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Biomedical subjects

M Sala

Publications and source records attributed to M Sala.

At least 73 records · Page 4Linked to original sources

Organochlorine in the serum of inhabitants living near an electrochemical factory.

OBJECTIVES: To measure the impact of occupational and lifestyle factors on concentrations of organochlorine compounds in a general population sample living near an electrochemical factory with a high airborne concentration of hexachlorobenzene (HCB). METHODS: Serum samples from 608 people (328 selected from a random sample) were collected in 1994. Information on lifestyles, occupation, and medical condition was obtained by questionnaire. RESULTS: HCB and polychlorinated biphenyls (PCBs) were detected in all samples (means 36.7 ng/ml and 4.3 ng/ml respectively), followed by dichlorodiphenyl dichloroethane (DDE) and beta-hexachlorocyclohexane (beta-HCH), found in 98.7% and 87.3% of the samples respectively (means 4.6 ng/ml and 2.5 ng/ml, respectively). Concentrations of HCB were the highest ever reported. Occupation in the factory was the main determinant of the variation in concentrations of HCB (regression coefficients 1.52 (SEM 0.14) in 1n (HCB) for workers in the production department, and 2.13 (0.23) for workers in maintenance department) and explained the highest concentrations of HCB found in men of middle age. In retired workers, concentrations of HCB declined with time since retirement. The PCBs, dichlorodiphenyl trichloroethane (DDT), and beta-HCH were independent of the occupation and concentrations were similar to those found in other populations. Concentrations of beta-HCH and DDE in the whole population, and HCB among non-workers, were higher in women than in men. Concentrations of all measured organochlorine compounds increased with age and body mass index. Consumption of locally caught fish was an independent determinant of HCB and PCB concentrations. CONCLUSIONS: This population incorporated HCB directly through occupation in the electrochemical factory, by airborne pollution, and consumption of locally caught fish. Concentrations of other common organochlorine compounds were not higher than expected. Environmental exposures to these compounds deserve attention due to their persistence and potential health effects.

Adolescent↗

Vertebral fracture in a fused spine for scoliosis. A case report.

STUDY DESIGN: A case report. OBJECTIVES: To document a fracture of the 11th thoracic vertebra after spine fusion for adult idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Three cases of vertebral fractures associated with spine fusion for scoliosis were found in the literature. METHODS: Medical and radiologic records and related literature were reviewed. RESULTS: A 30-year-old woman had undergone anterior and posterior fusion with Cotrel-Dubousset instrumentation for progressive idiopathic scoliosis. Two years after surgery, she was in a car accident. A radiographic study and computer tomographic scanning depicted a fracture of T11 and bending of the rods. Observation was instituted and symptoms resolved. CONCLUSIONS: Fracture of a vertebra within an extensive spine fusion for scoliosis is rare. The 360 degrees solid fusion together with strong posterior instrumentation may have had some protective effect in this patient.

Adult↗

Long-lasting antiamnesic effect of a novel anticholinesterase inhibitor (MF268).

In the present study a short (120 min) and long-lasting (360 min) antagonism of scopolamine-induced amnesia in rats was investigated in an eight-arm radial maze, by (3a S, 8a R)-1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo[2,3-b]indol-5-o l[8-(cis2,6-dimethyl-morpholin-4-yl)octyl]-carbamate L-bitartrate hydrate (MF268), a new cholinesterase inhibitor. Upon completing the training session, the rats were orally administered increasing doses of MF268 (2, 3, 6, 7, and 8 mg/kg) 60 min prior to s.c. injection of scopolamine (0.25 mg/kg). Following a further 60 min the rat was placed in the maze. The reversal of scopolamine-induced impairment was characterized by an inverted U-shaped dose-response curve. A significant reduction in the number of errors, and time taken to complete the maze was observed with a dose of 6 mg/kg. The compound improved memory retention without affecting scopolamine-induced hypermotility. When the same dose was administered 360 min prior to the test a significant reduction in the number of amnesic animals was observed, whereas no cognitive improvement was detected when either 1-Benzil-4-[(5,6-dimethoxy-1-indanon)-2-yl]-methyl piperidine hydrochloride (E2020) (0.25 mg/kg) or tacrine (0.5 mg/kg) were administered 360 min prior to the test. The kinetics of whole-brain cholinesterase confirmed the long-lasting activity for MF268. A clinical relevance for the use of MF268 in AD treatment is suggested.

