Topical versus systemic vancomycin for deep sternal wound infection caused by methicillin-resistant Staphylococcus aureus in a rodent experimental model

In 37 Wistar albino rats, we investigated the effects of topical vancomycin on deep sternal wound infection caused by methicillin-resistant Staphylococcus aureus. Partial median sternotomy was performed under sterile conditions. Group I (n=6) was the sham, and group II (n=7) was the control. Group III (n=8) received topical vancomycin, group IV (n=8) received systemic vancomycin, and group V (n=8) received topical and systemic vancomycin (combined). Rats in groups II through V were inoculated with 0.5 mL x 10(8) CFU/mL methicillin-resistant S. aureus in the mediastinum and sternum. No medication was given to groups I and II. Twenty-four hours after surgery, 40 mg/kg/day vancomycin was given topically in group III; systemically in group IV; and topically and systemically in group V After 7 days, smear samples from the mediastinum and tissue cultures from the sternum were obtained. We found 5.00 +/- 0 CFU/mL microorganisms in the mediastinum in group II, 1.90 +/- 1.70 in group III, 3.33 +/- 0.48 in group IV and 1.70 +/- 1.08 in group V. The quantity of microorganisms per gram of tissue in the sternum was 736 +/- 0.23 in group II, 6.01 +/- 0.33 in group III, 5.81 +/- 0.81 in group IV and 3.99 +/- 2.47 in group V The quantity of microorganisms was less in the 3 treatment groups than in the control group (P < 0.05). We conclude that topical plus systemic vancomycin treatment might be more effective in patients with deep sternal wound infections caused by methicillin-resistant S. aureus.     

Effect of 5-fluorouracil and leucovorin on the integrity of colonic anastomoses in the rat

PURPOSE: This study was designed to determine the effects of 5-fluorouracil and leucovorin on the healing of colonic anastomoses and assess the safety of conducting a colonic resection and anastomosis during and shortly after a course of this chemotherapy in a rat model. METHODS: Fifty-six male Wistar rats, weighing 200 to 250 gm, were divided into four groups, each consisting of 14 animals. Animals in Group I (control group) underwent colon resection and primary anastomosis. Animals in Group II received 10 mg/kg intravenous 5-fluorouracil and 10 mg/kg leucovorin once a week for four weeks and then underwent the same operation. Animals in Groups III and IV received the same drug dosage for six weeks and were operated at different intervals: Group III at one week and Group IV at two weeks after completion of chemotherapy. Within each group, one-half of the animals were sacrificed on the third postoperative day and one-half on the seventh postoperative day, and anastomotic bursting pressure measurements were performed. RESULTS: At three and seven days, mean bursting pressures of the anastomoses were determined: 98 mmHg and 180.7 mmHg in Group I, 95 and 197.8 in Group II, 85.7 and 189.2 in Group III, and 98.6 and 179.2 in Group IV, respectively. There was no significant difference in bursting pressure between treated animals and controls by the third postoperative day or by the seventh day. The burst occurred at the anastomosis in all specimens tested on the third postoperative day and in the bowel wall adjacent to the anastomosis in all specimens tested on the seventh postoperative day. CONCLUSION: This study demonstrates that the above regimen of chemotherapy has no effect on the healing of colonic anastomoses and that surgery can be performed safely during and shortly after this regimen of chemotherapy.     

Rat liver fibrosis regresses better with pegylated interferon alpha2b and ursodeoxycholic acid treatments than spontaneous recovery.

