumental to virulence factor production and biofilm development by Pseudomonas aeruginosa. In order to determine the importance of cell-to-cell signaling during the colonization of mechanically ventilated patients, we collected 442 P. aeruginosa pulmonary isolates from 13 patients. Phenotypic characterization showed that 81% of these isolates produced the AI-dependent virulence factors elastase, protease, and rhamnolipids. We identified nine genotypically distinct P. aeruginosa strains. Six of these strains produced AIs [N-butanoyl-homoserine lactone or N-(3-oxo-dodecanoyl)-homoserine lactone] and extracellular virulence factors (elastase, total exoprotease, rhamnolipid, hydrogen cyanide, or pyocyanin) in vitro. Three of the nine strains were defective in the production of both AIs and extracellular virulence factors. Two of these strains had mutational defects in both the lasR and rhlR genes, which encode the N-acyl-homoserine lactone-dependent transcriptional regulators LasR and RhlR, respectively. The third of these AI-deficient strains was only mutated in the lasR gene. Our observations suggest that most, but not all, strains colonizing intubated patients are able to produce virulence factors and that mutations affecting the cell-to-cell signaling circuit are preferentially located in the transcriptional regulator genes.

Base Sequence↗

Detection of Pseudomonas aeruginosa cell-to-cell signals in lung tissue of cystic fibrosis patients.

Chronic Pseudomonas aeruginosa infections lead to progressive lung tissue destruction in cystic fibrosis (CF) patients. Two bacterial cell-to-cell signals, 3-oxo-C(12)-HSL and C(4)-HSL are required for the production of several extracellular virulence factors. 3-oxo-C(12)-HSL is also required for the development of a differentiated biofilm, induces IL-8 production by epithelial cells and possesses immunomodulatory activities. These two signalling molecules are therefore believed to play a role in the pathogenesis of P. aeruginosa infections, but have never been isolated from infected human tissues. We extracted and quantified the two P. aeruginosa cell-to-cell signals from lung tissues of two CF patients infected by P. aeruginosa. 3-oxo-C(12)-HSL and C(4)-HSL were detected in the lung tissues in fmol/gram, respectively pmol/gram concentrations; the ratio C(4)-HSL/3-oxo-C(12)-HSL exceeded 100 in all tissue samples. Random Amplified Polymorphism DNA genotyping revealed that one genotype was present per lung. In vitro the P. aeruginosa isolates from the two lungs produced 3-oxo-C(12)-HSL, whereas some isolates did not produce detectable C(4)-HSL. Our results suggest that both P. aeruginosa cell-to-cell signals were produced in the lung tissue of these two cystic fibrosis patients.

4-Butyrolactone↗

Intercenter reproducibility of binary typing for Staphylococcus aureus.

The reproducibility of the binary typing (BT) protocol developed for epidemiological typing of Staphylococcus aureus was analyzed in a biphasic multicenter study. In a Dutch multicenter pilot study, 10 genetically unique isolates of methicillin-resistant S. aureus (MRSA) were characterized by the BT assay as presented by van Leeuwen et al. [J. Clin. Microbiol. 2001 39 (1) 328]. The BT assay, including a standardized DNA extraction protocol was performed in duplicate in eleven medical microbiology laboratories. Two different hybridization detection procedures were applied and a prelabeled DNA sample as process control was included. Only three laboratories accurately identified all strains. Divergence in technical procedures resulted in misinterpretation due to an increasing number of faint or absent hybridization signals in combination with high background staining. The binary type of the process control was determined correctly by all participating laboratories. The feasibility of the BT protocol was related directly to the skill of the laboratory personnel. On the basis of the national study, we concluded that the DNA extraction protocol needed modification to improve DNA yield and purity. Subsequently, seven European laboratories participated in an international study to determine the reproducibility of the modified BT protocol. Each center was asked to analyze 10 DNA samples previously extracted from 10 MRSA strains (phase 1) and, additionally, to analyze 10 MRSA strains, using the standardized or their in-house DNA isolation protocol (phase 2). A prelabeled DNA process control sample was included again. The binary types of all DNA samples were identified correctly by all but one laboratories. This latter laboratory diverged from the protocol by adding an excess of labeled DNA to the hybridization mixture, resulting in a high background and, therefore, noninterpretable BT results. All centers produced identical BT results for the process control. Five of the seven centers correctly identified the binary types of all 10 MRSA strains in phase 2 of the international study. Three of these centers used their in-house DNA extraction protocol. Divergence from the standard BT protocol in the remaining two centers resulted in no interpretable BT data for the 10 MRSA strains. The study demonstrated that each center that followed the BT protocol to the letter could generate reproducible results, irrespective whether or not an in-house DNA isolation protocol was used. The current BT protocol thus represents a simple method generating robust, reproducible genotype data for S. aureus strains.

