Continuous intraarterial infusion of protease inhibitors in acute pancreatitis

Low-molecular-weight protease inhibitors were synthesized and developed in Japan and are in clinical use there for the treatment of acute pancreatitis. However, protease inhibitors are not acknowledged as drugs for the treatment of pancreatitis in other countries. In a recent study in 30 patients with necrotizing pancreatitis, survival rate was improved (mortality rate 13.3%) by continuous intraarterial administration of low-molecular-weight protease inhibitors as compared to conventional treatment. In Italy it was reported that pancreatic disorder decreased after the administration of low-molecular-weight protease inhibitors before the start of endoscopic retrograde cholangiopancreatography. Low-molecular-weight protease inhibitors may be potential alternative drugs for the treatment and/or prevention of acute pancreatitis and, therefore, warrant further evaluation. (c) 2001 Prous Science. All rights reserved.     

Optimum Treatment Strategy for Superficial Esophageal Cancer: Endoscopic Mucosal Resection versus Radical Esophagectomy

This study was designed to determine the optimum treatment for a superficial esophageal cancer involving the mucosal or submucosal layer of the esophagus. The subjects were 150 patients with a superficial esophageal cancer who underwent endoscopic mucosal resection (EMR) or esophagectomy in Kurume University Hospital from 1981 to 1997. The mortality and morbidity rates, survival rate, and recurrence rate were retrospectively compared for (1) 35 patients who underwent EMR and 37 patients who underwent esophagectomy for a mucosal esophageal cancer and (2) 45 patients who underwent extended radical esophagectomy and 33 patients who underwent less radical esophagectomy for a submucosal esophageal cancer. Among the 72 patients with a mucosal cancer, lymph node metastasis/recurrence was observed in only one (1%); whereas of 78 patients with a submucosal cancer it was observed in 30 (38%). Among patients with a mucosal cancer the mortality and morbidity rates after EMR were lower than for those after esophagectomy. The survival rate after EMR was the same as that after esophagectomy. No recurrence was observed after either treatment modality. Among the patients with a submucosal cancer, the survival rate was higher and the recurrence rate lower after extended radical esophagectomy; than after less radical esophagectomy; the mortality and morbidity rates after extended radical esophagectomy were the same as those after less radical esophagectomy. Multivariate analysis demonstrated that the treatment modality (EMR versus esophagectomy) did not influence the survival of patients with a mucosal esophageal cancer, whereas it strongly influenced the survival of patients with a submucosal esophageal cancer. We concluded that EMR was the mainstay of treatment for a mucosal esophageal cancer, and extended radical esophagectomy was the mainstay of treatment for a submucosal esophageal cancer.     

Scopolamine fails to diminish chronic haloperidol-induced purposeless chewing in rats

Chronic haloperidol treatment for 4-12 months gradually induces spontaneous, irregular, purposeless oral chewing movements (CMs), apparently involuntary, in some but not all treated rats. Based on phenomenologic and pharmacologic similarities, this laboratory preparation has been used as an animal model of tardive dyskinesia (TD), which is the human hyperkinetic motor syndrome associated with chronic antipsychotic administration. This putative animal model has received the most severe challenge to its validity by claims that its oral movements can be suppressed by anticholinergic treatments, since resistance to anticholinergic suppression is an accepted pharmacologic feature of TD. In this experiment, we challenged a group of haloperidol-treated rats with CMs using three doses of scopolamine (0.1, 0.3, 1.0 mg/kg) and placebo and rated the change in dyskinetic movements. Each scopolamine dose reduced CMs by a similar magnitude, without any dose effect; the saline dose also reduced CMs to an equivalent degree. Therefore, we concluded that some component of the experiment, not the scopolamine, reduced the CMs. The handling component of the procedure was identified as a likely confound, and we tested this further. Rats with CMs were handled at several levels of "severity"; and the dyskinesias were rated at 1 and 3 h later. CMs were reduced by the experimental handling, in relation to the strength of the handling. Minimal handling produced modest CM reductions with quick recovery; whereas, the "strongest" handling plus the placebo injection produced the greatest CM reduction, evident over 3 h, resembling the CM reductions seen in the scopolamine and placebo experiment. Overall, these results suggest that anticholinergic drugs do not suppress chronic haloperidol-induced rat CMs. However, the movements are sensitive to stressful handling situations, and diminish with stress. In both of these characteristics, rat CMs resemble human TD, further supporting a role for this model in studies of human TD.     

