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Biomedical subjects

M Sala

Publications and source records attributed to M Sala.

At least 55 records · Page 3Linked to original sources
PubMed2000

Randomized controlled trial of interferon treatment for advanced hepatocellular carcinoma.

The aim of this randomized controlled trial was to assess the efficacy of interferon alfa-2b (IFN) for the treatment of advanced hepatocellular carcinoma (HCC). Fifty-eight patients with HCC who were not suitable for resection, transplantation, ethanol injection, or arterial embolization were stratified according to their Okuda stage and randomized to receive IFN (3 x 10(6), 3 times a week, for 1 year) (n = 30) or symptomatic treatment (n = 28). Both groups were identical in terms of age, sex, performance status, presence of constitutional syndrome, Child-Pugh class, Okuda stage, multinodularity, portal thrombosis, and extrahepatic spread. Adhesion to IFN treatment was adequate in 27 patients, with a mean duration of treatment of 8 +/- 3 months. However, IFN treatment was associated with side effects in 23 patients, leading to treatment discontinuation in 13 patients. Two of the 30 patients (6.6%) presented a partial response with greater than 50% size reduction and normalization of alpha-fetoprotein levels. The survival at 1 and 2 years according to intention to treat was not different between the 2 groups (58% and 38% vs. 36% and 12%, respectively, Breslow P =. 19, log rank P =.14) and the absence of difference was maintained when dividing patients according to their Okuda stage. The probability of presenting tumor progression (P =.17), or deterioration of Child-Pugh class (P =.37), performance status (P =. 07), or Okuda stage (P =.44) was not modified by IFN treatment. These results indicate that IFN is not properly tolerated in patients with cirrhosis and advanced HCC and that its administration prompts no benefit in terms of tumor progression rate and survival.

Aged↗
PubMed2000

Excitatory and inhibitory effects of second-generation cholinesterase inhibitors on rat gastrointestinal transit.

We investigated the influence of increasing oral doses of second generation acetylcholinesterase inhibitors (AChEI) such as tacrine (0.25, 0.5, 1, 2, 3, 4, 10, and 20 mg kg(-1)), eptastigmine (0.5, 4, 8, 12, 20 and 40 mg kg(-1)) and E2020 (0.18, 0.25, 0.5, 1, 2, 3, 4 and 10 mg kg(-1)) on the distance travelled by a charcoal meal administered 30 min after each compound, in comparison with physostigmine (0.5, 1, 2, 4, 8 and 12 mg kg(-1)). An inverted U regression was observed with a significant parabola between the centimetres travelled and the log of the doses for all AChEI. The maximal stimulating doses (mg kg(-1)) were 2 for physostigmine, 4 for eptastigmine, 3 for tacrine and E2020, while the inhibitory doses were 12 for physostigmine, 40 for eptastigmine, 20 for tacrine and 10 for E2020. The stimulating and inhibiting effects on gastrointestinal propulsion were significantly reversed by 0.25 mg kg(-1)of scopolamine hydrobromide. A dose of scopolamine hydrobromide (0.06 mg kg(-1)) or methylbromide (0.25 mg kg(-1)), pirenzepine dihydrochloride (0.25 mg kg(-1)) and mecamylamine hydrochloride (0.5 mg kg(-1)), which per se did not affect gastrointestinal propulsion, antagonized both the stimulating and inhibitory effect of eptastigmine. Thus, the biphasic effect is peripherally mediated through both muscarinic (at least M(1)) and nicotinic receptors.

Administration, Oral↗
PubMed2000

Eptastigmine improves eight-arm radial maze performance in aged rats.

Eptastigmine, a potent and long-lasting cholinesterase inhibitor on age-related memory deficits, was studied. Four groups of 3-, 18-, 23- and 27-month-old Wistar rats were first submitted to spontaneous motor activity evaluation and then trained in an eight-arm radial maze until they reached the criterion. The effect of introducing a 2-h delay between the fourth and fifth choices was then evaluated under the influence of acute oral dose of eptastigmine (0.5 mgkg(-1)) 120 min before the test. Eptastigmine reversed the impairment observed in vehicle-treated rats at all the tested ages. Two naive groups of 3- and 18-month-old rats were treated twice a day for 30 days with eptastigmine ( 0.25 mgkg(-1)p.o.) or vehicle and trained daily in the maze. Subchronic administration did not affect the performance in young rats, while in 18-month-old rats, the mean number of days needed to reach the criterion decreased and the percentage of animals reaching the criterion increased when compared to the vehicle group. The 18-month-old rats (ex-eptastigmine and ex-vehicle) were then allowed to age in their home cage without any further treatment for an additional 5 and 9 months, until they reached 23 and 27 months. The ex-eptastigmine rats tested at 23 months, without any treatment, showed better performance than that observed in ex-vehicle rats. When the same rats were tested again at 27 months of age, no difference was seen in comparison with ex-vehicle rats. Eptastigmine might, therefore, be helpful for correcting age-related memory impairment attributed to cholinergic hypofunction.

