Biomedical subjects
Publications and source records attributed to L Russo.
Enalapril, an angiotensin-converting enzyme inhibitor, has several adverse effects, but acute pancreatitis is uncommon. The case of a patient with enalapril-induced pancreatitis is described. Development of severe, necrotizing pancreatitis after inadvertent rechallenge confirmed the causal relationship between enalapril and acute pancreatitis.
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A number of observations point to chromosome 15 as a good candidate to harbor genes involved in epilepsy. This hypothesis is supported by at least two lines of evidence: one is the finding that haploinsufficiency of the 15q11-q13 region, of maternal origin, is responsible for Angelman syndrome, one of the cardinal manifestations of which is epilepsy; the second is the observation that extra copies of this same genomic region, in the form of inv-dup(15) or intrachromosomal duplications, again of maternal origin, are usually associated with a severe neurological phenotype characterized by developmental delay and untreatable seizures. Therefore, both reduced and increased dosage of genes from the 15q11-q13 region, possibly subjected to maternal imprinting, appear to be causally involved in severe forms of epilepsy. We tested the hypothesis that submicroscopic rearrangements of this genomic region might be responsible for nonsyndromic epilepsy in both familial and sporadic forms. To this purpose, we genotyped 118 epileptic patients and their parents with closely spaced microsatellite markers mapped within the 15q11-q13 region. We report on the results of these studies and review the relevant literature.
Reactive oxygen species (ROS) have been considered for a long time only as molecules for inducing oxidative damage to proteins, lipids, and nucleic acids. However, in the last few years some physiological effects of ROS have been hypothesized, consisting of the redox regulation of several biological processes, including the transduction of mitogenic signals. This means that intracellular generation of ROS could be necessary to maintain homeostasis, as well as that their formation/scavenging should be controlled processes. We developed an experimental procedure that causes redox perturbations in intact cells, based on the exposure of living cells to diethylmaleate (DEM), a GSH-depleting agent. By this procedure we demonstrated that ROS generated following DEM treatment induces a G1 arrest, that is accompanied by several redox-dependent changes in cell cycle-related proteins. One of these is the p53-independent accumulation of p21waf1/cip1, which requires the integrity of the ras-MAPK pathway. Accordingly, DEM treatment strongly activates ERK2. On the other hand, redox perturbations provoked by DEM induce several early phenomena, including p21waf1/cip1 and Rb dephosphorylation.
BACKGROUND: The rupture of an aortic aneurysm is the most frequent and most severe complication, with an incidence of approximately 20-40/100,000 persons each year. The aim of this study was to identify the preoperative, intraoperative and postoperative factors that may influence the mortality rate. METHODS: Between January 1996 and December 1999 145 patients underwent emergency abdominal aortic repair surgery. One hundred and twenty-three patients represented a ruptured AAA and 22 a fissured aneurysm. One hundred and thirty-one patients were males and 14 were females; their mean age was 75+/-5.06 years. We selected a number of parameters after a review of the international literature and these were analysed in the two classes of survivors. No statistical analyses were performed on fissured aneurysms owing to the scant number of cases examined. RESULTS: Mortality was 41.4% (44.7% in ruptured aneurysms alone). The following were negative preoperative prognostic factors: old age, hypertension, ASA V, intraoperative anuria and platelet count <100,000. Intraoperative factors included: hypotension, cardiac arrest, onset of anuria, aortic clamping in more than one site, duration of surgery, quantity of RBC and plasma transfused. The main postoperative variables correlated to mortality were: hypotension, hypothermia, onset of anuria, need for further transfusions, high creatinine levels. CONCLUSIONS: Rapid intervention can minimise mortality in structures with expert teams of surgeons and anesthetists experienced in treating this type of pathology.
