Long-term toxicity/carcinogenicity of musk xylol in B6C3F1 mice

The long-term toxicity/carcinogenicity of musk xylol, a synthetic nitro musk, was examined in B6C3F1 mice of both sexes. Musk xylol was administered at dietary levels of 0 (control), 0.075 or 0.15% for 80 wk. The overall tumour incidences in all treated groups of both sexes were significantly higher than those in the corresponding controls. Combined malignant and benign liver cell tumours were clearly increased in both sexes, and in males a positive significant trend was also noted for the occurrence of hepatocellular carcinomas. In males the incidence of Harderian gland tumours was also significantly greater in treated groups than in controls. Some other neoplasms, such as lung tumours in both sexes and Harderian gland tumours and lymphomas in females, occurred in greater numbers in the treated groups, although the differences were not statistically significant in comparison with the controls. In addition, the incidences and total numbers of malignant tumours were significantly increased in treated groups of both sexes, although the increases were not dose dependent. The results demonstrated that musk xylol is carcinogenic in B6C3F1 mice when given at dose levels of 0.075 or 0.15% in the diet for 80 wk.     

Phosphorus-31 magnetic resonance spectroscopy of cerebral ischemia in cats

The energy metabolism of the brain was measured in three types of ischemic models in the cat using phosphorus-31 magnetic resonance spectroscopy. The cerebral ischemia was produced as follows. In Group 1, two balloons were inflated in the left subclavian artery and the brachiocephalic trunk. In Group 2, the left middle cerebral artery was occluded through a transorbital approach. A combination of the two was employed in Group 3. Phosphorus-31 magnetic resonance spectra were obtained serially during 2 hours of ischemia. Immediately after occlusion, peaks of phosphocreatine and adenosine triphosphate decreased, whereas the peak of inorganic phosphate increased and split in two. Intracellular pH determined by chemical shift of the inorganic phosphate peak decreased. These changes were more pronounced in Group 3 when compared with the other groups. Histological study showed no infarction in Group 1 and infarcted areas in Groups 2 and 3. The size of the infarcted area in Group 3 was larger than that in Group 2. These results suggest that the model of middle cerebral artery occlusion potentiated with the occlusion of the brachiocephalic trunk and the left subclavian artery by balloon catheters is a reliable stroke model and that phosphorus-31 magnetic resonance spectroscopy is useful to understand the pathophysiological state of cerebral ischemia in vivo.     

Roles of kallikrein-kinin system in acute inflammation: studies on high- and low-molecular weight kininogens-deficient rats (B/N-Katholiek strain)

Carrageenin-induced paw edema in HMW- and LMW-kininogens-deficient rats was significantly less than that in normal rats. There are three kininogens, HMW-, LMW- and T-kininogens, in normal rat plasma, but B/N-Katholiek rat plasma contains only T-kininogen. The pretreatment with captopril, a kiniase II inhibitor, enhanced paw swelling of normal rats, but not that of the deficient rats, indicating that bradykinin released from HMW-kininogen may have a role for the swelling but T-kinin may not be released in this inflammation.     

Ammonia: a possible promotor in Helicobacter pylori-related gastric carcinogenesis.

Helicobacter pylori (HP) has been shown to possibly be a pathogen of gastric carcinoma. HP has urease activity and produces ammonia in the stomach. In this study, the role of ammonia on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in rats. After 24 weeks pretreatment with MNNG (83 mg/l), 0.01% ammonia or tap water as a drinking water was administered for 24 weeks. The ammonia-treated rats showed a significantly higher incidence of gastric cancer (percent of animals with tumors and number of tumors per rat). Ammonia would thus appear to have an important role in HP-related human gastric carcinogenesis.     

Limited vertical skin incision for median sternotomy.

The cosmetic deformity of the vertical skin incision for median sternotomy was decreased by using a mechanical traction system to increase exposure at the superior margin of a shorter wound. The limited vertical skin incision did not impede technical surgical maneuvers and produced a scar that was more acceptable than submammary incision or right anterior thoracotomy. The limited skin incision is especially useful in young women with congenital heart disease.     

