Adhesion formation is reduced after laparoscopic surgery

BACKGROUND: Adhesion formation after abdominal operations causes significant morbidity. METHODS: Adhesion formation in pigs was compared after placement of prosthetic mesh during celiotomy (group 1), laparoscopy with large incision (group 2), and laparoscopy (group 3). After peritoneum was excised, polypropylene mesh was fixed to the abdominal wall, then to the opposite abdominal wall in the preperitoneal space followed by peritoneal closure. Adhesion area, grade, and vascularity were measured. RESULTS: More adhesions (p < 0.02) covered intraperitoneal mesh (7.57 +/- 1.89 cm2) than covered reperitonealized mesh (2.16 +/- 1.13 cm2), and adhesion grade was significantly greater (p < 0.02). Adhesion areas were significantly greater in groups 1 and 2 than in group 3 (p = 0.001 and 0.03, respectively). Adhesion grade was significantly greater in groups 1 and 2 than in group 3 (p = 0.02 and p = 0.04, respectively). Groups 1 and 2 had more vascular adhesions than group 3 (p < 0.01 and p = 0.02, respectively) CONCLUSIONS: A foreign body within the peritoneum stimulates more numerous and denser adhesions. Tissue trauma distant from the site of adhesions increases their formation. A major advantage of laparoscopic surgery is decreased adhesion formation.     

The hamstring index

Hyperthyroidism is characterized by increased bone turnover and resorptive activity. Similar changes in remodeling are seen in osteoporosis. To study the pathogenetic role of thyroid hormone in osteoporosis, we measured concentrations of free and total thyroid hormones and investigated the sensitivity of the skeleton toward thyroid hormones in 14 osteoporotic, 16 estrogen-treated, and 15 normal postmenopausal women with comparable thyroid status. Triiodothyronine (T3, 60 microg/day for 7 days) was administered to the three groups. The skeletal response was assessed by monitoring bone alkaline phosphatase (BAP), osteocalcin (BGP), and pyridinium cross-linked telopeptide domain of type I collagen (ICTP) in serum and urinary excretion of hydroxyproline (OHP), pyridinoline (PYR), and deoxypyridinoline (DPR) at days 0, 8, 15, and 57. Women on estrogen replacement therapy exhibited lower bone turnover than the normal postmenopausal women. Markers of bone formation were reduced by 19-43% and markers of resorption by 22-48%. The osteoporotic women displayed lower bone mass at the lumbar spine and the distal forearm (p < 0.01-0.001), but the levels of biochemical markers of bone formation and resorption were comparable to values obtained in the normal postmenopausal women. T3 stimulation caused significant increases (p values ranging between 0.05-0.001) in all three groups of the resorptive markers: ICTP (47%, 47%, 45%), OHP (29%, 30%, 33%), PYR (43%, 27%, 51%), and DPR (42%, 24%, 59%). Of the formative markers, only BGP increased significantly (32%, 40%, 47%) (p < 0.001). At day 57, however, all three formative markers increased compared with day 15 (p < 0.05-0.001). No significant differences in bone markers were demonstrated between groups. In the osteoporotic group, as the only group, serum calcium increased (p < 0.05) and serum PTH fell (p < 0.05). In conclusion, osteoporosis and estrogen substitution are not characterized by altered concentrations of thyroid hormones or responsiveness to thyroid hormones at the level of individual bone cells; however, altered responses pertaining to PTH and calcium were detected.     

Prostaglandins inhibit pancreatic beta-cell replication and long-term insulin secretion by pertussis toxin-insensitive mechanisms but do not mediate the actions of interleukin-1 beta

The aim of the study was to investigate effects of CPAP treatment on diurnal catecholamine excretion in urine in patients with obstructive sleep apnea (OSA). 12 males with severe OSA (mean AHI = 63) were measured in 3 separate 8 hour samples by fluorimetric method. NA levels were higher in OSA patients in all urine samples than in obese, mildly hypertensive males (control group = C). In C group patients NA levels were significantly lower at night than during the day contrary to OSA patients in whom NA levels dropped insignificantly during sleep. In OSA patients NA levels during sleep correlated with severity of apneas (r = 0.42) and night hypoxaemia (r = -0.46). CPAP treatment resulted in significant fall in NA levels during sleep (p < 0.01). A levels did not change after CPAP treatment. We conclude that abnormally high NA level during sleep in OSA patients may be related to sleep fragmentation and hypoxia. CPAP treatment restores normal circadian rhythm of NA excretion.     