BACKGROUND/AIMS: Fibrosis and cirrhosis are common complications of chronic liver diseases. An imbalance between fibrogenesis and fibrolysis results in scarring of the liver parenchyma. We aimed to investigate the possible antifibrotic effectiveness of a newly modified interferon molecule peginterferon alpha2b (PEG-IFNalpha2b) which has better antiviral activity, and ursodeoxycholic acid (UDCA). METHODOLOGY: Liver fibrosis was established on 60 male Sprague Dawley rats with CCl4 in 12 weeks. After cessation of CCl4 Group I was left for spontaneous recovery. Group II was treated with PEG-IFN 1.5 microg/kg/week, Group III with UDCA 25 mg/kg/day and Group IV with combination of both drugs. All rats were killed at week 16. Histopathologic fibrosis scores, tissue hydroxyproline, TIMP-1 and MMP-13 levels were determined. Hepatic stellate cell apoptosis was detected by dual staining with TUNEL technique and anti-alpha smooth muscle actin. RESULTS: Fibrosis scores were lower in Group II, III and IV than Group I (p<0.05 for group I vs. II and III; p<0.01 for group I vs. IV). Tissue hydroxyproline levels were significantly decreased in Group II, III and IV when compared to Group I (p<0.05 for group I vs. II, p<0.01 for group I vs. III and IV). Lower liver TIMP-1 and higher MMP-13 levels were measured in Group II, III, and Group IV than Group I (p<0.01 for TIMP-1 and p<0.01, for MMP). Activated HSC apoptosis was significantly increased in Group II, III and IV when compared to Group I (p<0.01, for all). There was significantly higher apoptosis in Group II than Group III and IV (p<0.01). CONCLUSION: Treatment with both PEG-IFNalpha2b and UDCA improved CCl4 induced rat liver fibrosis. Significantly higher effects were obtained using these agents in combination.     

Combination of allopurinol and hyperbaric oxygen therapy： A new treatment in experimental acute necrotizing pancreatitis？

AIM： To investigate the individual and combined effects of allopurinol and hyperbaric oxygen （HBO） therapy on biochemical and histopathological changes, oxidative stress, and bacterial translocation （BT） in the experimental rat acute pancreatitis （AP）. METHODS： Eighty-five Sprague-Dawley rats were included in the study. Fifteen of the eighty-five rats were used as controls （sham, Group I ）. AP was induced via intraductal taurocholate infusion in the remaining seventy rats. Rats that survived to induction of acute necrotizing pancreatitis were randomized into four groups. Group H received saline, Group m allopurinol, Group IV allopurinol plus HBO and Group v HBO alone. Serum amylase levels, oxidative stress parameters, BT and histopathologic scores were determined. RESULTS： Serum amylase levels were lower in Groups Ⅲ, Ⅳ and v compared to Group H （974 ± 110, 384 ± 40, 851 ＋ 56, and 1664 Ⅳ 234 U/L, respectively, P 〈 0.05, for all）. Combining the two treatment optionsrevealed significantly lower median [25-75 percentiles] histopathological scores when compared to individual administrations （13 [12.5-15] in allopurinol group, 9.5 [7-11.75] in HBO group, and 6 [4.5-7.5] in combined group, P 〈 0.01）. Oxidative stress markers were significantly better in all treatment groups compared to the controls. Bacterial translocation into the pancreas and mesenteric lymph nodes was lower in Groups m, iV and v compared to Group H （54%, 23%, 50% vs 100% for translocation to pancreas, and 62%, 46%, 58% vs 100% for translocation to mesenteric lymph nodes, respectively, P 〈 0.05 for all）. CONCLUSION： The present study confirms the benefit of HBO and allopurinol treatment when administered separately in experimental rat AP. Combination of these treatment options appears to prevent progression of pancreatic injury parameters more effectively.     

Mechanisms involved in the progression to glomerular sclerosis induced by systemic hypertension during mild puromycin aminonucleoside nephrosis.

To evaluate the contribution of systemic hypertension in the progression of nephropathies to glomerular sclerosis, a mild form of puromycin aminonucleoside (PAN) nephrosis was associated with Goldblatt hypertension and studied after 18 weeks. We studied four groups: Group I, controls; Group II, Goldblatt hypertension; Group III, PAN nephrosis; and Group IV, both conditions. Systolic blood pressure, 24-h proteinuria, serum cholesterol, triglycerides, glomerular hemodynamics, and histological studies were compared among the groups. Rats in groups II and IV developed systemic hypertension, but only group IV rats showed persistent proteinuria. No alterations in lipid metabolism were present in any of the groups. The most striking findings in the micropuncture studies were a significant increase of glomerular capillary pressure in group IV rats (63.15 +/- 1.34 mm Hg) as compared to controls (48.74 +/- 0.97 mm Hg) and to groups II and III (55.31 +/- 2.11 and 48.17 +/- 1.23 mm Hg, respectively), and a marked fall in Kf in groups III and IV. Only group IV showed significant histological alterations such as glomerular sclerosis, interstitial damage, and increased glomerular area. These results suggest that, in the presence of an underlying nephropathy, a greater fraction of systemic pressure is transmitted to the glomerular capillaries when systemic hypertension is present; the resulting elevation in glomerular pressure and proteinuria seems to be responsible for the progression to glomerular sclerosis.     