The effect of adjuvant therapy with or without tamoxifen on the endocrine function of patients with breast cancer

The ovarian and pituitary functions of 64 operable breast cancer patients undergoing adjuvant therapy with cytotoxic chemotherapy and/or tamoxifen were investigated. The post menopausal patients, divided into 3 treatment groups, one with tamoxifen alone, one with tamoxifen and chemotherapy and the other with chemotherapy alone had serum estradiol 17-β (E2) and progesterone levels lower than the evaluable limits. Although there was no significant difference in the level of estrone sulfate (E1-S) between these three groups, the level of lutainizing hormone (LH) and follicle stimulating hormone (FSH) in the patients treated with tamoxifen alone and tamoxifen and chemotherapy were significantly lower than those treated with chemotherapy alone. The decrease in gonadotropin levels induced by tamoxifen treatment was reversible as it appeared after the initiation of tamoxifen and recovered after its cessation. In the premenopausal patients, a group treated with tamoxifen and chemotherapy had significantly higher E1-S, E2 and progesterone levels and significantly lower gonadotropin levels than a group treated with chemotherapy alone or one treated with a cyclophosphamide regimen. These increases in the levels of estrogen and progesterone were also reversible, and induced by tamoxifen. Thus, adjuvant endocrinochemotherapy causes profound alteration in the hypothalamo-pituitary-ovarian axis and therefore, monitoring a variety of hormonal levels is thought to be necessary for assessing the consequences of adjuvant therapy in breast cancer patients, especially in premenopausal patients using tamoxifen.     

Inhibitory effects of nisoldipine and saralasin on angiotensin II-induced antidiuresis in anesthetized dogs

Inhibitory effects of the calcium channel blocker nisoldipine on angiotensin II-induced antidiuresis were investigated in anesthetized dogs, and the findings were compared with those of saralasin. Intrarenal arterial infusion of 10 ng/kg/min angiotensin II resulted in marked decreases in renal blood flow (RBF) and urine formation, with a relatively moderate decrease in glomerular filtration rate. There were marked reductions in the fractional excretion of lithium, which is used as an index of the fractional proximal excretion of sodium, and the fractional distal excretion of sodium. Nisoldipine (50 ng/kg/min) administered intrarenally produced a partial inhibition on the decreased response of RBF to angiotensin II. The peptide-induced decreases in urine flow, urinary excretion of electrolytes and fractional excretion of electrolytes were abolished by nisoldipine. In contrast, when saralasin was administered intrarenally at 10 ng/kg/min, a dose which could partially inhibit the angiotensin II-induced decrease in RBF to the same extent as seen with nisoldipine, the antagonist attenuated, but did not abolish, the antidiuretic action of angiotensin II. Significant decreases in urine formation by angiotensin II were observed, even in the presence of saralasin. These results suggest that nisoldipine, unlike saralasin, preferentially interferes with the stimulatory effect of angiotensin II, as related to the renal tubular reabsorption of sodium and water.     

Internal jugular vein catheterization in infants undergoing cardiovascular surgery: an analysis of the factors influencing successful catheterization.

Central venous catheterization for pressure monitoring and drug administration is often important in the anesthetic management of infants undergoing cardiovascular surgery. We examined the effects of patient age, weight, and central venous pressure and the experience of the anesthesiologist on the rate of successful catheterization and catheterization time of the internal jugular vein (IJV) in a prospective study. We studied 106 infants undergoing IJV catheterization for cardiovascular surgery over a 7-mo period at our institution. We catheterized the IJV by the high approach. The direct venipuncture or the Seldinger method was used according to the patient's weight. Overall successful catheterization rate was 97.2%, and the average catheterization time was 353 +/- 21 s (mean +/- SEM). Complications included arterial puncture in 12 cases (11.3%), hematoma formation in four cases (3.8%), and catheter malposition in two cases (1.9%), but pneumothorax was not observed. When a patient was younger than 3 mo or weighed less than 4.0 kg, successful catheterization rate decreased significantly to 81.3% and 78.6%, respectively. Catheterization time was inversely correlated with both age and weight, whereas central venous pressure did not affect either successful catheterization rate or catheterization time. We were unable to demonstrate that the experience of the anesthesiologist plays a significant role in the success or complication of the catheterization procedure. Our results indicate that IJV catheterization by the high approach is a reliable and useful technique in infants, and that the weight and age of the patient significantly influence the rate of successful catheterization.