Matrix metalloproteinases (MMPs) belong to a class of extracellular proteinases responsible for maintaining and remodeling the extracellular matrix. In addition to multiple functions in normal physiology, abnormal MMP expression and activity may also participate in the pathophysiology of cerebral disease. Here, we show that MMP-9 (gelatinase B; EC.3.4.24.35) contributes to the pathophysiology of traumatic brain injury. After controlled cortical impact in mice, MMP-9 was increased in traumatized brain. Total MMP-9 levels at 24 hr were significantly increased as measured by a substrate cleavage assay. Zymograms showed that MMP-9 was elevated as early as 3 hr after traumatic brain injury, reaching a maximum at approximately 24 hr. Increased MMP-9 levels persisted for up to 1 week. Western blot analysis indicated increased profiles of MMP-9 expression that corresponded with the zymographic data. Knock-out mice deficient in MMP-9 gene expression were compared with wild-type littermates in terms of morphological and motor outcomes after trauma. Motor outcomes were measured at 1, 2, and 7 d after traumatic brain injury by the use of a rotarod device. MMP-9 knock-out mice had less motor deficits than wild-type mice. At 7 d, traumatic brain lesion volumes on Nissl-stained histological sections were significantly smaller in MMP-9 knock-out mice. These data demonstrate that MMP-9 contributes to the pathophysiology of traumatic brain injury and suggest that interruption of the MMP proteolytic cascade may be a possible therapeutic approach for preventing the secondary progression of damage after brain trauma.
The modification of intracellular redox conditions with diethylmaleate (DEM), a glutathione-depleting agent, induces a p53-independent growth arrest mediated by the accumulation of p21(waf1) mRNA and protein. The same treatment also induces the retinoblastoma protein (pRb) dephosphorylation. This dephosphorylation (i) is very fast, being observed already 5 min after the exposure of the cells to DEM, (ii) is dependent on the prooxidant effects of DEM, being prevented by the treatment with N-acetylcysteine and (iii) is completely reversible, since the rephosphorylation of pRb is promptly obtained upon the removal of the glutathione-depleting agent from the culture medium. The dephosphorylation of pRb is independent of the accumulation of p21(waf1) induced by DEM; in fact, p21(waf1) levels start to increase much later after DEM treatment and accordingly cyclin-dependent kinase activities are not yet induced when pRb is already dephosphorylated following DEM treatment. Finally, pRb dephosphorylation is catalyzed by phosphatases activated by DEM treatment.
AIMS: We compared the immunohistochemical profiles of the rete ovarii and endometriosis in order to identify a panel which distinguishes between these structures. The immune profiles of the epoophoron, Fallopian tube and ovarian surface epithelium were also studied. MATERIALS AND METHODS: Twenty-four women with no evidence of endometriosis and seven who had endometriosis in the uterine adnexae were studied using nine antibodies to intermediate filament proteins and cell surface markers. None of the structures studied shared an identical profile of immunohistochemical reaction. The immunoprofile of endometriosis showed some similarities to that of the Fallopian tube, but differed from that of the rete ovarii, epoophoron and ovarian surface epithelium CONCLUSIONS: A panel including Ca-125, epithelial membrane antigen and the epithelial glycoprotein BerEp4 would permit the distinction between endometriosis and the rete ovarii in problematic cases. The study showed some commonality in reaction between endometriosis and the Fallopian tube which indicates that they may share a common (paramesonephric) origin. There was little commonality in the immunoprofile of endometriosis and the ovarian surface epithelium implying that endometriosis is unlikely to develop as a result of serosal metaplasia.
A study to compare the immuno-histochemical profile of the human rete ovarii, and epoophoron, with the Fallopian tube and ovarian surface epithelium was performed with 31 antibodies and antisera. A reaction was present in the epithelial cytoplasm of the rete ovarii and epoophoron of mesonephric origin, for vimentin, GFAP, cytokeratin markers, (AE1/AE3, MNF116; Cam 5.2, 34 beta E12 and for the monospecific antibodies to cytokeratins 7 and 19), heat shock protein 27, in the cell membrane for HBME-1, EMA and in the subepithelial collagen for collagen IV. Reactions were present only in the epithelium in the rete ovarii for EGFR (one case) and CA-125 (four cases). A reaction was present in the epithelium of the epoophoron only for Ber-EP-4 and S100. There was no reaction with antibodies for desmin, neurofilament protein, cytokeratins 20 or 14, actin, calretinin, E-cadherin, C-erb-B2, or CEA (monoclonal and polyclonal reagents). The immuno-histochemical profile of the Fallopian tube was consistent with its para-mesonephric origin and that in the ovarian surface epithelium was consistent with a proposed modified mesothelial origin. This study provides an immunohistochemical profile of these structures with a large panel of commonly available antibodies and antisera, confirming and extending the findings described in previous studies.
OBJECTIVES: Exercise tolerance is reduced with advancing age. Identification of potentially reversible determinants of the age-related decrement in exercise tolerance, which remain largely unexplored in older subjects and in patients recovering from a recent myocardial infarction (MI), may have useful therapeutic implications. The objective of this study was to identify the independent determinants of exercise tolerance in older patients with a recent MI. DESIGN, SETTING, AND PARTICIPANTS: Data is from baseline assessment of 265 post-MI patients (age range 45-85 years) enrolled in the Cardiac Rehabilitation in Advanced Age randomized, controlled trial. Patients with major comorbidities or severe MI complications were excluded from the trial. Exercise tolerance was determined from symptom-limited exercise testing and expressed as total work capacity (TWC, kg.m) or peak oxygen consumption (VO2peak, mL/kg/min). The associations between both TWC and VO2peak and baseline demographic, social, clinical, and neuropsychological variables and an index of health-related quality of life were determined with univariate and multivariate analysis. RESULTS: With univariate analysis, TWC decreased by 1285 kg.m per decade of increasing age between 45 and 85 years of age. With multivariate analysis, TWC decreased by 922 kg.m per decade. Increasing age (P < .001), female gender (P < .001), a small body surface area (P < .001), a low level of usual physical exercise before MI (P < .002), and the presence of post-MI depressive symptoms (P < .024) were independently associated with a lower TWC. The same factors, in addition to a small arm muscle area (P < .002), were also independently associated with a lower VO2peak. CONCLUSIONS: Age per se accounts for approximately 70% of the age-related decay in TWC or VO2peak. However, the inclusion of modifiable factors such as physical exercise and depression in the prediction model reinforces the importance of a multidimensional approach to the evaluation and treatment of older patients with a recent MI.
OBJECTIVE: To describe the changes in rehabilitation therapy services in nursing homes based in the community during a period of rapid escalation of Medicare payments to nursing homes. SETTING: All Medicaid-certified nursing homes in Ohio. SUBJECTS: The 52,705 residents newly admitted to nursing homes in 1994 and 1995. DESIGN: Retrospective trend analysis of administrative data. MAIN OUTCOME MEASURES: For newly admitted residents receiving 90 or more minutes of rehabilitation therapy per week, the trends in percentage and in the amount and type of therapy received were determined for eight quarters. RESULTS: Of all newly admitted residents, 50.5% received 90 or more minutes of therapy. When they received such therapy it averaged 412 minutes per week (SD = 259). Those residents who received rehabilitation services increased by 2.2% each quarter (p<.001), and the amount of therapy they received increased by 6.4 minutes each quarter (p<.0001). All three types of rehabilitation therapy-physical, occupational, and speech-increased (p<.015) over the study period. CONCLUSIONS: The traditional nursing home is an important site for the provision of rehabilitation therapy services. Rehabilitation specialists should be aware of these trends as they plan for the future of rehabilitation. The effectiveness of this increased provision of therapy service in terms of measurable outcomes needs to be evaluated.
OBJECTIVE: To examine whether hypertension predicts the incidence of kidney stone disease. DESIGN: Prospective cohort study (the Olivetti Prospective Heart Study). SETTING: The Olivetti factory in Southern Italy. SUBJECTS: Five hundred and three male workers, aged 21 - 68 years, with no evidence of kidney stone disease at baseline. Follow-up 8 years. MAIN OUTCOME MEASURES: Anthropometry, blood pressure, biochemistry and history of kidney stone disease were evaluated at the baseline examination in 1987. Occurrence of kidney stone disease was evaluated again in 1994-1995. Hypertension was defined as systolic blood pressure > or = 160 or diastolic blood pressure, > or = 95 mmHg or both, or being on drug therapy for hypertension. Occurrence of kidney stone disease was defined as radiological or echographic evidence of calculi or documented passage of one or more stones. RESULTS: At baseline, 114/503 men (22.7%) had hypertension and 32 were on drug treatment. After 8 years, 52 (10.3%) incident cases of kidney stone disease were detected. The majority (n = 45) had a documented passage of one or more stones. The incidence of kidney stone disease was higher in hypertensive than in normotensive men (19/114 (16.7%) versus 33/389 (8.5%); P = 0.011). Hypertensive men had a greater risk of developing kidney stones than normotensive ones (RR 1.96; 95% confidence interval 1.16-3.32). The risk was unaffected by the exclusion of treated hypertensives (2.01; 1.13-3.59) and after adjustment for age (1.89; 1.12-3.18), body weight (1.78; 1.05-3.00) or height (2.00; 1.19-3.38). CONCLUSIONS: Hypertension in middle-aged men is a significant predictor of kidney stone disease rather than a consequence of renal damage caused by the kidney stones.
BACKGROUND: Head-up tilt testing is extensively used to determine the vasovagal origin of syncope in patients with otherwise unexplained loss of consciousness, although issues remain regarding the method of the test. The diagnostic value of a shortened head-up tilt test potentiated with sublingual nitroglycerin was assessed in patients with unexplained syncope. METHODS: Two hundred two patients (mean age 49+/-19 years) with syncope of unknown origin and 34 subjects in a control group (mean age 45+/-17 years) were studied. The patients and the subjects in the control group were tilted upright to 60 degrees for 20 minutes. If syncope did not occur, sublingual nitroglycerin (400 microg) was administered, and observation was continued for 25 more minutes. RESULTS: During the unmedicated phase syncope occurred in 22 (11%) patients and in one member of the control group. After nitroglycerin was administered, syncope occurred in 119 (59%) patients and in 1 (3%) member of the control group. False-positive response (exaggerated response) was observed in eight (4%) patients and in four (12%) subjects in the control group. The total positivity rate of the test was 70% with a specificity rate of 94%. CONCLUSIONS: Short-duration head-up tilt test potentiated with sublingual nitroglycerin provides an adequate specificity and positivity rate in patients with unexplained syncope.
BACKGROUND: Traditional management of chest tubes after a wedge resection of peripheral pulmonary tissue often lasts several days. We evaluated the safety and efficacy of early chest tube removal in the recovery room after uncomplicated video-assisted thoracoscopic surgical wedge resections of the lung. METHODS: From December 1995 to July 1997, 59 patients underwent video-assisted thoracoscopic surgical wedge resection for indeterminate pulmonary nodules (n = 33) or interstitial lung disease (n = 26). We prospectively evaluated early chest tube removal in the last 33 patients; 18 patients with nodules and 15 with interstitial lung disease. Patients who were in the early removal group had chest tubes removed within 90 minutes of the surgical procedure. Criteria for early removal were established and met before chest tube removal. There was no difference between groups with respect to age, sex, comorbidities, or pathologic evaluation of resection specimens. RESULTS: Ninety-four percent (31 of 33) of patients considered for early chest tube removal met criteria for immediate tube removal. Air leak and excessive drainage prohibited early removal in 2 patients. Patients who were managed traditionally averaged 3.3 days with chest tubes--1.8 days on suction, 1.3 days on water seal. Patients who had early removal of their chest tubes had a shorter postoperative stay (2.0+/-1.0 versus 3.9+/-2.1 days, p = 0.001) and fewer chest roentgenograms (2.8+/-2.1 versus 5.1+/-2.0, p = 0.001). There were no differences in complications including small pneumothoraces (5 in the early removal group, 7 in the traditional management group), which were managed with observation alone. Total narcotic requirements were greater in the traditional management group (54+/-44.8 versus 24.6+/-22.9 morphine milligram equivalents, p = 0.005). CONCLUSIONS: Early chest tube removal after video-assisted thoracoscopic surgical wedge resection of peripheral pulmonary tissue appears to be a safe and cost-effective practice if strict criteria for removal are met.