Bacterial Typing Techniques↗

Genotyping of European isolates of methicillin-resistant Staphylococcus aureus by fluorescent amplified-fragment length polymorphism analysis (FAFLP) and pulsed-field gel electrophoresis (PFGE) typing.

A representative panel of 50 European MRSA isolates was subjected to genotype analysis by fluorescent amplified-fragment length polymorphism (FAFLP) and by macrorestriction pulsed-field gel electrophoresis (PFGE). Each isolate had a unique profile with FAFLP. To model genetic relationships within the continuing MRSA epidemic, cluster analysis of FAFLP data was made, revealing nine clone complexes of MRSA. Most of these were also found by PFGE. A number of isolates had FAFLP profiles significantly different from others, and might represent emerging epidemic strains. FAFLP analysis proved particularly suitable for surveillance of the MRSA epidemic at national and international levels.

Disease Outbreaks↗

Lipschütz genital ulceration: a rare manifestation of paratyphoid fever.

In 1913, a distinctive clinical entity of acute genital ulcer occurring in an adolescent girl with a non-venereal infectious aetiology was described by Lipschütz. Since the initial description, several aetiologies have been discussed, and among them, paratyphoid fever is very uncommon. After her return from a trip, a 25-year-old girl developed high fever and diarrhoea. Examination of the vulva revealed a genital ulcer. The rest of the general examination was normal. Blood cultures identified Salmonella paratyphi A, and a diagnosis of Lipschütz's ulcer associated with paratyphoid fever was made. Bacteriaemia was then treated with antibiotics and the vulvar ulceration rapidly disappeared. Lipschütz described a distinctive clinical entity of acute genital ulcers occurring in adolescents. To our knowledge, we report herein the second case associated with proved paratyphoid fever. The authors thus recommend that typhoid or paratyphoid fever should be included in the differential diagnosis of genital ulcerations.

Adult↗

Minocycline-induced cutaneous polyarteritis nodosa with antineutrophil cytoplasmic antibodies.

Minocycline is an antibiotic widely used in the treatment of acne. Among the induced auto-immune disorders, cutaneous polyarteritis nodosa (PAN) is very rare. A new case is reported below. A 23-year-old female patient treated with minocycline for acne for 24 months developed sub-cutaneous nodules, livedo reticularis and pigmented lesions of the lower limbs. Antineutrophil cytoplasmic antibodies (ANCA) were positive at 1/320. Skin biopsy showed vasculitis of a medium-sized artery. The role of minocycline was suspected using the imputability criteria. The diagnosis of minocycline-induced cutaneous PAN with ANCA was sustained. After withdrawal of the treatment, the nodular lesions decreased spontaneously, whereas livedo disappeared and inflammatory parameters were normalized after oral corticosteroid therapy. Minocycline is a tetracycline which is efficient for treating acne. Auto-immune disorders are frequently observed. Among them, it is very rare to observe cutaneous PAN associated with positive ANCA. The pathophysiological mechanisms are discussed.

Acne Vulgaris↗