Prevention of adhesion formations following repair of abdominal wall defects with prosthetic materials (an experimental study)

BACKGROUND/AIMS: Adhesion formation after abdominal surgery or incisional hernia repair with prosthetic materials may cause chronic pain, intestinal obstruction, enterocutaneous fistulae, difficulty in reoperative procedures and infertility in females. The aim of this study was to compare different modalities in terms of adhesion prevention in a rat model of abdominal wall defect repaired with prosthetic materials. METHODOLOGY: Forty-eight female Wistar-Albino rats were divided into four groups. In all rats, laparotomy was performed through a 3-cm midline incision and an abdominal wall defect (2 x 3 cm) was created in rats in groups II, III and IV. Following procedures were performed in all rats: seroza of the cecum was abraded and sutured with 4-0 silk and two ischemic buttons were created by ligating with 4-0 silk on the left and right sides of abdominal parietal peritoneum. In Group I, abdominal closure was obtained with a running 4-0 prolene suture. In Group II, abdominal wall defect was repaired with polypropylene mesh. In Group III, Seprafilm, an absorbable adhesion barrier, was laid over the abdominal viscera and defect was repaired with polypropylene mesh. In Group IV, defect was repaired with Composix mesh. Adhesion density score, adhered organ and strength of mesh incorporation were evaluated. Biochemical analysis and histopathological examination were performed. RESULTS: Groups II and III had more adhesion density scores than groups I and IV, (P < 0.001). Group II had more cecal and ischemic button adhesions than groups I, III and IV, (P < 0.001). Strength of mesh incorporation was higher in groups II and III than group IV, (P < 0.001). Abscess formation was more common in group IV than those in groups II and III, (P < 0.001). There were no differences between groups, regarding serum levels of C-reactive protein and fibrinogen. The most common adhered organ was omentum. CONCLUSIONS: There is no single treatment modality to prevent adhesion formation after abdominal wall defect repaired with prosthetic materials. While intraperitoneal adhesions were less common in Seprafilm group, adhesions to mesh were less common in the Composix mesh group.     

Effects of a new steroidal aromatase inhibitor, TZA-2237, and/or chlormadinone acetate on hormone-induced and spontaneous canine benign prostatic hyperplasia

OBJECTIVE: It has been known for many years that human benign prostatic hyperplasia (BPH) is composed predominantly of hyperplastic stromal cells rather than epithelial cells. In the present study the effects of a new steroidal aromatase inhibitor on hormone-induced and spontaneous canine BPH were investigated. METHODS: (1) Effects of TZA-2237 on hormone-induced canine BPH. Ten castrated beagles were administered testosterone and androstenedione 6 days/week for 8 months, and divided randomly into three groups after 2 months of treatment as follows. Group I served as controls, Group II was given 0.5 and Group III was given 2.5 mg/kg/day TZA-2237 5 days/week for 6 months. (2) Effects of TZA-2237 on spontaneous canine BPH. Twenty aged beagles with BPH were divided into five groups, Group IV was untreated, Group V was treated with 1 and Group VI with 5mg/kg/day TZA-2237 5 days/week for 31 weeks. Group VII was treated with 5mg/kg/day Atamestane and Group VIII was treated with 0.3 mg/kg/day chlormadinone acetate (CMA) 5 days/week. (3) Effects of TZA-2237 combined with CMA on spontaneous canine BPH. Three aged beagles with BPH were treated with 1mg/kg/day TZA-2237 and 0.03 mg/kg/day CMA 5 days/week for 20 weeks (Group IX) and a further three aged beagles with BPH were treated with 0.3 mg/kg/day CMA alone 5 days/week (Group X). RESULTS: Hormone-induced prostatic growth was significantly suppressed in group III compared with that in other groups. In Group III, the intraprostatic aromatase activity, estradiol level and androgen receptor content decreased significantly in comparison with the values in Group I. The prostatic weights in Groups V, VI and VII increased significantly in comparison with the weight in Group IV. Serum LH and testosterone levels in Groups V, VI, and VII increased significantly in comparison with the level in Group IV. The prostatic weight in Group IX was decreased only slightly, but the smooth muscle component was decreased significantly. CONCLUSIONS: TZA-2237 is a new, unique and effective aromatase inhibitor that causes inhibition of both epithelial and stromal compartments in hormone-induced canine BPH. Dual inhibition of androgen and estrogen resulted in inhibition of smooth muscle growth, and should prove effective as a new method of treatment given the atrophic effects on not only the epithelium but also the stroma in human BPH.     

