The evaluation of meconium disease by distribution of cathepsin D in intestinal ganglion cells

Meconium disease (MD) results in intestinal obstruction in the neonate where tenacious meconium is found in the distal ileum and proximal colon. The obstructive symptoms improve at several days of age after some of the meconium is passed. We observed premature infants with MD who underwent ileostomy for intestinal obstruction due to tenacious meconium. Afterward, meconium was passed well and the clinical symptoms improved. After closing the ileostomy, growth and defecation became normal. The MD in our cases was documented by histologic changes in the maturation of ganglion cells observed at the time of ileostomy creation and closure. For an objective evaluation of the maturation of intestinal ganglion cells (IGC), we attempted to distinguish immature from mature cells by the expression of cathepsin D. We examined the distribution of cathepsin D in IGC in patients with MD to test the hypothesis that ganglion-cell immaturity might be related to MD. In ganglion cells at the time of ileostomy, cathepsin D was detected in the perinuclear cytoplasm (immature staining pattern), while at the time of ileostomy closure it was detected in intense granules throughout the cytoplasm (mature staining pattern). We propose that it would be possible to evaluate the maturation of IGC by the intracellular distribution of cathepsin D in MD and suggest that immaturity of IGC might be the cause of MD. Accepted: 28 June 1999     

Effect of 7-Bromo-5-(2-pyridyl)-3H-l, 4-benzodiazepine-2(1H)-one, Bromazepam (Ro 5–3350), a New Minor Tranquilizer, on Psychoneurosis with Special Reference to the Obsessive-Compulsive Symptoms

Clinical application of a minor tranquilizer bromazepam, 7-Bromo-5-(2-pyridyl)-3H-1,4-benzodiazepine-2(lH)-one (Ro 5–3350) was made on 18 cases of obsessive-compulsive neurosis, 10 of anxiety neurosis, 6 hypochondriasis, 4 hysteria and 3 of phobia of bodily odor.

• 1) In 18 cases of obsessive-compulsive neurosis, bromazepam was found markedly effective in 6, effective in 3, fairly effective in 5, ineffective in 2, and aggravated in 2 cases. The effective cases were those with obsessive thinking and manifest anxiety. In other kind of neurosis, bromazepam was markedly effective in 5 and effective in 2 of 10 anxiety neurotic cases, whereas it was almost ineffective in the cases of hypochondriasis, hysteria and phobia of bodily odor.
• 3) The maximum daily dose of bromazepam was 10 to 20 mg in many cases, and 20 to 30 mg in some other cases. The durg is quick-acting to such an extent that it took 2 to 5 days for its action to become manifest in markedly effective cases.
• 4) Various laboratory tests revealed no appreciable abnormality in most cases where bromazepam was employed. Physical side effects such as slight hypotension, dizziness, and sleepiness were observed in a few cases, and mental side effects such as loquaciousness and restlessness in about 20 cases.
• 5) The target symptoms of bromazepam were suggested to be anxiety, tension, and irritation like previously reported other benzodiazepines. The fact that its action of relieving anxiety and tension and of elevating mood was found to be more potent than those of other benzodiazepines and that it was effective on some obsessive-compulsive neurosis that showed little response to other benzodiazepines, suggested that bromazepam is a potent and characteristic new minor tranquilizer of clinical value.

     

Anti-Manic and Prophylactic Effects of Carbamazepine (Tegretol) on Manic Depressive Psychosis A Preliminary Report

• 1). The anti-manic, anti-depressive and prophylactic effects of carbamazepine (CAZP, Tegretol-Ciba Geigy) on the endogenous mani-depressive psychosis (MDP) were investigated on 50 MDP cases. The dosage of the drug ranged from 200 to 1,200 mg daily (usually 400 to 600 mg).
• 2). The effect of CAZP on 33 manic states was: “markedly effective” seven (23%), “effective” six (19%), “slightly effective” five (16%), “ineffective” 13 (42%), whereas the effect on six depressive states was: “markedly effective” one and “ineffective” five. No definite relationship was found between the kinds of drugs in combination use and the effect of CAZP. No significant difference of the CAZP effect was found in the four patient groups with different age of onset of the illness, nor among the “continuous,”“frequent” and “periodic” type cases.
• 3). The prophylactic effect of CAZP on 27 cases in which the assessment of the effect on the manic episode was possible was: “markedly effective” 13 (48%), “effective” seven (26%) and “ineffective” seven (26%), whereas that for depressive episode was: 12 (45%), two (7%) and 13 (48%), and the result of the general assessment on each patient was 14 (43%), 10 (30%) and nine (27%), respectively. The kinds of drugs in combination use, age of onset and type of course of the illness did not have any influence on the prophylactic effect of CAZP.
• 4). The prophylactic effect on MDP of CAZP did not parallel that of lithium salt, but CAZP may be effective on cases which did not respond to lithium and vice versa.
• 5). Side-effects such as ataxia, dizziness, exanthema, drowsiness and headache were observed in five of the cases, and the CAZP was discontinued in four of them.
• 6). The mechanism of effectiveness of the CAZP on MDP was discussed.

