Experimental study on phototoxicity and the photosensitization potential of ketoprofen,suprofen, tiaprofenic acid and benzophenone and the photocross-reactivity in guinea pigs

BACKGROUND: Ketoprofen, suprofen and tiaprofenic acid are arylpropionic anti-inflammatories. Their chemical structures share the same elements as the benzoyl radical and the tiophene ring. We experienced nine cases of ketoprofen photoallergy, seven cases of suprofen photoallergy and three cases of tiaprofenic photoallergy. PURPOSE: To find the key structure of photosensitivity and photocross-reactivity to ketoprofen, suprofen and tiaprofenic acid. METHODS: : Three animals were tested for phototoxicity and six animals for the photosensitization potentials of ketoprofen, suprofen, tiaprofenic acid and benzophenone, and the photocross-reactivity of the above chemicals. Test substances were applied symmetrically on both sides of the animals' backs. The animals were irradiated with 180 mJ/cm2 UVB ((1/2) MED) and 10 J/cm2 UVA on the left side. The reactions were read on days 2, 3 and 4. The photosensitization potentials of ketoprofen, suprofen, tiaprofenic acid and benzophenone were determined using the Adjuvant-Strip method. Six animals were assigned to each test group and to a control group. RESULTS: Ketoprofen, suprofen, tiaprofenic acid and propionic acid showed negative reactions with the phototoxic test. Benzophenone showed phototoxic reactions to 40% acetone (ac.), 20% ac. and 10% ac. Therefore, we used 5% aq. benzophenone with the photosensitization test. Ketoprofen was the strongest photosensitizer (6/6) and showed photocross-reactivities to suprofen (2/6), tiaprofenic acid (3/6) and benzophenone (6/6). Suprofen was a strong photosensitizer (4/6) and showed photocross-reactivities to ketoprofen (1/4) and tiaprofenic acid (2/4), but not to benzophenone. Tiaprofenic acid was also a photosensitizer (2/6) but showed a photocross-reactivity only to benzophenone (2/2). Benzophenone was also the strongest photosensitizer (6/6), but did not photocross-react to the above three chemicals. CONCLUSION: From the test results, it appears that benzoyl radical is the key structure for photosensitivity and the photocross-reactivity of ketoprofen, suprofen and tiaprofenic acid. The whole structure of benzophenone was needed to induce photosensitization of benzophenone. The animals that were photosensitized from the entire structure of benzophenone did not photocross-react to ketoprofen, suprofen or tiaprofenic acid.     

Tumor enucleation with preoperative endoscopic transpapillary stenting for pediatric insulinoma

The 13-year-old boy underwent tumor enucleation for pancreatic head insulinoma close to the pancreatic main duct after a preoperative endoscopic pancreatic stent placed by endoscopic retrograde cholangiopancreatography. The tumor was safely excised by identifying the indwelled pancreatic stent during the surgical procedure without pancreatic duct injury or postoperative complications.     

Alcohol Biomarkers: Clinical Significance and Biochemical Basis

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Raj Lakshman and Mikihiro Tsutsumi. The presentations were (1) Sialic acid index of apolipoprotein J: A new marker for chronic alcohol consumption, by P. Ghosh and M. R. Lakshman; (2) Microheterogeneity of serum glycoproteins in alcoholics, by M. Tsutsumi and S. Takase; (3) Probing protein-ethanol adducts with combinatorial peptide libraries displayed by filamentous phage, by H. Anni, O. Nikolaeva, and Y. Israel Y; (4) Carbohydrate-deficient transferrin as a marker for heavy alcohol use: What have we learned; Where do we go from here, by R. F. Anton; (5) Sensitivity and specificity of carbohydrate-deficient transferrin in drinking experiments and different patient groups, by O. M. Lesch; (6), Transferrin variants interfere with the measurement of carbohydrate-deficient transferrin, by A. Helender, G. Eriksson, and J-O. Jeppson; and (7) Chronic ethanol on protein trafficking in liver, by P. Marmillot, M. N. Rao, and M. R. Lakshman.     