Vascular graft infection by Staphylococcus aureus: efficacy of linezolid,teicoplanin and vancomycin systemic prophylaxis protocols in a rat model

Objective

We investigated experimentally the in vivo prophylactic efficacies of linezolid, teicoplanin and vancomycin in subcutaneously implanted dacron graft infection caused by methicillin-resistant Staphylococcus aureus (MRSA).

Materials and methods

Dacron grafts (1 cm²) were aseptically implanted into subcutaneous pockets that were surgically prepared in the backs of 50 rats. Ten of these rats were used as the control group (group I). Grafts in the remaining 40 rats were infected by inoculation of MRSA at the concentration of 2 × 10⁷ colony-forming units (CFU)/ml. Ten of these rats constituted the contaminated, untreated group II. The other three study groups comprising 10 rats each were contaminated and then treated with linezolid (group III), teicoplanin (group IV) and vancomycin (group V), respectively. All rats were sacrificed and the grafts were removed after seven days and evaluated.

Results

The bacterial count decreased in the rats from the groups treated with linezolid, teicoplanin and vancomycin. The linezolid and teicoplanin groups, however, showed a significantly lower bacterial number than the vancomycin group (p = 0.009 and p = 0.01). The intensity of inflammation was highest in the contaminated, untreated group, as expected.

Conclusions

Single-dose linezolid, teicoplanin and vancomycin for peri-operative prophylaxis may prevent bacterial growth in vascular graft infections. The effect of linezolid and teicoplanin seemed similar and their effect was greater than that of vancomycin.     

Autonomic neuropathy in diabetics--autonomic function and plasma catecholamines

Autonomic neuropathy is one of the complications of diabetes. Recently, several authors reported that measuring R-R interval variation of ECG is a noninvasive and useful method for testing parasympathetic function. However, there were few reports about sympathetic function in diabetics. In order to evaluate sympathetic function in diabetics quantitatively, we studied the responses of plasma norepinephrine (NE), epinephrine (E) and related factors after 60 min bed rest and sequentially during 10 min of upright posture and 5 min handgrip while still upright. We also studied the responses of NE and E during 5 min smoking in supine position. Subjects were divided into four age-matched groups. These were 15 normal subjects (Group I), 20 diabetics without complications (Group II), 20 diabetics with peripheral neuropathy but no autonomic symptoms (Group III) and 15 diabetics with autonomic symptoms (Group IV). We also studied R-R interval variation (CV: Coefficient of Variation) as a parameter of parasympathetic function and compared this with sympathetic function. Upon standing, blood pressure (BP) dropped precipitously in Group IV, whereas no significant changes were observed in the other three groups. Heart rate (HR) increased in Groups I and II, but not in Groups III and IV. During handgrip, BP and HR did not change significantly in all groups. Basal NE levels in Group IV were significantly smaller than those in Group I. NE responses to both standing and handgrip stimuli were markedly reduced in Group IV and, even in Group III, increments were significantly smaller than those in Groups I and II. Basal E levels did not differ, and significant changes were not observed after standing and handgrip in all groups. Both plasma renin activity (PRA) and plasma aldosterone concentrations (PAC) in Groups III and IV were lower than those in Groups I and II at rest and standing. After smoking, both BP and HR increased significantly in Groups I, II and III, whereas no changes were observed in Group IV. Both NE and E responses were markedly reduced in Group IV and, even in Group III, responses were significantly smaller than those in Groups I and II. CV in Groups III and IV were significantly smaller than those in Groups I and II. In diabetics, CV was strongly correlated with NE increments after standing (r = 0.78, p less than 0.01). Also, CV was correlated with both NE and E increments after smoking (r = 0.71 (NE), r = 0.82 (E), p less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)     

