Prenatal diagnosis of congenital diaphragmatic hernia and pulmonary hypoplasia and therapeutic strategy

The outcome of fetuses with congenital diaphragmatic hernia (CDH) has been reported to be fatal when pulmonary hypoplasia (PH) is severe. As an indicator of PH, we attempted to measure the lung-thorax transverse area ratio (L/T) using ultrasonic echography. Immediate postnatal surgery was performed using high-frequency oscillatory ventilation (HFOV) and sometimes followed by extracorporeal membrane oxygenation (ECMO). Eighteen fetuses were treated and 14 survived. L/T correlated well with the best preductal arterial blood gas data before surgical reduction during manual ventilation and HFOV, while preductal PO₂ and alveolar-arterial oxygen differences from patients managed with HFOV were better than those in patients with manual ventilation. Although L/T also correlated with the duration of O₂ therapy and hospitalization in survivors without major anomalies, there was no significant difference between L/T in survivors and nonsurvivors. Because delayed institution of ECMO and complications related to ECMO management seemed to be a major cause of death in non-survivors, the unsalvageable L/T due to PH was estimated to be below 0.06 for HFOV and below 0.1 for conventional ventilation based on the correlation between L/T and preductal P02. These results suggest that L/T is a useful indicator of PH in patients with CDH and also that HFOV is advantageous in treating CDH with PH. The advantage of prenatal diagnosis in predicting unsalvageable L/Ts, should be considered in the therapeutic strategy.     

A retrospective analysis of surgical operations on malignancies of the ear]

In the past 20 years from 1970 to 1990, 21 patients with malignancies of the ear were treated at Cancer Institute Hospital. The primary sites were the auricle and cartilaginous external auditory canal (group 1: n = 8), the bony external auditory canal (group 2: n = 6) and the middle ear (group 3:n = 7). In group 1, pathological types were squamous cell carcinoma in four patients and basal cell carcinoma in the other four patients. Seven patients were treated by surgery alone, and the remaining patient was treated by interstitial implant radiotherapy. No recurrence have been noted up to today in this group. In group 2, pathological types were squamous cell carcinoma in four patients and adenoid cystic carcinoma in the other two patients. All of the six patients underwent external canal resection or subtotal temporal resection. Two patients received postoperative radiotherapy. A five year survival rate of group 2 was 60%. In group 3, pathological types were squamous cell carcinoma in six patients and undifferentiated carcinoma in the remaining patient. Most of them underwent radical mastoidectomy followed by irradiation. However, all the patients died within two years after treatment. In group 2 and 3, cytodiagnosis was useful for early discovery. In group 2, temporomandibular joint seemed to be a key point in surgical treatment. In group 3, the combination of conservative surgery with radiotherapy was not a radical treatment. This suggested it necessary to perform subtotal temporal resection to treat malignancy of the middle ear.     

Mechanisms underlying the chronic pravastatin treatment-induced improvement in the impaired endothelium-dependent aortic relaxation seen in streptozotocin-induced diabetic rats

1. We investigated the effects of chronic pravastatin treatment on the impaired endothelium-dependent relaxation seen in aortae from established streptozotocin (STZ)-induced diabetic rats. Starting at 6 weeks of diabetes, pravastatin (10 mg kg(-1)) was administered to STZ-induced diabetic rats for 4 weeks. 2. The increased total cholesterol and low-density lipoprotein (LDL) cholesterol levels seen in STZ-induced diabetic rats were not restored to normal by pravastatin. Aortae from pravastatin-treated diabetic rats did not show an impaired endothelium-dependent relaxation to acetylcholine. The expression of the mRNA for endothelial nitric oxide synthase was unaffected by diabetes or pravastatin. 3. The enhanced level of malondialdehyde (MDA)-modified LDL seen in STZ-induced diabetic rats was normalized by pravastatin treatment. The resistance of LDL to oxidation was assessed by measuring the amount of MDA or conjugated dienes generated by incubation with copper ions. LDL isolated from diabetic rats, but not those from pravastatin-treated diabetics, showed enhanced the susceptibility to oxidation, but incubation in vitro with pravastatin had no effect on LDL oxidation. 4. Following incubation of control aortae for 6 h with LDL (0.1 mg protein ml(-1)) isolated from diabetic rats, the endothelium-dependent relaxation to acetylcholine or A23187 was impaired, but LDL isolated from control or pravastatin-treated rats had no such effect. This inhibitory effect of diabetic LDL was prevented by superoxide dismutase (SOD), a superoxide scavenger. 5. These results suggest that pravastatin preserves endothelial function in aortae from STZ-induced diabetic rats without lowering plasma cholesterol, and its effect may be due to decreased LDL oxidation.     