Arterial hypertension is frequently associated with metabolic abnormalities. An abnormal activity of the erythrocyte sodium/lithium countertransport (Na/Li CT), an ion transport system under strong genetic control, is also found in people with hypertension and concomitant metabolic abnormalities. However, little information exists with regard to these clinical associations in different racial groups. The aim of this international collaborative study was to investigate Na/Li CT and the metabolic correlates of hypertension in two comparable samples of normotensive and hypertensive populations in the cities of Naples, Italy, and Shanghai, China, using identical, carefully standardized techniques. Blood pressure, anthropometric and metabolic variables, Na/Li CT, and 24-h urinary Na and K excretion were measured in untreated essential hypertensive (HPT) and normotensive (NT) individuals selected by age (35-60 years), body mass index (BMI; < 30 kg/m2), and blood pressure (BP; HPT, DBP > or = 95 mm Hg; NT, DBP < 90 mm Hg). The analysis of variance with adjustment for age was used to compare the groups. In the Neapolitan population, hypertensive individuals had higher serum triglyceride (P < .05) and uric acid levels (P < .001) than the normotensive group and also had a reduced glucose tolerance (P < .01) and an enhanced insulin response to the oral glucose tolerance test (OGTT) (P < .05). No such differences were seen between normotensive and hypertensive Chinese participants. The Neapolitan population (both NT and HPT) had a higher BMI (P < .01) than their Chinese peers. In the comparison of hypertensive patients in Shanghai and in Naples, the Neapolitans were heavier (P < .001), had a lower HDL/total cholesterol ratio (P < .01), an elevated fasting blood glucose (P < .05), and also a higher glucose (P < .001) and insulin response (P < .001) to OGTT. By contrast, they showed a significantly lower urinary Na/K ratio (P < .001). Na/Li CT was significantly increased in HPT both in Naples (286 +/- 24 v 224 +/- 13 micromol/L RBC x h; P < .05, M +/- SE) and in Shanghai (388 +/- 45 v 265 +/- 30 micromol/L RBC x h; P < .05). Furthermore, Na/Li CT was significantly and inversely associated with HDL cholesterol both in the Neapolitan (P < .01) and in the Chinese (P < .05) population, whereas it was directly correlated with serum triglyceride (P < .001) and serum uric acid (P = .001) only in the Neapolitan population. These results indicate that essential hypertension is associated with a higher prevalence of obesity, impaired glucose tolerance, and hyperinsulinemia in Naples than in Shanghai; and Na/Li CT is linked to both high blood pressure and metabolic abnormalities in the Italian sample, whereas it is an isolated marker of hypertension in the Chinese sample.
p21waf1/cip1 mRNA and protein accumulate in intact cells exposed to oxidizing agents through a p53-independent, MAPK-dependent mechanism. Treatment with oxidizing agents also yields a second form of this protein (FM p21), characterized by a faster migration on SDS-PAGE. This phenomenon depends on the modification of intracellular redox conditions induced by diethylmaleate, a glutathione-depleting agent, being prevented by the pretreatment with the glutathione precursor N-acetylcysteine. The appearance of this FM p21 form is very early, being observed 5 min after exposure to diethylmaleate, long before the already observed accumulation of p21 induced by oxidative stress. Furthermore, experiments with dominant negative mutants of MEK demonstrate that, in contrast with that observed for the oxidative stress-induced accumulation of p21 mRNA and protein, the appearance of FM p21 form is not dependent from the activation of the MAPK pathway. It was previously observed (Tchou et al, 1996) that in some lung carcinoma cells long exposure to high doses of phorbol esters also induces the appearance of a faster-migrating p21 electrophoretic band and it was suggested that this could result from a different phosphorylation or from a proteolytic processing at the C-terminus of the protein. The latter is not the case for the diethylmaleate-induced FM p21 whose C-terminus is intact, as demonstrated by the expression of a C-terminus tagged p21 cDNA. On the contrary, the observed migration shift seems to be dependent on the hypophosphorylation of the protein; in fact, a pretreatment of cells with okadaic acid, an inhibitor of (serine/threonine) phosphatases, inhibits the oxidation-dependent appearance of the FM p21 and the block of protein synthesis, caused by cycloeximide, does not affect the appearance of FM p21, that thus could derive from the dephosphorylation of preexisting protein.