Partial adherence to antihypertensive therapy fails to achieve full cardiovascular benefits in hypertensive rats

BACKGROUND: Partial adherence to antihypertensive therapy remains a public health challenge and may be associated with increased cardiovascular risk. We quantitatively evaluated cardiovascular risk inherent in partial therapy adherence in spontaneously hypertensive rats with accelerated hypertension. METHODS: Adult spontaneously hypertensive rats were divided into 5 groups; Group 1 (controls) did not receive any treatment, whereas all other rats (Groups 2-5) were given nitric oxide synthase inhibitor N-nitro-l-arginine methyl ester (L-NAME) to exacerbate hypertension. Group 2 (untreated/nonadherers) was given L-NAME but not antihypertensive medication; Group 3 (Perfect Adherers) was treated daily with candesartan (10 mg/kg); Group 4 was given candesartan 3 times a week, whereas Group 5 received candesartan only during the last 6 days of the 3-week experiment (Partial Adherers). At the end, indices of systemic and regional (kidneys, brain, and heart) hemodynamics, and indices of left ventricular function were determined. RESULTS: Treatment with L-NAME aggravated hypertension, adversely affected target organ blood flows and resistances, and grossly impaired ventricular function. Perfect adherence with candesartan completely reversed the adverse cardiovascular effects of L-NAME intervention. In partial adherers (Groups 4 and 5), arterial pressure decreased and reached control values. However, target organ hemodynamics and heart function showed only slight improvements, if any. CONCLUSIONS: The results demonstrate that partial adherence to therapy reduces arterial pressure, but may not prevent target organ damage. If replicated in humans, these results may have important clinical implications in hypertensive patients.     

Verapamil and nifedipine limit hemodynamic changes in pulmonary circulation in rats with hypoxia]

The effect of hypobaric hypoxia on right ventricular pressure, right ventricular mass and hematocrit was assessed in Wistar rats divided into 4 groups. Group I comprised 20 control animals, kept in normal conditions. Groups II, III and IV consisted of 34-40 rats each at the beginning of the experiment. The animals were exposed to intermittent hypobaric hypoxia (380 mmHg, 10-12% O2, temperature 22 degrees C) 8 hours a day, 6 days a week, for 5 consecutive weeks. In group II no medication was given, in group III verapamil (Isoptin-Knoll) was administered in the drinking water at 30 mg/kg body mass/day, and in group IV nifedipine (Corotrend--Siegfried) was applied at 6 mg/kg body mass/day. Control animals were injected with i.p. nembutal (35 mg/kg) and then a polyethylene cannula was inserted in the right ventricle via external jugular vein, with consecutive measurement of right ventricular pressure. Hematocrit was measured in the arterial blood. After the animals had been sacrificed, the heart was isolated, right ventricle was excised and its mass was assessed as the ratio to mass of left ventricle-interventricular septum block. In groups II, III and IV right ventricular pressures were measured on days 10, 20 and 30 of the exposure to hypoxia. The hematocrit and ventricular mass were obtained at termination of the experiment. In the control group, mean right ventricular pressure was 28.5 +/- 3.5 mmHg, hematocrit 43.4 +/- 1.75% and right/left ventricular mass ratio was 0.267 +/- 0.03.(ABSTRACT TRUNCATED AT 250 WORDS)     

Recovery of severely decompensated hearts with a left ventricular assist device

We evaluated the limits of recovery of decompensated hearts experimentally and clinically and studied the problems of applying a left ventricular assist device (LVAD). In the chronic experiments, 16 adult goats were studied as follows: Group I consisted of seven with left ventricular infarction in a 70-80% area of the free wall induced by the multiple-ligation method; Group II, three with infarcted areas larger than 80% of the free wall; Group III, three with a 30 min anoxic arrest, and Group IV, a 45-min anoxic arrest. An LVAD was applied in all goats, and a right ventricular assist device was applied simultaneously for two goats in Group IV. Clinically, 21 patients receiving treatment with an LVAD from December 1982 to September 1988 in our center were examined. No goat in Groups II and IV could be weaned from the LVAD. Thus, the severity of artificial heart failure in Groups I and III was considered to be the limit for accomplishing restoration. In successfully-weaned cases, both in experimental and clinical settings, periods of LVAD therapy with or without IABP were less than two weeks, which was thought to be the upper time limits for LVAD application. All but one successfully-weaned patients were alive in the experiment, while clinically many patients died of multiple organ failures regardless of the results of the LVAD assistance. Analysis of data suggested that the difference was caused by the durations of the LVAD applications and weanings, the degree of right ventricular failure, the doses of catecholamine used, and the systemic care afforded, especially during tracheal intubation.     