     

A case report of hepatocellular carcinoma (Vp4)--an attempt to reduce residual tumor thrombus using combination therapy (hepatic arterial infusion, hepatic arterial embolization and radiation)

A 57-year-old man was found to have elevated levels of HCC markers during an observation of chronic hepatitis C. Diffused hepatoma was involved in the posterior lobe, and tumor thrombus extended into the main portal vein (Vp4). Posterior segmentectomy and tumor thrombectomy were performed. But, CT scan 45 days after the operation showed an enhancement at the residual tumor thrombus in the posterior branch. The patient received a hepatic arterial infusion of 5-FU, followed by hepatic arterial embolization. Then, we chose radiation therapy to the tumor thrombus. The most recent CT showed no enhancement at the reduced tumor thrombus. There have been almost no reports of treatment for residual portal thrombus. Careful observations are necessary in such patients.     

Transection of the innominate artery for tracheomalacia caused by persistent opisthotonus

Patients with cerebral palsy often develop opisthotonus. The trachea may be pinched between the innominate artery and the cervical spine. This compartmentalized thoracic inlet results in severe tracheomalacia. We successfully released tracheal compression by transection of the innominate artery. In case 1, a 4-year-old girl with cerebral palsy and opisthotonus was admitted due to respiratory distress. Bronchoscopy revealed severe tracheomalacia 2 cm above the carina. An endotracheal stent was placed through a tracheostomy. Two months later, she developed tracheal bleeding and bronchoscopy demonstrated a trachea-innominate artery fistula. Magnetic resonance brain angiography showed the presence of Willis circle, and transection of the innominate artery was justified. This was done through a low cervical skin incision. In case 2, a 6-year-old boy with cerebral palsy and opisthotonus had long-standing respiratory distress. Ventilatory support did not resolve the symptoms. The innominate artery was transected in the same fashion as in the first case. Case 1 has been free from respiratory distress for 4 months and case 2 for 3 years. Our experience suggests that the combination of tracheomalacia, opisthotonus causes severe respiratory distress. Transection of the innominate artery is a useful therapeutic strategy to release airway obstruction in this condition.     

Angioplasty for the intimal dissection of graft artery immediately after blood reflow: a successful case of renal transplantation

A 58-year-old woman, who had been suffering from chronic renal failure on hemodialysis since 1999, underwent living renal transplantation on January 14, 2003. The donor was her husband, and his left kidney was resected by a hand-assisted retroperitoneoscopic technique. Vascular clamps were removed after vascular anastomoses, but the color of two-thirds of the graft back side was dark, and urine excretion was not observed for 1 hour. The intimal dissection of the graft artery developed false lumen that occluded the blood flow to the transplanted kidney. The graft was resected from the recipient, and an angioplasty was performed for the false lumen of the graft artery after the second cold preservation. The graft with repaired artery was re-transplanted, and urine excretion was observed immediately after operation. Total ischemia time was 5 hours. Clinicopathological acute rejection episode and stenosis of graft artery did not occur for 6 months after operation. The intimal dissection of graft artery might occur at the time of catheterization on the perfusion for cold preservation and/or vascular anastomosis.     

