Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer

BACKGROUND: High-intensity focused ultrasound (HIFU) is a minimally invasive technique used in achieve coagulation necrosis. We evaluated biochemical disease-free survival rates, predictors of clinical outcome and morbidity in patients with localized prostate cancer treated with HIFU. METHODS: A total of 181 consecutive patients underwent HIFU with the use of Sonablate (Focus Surgery, Indianapolis, IN, USA). Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The median age and pretreatment prostate-specific antigen (PSA) level were 70 years (range 44-88) and 9.76 ng/mL (range 3.39-89.60). A total of 95 patients (52%) were treated with neoadjuvant hormones. The median follow-up period for all patients was 18.0 months (range 4-68). RESULTS: The biochemical disease-free survival rates at 1, 3 and 5 years in all patients were 84%, 80% and 78%, respectively. The biochemical disease-free survival rates at 3 years for patients with pretreatment PSA less than 10 ng/mL, 10.01-20.0 ng/mL and more than 20.0 ng/mL were 94%, 75% and 35%, respectively (P<0.0001). Multivariate analysis identified pretreatment PSA (P<0.0001) as a independent predictor of relapse. CONCLUSION: High-intensity focused ultrasound therapy appears to be a safe and efficacious minimally invasive therapy for patients with localized prostate cancer, especially those with a pretreatment PSA level less than 20 ng/mL.     

The Preclinical Safety Evaluation of Human Monoclonal Antibody against Cytomegalovirus

The human monoclonal antibody against cytomegalovinis (Mab C23)was examined pharmacokinetically and toxicologically as partof the preclinical studies prior to approval for human use.Rats given repeated intravenous administrations of Mab C23 producedno antibodies against Mab C23 and maintained a blood Mab C23level in a dose-dependent manner. However, pregnant rabbitsproduced antibodies against Mab C23. The half-life of Mab C23in plasma was 15.9 days in rats, which was similar to that ofnormal human serum -globulin (NHSG). Neither behavioral effectsnor circulatory disturbance was found in mice, rats, and dogseven after a single intravenous injection of 100 or 200 mg/kg,which corresponds to 50 or 100 times the intended clinical dosage.The repeated doses of 2, 10, or 20 mg/kg of Mab C23 on six occasionswith 1- or 2-week intervals elicited a transient decrease inleukocyte counts in rats given 10 or 20 mg/kg, but no adverseeffects in cynomolgus monkeys. Mab C23 did not cause any reproductiveor developmental toxicity when administered to rats and rabbitsat dose levels of 20 mg/kg or less. However, pregnant animalsshowed lower plasma levels of Mab C23 than non-pregnant animals.The chromosomal aberration test disclosed no clastogenicityin human lymphocytes. An immunostaining for Mab C23 revealedno localizations in several tissues of cynomolgus monkeys givenintravenous doses of Mab C23. The preclinical safety evaluationin animals other than rabbits, which produced no antibodiesagainst Mab C23, showed that the behavior of Mab C23 is pharmacokineticallysimilar to that of NHSG and is as safe as NHSG, which has longbeen used as a biological agent. However, because there wasa difference in blood levels of Mab C23 between pregnant andnonpregnant animals, its clinical administration to pregnantpatients should differ from that to non-pregnant patients.     

ETHANOL INDUCES HETEROGENEOUS REDUCTION OF CYTOCHROME aa3 WITHIN PERFUSED RAT LIVER LOBULE ASSESSED USING MICROSPECTROSCOPY

The redox state of cytochrome aa₃ was measured at microspots(20µm diameter) within the lobule of perfused rat livers,using reflectance microspectroscopy, and the effect of ethanolinfusion on sublobular distribution of the redox states wasevaluated. A sigmoidal relationship was observed between oxygendelivery and the reduction of cytochrome aa₃ in both the periportaland pericentral regions of the liver lobule when the influentO₂ concentration was decreased in a graduated manner. This sigmoidalcurve was shifted to the more reduced state by ethanol infusion,with ethanol (25–100mM) increasing the degree of cytochromeaa₃ reduction in a dose-dependent manner according to the distancefrom the periportal region along a sinusoid. This increase wasspatially heterogeneous within a liver lobule. These data indicatethat ethanol accelerates cytochrome aa₃ reduction, with a distinctgradient of reduction along sinusoids but a heterogeneous distributionwithin the liver lobule.     

