Clinical results of left ventricular free wall rupture following acute myocardial infarction

We studied 19 cases of Left Ventricular Free Wall Rupture (LVFWR) following acute myocardial infarction, admitted to our CCU between 1987 and 1996. We were able to treat 15 patients and diagnosed 4 cases as LVFWR at postmortem after sudden deaths. Of the treated 15 patients, 11 survived: 1 out of 2 repaired under cardiopulmonary bypass (CPB), 5 out of 7 repaired without CPB, and 5 out of 6 non-surgically treated. Although the survival rate for those able to be treated was 73%, overall rate was 58%. There were 7 cases of blow-out type: 4 of which were sudden deaths, and 3 were operated. Thoracotomy and direct closure of rupture without CPB was done at bed-side in 2 cases. Even though hemostasis was successful, they did not survive. The 3rd case survived with the patch closure under CPB. In this case, the circulation was maintained pre-operatively with the pericardial-central venous bypass drainage method. This method seems to be extremely effective in saving blow-out cases. There were 12 subacute patients. Although 2 cases were lost, total of 10 patients were saved, including 2 direct suture closures of rupture without CPB, 3 median sternotomy and fibrin-glue fixations, 1 where only pericardial drainage was done, and 4 in whom percutaneous intrapericardial fibrin-glue fixation therapy was utilized. Since the risk of secondary damage to the fragile infarcted are from direct suturing of ruptured myocardium exists in LVFWR, we changed to the Infarction Exclusion Technique under CPB during surgical repair, based on our experiences with ruptured intraventricular septum. In general, the only treatment believed to be available for LVFWR has been surgical. However, our experiences suggest that other treatments may also be effective. If the best suitable method could be chosen from various therapies, it may contribute to improving outcome statistics. The reduction of left ventricular pressure in the treatment is extremely important, being the key to improving survival rate.     

Phenotype of the obese Koletsky (f) rat due to Tyr763Stop mutation in the extracellular domain of the leptin receptor (Lepr): evidence for deficient plasma-to-CSF transport of leptin in both the Zucker and Koletsky obese rat

The obese phenotypes of the diabetes (db) mouse and fatty fa) rat are due to functional null mutations of the leptin receptor (Lepr). The recessive mutation in the Koletsky (f) obese rat maps to the same genetic intervals as db and fa and fails to complement the fa mutation. Comparison of the sequence of brain Lepr cDNA from +/+ and f/f animals reveals a T2349A transversion resulting in a Tyr763Stop nonsense mutation in the gene just before the transmembrane domain. Virtual absence of Lepr mRNA in whole brain from f/f animals is consistent with the presence of a null mutation. The predicted reduced cerebrospinal fluid (CSF) transport of leptin in both f/f and fa/fa mutants is reflected in the approximately 10-fold lower ratio of CSF/plasma leptin concentration in the obese versus lean animals. However, equivalent CSF leptin concentration between lean and obese rats (fa/fa, f/f) indicates that leptin can enter the CSF through a non-Lepr-mediated mechanism, which may be saturated at normal physiological plasma leptin concentration.     

Male/female differences in drug-induced emesis and motion sickness in Suncus murinus

In order to elucidate possible male/female differences in emesis, the effects of various emetogenic drugs (cisplatin, copper sulfate, veratrine, nicotine, serotonin) and motion stimulus were compared between male and female Suncus murinus. Cisplatin (IP), nicotine (SC), veratrine (SC) and copper sulfate (PO) induced dose-dependent emesis in either sex, and there was no apparent difference in estimated ED50 values. However, male animals tended to be more susceptible to serotonin-induced emesis. The ID50 values for tropisetron, a 5-HT3 receptor antagonist, to block serotonin-induced emesis were also similar between male and female animals. However, tropisetron was less effective against cisplatin-induced emesis in females. Therefore, cisplatin may release more serotonin to induce emesis in females. Reciprocal shaking (horizontal oscillation 40 mm, frequency 0.5 to 2.0 Hz, duration 5 min) induced more frequent emesis in male animals, and the latency to the first vomit was shorter in males than in females. These results suggest that there is substantial sex-dependent difference in the emetic responses and male animals are in general more susceptible. These results are discussed in the light of similar studies in man.     