Experimental study of the subacute toxicity of mitoxantrone and doxorubicin in rats (subcutaneous and/or intraperitoneal route)

The aims of this study were to compare experimentally the subacute cardiotoxicity of a new anthracycline, mitoxantrone (MIT) with doxorubicin (ADM), the reference anthracycline drug. Seventy nine male rats were divided into 5 groups receiving one of the drugs or a placebo by subcutaneous (SC) or intraperitoneal (IP) injection, each week for 13 weeks. The surviving rats were sacrificed at the 21st week. Group I comprised 16 rats which received 2 mg/kg AMD-IP. The mortality rate was 50% between the 14th and 18th week. Twelve of the 16 cases had a haemorrhagic ascites. The heart was normal macroscopically and on light microscopy. However, electro microscopy showed moderate myocytic degeneration. Group II comprised 16 rats which received 0.6 mg/kg MIT-IP. Morality was 100% at the 11th week. Groups III and IV comprised 32 rats; half of the animals were given 0.6 mg/kg MIT-SC and the other half 0.4 mg/kg MIT-SC. The results were identical: good clinical tolerance, normal macroscopy. Three cases of lymphocytic myocarditis and in 4 out of 8 cases very mild myocardial degeneration on electron microscopy. Group V comprised 15 rats which were given NaCl 9% SC or IP; there were no complications. These results show that mitoxantrone given IP produced major peritoneal toxicity. On the other hand, it was well tolerated when given SC and only produced mild myocardial degenerative changes.     

内毒素对SD大鼠急性肝功能衰竭模型血糖代谢影响的研究

研究D氨基半乳糖(D-GaLN)/脂多糖,内毒素(LPS,endotoxin)联合诱导的急性肝功能衰竭大鼠模型中,内毒素对血糖及其调节激素的影响。方法:24只雄性健康成年SD大鼠,随机分成4组,每组6只,组Ⅰ腹腔注射生理盐水;组Ⅱ腹腔注射400mg/kgD-GalN;组Ⅲ腹腔注射400mg/kgD-GalN 5μg/100gLPS;组Ⅳ腹腔注射400mg/kgD-GalN 50μg/100gLPS。LPS给予前1h、给于后2、6h监测血糖,在6h股静脉取血分离大鼠血清,检测肝功能、乳酸、胰岛素、胰高血糖素;取肝组织苏木素-伊红(HE)染色进行病理学分析。结果:组Ⅲ、Ⅳ均可以成功构建急性肝功能衰竭的模型;组Ⅰ与组Ⅱ比较血浆胰岛素,胰高血糖素水平无显著差异;组Ⅲ、Ⅳ与组Ⅰ比较血浆胰岛素、胰高血糖素均显著升高(P<0.05);组Ⅳ与组Ⅰ、Ⅱ、Ⅲ比较血糖明显降低,乳酸显著升高(P<0.05)。结论:急性肝功能衰竭的模型中有血糖调节机制的异常,大剂量的内毒素导致低血糖的发生。     

The effect of secretin on bile flow and bile acid and bilirubin excretion following relief of prolonged bile duct obstruction in the rat

Bile flow was re-established in rats whose bile ducts had been obstructed for 5, 10, 15 and 28 days (Groups I, II, III and IV, n = 5). The effect of i.v. secretin on bile flow in control rats, whose bile ducts had been cannulated, was minimal, but in cholestatic rats there was an immediate response which was related to the duration of the obstruction and the degree of bile duct proliferation. In 40 min the mean excess bile flow production amounted to 76, 258, 320 and 432 microliters/100 g body wt. in Groups I, II, III and IV, respectively. Choleresis was prolonged in the Group IV rats that had developed cirrhosis. Synthetic secretin had a minimal effect on bile acid and bilirubin excretion. It is postulated that the proliferating bile ductules are the site of secretin choleresis, although the possibility that reduced inactivation of the hormone plays a role cannot be excluded.     