Toxicity of the styrene metabolite, phenylglyoxylic acid, in rats after three months' oral dosing

Male Wistar rats were dosed with 0, 1250, 3750 or 5000 mg/l of phenylglyoxylic acid (PGA) (CAS no. 611-73-4) in the drinking water ad libitum for 3 months. During the entire treatment period, there were no gross signs of toxicity related to PGA. No changes in neurobehavior were found after using a functional observational battery or radial arm maze. An increased relative kidney weight was seen in the highest dose-group (Controls: 0.504 +/- 0.031 g/100 g b.wt.; 5000 mg PGA/l: 0.579 +/- 0.033 g/100 g b.wt.; p<0.01). No other organ weights were affected. Histopathology revealed no change in kidney structure. No changes in clinical biochemistry. In the highest dose-group three animals out of ten showed reduction in peripheral nerve myelin sheath thickness. No such changes were seen in the control group. The study revealed no changes in auditory brain stem response but minor changes in electroretinography. The noradrenaline (NA) concentration decreased in pons and thalamus whereas it increased in medulla oblongata and whole brain. The dopamine (DA) concentration increased in cerebellum, hippocampus, pons, and whole brain. The most marked DA increase was seen in hippocampus (Controls: 0.56 +/- 0.10 nmol/g tissue; 5000 mg/l: 1.04 +/- 0.11 nmol/g tissue; p<0.001). The 5-hydroxytryptamine (5-HT) concentration decreased in cerebellum, cerebral cortex, hippocampus, and medulla oblongata, whereas it increased in thalamus. The yield of synaptosomal protein, synaptosomal NA, DA, and 5-HT concentrations, and DA uptake rate were not affected. When dosed males were mated with naive females, there were no differences between groups in the pregnancy rate, number of corpora luteae, implantations, live or dead fetuses, resorptions, preimplantation loss, or postimplantation loss. It is concluded that a part of the effects on kidney, peripheral nerves, and vision, which have previously been reported after exposure to styrene, might be induced by the styrene metabolite, PGA. If PGA has ototoxic effects in rats, the dosing in the present study is not sufficient to induce the necessary ototoxic concentration in blood. Alternatively, the ototoxicity of styrene, like toluene, may be caused the parent compound itself and not by a metabolite like PGA.     

Association of autonomic neuropathies and gastrointestinal peptides in non-insulin dependent diabetics

Basal and postprandial levels of gastrin, somatostatin, vasoactive intestinal polypeptide (VIP) and pancreatic polypeptide (PP) were followed up in 105 patients with non insulin dependent diabetes mellitus (20 with autonomic neuropathy only, 35 with peripheric neuropathy only, 30 with autonomic and peripheric neuropathy simultaneously and 20 without any sign of neuropathy) and in the control group of 40 individuals. Serum levels of gastrin, somatostatin, VIP and PP are determined by a RIA (used kits of Prof. SR Bloom, Hammersmith Hospital, London). The results of investigation showed significantly higher basal and postprandial levels of gastrin and VIP in patients with autonomic neuropathy in comparison with the group without neuropathy and with the control group (p < 0.001). The serum levels of somatostatin did not differ significantly between the groups of diabetics with and without neuropathy. Basal level of PP was significantly lower and postprandial PP levels remained low in patients with autonomic neuropathy in comparison with the group without neuropathy (p < 0.001). We postulate that basal and postprandial gastrin and VIP levels raised secondary to partial vagotomy in diabetics with autonomic neuropathy. Measuring PP serum levels in diabetics after a protein rich meal can be useful to check vagus nerve function in the gastrointestinal tract in order to detect autonomic neuropathy.     