Animals↗
PubMed2000

Eptastigmine restores the aged rat's normal cortical spectral power pattern.

We studied the ability of eptastigmine, a second-generation acetylcholinesterase inhibitor (AChEI), to reverse the age-related increase of electroencephalogram (EEG) mean cortical spectral power in slow-wave delta activity and decrease in fast-wave alpha and beta activity. The relative basal spectral power profile evaluated for 50 min of the old (27-30 months) in comparison to young (4-6 months) awake rats was consistently different, showing a significant increase in delta(0.2-4.0 Hz) frequency and a significant decrease of alpha(8.2-13.0 Hz) and beta(13.2-25.0) bands. When 0.5, 1, 2, 4 mg kg(-1)of eptastigmine were administered orally as single increasing doses for old and young rats 2 h prior to the EEG recordings, lasting 2 h, the relative mean spectral power difference (Delta%) showed a linear log dose-related decrease in delta activity and a progressive increase in alpha and beta activity in old rats. Compared to vehicle, in young rats, the eptastigmine dose of 0.5 mg kg(-1)produced a significant decrease in delta activity and an increase in beta activity. The spontaneous motor activity, evaluated through cumulative horizontal and vertical counts for 30 min in old rats was significantly decreased when compared to young rats. Single oral treatment with eptastigmine (0.5 mg kg(-1)for young and 2 mg kg(-1)for old rats) given 2 h before the test did not significantly change motor activity in comparison to vehicle group of the same age. These results suggest a possible strategy to alleviate the severe slowing of neocortical EEG accompanying the cognitive decline.

Administration, Oral↗
PubMed2000

Are RNA viruses adapting or merely changing?

RNA viruses and retroviruses fix substitutions approximately 1 million-fold faster than their hosts. This diversification could represent an inevitable drift under purifying selection, the majority of substitutions being phenotypically neutral. The alternative is to suppose that most fixed mutations are beneficial to the virus, allowing it to keep ahead of the host and/or host population. Here, relative sequence diversification of different proteins encoded by viral genomes is found to be linear. The examples encompass a wide variety of retroviruses and RNA viruses. The smoothness of relative divergence spans quasispeciation following clonal infection, to variation among different isolates of the same virus, to viruses from different species or those associated with different diseases, indicating that the majority of fixed mutations likely reflects drift. This held for both mammalian and plant viruses, indicating that adaptive immunity doesn't necessarily shape the relative accumulation of amino acid substitutions. When compared to their hosts RNA viruses evolution appears conservative.

Adaptation, Physiological↗
PubMed2000

Prevalence and prognostic value of hepatocellular carcinoma in cirrhotic patients presenting with spontaneous bacterial peritonitis.

BACKGROUND/AIMS: This study examined the prognostic power of hepatocellular carcinoma in patients presenting an episode of spontaneous bacterial peritonitis treated with 3rd generation cephalosporins or quinolones, and subsequent prophylaxis with norfloxacin until death or transplantation. METHODS: The study comprises the prospective evaluation of 168 consecutive cirrhosis patients presenting an episode of spontaneous bacterial peritonitis. RESULTS: Hepatocellular carcinoma was diagnosed in 35 out of the 168 (20%) patients included in the study (10 single; 25 advanced tumors). Renal impairment developed in 82 patients. Resolution of infection was achieved in 90% of the cases, the hospital survival being 70%. Renal impairment, advanced tumor stage, albumin, and GGT showed independent prognostic value for hospital mortality. At the end of follow-up 101 patients had died, the 1- and 2-year survival being 36% and 31%, respectively. Four variables independently predicted survival: advanced tumor (OR: 3.9; p=0.00001), renal impairment (OR: 2.1; p=0.00001), bilirubin (OR: 1.6; p=0.02) and creatinine (OR: 1.3; p=0.03). Advanced tumor retained independent predictability in patients surviving hospitalization (OR: 7.5; p=0.0001), the 6-month survival being significantly lower in patients with advanced tumor (12% vs 57%, p<0.00001). CONCLUSION: The prevalence of hepatocellular carcinoma in cirrhotic patients with spontaneous bacterial peritonitis is high, and its presence should be actively sought. Advanced tumor impairs both hospital and long-term survival, and should be considered in the design of future trials.