Clinical studies on renal pelvic and ureteral carcinoma

In the past decade the use of theophylline was less extensive because of its narrow therapeutically index and due to its side effects. The widening of possibilities of monitoring the treatment by serum level determination, the introduction of slow release formula, and the demonstration of antiinflammatory effects made theophylline to become actual again. Theophylline is indicated for the chronic treatment of asthma in association with other medication. The authors study the efficacy and serum level of theophylline in 13 children with asthma who received slow release theophylline in a dosage of 15.2 mg/body weight/24 hours in average, administered 3 times a day. The efficacy was estimated by a clinical score and the serum level was determined by isotopic mass spectrometry with 15N-theophylline as internal standard. After a period of at least 2 months of therapy it was recorded the amelioration of clinical score (with 5.09 points, that represents 36.3% of the maximum initial score) and the reducing of circadian variation of peak expiratory flow from 27% to 15%. The serum level of theophylline was of 8.25 +/- 4.16 micrograms/ml at 4 hours after administration and of 5.69 +/- 2.6 micrograms/ml at 8 hours after administration of the last dose. The individual values less than 5 micrograms/ml was found in 3 of 13 children at 4 hours and in 7 of 13 children at 8 hours after the last dose. There were no patients with toxic serum levels of theophylline (> 20 micrograms/ml). The correlation between serum level of theophylline and the dosage was weak both at 4 hours (r = 0.054) and 8 hours (r = 0.229) after the last dose. At the same dose there were found high interindividual variations. These findings are arguments for the usefulness of determination of serum levels of theophylline, that together with clinical and functional parameters allowed the individualization of the dosage.     

Serotonin inhibits nitric oxide synthesis in rat vascular smooth muscle cells stimulated with interleukin-1

The elimination half-life of fluoride is significantly increased in patients with chronic renal failure. This led us to conduct a study of variations of its plasma levels in 35 patients receiving dialysis treatment. In this population, there is a gaussian distribution of the values before and after the hemodialysis session, with a significant decrease in the averages. Furthermore, there is a highly significant correlation between fluoride levels before and after the dialysis session (P < 0.00001), and also between the amount of time in hemodialysis (in months) and the average fluoride level before dialysis (r = 0.624; P = 0.008). The presence of a group of patients consuming fluoride waters such as Vichy St-Yorre Water was easily identified by their excessive fluoride levels (above 100 micrograms/l), which could have a tendency to increase the risks of this group.     

Protection afforded by a novel K channel opener (Y-26763), against glycerol-induced acute renal failure (ARF) in rats

Y-26763, a benzopyran derivative, is a newly developed ATp-sensitive K channel opener and has been reported to protect against ischemic acute renal failure (ARF). We examined the effects of Y-26763 on glycerol-induced myoglobinuric ARF in the rats. ARf was induced in 28 adult male Sprague-Dawley rats by hind-limb intramuscular injection of 50% glycerol (5 ml/kg) after 18 hrs of water deprivation. Y-26763, 7 micrograms/kg (GY group, n = 10) of vehicle (G group, n = 12) was given intravenously 15 min before glycerol injection. Glibenclamide (20 mg/kg), a K channel blocker was given prior to Y-26763 injection to see of the effects was due to the K-channel opener (GYG group, n = 6). Animals were sacrificed 24 or 96 hrs after glycerol injection. Y-26763 partially, but significantly, restored renal dysfunction 24 hrs after ARF. Pcr (mg/dl) and Ccr (ml/min), respectively were as follows: G group, 5.7 +/- 0.4, 0.015 +/- 0.006; GY group, 4.1 +/- 0.4, 0.061 +/- 0.027 (p < 0.05). These favorable effects were antagonized by glibenclamide (Pcr in GYG group, 5.4 +/- 0.3 mg/dl, p < 0.05). Renal calcium content was not statistically significant (3.5 +/- 1.2 vs. 3.4 +/- 1.2 micrograms/mg dry weight). Histological examinations revealed that extensive tubular necrosis and cast formation seen in the G group were reduced in the GY group. At the recovery phase, 96 hrs after glycerol injection, Y-26763 accelerated the recovery from ARF as shown in Pcr (mg/dl) and Ccr (ml/min): 4.3 +/- 0.2, 0.05 +/- 0.01 in the G group, 2.8 +/- 0.2, 0.13 +/- 0.02) in the GY group (p < 0.01). In conclusion, Y-26763 partially protected against glycerol-induced ARF.     

