Bacterial components regulate the expression of Toll-like receptor 4 on human mast cells

Objectives and design: The aim of this study was to investigate whether the exposure of mast cells (MCs) to bacterial components affects the expression of Toll-like receptor (TLR) 4, and to elucidate the behavior of MCs during the early response to infection. Materials: Two human MC lines, HMC-1 and LAD2, were employed. Messenger RNA expression was observed by RT and real-time PCR. TLR4 expression was determined by Western blotting. TNF-α secretion was analyzed with ELISA. The degranulation ratio was measured with betahexosaminidase assay. Results: Although bacterial components increased TLR4 mRNA, only lipopolysaccharide (LPS) augmented the TLR4 protein expression. LAD2 pre-treated with LPS for 8 h resulted in 2-fold increased TNF-α secretion on LPS restimulation. Conclusion: These results suggest that the exposure of MCs to LPS may reinforce the innate immune system due to up-regulation of MC TLR4, followed by increased TNF-α release. Received 20 April 2006; returned for revision 14 July 2006; accepted by G. Wallace 11 August 2006     

Wachstumsretardierung durch A.-iliaca-Verschluss nach Herzkatheteruntersuchung

Cardiac catheterisations in newborns and infants are being performed routinely in increasing numbers for diagnostic and therapeutic purposes. Rarely, the femoral artery or the iliac artery will be completely occluded after such a procedure, and growth retardation of the lower extremity can result. We report on a case of iliofemoral artery occlusion following cardiac catheterisation in an infant. Twelve years later, a difference of 5.5 cm in leg length was noted, as well as a difference in shoe size and intermittent claudication. Following operative reconstruction, the child’s leg pain ceased. Two years after surgery, differences in leg lengths and shoe sizes are no longer significant. Vascular complications should not be underestimated despite the juvenile potential for collateral vessels. Even in the absence of signs of ischaemia, these complications necessitate further investigation and adequate treatment in due course.     

Health literacy and contraception: a readability evaluation of contraceptive instructions for condoms, spermicides and emergency contraception in the USA.

OBJECTIVE: To assess readability of over-the-counter (OTC) contraceptive product instructions currently available, compare the results with previous studies from a decade ago, and review the implications for health care providers, in particular pharmacists counseling on OTC contraceptives. METHODS: A sample of contraceptive instructions was submitted to a readability analysis using four standard readability formulas. Products included condoms, spermicides, and emergency contraception instruction pamphlets. RESULTS: Reading grade levels for condoms ranged from 6th to 12th grade. The average reading levels for the spermicides were 9th-10th grade and for the emergency contraceptives 10th-12th grade. These results were consistent with those of similar studies performed a decade ago. CONCLUSIONS: Consumers need to have at least a high school reading level in order to comprehend current product instructions. Very little has changed in the past decade regarding readability of OTC contraceptive patient instructions, despite calls to simplify written instructions. Healthcare providers, in particular pharmacists, must be aware of these disparities to enhance patient education and advocate for simpler reading materials.     

Comparison of characteristics of esophageal squamous cell carcinoma associated with head and neck cancer and those with gastric cancer

In ongoing reviews of 339 patients with surgically treated primary squamous cell carcinoma, there were 19 (5.6%) with concurrent gastric cancer and 11 (3.2%) with head and neck cancer. The incidences of intra-esophageal multiple occurrence of esophageal cancer are 27.3% and 26.3% in those with associated head and neck cancer and gastric cancer, respectively, and higher than 7.1% in those without such a concurrent cancer. There was no difference in the clinicopathological characteristics of those with concurrent head and neck and gastric cancers, except for the higher incidence of metachronous occurrence in the former. These findings suggest that, in cases of esophageal cancer associated with concurrent head and neck cancer and gastric cancer, intraesophageal multiplicity of the esophageal carcinoma is frequent and that preoperative serial evaluations is most important to design treatment and estimate the prognosis.     

Radiation-induced chondrosarcoma of the clavicle complicating Hodgkin's disease. A case report

Review of the literature reveals that postradiation chondrosarcoma is a rare secondary malignant bone tumor. This case report demonstrates a Grade 1 chondrosarcoma of the proximal right clavicle in a 17-year-old boy, eight years after extensive chemotherapy and radiation therapy for a Stage IIB Hodgkin's disease.     