Aged↗
PubMed2000

A phase II trial of cyclophosphamide, epirubicin and vinorelbine in the treatment of advanced breast cancer.

BACKGROUND: Vinorelbine (Navelbin; N) has proven to be active in patients with advanced breast cancer (ABC) and cyclophosphamide (C) and epirubicin (Epiadriamycin: E) are still among the main cytostatic agents against this tumor. On this basis was carried out a study to determine the activity and toxicity of the combination of these three agents (CEN). PATIENTS AND METHOD: From April 1996 to March 1998, 59 patients with ABC were recruited of whom 56 were found eligible and evaluable for toxicity and 55 for activity. The treatment regimen was C: 400 mg/m2, E: 30 mg/m2 and N: 25 mg/m2 administered intravenously on days 1 and 8 of a 28-day cycle. RESULTS: The median number of cycles administered was 6 (range: 1-16). The most common hematological toxicity was grade (G) 3 and 4 neutropenia occurring in 36% of patients, associated with fever in 7% of them. Grade 3-4 thrombocytopenia and anemia occurred in 5% and 7%, respectively. Other G2-G3 non hematologic toxicities were: N/vomiting in 34%, alopecia in 73% and mucositis in 11% of patients. An objective response was achieved in 28 of 56 patients (50%) (95% confidence interval (CI): 37-63%): complete response (CR) in 9%, partial response (PR) in 41%. The median duration of response, time to progression and overall survival time was 54, 47 and 90 weeks, respectively. CONCLUSION: The CEN combination at these doses and treatment schedule appears to have acceptable tolerability but there is no apparent improvement in therapeutic efficacy when compared to other regimens used as first line treatment in ABC.

Adult↗
PubMed2000

Coffee consumption and bladder cancer in nonsmokers: a pooled analysis of case-control studies in European countries.

BACKGROUND: Coffee consumption has been associated with an excess bladder cancer risk, but results from epidemiological studies are inconsistent. This association has been long debated, in part due to the potential confounding by smoking. We examined the risk associated with coffee consumption in nonsmokers in a pooled analysis of ten European bladder cancer case-control studies. METHODS: The pooled data set comprises 564 cases and 2929 hospital or population controls who had never smoked. They were enrolled in ten studies conducted in Denmark, Germany, Greece, France, Italy and Spain. Information on coffee consumption and occupation was re-coded following standard criteria. Unconditional logistic regression was applied adjusting for age, study center, occupation and gender. RESULTS: Seventy-nine percent of the study population reported having drunk coffee, and 2.4% were heavy drinkers, reporting having drunk on average ten or more cups per day. There was no excess risk in ever coffee drinkers (OR = 1.0, 95% CI 0.8-1.3) compared to never drinkers. The risk did not increase monotonically with dose but a statistically significant excess risk was seen for subjects having drunk ten or more cups per day (OR = 1.8, 95% CI 1.0-3.3). This excess was seen in both men and women. There was no evidence of an association of the risk with duration or type of coffee consumption. The pooled results were not dependent on the findings of any specific study, but they depended on the type of controls with an overall excess risk observed only for studies using hospital controls. CONCLUSION: Nonsmokers who are heavy coffee drinkers may have a small excess risk of bladder cancer. Although these results cannot be attributed to confounding by smoking, the possibility of bias in control selection cannot be discarded. On the basis of these results, only a very small proportion of cancers of the bladder among nonsmokers could be attributed to coffee drinking.

Bias↗
PubMed2000

Nonsurgical treatment of hepatocellular carcinoma.

1. Outcome from nonsurgical treatment is directly related to stage of hepatocellular cancer (HCC) and degree of liver function impairment. 2. Ablative percutaneous procedures, such as alcohol injection or radiofrequency thermal therapy, are most effective in the destruction of solitary tumors of 3 cm or less. 3. In most cases, nonsurgical treatments are not curative, but may slow tumor progression and can provide palliation. 4. Arterial embolization or chemoembolization has an antitumor effect, but it has not been shown to affect patient outcome. 5. Radiation therapy, chemotherapy, hormonal manipulation, and interferon have not been consistently effective in HCC. 6. Ablative procedures, embolization, and systemic chemotherapy should be avoided in patients with advanced cirrhosis.

Antineoplastic Agents↗
PubMed2000

Excretion of hexachlorobenzene and metabolites in feces in a highly exposed human population.

