Brighton epistaxis balloon: application for cranio-facial injury

Head injury patients often complicate facial and/or multiple injuries other than cranio-cerebral insults and perplex the emergency staffs. The authors used Brighton epistaxis balloon for such patients with massive nasal bleeding and reported the utility of the balloon not only in such state of emergency but also for a few days to control the hemorrhage mostly caused by craniobasal fractures or rupture of the adjacent vessels. One hundred and twenty-nine patients were transported and hospitalized in Department of Emergency Medicine, University of Tokyo Hospital, Tokyo, Japan during the period from October, 1981 to January, 1983. Nasal bleeding was noted in 29 cases of them and the balloon was used in 10 cases, who were from 19 to 76 years of age, all males and suffered from basal fractures or craniofacial injuries. Six cases of them were also accompanied with fractures in the extremities or pelvis, hemopneumothorax and/or intra-abdominal bleeding and could not but put on "Military anti-shock trousers" for the management of hypovolemic shock, hence the nasal bleeding should be managed immediately in the emergency room. In these situations the balloon was inserted into both nasal cavities in all the patients, to control successfully the nasal hemorrhages one of which contaminated cerebrospinal fluid and three of which were sure to be pulsatile due to arterial injury. The Brighton epistaxis balloon is to be removed within twelve or twenty-four hours, but in the authors' cases the mean duration for the hemostasis was 58.9 hours for 6 survivors and 49.6 hours for all 10 cases.(ABSTRACT TRUNCATED AT 250 WORDS)     

A combination therapy with mitomycin c, etoposide, doxifluridine and medroxyprogesterone acetate as second line therapy for advanced breast cancer refractory to combination chemotherapy of cyclophosphamide, doxorubicin and 5 fluorouracil

Thirty-two patients with advanced breast cancer refractory to combination chemotherapy with cyclophosphamide (CPA), doxorubicin (ADR) and 5-fluorouracil (5-FU) (CAF) were treated with the combination of mitomycin C, etoposide, doxifluridine and medroxyprogesterone acetate as second line therapy. Observed responses included 6 patients (18.7%) with complete response (CR) and 7 (21.9%) with partial response (PR). Two (50%) out of 4 patients who had bone pain due to bone metastasis noted pain relief. CR or PR were obtained in 4 out of 12 patients who had not responded to the previous CAF therapy. While grade III myelosuppression was observed in 3 patients, other adverse effects were minimal. It is suggested that this combination therapy may be recommended for advanced breast cancer patients as a second therapy.     

Inhibitory effects of adhesion oligopeptides on the invasion of squamous carcinoma cells with special reference to implication of αv integrins

We studied invasion-related adhesion events in vitro using three squamous carcinoma cell lines (HSC-3, poorly differentiated type; OSC-19, well-differentiated type; and KB cells, undifferentiated type). An in vitro invasion assay through matrigel in the transwell chamber revealed that HSC-3 cells were most invasive, OSC-19 cells moderately invasive and KB cells least invasive. Inhibition assay of invasion using synthetic peptides RGD, RGDV, RGDS, RGDT, IKVAV and YIGSR, showed that invasion of the three cell lines was significantly inhibited by RGDV. There were other peptides that inhibited invasion significantly including IKVAV for HSC-3, and RGDS and YIGSR for OSC-19. HSC-3 cells and OSC-19 cells adhered to fibronectin, laminin, vitronectin, and type IV collagen, and KB cells did not adhere to laminin but did to fibronectin, vitronectin and collagen type IV. Pretreatment of cells with RGDV peptide in the attachment assay reduced the ability of these cells to bind to vitronectin and fibronectin more efficiently than pretreatment with RGDS. Anti-v antibodies inhibited adhesion of HSC-3, OSC-19 and KB cells to vitronectin, but anti-1 antibodies did not inhibit adhesion. Immunofluorescent microscopic examinations showed that all cell lines were positive for anti-5 and anti-v antibodies, and only HSC-3 cells were positive for anti-3 antibody. 51 was not clearly demonstrated in any of the cell lines. RGDV was the most effective inhibitor of squamous cell carcinoma invasion among the synthetic oligopeptides used in this experiment, and it is suggested that it affects v3-and/or v5-mediated carcinoma cell invasion.Abbreviations BSA bovine serum albumin - MEM Eagle's minimal essential medium - MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide - PBS phosphatebuffered saline - FITC fluorescein isothiocyanate This work supported in part by a grant from the Osaka Cancer Research Foundation     