Changed diastolic function at rest in patients with perfusion defects in exertion myocardial scintigraphy with TI-201

Myocardial perfusion scintigraphy with TI-201 after exercise allows distinction between areas of scar (irreversible defect) and areas of ischemia (reversible defects). Accordingly 4 major groups of patients can be identified: with normal perfusion pattern (Group I); with reversible ischemia (Group II); with scar of previous myocardial infarction (Group III); with both evidence of scar and ischemia (Group IV). Sixty-nine patients (59 m; 10 f; mean age 55.7 +/- 9 years) with suspected or demonstrated ischemic heart disease underwent stress TI-201 myocardial scintigraphy and on the basis of the scintigraphic results were assigned as follows: 11 to group 1, 14 to group II, 31 to group III and 13 to group IV. In order to investigate the behaviour of ventricular diastolic function in these different subsets, all the patients underwent subsequently a radionuclide angiography at rest (both first pass and equilibrium gated blood pool studies), which allowed the assessment of left ventricular ejection fraction (EF), peak filling rate (PFR)--as expression of diastolic function--and regional wall motion pattern. The values of EF and PFR were significantly reduced (p less than 0.05) in the patients with defects of perfusion (Groups II, III and IV) in comparison to the patients with normal perfusion (Group I); abnormal wall motion was found in 0 (I), 8 (II), 22 (III) and 7 (IV) patients. The diastolic function was more frequently altered (PFR less than 2.5 EDV/sec) than the systolic function (EF less than 50%) or regional wall motion, mainly in patients with reversible scintigraphic defects (prevalence of alterations in the groups II and IV: PFR: 78%, EF: 22%, abnormal wall motion: 56%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute Effect of Inhaled Budesonide on Bronchial Inflammation in Asthmatic Rats

Although anti-inflammatory potency of inhaled corticosteroids is well established, little is known about their role in the acute phase. The aim of this study was to compare the acute anti-inflammatory effect of inhaled budesonide with systemic dexamethasone on allergen-induced inflammatory changes in asthmatic rats. Eighty-four Sprague Dawley rats were divided into four groups; group I (control, n = 24), group II (ovalbumin sensitized, n = 24), group III (systemic dexamethasone, n = 24), and group IV (budesonide, n = 12). All groups except group I were given ovalbumin aerosol challenges 14 days after sensitization with ovalbumin. The same procedure was applied to the control group using 0.9% saline. Group III received dexamethasone 0.3 mg/kg intraperitoneally and group IV received inhaled budesonide 10 mL (0.5 mg/mL) twice before the challenge. Eight hours after the challenge, bronchi of all the rats were evaluated for the degree of peribronchial inflammation. The most severe inflammation was seen in 8 of 24 rats (33%) in the second group, in 1 of 24 rats (4%) in the third group, and in 1 of 24 rats (4%) in the control group. None of the rats in group IV showed severe inflammation. No statistically significant difference was detected with respect to the presence of 3+ inflammation between the control vs. dexamethasone-, control vs. budesonide-, and dexamethasone vs. budesonide-receiving groups. Budesonide administration via nebulizer prior to exposure to an allergen may attenuate bronchial inflammation as effectively as systemic dexamethasone in rats.     

Hyperammonemia, brain edema and blood-brain barrier alterations in prehepatic portal hypertensive rats and paracetamol intoxication