Assessment of fetal pulmonic stenosis by ultrasonography

This study was designed to determine (1) the value of Doppler echocardiography in depicting the presence of a fetal pulmonary stenosis, (2) its reliability in the assessment of the severity of the lesion, and (3) the usefulness of additional markers from the left side of the heart as criteria of severity. Fourteen pregnant ewes were included in this study (gestational age, 90 to 120 days). Banding of the fetal main pulmonary artery created mild (n = 3), moderate (n = 3), and severe (n = 5) stenosis. Three lambs were sham operated. Intrauterine fetal Doppler echocardiographic data obtained 15 days after surgery were compared with preoperative values. Peak velocities recorded through the band increased linearly from baseline in the groups with mild and moderate stenosis but did not show any further increase in the group with severe stenosis. Compared with the sham-operated group, right ventricular output in the group with stenosis was either similar or reduced significantly. The increase in right ventricular free wall thickness was significantly greater in the groups with stenosis compared with that of the sham-operated group; the correlation with the degree of severity was r = 0.65 and p < 0.05. A A stronger positive correlation was found between the severity of stenosis and aortic valve diameters: r = 0.82 and p < 0.01. The strongest correlation was found for right ventricular/left ventricular outputs (r = 0.92; p < 0.001). Thus Doppler peak velocities through the obstruction can help detect pulmonic stenosis but are not reliable for the assessment of its severity during fetal life. Other ultrasound measurements such as the size of the aortic anulus and especially the ratio of right ventricular/left ventricular output could be used as sensitive markers of the severity of stenosis.     

Behavior of soluble intercellular adhesion molecule-1 and endothelial-leukocyte adhesion molecule-1 concentrations in patients with Graves' disease with or without ophthalmopathy and in patients with toxic adenoma

Expression of intercellular adhesion molecule-1 (ICAM-1) and endothelial-leukocyte adhesion molecule-1 (ELAM-1) on endothelium can be considered a critical early step for leukocyte migration from blood to tissues during inflammatory processes. Increased circulating soluble ICAM-1 (sICAM-1) levels have been found in sera from patients with Graves' disease (GD) with or without ophthalmopathy. Serum soluble ELAM-1 (sELAM-1) levels have not been measured in these patients. The aim of this study was to clarify the behavior of sICAM-1 and sELAM-1 levels in patients with hyperthyroidism due to GD with or with or without ophthalmopathy and in hyperthyroid patients with toxic thyroid adenoma. We studied sICAM-1 and sELAM-1 levels in 130 subjects (age 23-54 yr), grouped as follows: group 1, 30 untreated hyperthyroid GD patients (21 females and 9 males) with active ophthalmopathy; group 2, 26 euthyroid GD patients (16 females and 10 males) with active ophthalmopathy; group 3, 33 hyperthyroid GD patients (22 females and 11 males) without ophthalmopathy; group 4, 11 untreated hyperthyroid patients (7 females and 4 males) with single toxic adenoma; and a control group of 30 healthy subjects (21 females and 9 males). sICAM-1 and sELAM-1 concentrations were measured by a sandwich enzyme linked immunosorbent assay (ELISA) method. Groups 1, 2, and 3 (P < 0.001 for all 3 groups) but not group 4 showed increased sICAM-1 levels compared with the control group. However, groups 1 and 2 (P < 0.001 for both) showed higher values of sICAM-1 than group 3, and group 1 showed higher sICAM-1 levels than group 2 (P < 0.002). Groups 1 and 2 (P < 0.001 for both) but not groups 3 and 4 showed sELAM-1 levels significantly higher than the control group and positively correlated to the severity score of Graves' ophthalmopathy (GO) (P < 0.002 for group 1 and < 0.01 for group 2). Our results confirm that increased sICAM levels in GD patients with or without ophthalmopathy (with higher levels in patients with GO) but not in hyperthyroid nonautoimmune patients may be the consequence of orbital and thyroid inflammation, and they also suggest that sICAM concentrations could reflect the degree of inflammatory activity. Increased sELAM-1 concentrations only, in patients with ophthalmopathy with or without hyperthyroidism significantly correlated to severity score of GO, suggest the measurement of sELAM-1 levels as a specific marker of endothelium activation in GO.     

Regulatory mechanism of non-shivering thermogenesis in cold acclimation--with special reference to in vitro thermogenic activity and lipolysis of brown adipose tissue