Amnesia↗

A novel method for self-administering addicting drugs intracerebroventricularly in a free-choice procedure.

This paper describes a safe method for long term intracerebroventricular (i.c.v.) drug administration. Employing a non-preferred lever to control the self-administration the technique offers advantages over existing experimental methods. To check for any innate preference for one of two levers, male Wistar rats were allowed during the training procedure, to press two levers (L1 and L2) for one hour/day to obtain water as reinforcer for one week in a continuous reinforcement schedule (CRF). One week after surgery, during which a double-guide stainless steel cannula was inserted into both lateral ventricles, rats received 2 microliter of sterile cerebrospinal fluid (CEPH) each time they pressed one of two levers during the daily one-hour session. When a stable baseline was reached, rats were divided into three groups on the basis of their lever preference, and submitted to the testing procedure. A potent mu-opiate receptor agonist, etonitazene (0.1-0.2-1 microgram/infusion), was always associated with the non-preferred lever for each rat. When no obvious preference was shown for either lever the opiate was firstly delivered by L1(for 11 days) and then by L2 (for 20 days). The results indicate that, regardless of which lever had been preferred initially, the rats increased the pressing of only the lever associated with the opiate. The daily amount taken increased linearly and was behaviorally active. This model highlights for the first time the reinforcing properties of drugs given i.c.v. in a free-choice situation.

Analgesics, Opioid↗

A death certificate-based study of occupation and mortality from reproductive cancers among women in 24 US states.

We conducted a study of occupation and mortality from reproductive cancers among women, based on death certificates from 24 US states for the period 1984-1993. There were 9,523 cervical cancer deaths, 12,335 endometrial cancer deaths, and 25,212 ovarian cancer deaths. Usual occupation and industry, which were obtained from death certificates, were coded using the 1980 Bureau of Census classification system. Mortality odds ratios (MORs) and 95% confidence intervals (CIs) were calculated, using all non-cancer deaths as the referent disease category. In general, jobs involving professional or administrative occupations were related to increased risk of mortality from endometrial and ovarian cancer, while cervical cancer mortality was increased among women employed in manufacturing, service, farm work, and health care technician and aide occupations. Associations with some occupations involving exposure to chemicals and metals, such as the associations between cervical cancer and employment in printing, typesetting, and machine operating occupations, deserve further attention. Similarly, further investigations should be made into the excess of ovarian cancer observed in several occupations in health care, an industry that has numerous hazardous exposures, including radiation, chemotherapeutic drugs, and viruses. The study results reflect, in part, socioeconomic factors and reproductive patterns but may also indicate a possible etiologic role for occupational chemical exposures.

Adult↗

Cancer risk in the rubber industry: a review of the recent epidemiological evidence.

OBJECTIVES: To examine the recent epidemiological evidence on cancer risk among workers in the rubber industry. METHODS: Epidemiological studies published after the last detailed review by the International Agency for Research on Cancer (IARC) in 1982 were reviewed. 12 cohort studies in nine countries that examined distinct populations of workers in the rubber industry, seven industry based nested case-control studies, 48 community based case-control studies in 16 countries, and 23 studies based on administrative data that reported risks for employment in the rubber industry were identified. RESULTS: Excess risks of bladder cancer, lung cancer, and leukaemia were found in most studies, with risks above 1.5 in about half of the studies. A moderate excess risk for laryngeal cancer was consistent across studies. Excess risks were found in a few studies for cancers of the oesophagus, stomach, colon, liver, pancreas, skin, prostate, kidney, brain, and thyroid, and for malignant lymphoma and multiple myeloma, but overall results were not consistent for these neoplasms. CONCLUSIONS: Magnitude of the observed risks varied considerably between studies, but overall the findings indicate the presence of a widespread moderate increased cancer risk among rubber workers. The most consistent results were for bladder, laryngeal, and lung cancer and for leukaemia. Excess risks were also found for other neoplasms but an evaluation of the consistency of the findings is difficult because of the possible selective reporting of results. