Elevated Serum Growth Hormone Accelerates Gastric Tumorigenesis in F344 Rats after Treatment with N-Methyl-N-nitrosourea in Their Drinking Water

We examined the effects of growth hormone on tumorigenesis in F344 rats treated with N -methyl- N -nitrosourea (MNU). Four-week-old male F344 rats were exposed to 100 ppm MNU in their drinking water for 15 weeks. Thereafter Group II animals received 100 μCi/100 g body weight of ¹³¹I (radiothyroidectomy, Tx) injected i.p. and Group III rats were implanted with pituitary tumors (MtT) secreting growth hormone while Group I received no further treatment after MNU. Non-carcinogen control animals received MtT, Tx or no treatment. Animals were killed at 39 weeks after starting MNU administration. Gastric tumors were present in 13 of 31 (43%), 15 of 32 (47%) and 17 of 32 (53%) rats in Groups I to III, respectively. All tumors were of well-differentiated type. Spinal cord tumors appeared in 15 of 31 (47%) in Group I, 10 of 32 (32%) in Group II and 10 of 32 (32%) in Group III, most being malignant schwannomas. Thymic lymphornas also appeared in 10 of 31 (32%), 5 of 32 (16%) and 6 of 32 (19%) animals in Groups I to III, respectively. There were no significant differences among the groups. However, tumors in Group III developed significantly earlier than in Groups I or II. This was mainly due to gastric tumors, and cumulative incidence curves for spinal cord tumors or thymic lymphomas were similar in all groups. The results indicate that gastric tumors induced by MNU in F344 male rats are influenced by elevated levels of growth hormone.     

Influence of Paternal 252Cf Neutron Exposure on Abnormal Sperm, Embryonal Lethality, and Liver Tumorigenesis in the F1 Offspring of Mice

Experiments were conducted to determine whether neutron-induced genetic damage in parental germline cells can lead to the development of cancer in the offspring. Seven-week-old C3H male mice were irradiated with ²⁵²Cf neutrons at a dose of 0, 50, 100, or 200 cGy. Two weeks or 3 months after irradiation, the male mice were mated with virgin 9-week-old C57BL females. Two weeks after irradiation, the irradiated male mice showed an increased incidence of sperm abnormalities, which led to embryo lethalities in a dose-dependent manner when they were mated with unirradiated female mice. Furthermore, liver tumors in male offspring of male mice in the 50 cGy group were significantly increased in 19 of 44 (43.2%) animals, in clear contrast to the unirradiated group (1 of 31; 3.2%) ( P < 0.01). In the 100 cGy group, 6 of 39 (15%) mice had lesions. At 3 months after irradiation abnormal sperm and embryonal lethality were not significantly increased. The incidences of liver tumors in male offspring from the 50 cGy, 100 cGy and 200 cGy groups were 6 of 20 (30%), 5 of 22 (23%) and 1 of 19 (5%), respectively, which are not significantly increased compared with the control. It is concluded that increased hepatic tumor risk in the F₁ generation may be caused by genetic transmission of hepatoma-associated trait(s) induced by ²⁵²Cf neutron irradiation.     

The results of antibiotic susceptibility of gram-negative rods at Tottori University Hospital--the possibility of the sensible use of narrow-spectrum antimicrobial agents

The control of hospital-acquired infections is a matter of social concern, especially in the proper use of antimicrobial agents. The fundamentals of treatment for infectious diseases involve the exact identification of the responsible bacteria, and the minimum essential use of narrow-spectrum antimicrobial agents for the identified bacteria. We tested the antimicrobial susceptibility of 13 species which belong to the gram-negative rod type and isolated 50 or more strains at Tottori University Hospital in 2001. We evaluated the susceptibility pattern for every species, and have proposed a plan for the sensible use of narrow-spectrum antimicrobial agents. The resistant frequency in the present study was equal to or lower than previously reported. We think that it is possible to use narrow-spectrum antimicrobial agents more often, because the susceptible frequency to these agents was fairly high for some species. It is not too much to say that the history of the development of antimicrobial agents has been a road to broad-spectrum. Though the proper use of antimicrobial agents seems to go against this view, we should remain farsighted. Not only is the publicity of proper use indispensable but excellent surveillance is also highly necessary. We hope for the establishment of a good surveillance system gifted with simplicity, universality, high reproduction and continuity.     

Superior efficacy of MMCP regimen compared with VMCP and MMPP regimens in the treatment of multiple myeloma

OBJECTIVE: A newly designed combination chemotherapy for multiple myeloma, MMCP [ranimustine (MCNU), melphalan (MPH), cyclophosphamide (CPM) and prednisolone (PSL)], was analyzed and compared with the results of our previous randomized trial of VMCP [vincristine, MPH, CPM and PSL] and MMPP [MCNU, MPH, procarbazine and PSL]. METHODS: MCNU (33.3 mg/m2, div) on day 1 and MPH (4 mg/m2, po), CPM (66.7 mg/m2, po) and PSL (30 mg/m2, po) from day 1 to 4, were administered. Each cycle was repeated every 3 weeks. PATIENTS OR MATERIALS: From January 1991 until August 1995, 104 patients with multiple myeloma diagnosed at 10 hospitals of Nagoya Cooperative Study Group were enrolled. RESULTS: Of the 87 evaluable patients, partial response rate for MMCP was 65.5% and was significantly higher than that of VMCP (13/47=27.7%, p<0.0001) and that of MMPP (21/47=44.7%, p=0.0196). A plateau attainment was observed in 49.4%. The percentage of the patients who attained plateau was significantly increased in the MMCP arm than in the VMCP arm (19.1 %, p=0.0017) but was not in comparison with that of MMPP arm (42.6%, p=0.6790). Patients treated with MMCP survived significantly longer than those treated with VMCP or MMPP (p=0.0009 by generalized Wilcoxon test, p=0.0023 by log-rank test) with median survival for MMCP being 31.6 months, for VMCP 22.5 months, and for MMPP 22.9 months. No significant differences were observed with respect to adverse effects among the three regimens. CONCLUSION: The newly designed MMCP is a candidate as an induction chemotherapy for multiple myeloma.     