In vitro brown adipose tissue (BAT) thermogenesis from cold-acclimated (CA) rats has been shown to exhibit the decreased responses to noradrenaline (NA) and glucagon (G), although an enhanced biochemical machinery for thermogenesis develops in the tissue. The present study was undertaken to clarify the inhibitory mechanism of in vitro thermogenic responses of BAT in CA rats. NA-treated rats were injected NA (40 micrograms/100g BW) twice a day for 2 or 4 weeks. The other rats were kept at 25 +/- 1 degree C (warm controls: WC), 5 +/- 1 degree C (CA), or 5 +/- 1 degree C/6h/day (intermittent cold exposure: ICE) for 5-6 weeks. The oxygen consumption, and glycerol as well as free fatty acids (FFA) release were measured on finely minced tissue blocks in Krebs-Ringer phosphate buffer at 37 degrees C. In vitro BAT thermogenic responses to NA and G in NA-treated rats did not differ from those in vehicle-injected controls. NA as well as G increased-oxygen consumption was greatest in WC, followed by ICE and CA. NA as well as G increased glycerol and FFA releases in WC and ICE, but the degree of increment was greater in WC than that in ICE, while NA or G did not increase glycerol and FFA releases in CA. FFA/glycerol ratio in WC was decreased by NA as well as G, but it was not changed in ICE, and increased in CA. Mitochondrial GDP binding as an index of BAT thermogenic capacity did not differ between CA and WC under resting state (CA rats were transferred in warm condition before 18h at the beginning of the experiment), but it was significantly greater in ICE. GDP binding was significantly greater in CA sacrificed at 5 degrees C compared with WC and CA resting. Acute cold exposure (5 degrees C/1h) enhanced GDP binding in WC, resting CA and ICE resting, but the degree of increment was greater in CA and ICE than in WC. These findings suggest that cold exposure inhibits BAT thermogenic responses according to the duration NA action during cold exposure, by means of suppressing fatty acid utilization and/or masking uncoupling protein.     

Association between low contents of dopamine and serotonin in the nucleus accumbens and high alcohol preference

The contents of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were determined in the nucleus accumbens (ACB), frontal cortex (FR), anterior striatum (AST), and hippocampus (HIP) of adult male rats from the F2 generation of P x NP intercrosses. Rats were tested for their alcohol preference and were divided into two groups, depending on their alcohol intake. Rats in the high drinking group (n = 11) had ethanol intakes > 5g/kg/day, whereas the low drinking group (n = 15) had values < 1 g/kg/day. The content of DA in the ACB was lower (p < 0.001) in the high alcohol drinking group (46 +/- 2 pmol/mg tissue) than in the low intake rats (61 +/- 3 pmol/mg tissue). However, the contents of DOPAC and HVA in the ACB were similar for both groups. There were no differences between the two groups in the contents of DA in the FR or AST. The content of 5-HT in the ACB was lower (p < 0.05) in high alcohol drinking rats (6.3 +/- 0.3 pmol/mg tissue) than in the low intake group (7.0 +/- 0.2 pmol/mg tissue). The content of 5-HIAA in the ACB of the high intake rats was also lower than the level for the low drinking rats. There were no differences in the contents of 5-HT or 5-HIAA in the FR, HIP, and AST between the two groups. The results confirm a phenotypic association between abnormal DA and 5-HT systems projecting to the ACB and high alcohol drinking behavior in the P line of rats.     

Beta-thromboglobulin plasma levels in the first week after myocardial infarction: influence of thrombolytic therapy

In vitro and in vivo studies have shown both an inhibition and an activation of platelets after thrombolysis in acute myocardial infarction. Plasma beta-thromboglobulin, a marker of platelet activity, was evaluated daily during the first week after myocardial infarction in 24 patients who received intravenous streptokinase (group 1) and 26 who did not (group 2). On admission, levels of beta-thromboglobulin, as compared to those in healthy subjects (35 +/- 9 IU/ml), were similarly augmented in group 1 (105 +/- 27 IU/ml) and in group 2 (115 +/- 30 IU/ml); 3 hours later, values averaged 191 +/- 58 IU/ml in group 1 (p < 0.001 vs baseline) and 95 +/- 28 IU/ml in group 2 (not significant vs baseline; p < 0.001 between the two groups). From the second to the seventh day, beta-thromboglobulin augmented in those patients in both groups with postinfarction angina. From day 5 to day 7, patients of group 1 without angina had lower beta-thromboglobulin levels than patients of group 2 who had no symptoms. The lowest levels of platelet activity were observed in group 1 reperfused patients. These data indicate that in myocardial infarction an early platelet activation takes place that is enhanced by thrombolytic treatment; recurrence of angina is associated with persistent activation; in the absence of recurrent angina, thrombolysis can limit late platelet activation.     