Osteoplastic laminoplasty for cervical myeloradiculopathy secondary to ossification of the posterior longitudinal ligament

Summary Forty-seven patients with cervical myeloradiculopathy due to ossification of the posterior longitudinal ligament were treated by laminoplasty. The spinal canal from C3 to C7 was opened en bloc unilaterally and a spacer bone graft inserted to separate the floating laminae. The average follow up was 7.3 years (range 5 to 11 years). Favourable results were obtained in 35 patients and even though they had serious postoperative symptoms those with advanced neurological symptoms before operation showed considerable improvement. Late results were poor in patients who had greater than 50% compromise of the spinal canal by the ossified lesion. Laminoplasty is a safer method of obtaining favourable late results in patients with involvement of more than 3 vertebrae, but in those with a more severe compromise of the spinal canal by ossification, additional anterior decompression may be necessary later.

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Résumé Cet article présente les résultats à long terme de laminoplasties pratiquées pour myéloradiculopathie cervicale due à l'ossification du ligament vertébral commun postérieur, ainsi que les modifications observées dans les canaux rachidiens élargis. Habituellement le canal rachidien a été ouvert en bloc de C3 à C7, d'un seul côté, puis complété par une greffe osseuse afin de maintenir l'ouverture au niveau de la lame. On a utilisé la cotation de l'Association orthopédique japonaise, concernant la myélopathie cervicale, pour évaluer l'état des patients avant l'intervention chirurgicale, puis 2 ou 3 mois après la sortie et durant la période de surveillance. Les 47 patients de cette étude ont été suivis de 5 à 11 ans, soit en moyenne 7,3 ans. Les résultats finaux ont été favorables chez 35 patients et, même quand la symptomatologie postopératoire avait été assez préoccupante, les malades qui présentaient des symptômes neurologiques majeurs étaient notablement améliorés. Les résultats étaient mauvais chez les patients dont le rétrécissement du canal rachidien était supérieur à 50% (p<0.05). Il semble que la laminoplastie soit le moyen le plus sûr d'obtenir un résultat favorable mais une décompression antérieure complémentaire peut être nécessaire chez les patients atteints d'une sténose sévère due à une ossification du ligament vertébral postérieur.

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Presented in part at SICOT 93, Seoul, Korea, 28 August–3 September, 1993     

Resection and reconstruction of the great vessels for lung cancer and mediastinal tumor

Between January 1994 and December 1997, 17 patients with lung cancer and 5 patients with mediastinal tumor underwent extensive resection and reconstruction of the great vessels. In patients with lung cancer, the aorta was resected under cardiopulmonary bypass in 4 patients, the superior vena cava in 12, and the left main pulmonary artery with combined resection of the left atrium in 1 and the aorta in 1. In five patients who underwent resection of the superior vena cava, subcarinal resection and reconstruction were also performed. Three patients died within 30 days after surgery. Six patients died of cancer between 3 months and 2 years after surgery. Two patients who underwent aortic resection for node negative lung cancer have survived more than 3 years after surgery. Six patients have survived between 6 months and 2 years after surgery. The histologic type of mediastinal tumor was thymic cancer in 3 patients, invasive thymoma in 1 and malignant lymphoma in 1. In patients who underwent resection of the superior vena cava for mediastinal tumor, bilateral brachiocephalic vein reconstruction was performed in 4 patients and the left brachiocephalic vein reconstruction in 1. One patient underwent resection of the right atrium. The patient with invasive thymoma has survived for more than 3 years. Two of 3 patients with thymic cancer died within 2 years. When complete resection is achieved with combined resection of the great vessels, survival may be anticipated in patients with N0 lung cancer or in those with invasive thymoma.     