Effects of Helicobacter pylori infection on genetic instability,the aberrant CpG island methylation status and the cellular phenotype in Barrett's esophagus in a Japanese population

Genetic or epigenetic alterations in Barrett's esophagus (BE) with/without Helicobacter pylori (H. pylori) infection remain unclear. We examined the effects of H. pylori infection on genetic instability (GIN), the CpG island methylation status and a biomarker related to BE carcinogenesis. We analyzed 113 Japanese individuals with endoscopically suspected BE. The patients included, Group CLE (n = 25): no specialized intestinal metaplasia (SIM) in a columnar lined epithelium (control); Group BE (n = 88): all had SIM. Microsatellite instability and a loss of heterozygosity as GIN, the methylation status at hMLH1, E‐cadherin, p16 and APC, and immunoreactivity using a monoclonal antibody (mAb) Das‐1, which specifically reacts with BE, were evaluated. Nine additional patients with BE were prospectively followed up for 2 years after successful H. pylori eradication. The frequency of GIN, methylation at E‐cadherin and APC, and mAb Das‐1 reactivity in Group BE was significantly higher than that in Group CLE (p < 0.0001, p < 0.0001 and p < 0.005, and p < 0.0001, respectively). Furthermore, GIN, E‐cadherin methylation and mAb Das‐1 reactivity showed a significantly higher incidence in patients with H.pylori infection than in those without H. pylori infection (p < 0.01, p < 0.005, and p < 0.01, respectively). Interestingly, the patients from Group BE were observed to change to a stable state of molecular alterations in 60% for GIN, 42.9% for E‐cadherin methylation and 55.6% for APC methylation, or a reduction of mAb Das‐1 reactivity was noted in 25% following eradication. H. pylori infection may therefore affect these molecular alterations associated with the pathogenesis of BE, to some degree, in the Japanese population. © 2008 Wiley‐Liss, Inc.     

Congenital diaphragmatic hernia with a pure duplication of chromosome 1q: report of the first surviving case

Congenital diaphragmatic hernia (CDH) occurs in multiple malformation syndromes and associations, and has been associated with cytogenetic aberrations on almost every chromosome arm. However, CDH with a duplication of chromosome 1q is very rare in the literature, and all previously reported cases with detailed clinical courses died soon after birth. We present the first surviving case of CDH with a duplication of 1q12–q23, who had arthrogryposis multiplex congenita and hypertrophic cardiomyopathy. CDH patients with a proximal duplication of chromosome 1q may have a chance for survival, and CDH with a duplication of chromosome 1q is not necessarily a lethal association.     

Mammary ductoscopy for diagnosis and treatment of intraductal lesions of the breast

BACKGROUND: Mammary ductoscopy (mammoscopy) is an ideal diagnostic method for intraductal lesions. The usefulness of mammoscopy for intraductal lesions was evaluated. METHODS: Mammoscopy was performed in 315 cases with nipple discharge. The mammoscopic findings of 46 breast cancer cases (47 lesions) and 109 intraductal papilloma cases (119 lesions) were compared with pathological findings. RESULTS: Carcinoma was recognized by mammoscopy in 38 of 47 lesions (80.9%). Intraductal masses were detected by mammoscopy in 115 of 119 intraductal papilloma lesions. The shape of the mass was classified as hemispheric, papillary, or flat protrusion. The hemispheric and papillary shapes were most common in cases of intraductal papilloma and the flat protrusion type was most common in cases of carcinoma. The amount of material collected by intraductal biopsy under mammoscopic observation was smaller in carcinoma than in intraductal papilloma because the carcinoma lesions were usually located in peripheral duct-lobular units and had weak tissue cohesion compared with that of intraductal papilloma. Of 133 intraductal biopsies performed for 69 intraductal papillomas, 17 biopsies yielded material insufficient for diagnosis in. The effectiveness of treatment by intraductal biopsy was recognized in 38 of 46 intraductal papillomas in which clinical follow-up continued for more than two years (82.6%). The therapeutic results of biopsy were poor in cases of multiple intraductal masses in multiple duct-lobular units. CONCLUSIONS: Mammoscopy contributes not only the diagnosis in cases of nipple discharge, but is also of benefit in the treatment of intraductal papilloma.     