Basic and clinical studies on imipenem/cilastatin sodium in the pediatric field

Basic and clinical studies have been performed on imipenem/cilastatin sodium (MK-0787/MK-0791) in the pediatric field. Antibacterial activities of MK-0787 against 14 clinical isolates of S. aureus and 67 isolates of E. coli were determined. The MIC of MK-0787 was 0.10 microgram/ml or less against all 14 strains of S. aureus. The MIC of MK-0787 was 0.39 microgram/ml or less against all 67 strains of E. coli. The pharmacokinetics of MK-0787/MK-0791 was studied at dose levels of 10 mg/10 mg/kg and 20 mg/20 mg/kg. The peak serum levels of MK-0787 achieved approximately 1 hour after the administration of 10 mg/10 mg/kg and 20 mg/20 mg/kg doses were 38.6 micrograms/ml and 36.2 micrograms/ml, respectively. The serum half-lives were 0.8 hour and 0.9 hour, respectively. The total 6-hour urinary excretions were 82.1% and 66.7%, respectively. The MK-0787/MK-0791 was administered to 13 children with bacterial infections. The clinical results were excellent or good in all cases. The overall efficacy rate was 100%. As a side effect, diarrhea was observed in 1 patient. Abnormalities in laboratory findings observed were elevation of direct bilirubin in 1 patient, thrombocytosis in 2, and a prolonged prothrombin time in 1 patient. Based on the above results, it can be concluded that MK-0787/MK-0791 is a safe and effective drug to use for the treatment of pediatric infections.     

Effect of (2"R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic, on the cardiac function of hamsters

Cardiovascular effects of (2'R)-4'-O-tetrahydropylanyladriamycin X HCl (THP) and doxorubicin (adriamycin, ADM) were studied in hamsters. In experiments to observe acute effects, THP was administered intravenously at a dose of 12.5, 25.0 or 50.0 mg/kg, and ADM at 1.56, 3.13 or 6.25 mg/kg was given to different subjects. The THP caused slight ECG alterations at a dose of 12.5 mg/kg. At a dose of 25.0 mg/kg or 50.0 mg/kg, THP caused moderate to remarkable alterations in ECG like a widening of PR and PRc interval, A-V block, ST segment depression and T wave flattening. The ADM caused moderate to remarkable alterations in ECG at a dose of 3.13 mg/kg or 6.25 mg/kg, including arrhythmia, bradycardia, A-V block, ST segment changes and T wave flattening. These changes caused by THP and ADM recovered within 5 approximately 10 minutes after injection. Alterations in the ultrastructure of the myocardium caused by THP at a dose of 50.0 mg/kg included some cells with slight changes like swelling of mitochondria, focal intracellular edema, and enlargement of myofibrils. The ADM, at a dose of 3.13 mg/kg, induced severer swelling of mitochondria than THP, dilatation of sarcoplasmic reticulum, intracellular edema, and disorganization of myofilaments. At a dose of 6.25 mg/kg of ADM, these changes became more pronounced. In experiments to observe subacute effects, hamsters were treated with THP or ADM by daily intraperitoneal injections for 15 consecutive days, and then allowed to be recovered for 15 days. Dose levels of THP or ADM were 0.125, 0.25, 0.5 and 1.0 mg/kg. General toxicity, ECG, hematological and blood biochemical analysis, and electron microscopic examination were studied. In the ECG study, THP-treated hamsters showed a reversible elevation of R wave amplitude at a daily dose of 0.5 mg/kg. Widening of PR and PRc interval, elevation of R and S wave amplitude, and reduction of T wave amplitude were observed at a daily dose of 1.0 mg/kg of THP. Hamsters treated with ADM showed increase of heart rate, reduction of T wave amplitude, and shortening of PR and PRc interval at a daily dose of 0.5 mg/kg. Severe changes were observed at a daily dose of 1.0 mg/kg of ADM including an increase of heart rate, elevation of R wave amplitude, reduction of S and T wave amplitude, and shortening of QT interval. The electron microscopic examination revealed that THP-treated hamsters showed separation of intercalated discs, formation of myelin structure, and dilatation of T-tubules at a daily dose of 1.0 mg/kg. Similar changes were caused by ADM at a daily dose of 0.25 to 1.0 mg/kg.(ABSTRACT TRUNCATED AT 400 WORDS)     

Reelin expression is upregulated following ocular tissue injury

Purpose Reelin is important in the guidance of neuronal stem cells in the central nervous system during normal development. We wished to determine whether reelin is expressed in the retina and cornea after injury. Methods Mice underwent laceration of their retina as well as corneal epithelial debridement. The mice were sacrificed at 3 days, and eyes were fixed and stained for reelin expression and reelin messenger ribonucleic acid (mRNA). Results In normal eyes, reelin was expressed only at very low levels in the ganglion cell layer of the retina and the endothelial cell layer of the cornea. In injured eyes, there was marked expression in reelin immunoreactivity in the retina and cornea. Reelin gene expression was seen in the retina and cornea. Conclusions Reelin is expressed during normal retinogenesis. This study shows that reelin is also upregulated following injury to the retina and cornea. The expression of reelin following injury suggests that reelin may play an important role in regulating stem cell trafficking in neuronal and nonneuronal tissues following injury similar to its role in normal organogenesis. For consideration of publication in Graefe’s Archive for Clinical and Experimental Ophthalmology.