The effect of limited exposure to antimycotics on the relative cell-surface hydrophobicity and the adhesion of oral Candida albicans to buccal epithelial cells

Candida albicans is the major aetiological agent of oral candidosis. Adhesion to oral mucosal surfaces is considered a prerequisite for its successful colonization and subsequent infection, and its relative cell-surface hydrophobicity (CSH) is a contributory physical force. Thus, the main aim here was to determine the CSH of 10 isolates of oral C. albicans after a short exposure to sublethal concentrations of four antifungal agents and to correlate these findings with their adhesion to human buccal epithelial cells (BEC). The yeasts were exposed to sublethal concentrations of nystatin [x 6 minimal inhibitory concentration (MIC)], 5-fluorocytosine (x 8 MIC), ketoconazole (x 4 MIC) and fluconazole (x 4 MIC) for 1 h. The drug was then removed, and the CSH and BEC adhesion assessed by a biphasic aqueous-hydrocarbon assay and a microscopic method, respectively. The mean percentage reductions of CSH after exposure to nystatin, 5-fluorocytosine, ketoconazole and fluconazole were 27.14% (p = 0.01), 9.46% (p = 0.43), 19.47% (p = 0.04) and 6.16% (p = 0.59). Similarly, exposure to all the drugs except 5-fluorocytosine resulted in a significant inhibition of yeast adhesion to BEC, with nystatin eliciting the highest and fluconazole the least inhibition. Further, on regression analysis a strong positive correlation was observed between CSH and adhesion to BEC after limited exposure to 5-fluorocytosine (r = 0.48, p < 0.0001), ketoconazole (r = 0.48, p < 0.0001), fluconazole (r = 0.55, p < 0.0001) as well as in the unexposed controls (r = 0.41, p = 0.001), although nystatin was an exception (r = 0.09, p = 0.44). Taken together, these data elucidate further mechanisms by which antimycotics may operate in vivo to suppress candidal pathogenicity.     

TQI in the Albuquerque Veterans Affairs Medical Center''s long-term oxygen therapy program

Stroke patients were assessed by brain CT scan, accompanied by demographic and clinical factors to predict the development of dementia following an ischemic episode. Vascular dementia was defined by NINDS-AIREN criteria. From 50 demented and 50 non-demented stroke patients, we analyzed the location of lesion, counted the numbers of lacunae, and semiquantitatively assessed the size of infarction, severity of overall white matter lesions (WML), and degree of brain atrophy. Compared to the non-demented patients, the demented patients: 1) encountered more stroke episodes (p < 0.001); 2) had more lacunae at bilateral basal ganglion (p < 0.001) or thalamus (p < 0.01); and 3) tended to have lesions in left cortex (p < 0.001), particularly a large infarct at the parietal (p < 0.001) or temporal lobe (p < 0.001). Periventricular changes (p < 0.001), subcortical WML (p < 0.001), overall WML (p < 0.001), and brain atrophy (p < 0.05) were also more severe in the demented group. However, no difference existed in demographic factors between the two groups. We concluded that several factors were important in developing dementia following an ischemic stroke, and the order by logistic regression would be: the severity of overall WML, left parietal infarct, and numbers of thalamic lacunae.     

Tissue markers as predictors of postoperative adhesions

BACKGROUND: Postoperative adhesion formation has been associated with a decreased capacity to degrade intra-abdominally deposited fibrin. Adhesions, once lysed, have a high propensity for reformation. This study tested the hypothesis that patients with a high propensity for adhesion formation as well as adhesion tissue had a reduced fibrinolytic capacity. METHODS: Peritoneal biopsies were taken during abdominal surgery from 21 patients who had previously undergone operation; previously formed adhesion tissue was sampled from ten of these patients. Adhesion formation was scored. The fibrinolytic capacity of peritoneum was determined in tissue extracts. RESULTS: At the time of opening of the abdominal cavity, levels of plasminogen activator inhibitor (PAI) type 1 (P = 0.009) and tissue-type plasminogen activator (tPA)/PAI complex (P = 0.008) were increased in peritoneal samples from patients with severe adhesions compared with those in samples from patients with less severe adhesions. Adhesion tissue similarly had reduced fibrinolytic capacity as judged by a decrease in tPA activity (P = 0.005) and an increase in PAI-1 level (P = 0.01), reflected in an increased level of tPA/PAI complex (P = 0.008) compared with unaffected peritoneum. CONCLUSION: These observations demonstrate reduced fibrinolytic capacity in peritoneal tissue in patients with a greater propensity for development of adhesions and likewise in adhesion tissue. This suggests that components of the fibrinolytic system may be used as markers of an increased risk of adhesion development.     