A set of 53 individuals from a population highly exposed to airborne hexachlorobenzene (HCB) were selected to study the elimination kinetics of this chemical in humans. The volunteers provided blood, 24-hr urine, and feces samples for analysis of HCB and metabolites. The serum HCB concentrations ranged from 2.4 to 1,485 ng/mL (mean +/- SD, 124 +/- 278), confirming that this human population has the highest HCB blood levels ever reported. All analyzed feces samples contained unchanged HCB (range, 11-3,025 ng/g dry weight; mean +/- SD, 395 +/- 629). The HCB concentration in feces strongly correlated with HCB in serum (r = 0.85; p < 0.001), suggesting an equilibrium in feces/serum that is compatible with a main pulmonary entrance of the chemical and low intestinal excretion of nonabsorbed foodborne HCB. The equilibrium is also compatible with a nonbiliary passive transfer of the chemical to the intestinal lumen. Two HCB main metabolites, pentachlorophenol (PCP) and pentachlorobenzenethiol (PCBT), were detected in 51% and 54% of feces samples, respectively. All urine samples contained PCP and PCBT, confirming the conclusions of a previous study [Environ Health Perspect 105:78-83 (1997)]. The comparison between feces and urine showed that whereas daily urinary elimination of metabolites may account for 3% of total HCB in blood, intestinal excretion of unchanged HCB may account for about 6%, thus showing the importance of metabolism in the overall elimination of HCB. The elimination of HCB and metabolites by both routes, however, appears to be very small (< 0.05%/day) as compared to the estimated HCB adipose depots. Features of HCB kinetics that we present in this study, i.e., nonsaturated intestinal elimination of HCB and excretion in feces and urine of inert glutathione derivatives, may explain, in part, the absence of porphyria cutanea in this human population heavily exposed to HCB.

Adolescent↗
PubMed2000

Serum concentrations of hexachlorobenzene in family members of workers in an electrochemical factory.

OBJECTIVES: This study analyzed the effect of living in the same household with a worker employed in an electrochemical factory on the hexachlorobenzene (HCB) concentrations of serum in the general population of Flix, Spain. METHODS: A total of 608 subjects from the general population (response rate 42%) completed a questionnaire about residence, occupation, life-styles, and medical history and provided blood samples. Among them, 412 had never worked in the electrochemical factory. Information about the occupation of the family members was completed, and the subjects were classified with the degree of relationship with the worker having been taken into account. A multiple linear regression analysis was conducted to model HCB serum for nonfactory workers. RESULTS: Having a spouse who worked in the factory was associated with elevated HCB concentrations in serum. The adjusted relative increases were 1.28 (P=0.0004) and 1.23 (P=0.0022) times the corresponding value of people not living with workers of the factory, respectively for spouses of current and past workers. Relatives other than spouses did not show any increase. CONCLUSIONS: The results of this study suggest that, among nonworkers, living with a worker of the electrochemical factory in Flix is associated with an increase in concentrations of HCB in blood. These findings may suggest a source of exposure to HCB that has thus far not been studied and that could be important in populations not occupationally exposed to organochlorines.

Adult↗
PubMed2000

[Does PSA density of the transition zone represent a useful parameter in the diagnosis of prostate carcinoma?].

Prostate specific antigen (PSA) has unequivocally proved its clinical usefulness ad a serum marker for prostate cancer. In order to enhance the specificity of serum PSA, several diagnostic parameters have been employed including PSA density of transition zone (TZ). The authors report their experience on the efficacy of PSA density TZ with level of PSA < 4 ng/ml, between 4-10 ng/ml, > 10 ng/ml, in the diagnostic of prostate cancer. The PSA density of TZ resulted uscless for PSA levels < 4 ng/ml, but improved the diagnostic specificity associated to PSA serum in the PSA levels ranging between 4-10 ng/ml and > 10 ng/ml.

Humans↗
PubMed1999

New case of the Richieri-Costa/Guion-Almeida syndrome.

We describe a boy with multiple congenital anomalies/mental retardation (MCA/MR) syndrome. He has growth retardation, microbrachycephaly, coloboma of the iris, and typical facial anomalies including cleft lip/palate. This phenotype overlaps with that described by Richieri-Costa and Guion-Almeida in three Brazilian brothers. The new patient provides further evidence of the existence of this rare clinical entity.

Abnormalities, Multiple↗
PubMed1999

Urinary porphyrin excretion in a human population highly exposed to hexachlorobenzene.