AIM: To study the blood-brain barrier integrity, brain edema, animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication. METHODS: Adults male Wistar rats were divided into four groups. Group I: sham operation; II: Prehepatic portal hypertension, produced by partial portal vein ligation; III: Acetaminophen intoxication and IV: Prehepatic portal hypertension plus acetaminophen. Acetaminophen was administered to produce acute hepatic injury. Portal pressure, liver serum enzymes and ammonia plasma levels were determined. Brain cortex water content was registered and trypan blue was utilized to study blood brain barrier integrity. Reflexes and behavioral tests were recorded. RESULTS: Portal hypertension was significantly elevated in groups II and IV. Liver enzymes and ammonia plasma levels were increased in groups II, III and IV. Prehepatic portal hypertension (group II), acetaminophen intoxication (group III) and both (group IV) had changes in the blood brain-barrier integrity (trypan blue) and hyperammonemia. Cortical edema was present in rats with acute hepatic injury in groups III and IV. Behavioral test (rota rod) was altered in group IV. CONCLUSION: These results suggest the possibility of another pathway for cortical edema production because blood brain barrier was altered (vasogenic) and hyperammonemia was registered (cytotoxic). Group IV, with behavioral altered test, can be considered as a model for study at an early stage of portal-systemic encephalopathy.     

The efficacy of shock wave therapy in patients with knee osteoarthritis and popliteal cyamella

This randomized, controlled study was performed to compare the effects of extracorporeal shockwave therapy (ESWT) and ultrasound on the rehabilitation of knee osteoarthritis with popliteal cyamella. One hundred and twenty patients with bilateral moderate knee osteoarthritis (Altman III) and popliteal cyamella were selected and randomly assigned to four groups (GI–GIV). Patients in Groups I–III received isokinetic muscular strengthening exercises three times weekly for 8 weeks. Group II received pulse ultrasound treatment for popliteal cyamella three times weekly for 8 weeks, Group III received weekly shock wave therapy for popliteal cyamella for the first 6 weeks, and Group IV acted as controls. The therapeutic effects were evaluated by changes in the arthritic knees range of motion (ROM), visual analogue scale, Lequesne's index, and muscle peak torques after treatment and at follow-up 6 months later. Each treated group exhibited increased muscle peak torques and significantly reduced pain and disability after treatment and at follow-ups. However, only patients in Groups II and III showed significant improvements in ROM after treatment, and only participants in Group III showed immediate improvement in ROM after each treatment. Patients in Group III also showed the greatest increase in muscular strength and the greatest decrease in disability after treatment and at the follow-ups. ESWT is better than pulse ultrasound in rehabilitation of patients with knee osteoarthritis and popliteal cyamella results in more functional improvements.     

Effects of preoperative fractionated irradiation on left colonic anastomoses in the rat

PURPOSE: Radiotherapy is frequently used as a (neo)adjuvant to surgery in colorectal cancer patients, and because such therapy could influence the integrity of the anastomosis, we decided to investigate the effect of preoperative irradiation on colonic anastomosis. METHODS: Seventy-two male Wistar rats, weighing 200 to 348 g, were divided into three groups: a control group (I) underwent left colon resection and primary anastomosis (n=20); a sham irradiated group (II, n=20); a study group (III) that received fractionated irradiation to the whole pelvis (anterior-posterior pelvic field), for a total dose of 22 Gy, 5.5 Gy per fraction, on four consecutive days with linear accelerator (n=32). Four days after irradiation, both Groups II and III underwent the same operation as performed in Group I. Within each group, one-half of the animals were anesthetized on the third postoperative day and one-half on the seventh postoperative day. Abdominal wound-healing, anastomotic complications, and anastomotic bursting pressure measurements were recorded. Following these measurements, the anastomotic segment was resected for hydroxyproline content and myeloperoxidase activity. RESULTS: Irradiated animals had more pronounced weight loss during therapy. There were no differences with abdominal wound-healing, intraperitoneal adhesions, and anastomotic complications between groups. At days 3 and 7, mean bursting pressures of the anastomosis were determined at 36.5 and 208 mmHg in Group I, 34.5 and 228 mmHg in Group II, and 25 and 150 mmHg in Group III, respectively (P<0.01 Group IIIvs. both Groups I and II on days 3 and 7). The burst occurred at the anastomosis in all animals tested on the third postoperative day and one in Group I (10 percent), none in Group II, and six in Group III (37.5 percent) on the seventh postoperative day. In addition, hydroxyproline content and myeloperoxidase activity was significantly lower in Group III. CONCLUSION: Although preoperative fractionated irradiation significantly decreased the anastomotic bursting pressure and more burst occurred in the anastomotic line on postoperative day 7, the clinical outcome was similar among the groups.Presented at the 37th World Congress of Surgery of the ISS/SIC, Acapulco, Mexico, August 24 to 30, 1997.