Metabolic interferences in subjects occupationally exposed to binary styrene-acetone mixtures

OBJECTIVE: To investigate the excretion of styrene metabolites (mandelic acid, MA, and phenylglyoxylic acid, PGA) in workers employed in plastic manufacturing to verify the possible influence of coexposure to acetone on styrene metabolism. METHODS: This study was carried out on 50 workers employed in 3 factories producing polyester buttons. The workers were divided into three groups according to three different levels of acetone exposure. The trend of excretion for metabolites was examined during and after work shifts. Styrene and acetone were monitored on Thursday during the entire work shift by passive dosimeters placed on the lapel of the workers' uniforms, desorbed by carbon disulfide, and analyzed by gas chromatography. Biological monitoring was performed by determination of the urinary metabolites of styrene in urine samples collected on Thursday at the middle and the end of the work shift. MA and PGA were determined by a high-pressure liquid chromatographic method. RESULTS: The styrene concentrations ranged between 16 and 439 mg/m3, and in ten samples they exceeded the TLV-TWA (213 mg/m3). The acetone concentration ranged between 15 and 700 mg/m3 (TLV-TWA 1780 mg/m3), with the mean value being 208 mg/m3. During cleaning operations higher exposures to acetone demonstrated, with concentrations ranging between 500 and 3400 mg/m3. The amounts of MA and PGA determined at the end of workshifts did not significantly differ between the groups with different levels of acetone coexposure. Analysis of variance (ANOVA) between the groups confirmed that MA and PGA excretion did not significantly differ, although the metabolite values measured on the "morning of the day after" appeared higher in those groups with high levels of acetone exposure and were related to the average airborne concentrations of the solvent. In addition, the range and degree of correlation between styrene in air and biological levels of metabolites were modified by coexposure to acetone. CONCLUSIONS: Our data demonstrate that amounts of MA and PGA did not differ in groups with different levels of acetone exposure, but when the acetone air concentration increased the degree of correlation between styrene and MA and PGA decreased. Furthermore, coexposure to acetone levels similar to those described herein may hamper the use of urinary metabolites for the assessment of exposure to styrene, especially on an individual basis.     

Recommended restrictions after 131I therapy: measured doses in family members

Previous studies have shown that levels of plasma brain natriuretic peptide (BNP) increase in an early phase of acute myocardial infarction. However, the relations between plasma BNP levels and left ventricular remodelling, which occurs long after acute myocardial infarction, are not fully understood. Venous plasma BNP levels were measured 2, 7, 14, 30, 90 and 180 days after the onset of acute myocardial infarction in 21 patients. Left ventricular end-diastolic volume index (EDVI, ml/m2) in acute (5 days) and chronic (6 months) phases were assessed by electron-beam computed tomography using Simpson's method. The remodelling group (n=9) was defined by an increase in EDVI >/=5 ml/m2 relative to the baseline value. Plasma BNP levels on days 2, 7, 14, 30 and 90 were significantly higher in the remodelling group than in the non-remodelling group (n=12, P<0.05). Sustained elevation of plasma BNP levels was noted from day 2 (61+/-12 pmol/l) to day 90 (55+/-12 pmol/l) and significantly decreased on day 180 (24+/-3 pmol/l) in the remodelling group. In contrast, plasma BNP levels significantly decreased from day 2 (25+/-4 pmol/l) to day 90 (9+/-1 pmol/l) and reached a steady level thereafter in the non-remodelling group. Plasma BNP levels on day 7 correlated positively with an increase in EDVI (r=0.70, P<0.001) from the acute to chronic phase. More importantly, the sustained elevation of plasma BNP (percentage decrease smaller than 25%) from day 30 to day 90 identified patients in the remodelling group with a sensitivity of 100% and a specificity of 83%. In conclusion, not only the high levels of plasma BNP in an acute phase, but also the sustained elevation of plasma BNP in a chronic phase, may be associated with progressive ventricular remodelling occurring long after acute myocardial infarction.     