BACKGROUND: A combination of an antisecretory agent with two antibiotics is considered the 'gold standard' for Helicobacter pylori eradication. OBJECTIVES: To compare the eradication rates and the safety profile of two short-term triple therapies containing lansoprazole (L) or ranitidine bismuth citrate (RBC) as antisecretory agents. METHODS: One hundred and twelve H. pylori-positive patients either with peptic ulcer (56 duodenal ulcers: 25 active and 31 with a history of ulcer; 13 gastric ulcers: nine active and four with a history of ulcer) or gastritis (43) were included in an open, randomized, controlled trial. H. pylori infection was initially detected by CLO-test and histology on antral and corpus biopsies. H. pylori-positive patients were randomized to receive L plus clarithromycin (C) 250 mg b.d. plus tinidazole (T) 500 mg b.d. (LCT) or RBC plus C 250 mg b.d. and T 500 mg b.d. for 7 days (RbcCT). L or RBC were administered for a further 3 weeks in patients with active peptic ulcers. A second endoscopy was performed at least 6 weeks after the end of therapy for the assessment of H. pylori infection by CLO-test and histology. Eradication was assumed if all the tests were negative for H. pylori. RESULTS: Forty-eight patients in the LCT group and 4 5 in the RbcCT group were assessed for H. pylori eradication. The eradication rates, according to intention-to-treat (ITT) and per protocol (PP) analyses were, respectively, 76.8% and 89.5% for the LCT group, and 73.2% and 91.1% for the RbcCT group. No statistically significant difference in eradication rates was found between the two groups by Mantel-Haenszel test. All peptic ulcers were healed. In patients in whom H. pylori had been eradicated, the severity of gastritis was significantly reduced. Side-effects were rare. One patient in the LCT group and two in the RbcCT group were withdrawn because of adverse events. CONCLUSION: Short-term triple therapy with either lansoprazole or RBC is equally effective and well tolerated.
An elevated red blood cell (RBC) sodium-lithium countertransport (Na-Li CT) is associated with high blood pressure (BP) in cross-sectional investigations; however, its value as a predictor of future hypertension, and thus of cardiovascular risk, has not been defined. The present study evaluated the association between Na-Li CT and risk of future hypertension in a sample of 106 untreated normotensive middle-aged men participating in the Olivetti Prospective Heart Study in southern Italy. BP, anthropometric and metabolic variables, and RBC Na-Li CT were measured at baseline in 1987 and at a follow-up visit in 1994 through 1995. Na-Li CT was stable over time (r=0.85) and was significantly associated to systolic BP in both visits. Of the 106 initially normotensive participants, 14 were found to be hypertensive at the 8-year follow-up examination. Eleven of these 14 hypertensives were in the highest tertile of systolic BP at baseline, and 9 of 11 also had an elevated baseline Na-Li CT. In multiple logistic regression analysis, baseline BP, Na-Li CT, and age were all significant predictors of the risk of future hypertension. Individuals with baseline systolic BP in the highest tertile had a 60% risk of developing hypertension if their Na-Li CT was also high, whereas their risk was only 5% if Na-Li CT was in the two lowest tertiles (P=0.003). RBC Na-Li CT was a valuable predictor of subsequent hypertension in middle-aged men with a high-normal BP level for their age.