Dietary Restriction Reduces the Prevalence of Osteonecrosis of the Caput Femoris in Spontaneously Hypertensive Rats

We investigated the effects of dietary restriction (DR), an experimental intervention known to suppress several strain-specific diseases, on the prevalence of osteonecrosis of the caput femoris in spontaneously hypertensive rats (SHR). At 6 weeks of age, the food intake of DR rats was restricted to 65% of the mean intake of control rats fed ad libitum (AL). Acute osteonecrosis of the caput femoris without reparative tissue response (RTR) was observed at 10 and 15 weeks in both DR and AL groups; no such acute lesion was seen at 20 and 30 weeks. The prevalence of osteonecrosis, osteonecrosis with/without reparative tissue response was significantly reduced in DR rats at 15 and 20 weeks, but not at 10 weeks. DR reduced the body weight by 30% and the length of the femur by 10%. Ossification of the caput femoris, known to be delayed in AL rats compared with Wistar Kyoto rats, was also restored by DR. Our results showed that dietary restriction reduced the prevalence of osteonecrosis and modulated the mechanical factors involved in the lesion. They also indicate that utilization of dietary restriction is a useful research tool for investigating the underlying mechanisms of osteonecrosis of the caput femoris in SHR. Received: 4 March 1997 / Accepted: 9 July 1998     

A mild transient decrease of peripheral red blood cell counts induced by a suprapharmacological dose of pegylated human megakaryocyte growth and development factor in rats.

Previous studies have shown that pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) at suprapharmacological dose induces a mild transient decrease of red blood cell counts according to thrombopoiesis in normal mice. To unravel the mechanism underlying this mild transient decrease of red blood cells, we have studied the effect of PEG-rHuMGDF on the circulating plasma and blood volume, and the serum biochemical parameters of anaemia and splenectomy. Also, we have performed histological studies of the bone marrow and the spleen of PEG-rHuMGDF-treated rats. PEG-rHuMGDF (300 microg kg(-1)]) or vehicle was subcutaneously administered to rats once a day for up to five days. From day 6 after the start of PEG-rHuMGDF administration, the platelet counts and plateletcrit levels were significantly increased, reaching peak values on day 10, and recovering to normal by day 20. The red blood cell counts and the haematocrit levels were significantly decreased on day 6 to 13. The decreases in red blood cell levels and haematocrit produced by PEG-rHuMGDF treatment were mild and had recovered by day 15. The plasma and blood volumes were significantly increased on day 10 in PEG-rHuMGDF-treated rats. No alteration of the serum biochemical parameters for anaemia, iron or total bilirubin, were observed on day 10. The histological examination on day 10 revealed a marked increase in megakaryocytes and a slight decrease in erythropoiesis in the bone marrow of rats that received PEG-rHuMGDF (300 microg kg(-1)). There was also a slight increase in splenic megakaryocytes and erythropoiesis. The decrease of red blood cells by PEG-rHuMGDF was not affected by splenectomy. These results suggest that the mild transient decrease of red blood cells induced by PEG-rHuMGDF treatment for up to five days is based mainly on the increases in the plasma and blood volume. These events are secondary changes due to the regulation of the excess production of megakaryocytes in the marrow and the peripheral platelets.     

