Sonodynamic Therapy: Advances and Challenges in Clinical Translation

Sonodynamic therapy (SDT) consists of the synergetic interaction between ultrasound and a chemical agent. In SDT, the cytotoxicity is triggered by ultrasonic stimuli, notably through cavitation. The unique features of SDT are relevant in the clinical context more than ever: the need for efficacy, accuracy, and safety while being noninvasive and preserving the patient's quality of life. However, despite the promising results of this technique, only a few clinical reports describe the use of SDT. The objective of this article is to provide an extensive overview of the clinical and preclinical research conducted in vivo on SDT, to identify the limitations, and to detail the developed strategies to overcome them.     

IMPROVED BALLOON‐TIPPED TRANS‐ANAL ILEUS TUBE

Background: For management of bowel obstruction due to colorectal cancer, endoscopic trans‐anal decompression technique has been first reported by Lelcuk et al. in 1986 using balloon dilatation technique. Since then, various types of trans‐anal decompression tubes have been clinically used for patients suffering from left side obstructing colorectal cancer as an emergent decompressing device. At present, two types of trans‐anal ileus tube (trans‐anal decompression tube) have been available for clinical use, but they have two main problems that are late colon perforations caused by the tip of the tube and tube obstruction by stool. Methods: Analysis on three late colon perforations experienced with the use of conventional devices drew possible improvements to make a trans‐anal ileus tube less harmful. To overcome the pitfalls inherent to conventional tubes, the author has developed an improved trans‐anal ileus tube with a balloon installed at the very end of the tube (‘balloon‐tipped type’) made of silicone, measuring 1200 or 1700 mm in total length and 22 Fr in outer diameter. It has been used for 12 cases with obstructing colorectal cancer etc. and its outcomes were compared with those obtained by the use of conventional trans‐anal ileus tube. Results: No late perforations have been encountered, but tube obstruction did occur in one of 12 cases. Conclusion: The new trans‐anal ileus tube with a balloon installed at the tip of ileus tube is considered to be safer and especially effective in preventing late colon perforation and tube obstruction.     

Cibenzoline-induced respiratory muscular paralysis in a hemodialysis patient

A 69-year-old man was admitted to our kidney center with endstage renal failure. We started intermittent peritoneal dialysis immediately because of severe azotemia, hyperkalemia, and metabolic acidosis. Two weeks after admission, he developed uremic pericarditis with frequent ventricular premature contractions and supraventricular premature contractions. The intermittent peritoneal dialysis was then replaced by intensive hemodialysis, and oral administration of 300 mg/d of cibenzoline was started. Four days later, he developed thirst, weakness, and dyspnea due to respiratory muscular paralysis. We initiated respiratory support with a respirator because analysis of his blood gases revealed marked hypercapnia and hypoxia. He also developed hypoglycemia and prolonged PQ and QRS intervals on the electrocardiogram, which we believed were due to cibenzoline intoxication; we discontinued the cibenzoline immediately. All symptoms improved, and he was extubated 5 days later. After 2 months, his pericardial effusion disappeared. He now continues maintenance hemodialysis as an outpatient. We suspect that the cibenzoline induced the respiratory muscular paralysis for 2 reasons: 1) the patient experienced the respiratory muscular paralysis, at the same time he also experienced thirst, weakness, hypoglycemia, and prolonged PQ and QRS intervals on electrocardiogram, and all of these symptoms improved after the discontinuation of cibenzoline, and 2) his plasma concentration of cibenzoline became remarkably elevated, to 20 times above the standard therapeutic level. This patient's clinical course indicates that hemodialysis might be superior to intermittent peritoneal dialysis for treatment of cibenzoline intoxication.     

Monoclonal antibody analysis of glomerular, tubulo-interstitial infiltrating immune cells in various glomerulonephritis

To investigate the role of cell-mediated immunity (CMI) in glomerulonephritis (GN), we identified the infiltrating immune cells both within the glomerulus and in the interstitium. Frozen sections from 103 patients with various forms of GN: 10 with minor glomerular abnormality (MGA) as control, 10 with minimal change nephrotic syndrome (MCNS), 10 with membranous nephropathy (MN), 9 with focal glomerulosclerosis (FGS), 30 with IgA nephropathy (IgAN), 22 with acute post streptococcal glomerulonephritis (APSGN), and 2 with rapidly progressive glomerulonephritis (RPGN) were examined using monoclonal antibodies (MoAb) by indirect immunoalkaline-phosphatase labelling. In most glomerulonephritis, monocyte/M phi and helper/inducer T cells were predominantly infiltrating in the interstitium, but intraglomerular infiltration was rare, except for APSGN. This interstitial infiltration increased proportionally to the level of serum creatinine, and was most prominent in RPGN. Apparently different distribution was seen in APSGN, that is, prominent increase in total number of intra-glomerular monocyte/M phi infiltration with slightly increased T cells. The change was correlated with time after onset; namely the more leucocytic infiltration was observed when the tissue was taken earlier. These data suggest that in APSGN, monocyte/M phi accumulate in glomeruli via cell mediated immunity in addition to humoral immune mechanism resulting in glomerular hypercellularity, whereas in most chronic glomerulonephritis interstitial leucocyte infiltration, particularly helper T cells and monocyte/M phi may play an important role in the progression of glomerulonephritis.     