Captopril plus losartan in early post-infarction. Neurohormonal effects: a pilot study

BACKGROUND: Suppression of the formation of angiotensin II (A II) is thought to be a major contributor to the hemodynamic response to angiotensin-converting enzyme inhibition (ACE-inhibitor) therapy. However, during ACE-inhibitor treatment, A II plasma levels may also recover through tissue chymase. This study has attempted to verify the feasibility, safety and tolerability of a combined treatment using captopril (75 mg/day) and losartan (25 mg/day), and to ascertain its ability to reduce the formation and action of A II in the early post-infarction phase of reperfused anterior myocardial infarction (AMI). METHOD: Forty-four patients hospitalized for suspected AMI within 4 hours of the onset of symptoms, who were suitable for thrombolysis (first episode), in Killip class I-II, reperfused, treated with 75 mg/day of captopril within 3 days of admission and with a blood pressure level of more than 120 mmHg, were randomized (single-blind) into two groups that were similar with regard to age, sex, blood pressure, CK peak, ejection fraction, end-systolic volume and risk factors. Group A (22 subjects: 6 women/16 men) received captopril (75 mg/day) and placebo, while group B (22 subjects: 5 women/17 men) was given captopril (75 mg/day) plus losartan, initially at 12.5 mg and then at 25 mg/day thereafter (BP > 110 mmHg). Norepinephrine (NE) and A II plasma levels were measured on the third and tenth day after admission. RESULTS: Ten days after admission, group B (captopril plus losartan) showed a significant decrease in blood pressure (BP) on an intragroup level (p < 0.001) as well as in comparison with group A (p < 0.001), with values of 108 + 6.4 and 118 + 11 mmHg respectively. At the same time interval, NE and A II values did not show significant differences within or between groups. CONCLUSIONS. For the first time, our data suggest that a combined captopril-losartan treatment is feasible and that it has no particular side effects. In addition, it shows no significant increase of A II that would be produced by losartan alone.     

Fiber morphometry of the external intercostal muscle. Comparison of dominant and nondominant sides in patients with severe COPD]

OBJECTIVES: Contribution of cellular immunity to the onset and perpetuation of alcohol-induced liver damage remains controversial. The aim of this work was to know whether T-cells participate in the pathogenesis of alcoholic liver injury by measuring the serum levels of sIL-2R in alcoholic patients with different degree of hepatic damage. PATIENTS AND METHODS: Fifty two patients and eighteen healthy subjects (Control group) were included. All patients were active drinkers of at least 100 grams/day of ethanol over a ten-years period. Serum sIL-2R was determined by ELISA. Liver biopsy was performed in all patients and liver function tests, serum immunoglobulins and complement proteins C3 and C4 were measured in all participants. The relationship between the sIL-2R and the severity of liver disease was studied. RESULTS: Circulating sIL-2R was higher in the group of patients than in the control (2.388 +/- 275.7 U/ml vs. 795.7 +/- 48.7 IU/mL; p < 0.001). There were not increased circulating sIL2R in those patients with alcoholic hepatitis. However, patients with cirrhosis showed increased serum sIL-2R regardless of the presence of alcoholic hepatitis. Furthermore, serum levels of sIL-2R inversely correlated with hepatic function test (r = -0.69; p < 0.001 for serum albumin; and r = -0.73; p < 0.001 for the prothrombin time) and were highest in those patients of the Child-Turcotte's class C. CONCLUSIONS: Circulating sIL-2R increases in alcoholic cirrhosis. However, our data do not support a contributory role of the cellular immunity, as assessed by circulating sIL-2R levels to the alcoholic liver damage. The increased serum sIL-2R in cirrhosis may result from defective heptic clearance of this molecule.     

Tissue repair in the fetal intestinal tract occurs with adhesions, fibrosis, and neovascularization