A novel antireflux technique using an intussuscepted ileal segment

A novel surgical technique of antireflux with an ileal conduit for urinary diversion is presented with our early results. The mid 8-cm portion of an isolated terminal ileum is intussuscepted. After skeletonization of the mesenterial vasculature, 3 rows of 4 mattress seromuscular silk sutures are placed on the ileum. By tying the sutures successively, the ileum is intussuscepted and the resultant nipple is secured simultaneously between its outer and inner layers. The outer nipple layer and the recipient ileal layer are further fixed as a whole by placing 3 rows of metal staples. The nipple base is secured by interrupted silk sutures and the mesenterial defect is closed. This technique was applied to 30 patients undergoing rectosigmoidal bladder procedure, a modified ileocecal rectal bladder, in which the antireflux conduit was interposed between the ureters and the rectosigmoidal pouch. Ureteral reflux was observed in none of the patients during a mean follow-up period of 29.9 months. Of the 60 renal units, 53 (88.3%) had normal pyelography and 7 (12.7%) showed mild hydronephrosis at 3-6 months postoperatively. This antireflux technique is simple and reliable, and can be applied to other urinary diversion/reconstruction surgeries, such as the continent reservoir, orthotopic neobladder, and/or bladder augmentation.     

Early and large-dose intravesical instillation of epirubicin to prevent superficial bladder carcinoma recurrence after transurethral resection

OBJECTIVE: To prospectively compare the prevention of tumour recurrence by four intravesical adjuvant administration protocols, and thus elucidate the efficacy of early and high total dose instillations of epirubicin to prevent superficial bladder tumour recurrence after transurethral resection of bladder tumour (TURBT). PATIENTS AND METHODS: In all, 69 patients with Ta/T1 bladder cancer were randomly assigned to four intravesical administration protocols: A, delayed instillation (first instillation 7 days after TURBT) and low-dose (30 mg once every 2 weeks, six times): B, early instillation (three instillations before 7 days after TURBT) and low-dose; C, delayed and high-dose (30 mg once weekly 12 times) instillation; D, early and high-dose. The influence of the instillation protocols and tumour characteristics on the probability of recurrence-free survival was examined using Kaplan-Meier analysis and a Cox regression hazard model. RESULTS: The early-instillation and high-dose groups had relatively lower recurrence rates after 6 months (A, 30%; B, 25%; C, one of 12; and D, none) and 1 year (50%, 35%, four of nine and one of eight, respectively). Patients who received 360 mg epirubicin (C and D) had a significantly better recurrence-free survival than those receiving 180 mg (A and B; P = 0.012). Preoperative urine cytology and tumour multiplicity were significantly associated with recurrence. However, multivariate analysis of the risk of recurrence using a Cox proportional hazard model showed that urine cytology (hazard ratio 3.11, 95% confidence interval 1.08-8.94, P = 0.04) and total dose (0.32, 0.11-0.92, P = 0.03) were independent prognostic factors for recurrence. CONCLUSION: Patients who received a high-dose epirubicin instillation had a significantly lower recurrence rate but the benefit of early instillation was not confirmed, as the study group was too small.     

Evaluation of immunotoxic and immunodisruptive effects of inorganic arsenite on human monocytes/macrophages

A trivalent inorganic arsenic, arsenite, has been causing chronic inflammation in humans through the consumption of contaminated well water. The total peripheral blood arsenic concentrations of chronic arsenic-exposed patients, who had inflammatory-like immune responses, are less than 1 microM, thus, nM concentrations may be very important regarding the chronic inflammatory effects by arsenite. However, there are few reports about the biological effects of low concentrations of arsenite in mammalian cells, especially in normal immune effector cells. In this study, we examined whether arsenite has any biological and/or toxicological effects on the differentiation of human peripheral blood monocytes into macrophages using the colony-stimulating factor (CSF) in vitro compared with that of other metallic compounds, and found that arsenite sensitively inhibited the CSF-induced in vitro maturation of monocytes into macrophages at nM levels, and it also induced small, nonadhesive and CD14-positive abnormal macrophage generation from monocytes with granulocyte-macrophage CSF (GM-CSF) at 50-500 nM without cell death. The addition of other metallic compounds, including chromium, selenium, mercury, cadmium, nickel, copper, zinc, cobalt, manganese and other human pentavalent arsenic metabolites, such as inorganic arsenate, monomethylarsonic acid and dimethylarsinic acid, could not induce the same abnormal cell generation from monocytes with CSFs at any concentration and any additional time schedules; they showed only simple cytolethality in monocytes and macrophages at n-mM levels accompanied by cell death. This work may have implications in the arsenic-induced chronic inflammation in humans.