Study of hepatitis C virus genotype in Guizhou area of southwestern China

OBJECTIVE: To determine the concordance in various hepatitis C (HCV) genotyping methods and to investigate the distribution of HCV genotypes in Guizhou area of Southwest China. METHODS: Serum samples from 206 patients (100 with chronic hepatitis and 106 with hemopathy) were detected for antibody of HCV by second generation enzyme-labelled immunosorbent assay (ELISA). Thirty-five anti-HCV positive samples were detected for HCV RNA by RT-polymerase chain reaction (PCR) and 30 HCV RNA positive samples were determined for their genotypes by three various genotyping methods [PCR with type-specific primers at the core region (primer-set), slot-blot hybridization with type-specific probes at NS5B region (blotting) and the restric fragment length polymorphism analysis of PCR products of 5' NC region (RFLP)]. Ten samples with the known genotype were analysed by the direct sequencing. RESULTS: Of 30 samples with positive HCV RNA, the types of 22 could be classified by three methods, and the genotypes determined by various methods had complete concordance. The types of 6 samples could be classified by two methods and 5 had agreement subtypes. The types of two samples could be classified only by RFLP. Overall, 27 (90.0%) had subtype 1b infection and 3 (10.0%) had subtype 2a infection. The nucleotide sequence of 8 samples with subtype 1b and one with subtype 2a were analysed by the direct sequencing. The subtypes determined by sequence analysis were in complete concordance with those decided by various genotyping methods. CONCLUSIONS: Subtype 1b is the predominent HCV genotype in Guizhou area, while subtype 2a is less common. There was a good concordance with the genotyping results obtained by various HCV genotyping methods.     

Computerized image analysis of clustered microcalcifications on mammography: Morphometric comparison between mammography and pathology

The clusters of microcalcifications under 2 cm in greatest dimension were analyzed in terms of size and shape by an image processor with a computer after being magnified 33 times. The mean diameter of mammographic microcalcifications was 188 μm in benign cases, 226 μm in cribriform or papillary type cancer cases, 213 μm in intermediate type cancer cases, and 324 μm in comedo type cancer cases, showing significant differences among the groups. The size distribution of mammographic microcalcifications in the comedo type was characteristic, showing a second peak in distribution between 500 and 700 μm. The radiodensity of microcalcifications compared to the breast parenchyma, the caliber of breast ducts containing the malignant calcifications, and the unit volume of calcium deposits within the ductal lumens were greater in cancer cases.     

Long-term functional outcome after untethering surgery for a tethered spinal cord in patients with anorectal malformations

Background

Anorectal malformation (ARM) is associated with a tethered spinal cord (TSC). Long-term functional outcome of untethering surgery for TSC in patients with ARM has not been well evaluated.

Methods

Patients aged 7 years and older who underwent repair of ARM and spinal magnetic resonance imaging from January 1995 to December 2008 were reviewed retrospectively. Untethering surgery was performed in all patients who were diagnosed with TSC, regardless of the presence or of neurological symptoms. Clinical symptoms reflecting anorectal, urinary, and lower limb function were compared between patients complicated with TSC (TSC group, n = 17) and those without TSC (non-TSC group, n = 14).

Results

The median age at functional evaluation was 11.7 and 12.9 years in the TSC and non-TSC groups, respectively (p = 0.52). Untethering surgery for TSC was performed at a median age of 1.3 years. Preoperative urinary and lower limb dysfunction, except for vesicoureteral reflux in the TSC group in one patient, was improved after surgical detethering. Current anorectal function was comparable between the groups.

Conclusions

Long-term functional outcome in patients with ARM and TSC undergoing untethering surgery is equivalent to that in those without TSC. Prophylactic surgical detethering for patients with ARM and TSC can be a treatment of choice to maximize neurological functional outcome.