BACKGROUND: Data from an epidemic reported in Turkey (1955-1959) is the only information about the relationship between hexachlorobenzene (HCB) intake and porphyria cutanea tarda in humans. No information is available on the HCB threshold exposure level to induce porphyria cutanea tarda. OBJECTIVES: To study HCB serum levels and urinary porphyrin excretion in the inhabitants of a village located near an organochlorine compound factory with high HCB concentrations in the air and to detect possible alterations in urinary porphyrin excretion and examine their relationship with HCB serum levels. DESIGN: Cross-sectional study. SETTING: Unit of Porphyrias of a tertiary care facility in Barcelona, Spain. PARTICIPANTS: Six hundred four inhabitants of the village who were older than 14 years provided serum and urine samples (185 participants were factory workers). MAIN OUTCOME MEASURES: Serum HCB was analyzed by gas chromatography coupled to electron capture detection. Quantification of urinary total porphyrins was performed by spectrofluorimetry. Porphyrin profile was determined by high-pressure liquid chromatography. RESULTS: Hexachlorobenzene was detected in all serum samples (mean, 39.8 ng/mL; range, 1.1-1616.0 ng/mL), and levels were higher in factory workers. Mean +/- SD level urinary total porphyrin average concentration was 98 +/- 69 nmol/L (range, 9-1009 nmol/L). Only the urine sample with the highest porphyrin concentration showed an increase of highly carboxylated porphyrins, with a typical profile of porphyria cutanea tarda. In the remaining 603 urine samples, coproporphyrin was the predominant fraction. CONCLUSION: The airborne exposure to and increased body burden of HCB in the Flix village population are not enough to trigger a significant alteration of the heme biosynthesis pathway.

Adolescent↗
PubMed1999

Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials.

This study analyzed the natural history and prognostic factors of patients with nonsurgical hepatocellular carcinoma (HCC). Twenty variables from 102 cirrhotic patients with HCC who were not treated within prospective randomized controlled trials (RCT) were investigated through uni- and multivariate analyses. None of them was suitable for radical therapies (surgical resection, liver transplantation, or ethanol injection) or presented end-stage disease as reflected by an Okuda stage 3 or a Performance Status >/=3. Sixty-five patients were Child-Pugh A, 34 were B, and 3 were C. Most of them exhibited a preserved Performance Status Test (PST) (0 = 56; 1 = 38; 2 = 8). Tumor was solitary in 26 (</=5 cm in 16) and multinodular/massive in 76. After a median follow-up of 17 months, 79 patients died, the 1-, 2-, and 3-year survival being 54%, 40%, and 28%. The multivariate study identified PST (P =.01), constitutional syndrome (P =.04), vascular invasion (P =.001), and extrahepatic spread (P =.04) as independent predictors for mortality. The 1-, 2-, and 3-year survival for the 48 patients without adverse factors (Stage 0) was 80%, 65%, and 50%, respectively, and 29%, 16%, and 8% in the 54 patients with at least one adverse parameter (Stage I). Therefore, Stage 0 would correspond to an intermediate stage, while Stage I would represent an advanced status, before reaching an end-stage phase. In conclusion, the outcome of nonsurgical HCC is not homogeneously grim and may be predicted by assessing the presence of symptoms and of an invasive tumoral pattern. Therapeutic trials should be designed and evaluated considering these characteristics.

Adult↗
PubMed1999

Torsional stability of primary total knee replacement tibial prostheses: a biomechanical study in cadaveric bone.

The significance of torsional loads on the tibial component of total knee replacement prostheses is not clearly established. This study investigated the micromotion induced by torsion, under physiologic loads. Three forms of fixation were sequentially tested in cadaveric tibiae: press-fit, press-fit plus 4 peripheral corticocancellous screws, and horizontally cemented. The implanted tibia was loaded with an axial force between 0.5 and 2.2 kN and a cyclic torque of +/- 5 Nm. The relative motion between the prosthesis and the bone was measured. Our results show little difference between the 3 methods of fixation at high axial loads. At low axial loads, however, the press-fit prosthesis may permit micromotions high enough to interfere (theoretically) with bone ingrowth. Motion is reduced when the same prosthesis is augmented with screws. The cemented prosthesis produces the lowest average micromotion. Our study indicates that rotational micromotion is unlikely to contribute to the failure of ingrowth into the uncemented tibial prosthesis under normal physiologic loads. At low axial loads, which may be encountered in the immediate postoperative period, ingrowth may be compromised. Thus, initial rotational stability is an important consideration in uncemented total knee replacement design and postoperative management. In poor-quality tibiae, cementation may be the only method of fixation to provide sufficient torsional stability.

Adult↗