High Efficacy of Disopyramide in the Management of Ventricular Fibrillation Storms in a Patient with Brugada Syndrome

The patient was a 57‐year‐old man with Brugada syndrome, who had been implanted with a implantable cardioverter defibrillator (ICD). The frequency of ventricular fibrillation (VF) started to increase about 4 years after ICD implantation, occurring, at worst, six times in one night. Immediately after starting oral administration of disopyramide, VF stopped occurring. He then discontinued taking disopyramide, but immediately after the discontinuation VF started occurring again, so he restarted taking disopyramide. Thereafter, VF completely stopped occurring. Findings observed in our case suggest that disopyramide could be added in our arsenal of medications for treating arrhythmic storms in patient with Brugada syndrome. (PACE 2010; 33:e53–e56)     

A study of ring 20 chromosome karyotype with epilepsy

Abstract We reported a 24-year-old woman with moderate mental retardation and partial epilepsy. She developed complex partial seizures at 3 years of age and generalized tonic convulsions at 9 years. Chromosome analysis revealed that she had mosaicism (87%) of 46, XX, and r(20) (p13, q13.3). Her electroencephalogram showed bilateral 2–3 Hz sharp and wave complex over the bilateral frontopolar, and centro-parieto-occipital areas. Computed tomographic and magnetic resonance image examinations were normal. Twenty-five cases of ring 20 chromosome karyotypes (including this case) have been reported in the literature; 19 showed epilepsy, and 18 showed moderate mental retardation. Many of the patients showed growth retardation and minor malformations. The ring 20 syndrome is associated with a high incidence of epilepsy, particularly partial epilepsy. Our findings indicate that the main features of the ring 20 syndrome are partial epilepsy and mental retardation.     

METHIMAZOLE-INDUCED AGRANULOCYTOSIS IN JAPANESE PATIENTS WITH GRAVES'' DISEASE

We reviewed the records of approximately 7000 Japanese patients whose hyperthyroidism was treated with methimazole (MMI) alone. Four patients (Group I) developed agranulocytosis during a second course of MMI therapy and eight patients (Group II) during an initial course. Six patients (three in each group) received less than 30 mg MMI daily. Agranulocytosis occurred after more than 2 months of therapy (12 weeks-1 year) in five patients. Seven patients were less than 40 years of age. One patient displayed a gradual protracted development of agranulocytosis. These results indicate that agranulocytosis after MMI may occur irrespective of dose, age, duration of treatment, and with a second exposure.     

Hallucinations after a therapeutic dose of benzodiazepine hypnotics with co-administration of erythromycin

Abstract A case of repetitive hallucinations during treatment with a therapeutic dosage of triazolam (0.25 mg/day) and nitrazepam (5 mg/day) is presented. The patient suffered from acute pneumonia and chronic renal failure. Such non-psychotic symptoms as anxiety, tremor and depressed feeling were observed initially. However, after co-administration of erythromycin (600 mg/day), visual hallucinations and abnormal bodily sensations developed repeatedly after each administration of triazolam or nitrazepam. This report suggests that benzodiazepine hypnotics even at a therapeutic dosage with co-administration of erythromycin causes serious psychotic symptoms in vulnerable patients with physical complications.     

CHANGES IN CYCLIC AMP AND ELECTROLYTES AFTER PARATHYROIDECTOMY IN PRIMARY HYPERPARATHYROIDISM

Changes in the excretion of urinary cyclic AMP, calcium and phosphate, and serum calcium, ionized calcium, and magnesium were studied after parathyroidectomy for primary hyperparathyroidism. Urinary cyclic AMP decreased rapidly and 8 of 11 patients had a significant reduction 1 h postoperatively, but changes in serum calcium and ionized calcium were delayed. Serum calcium concentrations closely parallelled those of serum ionized calcium and phosphate excretion returned to normal almost 7 h later than that of cyclic AMP. Excretion of urinary calcium rose rapidly at 4 h after surgery because calcium clearance improved after the reduction in circulating parathyroid hormone. The fall in urinary calcium at about 24 h was due to the subsequent reduction in serum calcium.     

Effects of loxoprofen sodium, a newly synthesized non-steroidal anti-inflammatory drug, and indomethacin on gastric mucosal haemodynamics in the human

Abstract Non-steroidal anti-inflammatory drugs (NSAID) are, and have been, frequently used for alleviation of pain in patients; however, they are known to cause gastric mucosal injury in experimental animals and in humans. A decrease in the gastric mucosal blood flow also plays an important role in the aetiology of acute gastric mucosal injury, as we previously reported. This study investigated the effect of a newly synthesized NSAID, loxoprofen sodium (sodium 2[p-2 oxocyclopentylmethyl) phenyl]propionate dihydrate, on gastric mucosal haemodynamics using a reflectance spectrophotometry system. Both single and cross-over methods were used in five volunteer subjects. Loxoprofen sodium 60 mg (one tablet) or indomethacin 25 mg (one tablet), was diluted in 10 mL water at 25°C and sprayed on the gastric mucosa via a polyethylene tube inserted into the biopsy channel of an endoscope. After drug administration, reflectance spectra were taken every 5 min for 30 min. The indices of mucosal haemoglobin content (IHb) and oxygen saturation of haemoglobin (ISO₂) were determined by the method previously reported by the authors. Indomethacin administration produced a significant decrease in both IHb and ISO₂ values, indication ischaemia. Loxoprofen sodium, however, showed no significant differences in either of the parameters. Haemorrhagic erosions were evident after indomethacin administration, but none were found after loxoprofen sodium administration. The conclusion reached on the basis of this evidence is that one-time topical application of loxoprofen sodium is safer than indomethacin.