Cycloprodigiosin hydrochloride, H(+)/CL(-) symporter, induces apoptosis and differentiation in HL-60 cells

Cycloprodigiosin hydrochloride (cPrG * HCl), a novel H(+)/Cl(-) symporter, induces acidification of the cytosol and leads to apoptosis in rat and human liver cancer cells. In the present study, the effect of cPrG * HCl on a promyelocytic leukemia cell line (HL-60) was examined. cPrG * HCl lowered intracellular pH and induced apoptosis through up-regulation of Fas ligand, activation of stress-activated protein kinase (SAPK/JNK) and caspase. Apoptosis induced by cPrG * HCl was strongly suppressed when a cell-permeable weak base, imidazole, was present, indicating that cytosol acidification introduced by cPrG * HCl triggered caspase activation, leading to apoptosis. Concomitantly, cell differentiation into monocyte was also induced by cPrG * HCl both morphologically and functionally. However, the cPrG * HCl-induced differentiation was not suppressed by addition of imidazole, indicating that the differentiation process is unrelated to cytosol acidification. Further, the differentiation induced by cPrG * HCl was blocked by tyrosine kinase inhibitors (lavendustin A and HMA) but unaffected by the inhibitors of A-kinase (H-89) or C-kinase (H-7). Taken together, these findings suggest that cPrG * HCl, through apoptosis and differentiation induction, may be useful in leukemia treatment.     

Mechanisms underlying the attenuation of endothelium-dependent vasodilatation in the mesenteric arterial bed of the streptozotocin-induced diabetic rat

Experiments were designed to investigate the mechanisms underlying the diabetes-related impairment of the vasodilatations of the perfused mesenteric arterial bed induced by acetylcholine (ACh) and K(+). In streptozotocin (STZ)-diabetic rats, the ACh-induced endothelium-dependent vasodilatation was attenuated. The dose-response curves for ACh in control and diabetic rats were each shifted to the right by N(G)-nitro-L-arginine (L-NOARG) and by isotonic high K(+) (60 mM). The ACh dose-response curves under isotonic high K(+) were not different between control and diabetic rats. We also examined the vasodilatation induced by K(+), which is a putative endothelium-derived hyperpolarizing factor (EDHF). The mesenteric vasodilatation induced by a single administration of K(+) was greatly impaired in STZ-induced diabetic rats. Treatment with charybdotoxin plus apamin abolished the ACh-induced vasodilatation but enhanced the K(+)-induced response in controls and diabetic rats. After pretreatment with ouabain plus BaCl(2), the ACh-induced vasodilatation was significantly impaired and the K(+)-induced relaxation was abolished in both control and diabetic rats. The impairment of the endothelium-dependent vasodilatation of the mesenteric arterial bed seen in STZ-induced diabetic rats may be largely due to a defective vascular response to EDHF. It is further suggested that K(+) is one of the endothelium-derived hyperpolarizing factors and that the vasodilatation response to K(+) is impaired in the mesenteric arterial bed from diabetic rats.     

Further dopaminergic supersensitivity to dopamine agonists by subchronic administration of haloperidol in rats treated with colchicine

Effects of subchronic administration of haloperidol on the circling behavior induced by dopamine agonists were examined in rats treated with colchicine. Methamphetamine and apomorphine produced contralateral or ipsilateral rotation in colchicine-treated rats, and these circling behaviors were significantly increased by subchronic treatment with haloperidol. These results suggest that development of supersensitivity following colchicine and subchronic haloperidol may occur through different mechanisms.     

A dissecting aneurysm of the vertebral artery

A rare case of dissecting aneurysm of the vertebral artery evidenced by ischemic attacks is reported. The aneurysm was treated by proximal ligation of the artery. There have been no repeated ischemic attacks and bleeding for 20 months. Analysis of 51 cases of vertebral artery aneurysm failed to disclose any comparable case. A review of the literature also revealed that clinically diagnosed dissecting aneurysms of the vertebrobasilar system have been reported rarely. Most of these cases were found at autopsy.     

Clinical studies on gentamicin in complicated urinary tract infections (author's transl)]

Twenty cases with complicated urinary tract infections were treated with gentamicin. Good results were obtained in 7 of 14 cases with chronic pyelonephritis and 2 of 4 cases with chronic cystitis and in 1 of 2 cases with acute prostatitis. No side effect was observed throughout this treatment. But in laboratory examination, slight elevation of S-GOT and S-GPT was observed in 3 of 20 cases after gentamicin treatment.