Immediate increase in circulating hepatocyte growth factor/scatter factor by heparin

Circulating levels of hepatocyte growth factor (HGF)/scatter factor have been recently found to be increased in the early phase of myocardial infarction, and it has been hypothesized that HGF plays a role in angiogenesis and collateral vessel growth. Heparin has also been shown to enhance angiogenesis and to improve collateral blood flow. This study was designed to study the effect of heparin on the release of HGF. In an experimental study, heparin was given to rats intravenously and plasma was collected for measurements of HGF by enzyme-linked immunosorbent assay. A dose-dependent increase in circulating HGF was measured with peak levels occurring 10 min after injection of 300 units/kg of heparin (15.4+/-2.0 ng/ml after v 0. 17+/-0.14 ng/ml before injection,P<0.0001). In a subsequent clinical study, 12 patients received 3000 units of heparin during cardiac catheterization. Circulating HGF increased steeply within 3 min of the injection. Comparable changes in plasma concentrations were measured in samples obtained from femoral vein (8.7+/-3.5 after v 0. 33+/-0.07 before injection P<0.05) or artery (10.5+/-3.2 ng/mlv 0. 27+/-0.05 P<0.01), pulmonary artery (9.1+/-2.0 ng/mlv 0.36+/-0.06 ng/ml,P=0.07 ) or right atrium (8.5+/-1.6 ng/mlv 0.42+/-0.11,P<0.01). This study suggests that heparin-induced effects such as the promotion of angiogenesis may be at least partly due to the release of HGF.     

A physiologic role of Bcl-xL induced in activated macrophages

Activated macrophages produce nitric oxide (NO) that is an important effector molecule for their antimicrobial and antitumor activities. Since this NO is also toxic for themselves, they have self-defense mechanisms. To elucidate the mechanisms in a physiologic condition, expression of bcl-2 family genes were examined in peritoneal macrophages and RAW264 macrophage cell line activated with IFN-gamma and LPS. Bcl-xL, but not bcl-2 and bax mRNA, was highly inducible within 3 h after stimulation. The induction required new protein synthesis, but was independent of effects of synthesized NO. Since activated RAW264 were more resistant to NO-induced apoptosis mediated by the exposure to S-nitroso-N-acetyl-penicillamine (SNAP) than nonactivated RAW264, the inducible Bcl-xL may play a role in the protection from NO toxicity. To confirm the protective function, RAW264 were stably transfected with bcl-xL. Those transfectants activated with IFN-gamma and LPS appeared highly resistant to NO-induced cell death detected within 24 h after stimulation, although their NO production was similar to those of parental RAW264 and neomycin control-transfected cells. Furthermore, bcl-xL transfectants displayed substantial protection from SNAP-induced apoptosis. These results establish a link between self-defense to the synthesized NO and the induction of Bcl-xL in activated macrophages.     

Molecular cloning of a cDNA encoding a pollen extracellular protein as a potential source of a pollen allergen in Brassica rapa

Gastritis caused by infection with Helicobacter pylori is one of the most common infectious diseases worldwide. There are data on the epidemiology, pathophysiology and histology of this disease that show that Helicobacter pylori gastritis plays an important role in gastric carcinogenesis. However, we must remember that only a very few among those infected with Helicobacter pylori will develop gastric cancer. Hence, one of the main targets of future research will be to identify individuals who carry a greater risk for developing gastric cancer and may therefore benefit from eradication of Helicobacter pylori in terms of gastric cancer prevention.