Contribution of P-glycoprotein to bunitrolol efflux across blood-brain barrier

In this study, we investigated the mechanism of the blood-brain barrier (BBB) transport of bunitrolol (BTL), as a model of beta-blocker, in vivo and in vitro. In order to define the contribution of P-glycoprotein (P-gp) to the active efflux of BTL from brain to blood, we examined the in vivo brain distribution of BTL in mdr1a(-/-) mice with a disrupted mdr1a gene. After intravenous administration of BTL to mdr1a(-/-) mice, the brain concentration and Kp value of BTL were significantly increased as compared with those in mdr1a(+/+) mice. Next, the contribution of the mdr1a P-gp to in vitro uptake of BTL was compared in LV500 cells and L cells (mouse mdr1a-expressing cells and host cells, respectively). The intracellular accumulations of [3H]vinblastine and BTL by LV500 cells were lower than those by L cells, but were significantly increased by verapamil, a P-gp inhibitor. Furthermore, the BTL uptake by KB-VJ300 cells, which express human P-gp, was also significantly lower than that by KB host cells, and was increased by verapamil. The steady-state uptake of BTL by LLC-GA5-COL300 cells, expressing human P-gp, was significantly increased in the presence of 20 microM cyclosporin A (another P-gp inhibitor), which had no effect in the LLC-PK1 host cells. On the other hand, the steady-state intracellular accumulation of BTL by MBEC4 cells, which express mdr1b P-gp instead of mdr1a P-gp, was not significantly changed in the presence of verapamil. This finding suggested that BTL is not a good substrate for mdr1b P-gp. In conclusion, our results suggest that BTL is transported from brain to blood by mdr1a P-gp in mice and by MDR1 in humans, and this presumably accounts for the low brain distribution of BTL.     

Antihypertensive properties of KRN4884, a novel long-lasting potassium channel opener

The antihypertensive action of KRN4884 (5-amino-N-[2-(2-chlorophenyl)ethyl]-N'-cyano-3-pyridinecarboxamidine ), a newly synthesized 3-pyridine derivative was examined in conscious spontaneously hypertensive rats (SHRs). A single administration of KRN4884 (0.5, 1.5 mg/kg, p.o.) produced a dose-dependent and long-lasting antihypertensive effect. The 7-day repeated administration of KRN4884 (0.5, 1.5 mg/kg, p.o.) did not diminish antihypertensive activity during the treatment period or induce rebound hypertension after the discontinuation of treatment. To examine the mechanism of the antihypertensive effect of KRN4884, we studied its vasorelaxing effects in rat isolated aortae precontracted with 25 mM KCl. Single application of KRN4884 showed a slower onset of inhibitory action than that of levcromakalim. KRN4884 was approximately 26-fold more potent than levcromakalim and 10-fold less potent than nilvadipine. KRN4884- and levcromakalim-induced vasorelaxation were antagonized by glibenclamide. Furthermore, we observed the recovery of the contraction inhibited by these drugs after repeated washing. The inhibitory effect of KRN4884 was restored only after four washes, whereas that of levcromakalim was completely restored after one wash. The nilvadipine-induced inhibitory effect was the most resistant to washing among these drugs. These results suggest that KRN4884 shows a long-lasting antihypertensive effect based on its potent potassium channel-opening action. The long-lasting action may be due to a slow association/dissociation with/from the binding sites on vascular smooth muscle.     

Pharmacokinetics of temocapril hydrochloride,a novel angiotensin converting enzyme inhibitor,in renal insufficiency

Summary The pharmacokinetics of temocapril hydrochloride, a novel prodrug-type angiotensin-I converting enzyme (ACE) inhibitor, has been studied in patients with mild (Group II) to severe (Group III) renal insufficiency in comparison with subjects with normal renal function (Group I).The pharmacokinetic parameters of the active diacid metabolite, including C_max, AUC and half-life (t_1/2), showed only slight changes between the three groups: AUC (0–) was significantly larger in Group III than Group I, and t1/2 tended to be prolonged in Group III, but the change was not significant.The urinary recovery of the diacid was significantly decreased in Group III. (Group I, 28.1 %, Group II, 21.6 %, Group III, 12.8 %). Compared with other ACE inhibitors, which are mainly excreted through the kidney, the plasma concentration of the active diacid metabolite was hardly influenced by renal function. It was speculated that lowering of the dose of temocapril might be recommended only in patients with severe renal insufficiency.