Assessing liver function by magnetic resonance imaging two-dimensional phase-shift flow measurement of portal venous blood flow after oral intake of glucose

We have already reported that the ratio of portal venous flow 30 min after oral intake of glucose 75 g to that before intake (PVFR30), measured using pulsed-Doppler ultrasonography (US), correlated significantly with other indicators of liver function and that it could be used to estimate hepatic function before surgery, including liver resection. In this study, to assess the disadvantages of pulsed-Doppler ultrasonography, PVFR30 was measured using two-dimensional (2D) phase-shift (PS) magnetic resonance imaging (MRI). PVFR30 was measured in 17 patients and 7 volunteers: 13 with liver cirrhosis (LC) and 11 without LC (non-LC). Portal venous flow could be measured in all patients without any disturbance of intestinal gas or patient fat, or the high degree of technical skill that Doppler US requires. PVFR30 was significantly lower in the LC group than in the non-LC group. In addition, it correlated significantly with other indicators of liver function, including the indocyanine green clearance test, prothrombin time, hepaplastin test, and cholinesterase activity. These results suggest that PVFR30 measured by 2D PS MRI can be used to estimate liver function, and that this MRI method can be performed more easily than pulsed-Doppler US.     

New Pancreatic Duct-Invagination Anastomosis Using UltrasonicDissection for Nonfibrotic Pancreas with a Nondilated Duct

Nonfibrotic pancreases with a nondilated duct are susceptible to pancreatic fistula or leakage following pancreaticoduodenectomy. We developed a novel pancreatic duct-invagination anastomosis using an ultrasonic dissector and applied this technique to 14 consecutive pancreaticoduodenectomies and 1 segmental pancreatectomy for otherwise normal pancreases. With the aid of an ultrasonic dissector, even branch pancreatic ducts were skeletonized, ligated securely, and divided during pancreatic transection. Moreover, the main duct was exposed (> 1 cm) easily by ultrasonic dissection and a small-caliber pancreatic tube was inserted into the duct on the stump. Subsequently, pancreatic duct invagination could be easily done through a 10 G intravenous catheter passed through the gastrointestinal tract. The main duct was anchored to the adjacent serosa, but any pancreatic parenchymal sutures, possibly leading to internal laceration and/or parenchymal ischemia particularly in soft nonfibrotic pancreases, were avoidable during the procedures. All the anastomoses were done within 10 minutes. Only 1 patient (6.7%)developed pancreatic fistula, which resolved spontaneously in 21 days postoperatively. Neither anastomotic leakage nor remnant pancreatitis was seen in this series. Although a prospective, randomized study is needed, this technique may contribute to reduced morbidity after pancreaticoduodenectomy for a nonfibrotic pancreas with a nondilated main duct.     

The efficiency of β2-agonist delivery through tracheal tubes with the metered-dose inhaler: an in vitro study

Purpose. To study the delivery efficiency of procaterol aerosols administered through the tracheal tube (ETT) with a metered-dose inhaler (MDI) during apnea. Methods. First, in a normal room air environment (at ambient temperatures of 24° to 26°C), we measured the amount of aerosol delivered through the ETT by comparing the weight of a 2-l bottle before and after firing the MDI directly into the 15-mm adapter of the ETT. The distal half of the ETT was inserted in the bottle. This procedure was repeated using five different ETTs with an internal diameter of 4–8.5 mm. The delivery efficiency was obtained by dividing the amount of aerosol delivered through the ETT by the total aerosol output per MDI puff. Next, we investigated whether the connector attached to the 15-mm ETT adapter could reduce the delivery, by repeating the same procedure with 4-mm and 5-mm ETTs. Finally, we compared the efficiencies of aerosol delivery through the 5-mm ETT and the 7.5-mm ETT in a normal room air environment with results obtained under a humidified condition (100% humid air at 37°C). Results. The percentages of aerosol delivered through the ETTs in a normal room air environment were 40%–60%, except for the 4-mm ETT, for which the percentage was 32.7% ± 6.6% (P < 0.05 vs that with the 5-mm ETT or the 6-mm ETT). A connector attached to the 15-mm ETT adapter significantly decreased the delivery efficiencies (19.0% ± 5.8% vs 32.7% ± 6.6% with the 4-mm ETT, 24.6% ± 11.8% vs 51.7% ± 10.8% in the 5-mm ETT) when compared with those without a connector. The delivery efficiencies under the humidified condition in the 5-mm ETT and the 7.5-mm ETT were 65.5% (P < 0.05) and 89.8% of those in the normal room air environment, respectively. Conclusion. The efficiency of delivery of procaterol aerosol through the ETTs was unexpectedly high (approximately half of the total aerosol output per MDI puff in the 5-mm to 8.5-mm ETTs, and one third of the total aerosol output per MDI puff in the 4-mm ETT). A connector attached to the 15-mm ETT adapter noticeably decreased the delivery efficiency. In the smaller-sized ETT, delivery efficiency was significantly lower under the humidified condition than in the normal room air environment. Received: September 28, 2001 / Accepted: June 24, 2002 Address correspondence to: T. Takaya