Pharmacokinetics of fluorinated 2-nitroimidazole hypoxic cell radiosensitizers in murine peripheral nervous tissue.

We have previously reported that KU-2285, a 2-nitroimidazole with a fluorinated N1-substituent (-CH2-CF2CONH(CH2)nOH, n = 2), was a promising hypoxic cell radiosensitizer. In this study the pharmacokinetics of KU-2285 and its related compounds (n = 3 and n = 4) were compared with those of etanidazole (a 2-nitroimidazole with an N1-substituent of -CH2CONH(CH2)nOH, n = 2) and its related compounds (n = 3 and n = 4) to assess the effects of incorporation of a CF2 group. The lipophilicity of the fluorinated compounds was higher than that of etanidazole, as measured by the octanol/water partition coefficient. As the number of CH2 groups increased, the lipophilicity of the compounds in both the KU-2285 and etanidazole series increased. The brain tissue levels of the fluorinated compounds were as low as those of the etanidazole derivatives, while the biological half-lives of the fluorinated compounds in peripheral nervous tissues were shorter than those of related non-fluorinated compounds.     

Carinal resection and reconstruction for recurrent lung cancer

A patient with a recurrent tumor in the trachea adjacent to the right main bronchus was treated by surgical resection 19 months after undergoing surgery for the primary cancer. The patient had previously undergone right upper lobectomy for T1N0M0 stage I squamous cell carcinoma. A carinal resection was performed which included 4 rings of the trachea, 2 rings of the righ main bronchus, and 1 ring of the left main bronchus. Reconstruction consisted of an end-to-end anastomosis of the trachea and left main bronchus, and an end-to-side anastomosis of the right and left main bronchi. The postoperative course was uneventful, and at present the patient is healthy 12 months following reoperation.     

Presence of ghost cells and the Wnt signaling pathway in odontomas

BACKGROUND: Although it has been reported that ghost cells are present in odontomas, the generation mechanism of these cells is unclear. To evaluate the presence of ghost cells and involvement of the Wnt signaling pathway, we examined the expression of hard keratins, beta-catenin and Lef-1 in odontomas. METHODS: Sixty-nine cases of odontoma were examined immunohistochemically with the use of antibodies against human hair proteins, beta-catenin and Lef-1. RESULTS: Expression of hard keratins was found only in the cytoplasm of ghost cells in 46 (66.7%) of the 69 odontomas. Compound odontomas (78.8%) showed a higher incidence of ghost cells than complex odontomas (29.4%). Histopathologically, ghost cells were found within odontogenic epithelium adjacent to immature enamel and in the centre of Liesegang-ring-like calcified materials. Expression of beta-catenin and Lef-1 was observed in the cytoplasm and nucleus of odontogenic epithelial cells adjacent to the ghost cells in immature odontomas. CONCLUSION: These findings suggest that odontoma is a hard keratin-expressing tumor-like lesion, and that the Wnt signaling pathway may be involved in the formation of ghost cells in odontomas.     

Relationship of alcohol consumption to diet: a population-based study in Hawaii

The relationship of alcohol use to diet was examined in 2272 male and 2337 female adults aged 45 y and older who provided a quantitative diet history during 1977-1979. Mean values for each dietary variable, adjusted for smoking, ethnicity, income, and education, were compared in each sex between abstainers and drinkers and by tertile of ethanol intake. Linear relationships with extent of drinking were also sought. Drinkers were found to be less obese than abstainers. Consumption of carbohydrate, vitamins, calcium, fruits, fruit juices, and raw vegetables was greater among abstainers whereas consumption of fat (particularly polyunsaturated fatty acids), cholesterol, zinc, meat, pickled vegetables, and dried fish was greater among drinkers. Because validations of dietary questionnaires have shown that alcohol consumption is more accurately recalled than food intake, the possibility of a residual confounding effect for these dietary variables should be considered in epidemiologic studies of alcohol and health.     

A case of autoimmune pancreatitis complicated with immune thrombocytopenia]

A 80-year old man was referred to our hospital because of an elevation of serum amylase level. Diffuse enlargement of the pancreas was detected by abdominal computed tomography, and also diffuse narrowing of the main pancreatic duct was revealed using endoscopic retrograde cholangiopancreatography. The serum level of IgG was elevated to 3450mg/dl. Besides, on the 10th hospital day, petechia developed and the platelet level decreased to 1.5 x 10(4)/microl. The platelet-associated IgG, antiplatelet antibody and antinuclear antibody in serum were positive. The levels of serum complements were low. From all these findings the patient was diagnosed as autoimmune pancreatitis complicated with immune thrombocytopenia. The treatment with prednisolone was started, which was effective on each disease. The medication was suspended a year ago, and so far there is no data suggesting the recurrence of autoimmune pancreatitis or immune thrombocytopenia.