Cutaneous wound healing in the fetus can occur in a nonfibrotic, regenerative manner. However, other fetal tissues such as bone and stomach heal with scar formation. In light of potential ramifications for adult hollow visceral scarring (biliary and intestinal strictures), this study was undertaken to determine if tubular visceral tissue repair in the fetus is regenerative or fibrotic. Fetal rabbits underwent laparotomy on day 24 of gestation, during which a controlled intestinal enterotomy was created and suture repaired immediately using microsurgical techniques. Maternal rabbits and adult male rabbits also underwent enterotomy and repair. After 5 days all animals were sacrificed and the wounds analyzed histologically by a pathologist in a blinded fashion. All animals demonstrated a similar degree of peri-intestinal adhesion formation. Fetal and maternal wounds contained fibroblastic and smooth muscle cell proliferation, mild inflammatory infiltration, and new blood vessel formation. The male adult wounds demonstrated a more pronounced fibrovascular healing response. Immunohistochemical staining for CD31 (endothelial cell marker) was quantitated on a scale of 0 to 4+, indicating degree of neovascularization. The mean scores for the fetal and maternal groups were similar (1.70 +/- 0.68 and 1.23 +/- 1.07 respectively), but were significantly greater for male adults (2.93 +/- 0.12; p = 0.001 by analysis of variance). The results of this study indicate that hollow visceral tissue repair in the fetal rabbit intestine occurs in a similar fibrotic manner as adult healing. This provides further evidence that regenerative healing in the fetus is not ubiquitous. Differences in the degrees of fibrosis and neovascularization between adult male and pregnant female wounds deserve further investigation.     

New frontiers in physiology of presby-cardia

OBJECTIVE: To find out if the in vitro responses of neutrophils (PMN) and monocytes preoperatively can predict their activation postoperatively. DESIGN: Prospective open study. SETTING: Teaching hospital, Ireland. SUBJECTS: 46 Patients (32 men, 14 women, mean age 65 years, range 33-85) who were to undergo elective major vascular or gastrointestinal operations for benign (n = 18) or malignant (n = 28) diseases. INTERVENTIONS: Measurement by flow cytometry of functional (PMN and monocyte respiratory burst activity) and phenotypic (expression of PMN CD 11b adhesion receptors and monocyte CD14 receptors) markers of activation. MAIN OUTCOME MEASURES: Correlation between mean channel fluorescence (MCF) preoperatively and postoperatively. RESULTS: In 24 patients PMN respiratory burst activity was increased before operation and had decreased significantly (p < 0.01) on postoperative day 1 (high responders group). In the remaining 22 patients (low responders group) respiratory burst activity was low before operation and had increased significantly (p < 0.05) on postoperative day 1. PMN CD 11b activity followed a similar trend. Monocyte activity responded similarly (in the high group mean (SEM) MCF preoperatively was 69.14 (13.15) compared with 58.23 (10.8) on day 1, and in the low group the corresponding figures were 38.5 (7.01) and 8.43 (5.2). Expression of CD14 did not differ between the groups and was less postoperatively than preoperatively. The groups did not differ in age, sex, APACHE 11 scores, smoking habits or types of disease and there was no major infective complications in either group. CONCLUSION: There are two distinct patterns of PMN and monocyte responses to injury that are independant of age, sex and severity of operation. These may be associated with the degree of stress preoperatively or with genetic factors.     

Effect of extended-release isosorbide mononitrate one hour after dosing in patients with stable angina pectoris. IMDUR Study Group

The effect of extended-release isosorbide mononitrate (ER-ISMN) on exercise tolerance 1 hour after dosing was compared with that of placebo in a multicenter, randomized, double-blind study of 151 patients with stable effort-induced angina. During a 9- to 24-day placebo run-in, patients underwent Bruce protocol baseline exercise tolerance tests, after which they received ER-ISMN or placebo for 5 days. ER-ISMN patients took 60 mg each morning for the first 4 days and 120 mg on the morning of the fifth day. One hour after dosing, ER-ISMN patients had a significantly greater increase in total exercise time (days 1 to 4: 5 +/- 53 seconds; day 5: 53 +/- 58 seconds) than the placebo-treated patients (days 1 to 4: 14 +/- 37 seconds; day 5: 21 +/- 48) (p <0.001). The times to development of angina and 1-mm ST-segment depression were significantly longer in the ER-ISMN group than in the placebo group. The difference between the groups in mean time to onset of angina was 34 seconds after the 60-mg dose (p = 0.004) and 49 seconds after the 120-mg dose (p <0.001). The mean time to development of a 1-mm ST-segment depression was 51 and 61 seconds longer after the 60-mg and 120-mg ER-ISMN doses, respectively, than after placebo (p <0.001). Treatment-related adverse events were reported in 37% (28 of 75) and 7% (5 of 76) of patients in the ER-ISMN and placebo groups, respectively. As expected, headache was more frequent in the ER-ISMN group than in the placebo group (28% and 1%, respectively). The effects of ER-ISMN (60 mg and 120 mg) are clinically evident 1 hour after dosing, resulting in better exercise tolerance in patients with angina pectoris.