Antidepressant-like effects of aniracetam in aged rats and its mode of action

RATIONALE: Conventional as well as newer antipsychotics cause weight gain, and, in the regulation of body weight, both insulin and leptin are hormones involved. OBJECTIVE: The aim of the present study was to compare these hormonal levels in patients on treatment with different antipsychotics. METHODS: Nineteen patients receiving conventional antipsychotics, 14 patients receiving clozapine and 14 patients receiving olanzapine, were studied. Fasting blood samples for insulin, leptin, glucose, and drug serum concentrations were analyzed. In addition, body mass index (BMI) was calculated. RESULTS: The median insulin level was significantly higher in the patients receiving olanzapine than in those receiving conventional agents, whereas there was no significant difference in insulin between the clozapine and the other two groups. However, in the clozapine group, insulin levels were positively correlated to the drug serum concentration. BMI was elevated in about half of the patients, with no difference being found between the groups. The leptin level was significantly higher in the women than in the men in the conventional agent group, but not in the olanzapine or clozapine groups. CONCLUSIONS: The higher insulin level in the patients receiving olanzapine than in those receiving conventional antipsychotics, despite similar BMI, points to a probable influence of olanzapine on insulin secretion. The correlation between the insulin levels and the clozapine concentration indicates, in addition, an influence of clozapine on insulin secretion. The gender difference in leptin, i.e. females normally having higher leptin levels than males, was found in the conventional agent group, but not in the olanzapine or clozapine groups, suggesting that also leptin regulation is altered during olanzapine or clozapine treatments. Moreover, it was mainly due to an increase of leptin in the males that leptin levels were equalized between sexes in the olanzapine group. We conclude that the influence of olanzapine and clozapine on both insulin and leptin levels might be associated with their weight-gain-inducing ability, while other mechanisms may be involved in the weight gain caused by conventional antipsychotics.     

Factors influencing satisfaction of cochlear implant users--a questionnaire-based study

We surveyed on cochlear implant (CI) users using a questionnaire to determine how they use their CIs in daily life and to what degree they are satisfied with them. We also studied the relationship between the degree of satisfaction and speech perception score, age at operation, and deafness duration. Subjects were 37, postlingually-deafened adult CI users were subjected to this study. Average CI use per day was 13.6 hours. Some 60% of subjects understood person-to-person conversation without lipreading, but most could not communicate on the telephone, in meetings, or in noisy places, for example. Most--about 80%--were satisfied with CI, but 20% were not. Those not satisfied tended to be unable to understand person-to-person conversation even with CI and lipreading, indicating that understanding person-to-person conversation is one of the most important reasons for satisfaction in CI users. Speech recognition scores improved in all cases after implantation. Most patients with high speech recognition score-->40% in consonant recognition--were satisfied with CI, but those with recognition scores < 40% in consonant recognition, the degree of satisfaction varied. These results indicate that the degree of satisfaction in CI users does not always correspond to the degree of improvement in speech recognition score. Two patients not satisfied with CI had undergone surgery after the age of 65 years and deafness duration exceeding 20 years. Advanced age and a long deafness duration may thus reduce satisfaction with CIs.     

Soft-wall reconstruction for cholesteatoma surgery: reappraisal

OBJECTIVE: To reevaluate the validity of the soft-wall reconstruction method of the posterior meatal wall in surgeries for cholesteatomas. STUDY DESIGN: Retrospective case review. PATIENTS: Subjects consisted of 52 patients (54 ears) with fresh cholesteatoma (excluding residual or recurrent cholesteatomas) who were operated by the soft-wall reconstruction method in our clinic and observed for more than 2 years after surgery, and 29 patients (29 ears) who were operated by canal-wall-down and open method. MAIN OUTCOME MEASURES: Postoperative period required for complete epithelization (dry ear), hearing, and incidence of the residual and recurrent cholesteatomas were compared with those operated by canal-wall-down and open method. The postoperative conditions of the soft posterior meatal wall was also investigated. RESULTS: Postoperative period to be a dry ear was significantly shorter in the soft-wall reconstruction group than in the canal-wall-down and open group (Student's t-test, t = 2.99, p < 0.01). There was no significant difference in the postoperative hearing or incidence of residual and recurrent cholesteatomas between the two groups. CONCLUSIONS: These results indicate that the soft-wall reconstruction method seems more versatile than the canal-wall-down and open method for cholesteatoma surgery.     

Differential Distribution of Stem Cells in the Auditory and Vestibular Organs of the Inner Ear

The adult mammalian cochlea lacks regenerative capacity, which is the main reason for the permanence of hearing loss. Vestibular organs, in contrast, replace a small number of lost hair cells. The reason for this difference is unknown. In this work we show isolation of sphere-forming stem cells from the early postnatal organ of Corti, vestibular sensory epithelia, the spiral ganglion, and the stria vascularis. Organ of Corti and vestibular sensory epithelial stem cells give rise to cells that express multiple hair cell markers and express functional ion channels reminiscent of nascent hair cells. Spiral ganglion stem cells display features of neural stem cells and can give rise to neurons and glial cell types. We found that the ability for sphere formation in the mouse cochlea decreases about 100-fold during the second and third postnatal weeks; this decrease is substantially faster than the reduction of stem cells in vestibular organs, which maintain their stem cell population also at older ages. Coincidentally, the relative expression of developmental and progenitor cell markers in the cochlea decreases during the first 3 postnatal weeks, which is in sharp contrast to the vestibular system, where expression of progenitor cell markers remains constant or even increases during this period. Our findings indicate that the lack of regenerative capacity in the adult mammalian cochlea is either a result of an early postnatal loss of stem cells or diminishment of stem cell features of maturing cochlear cells.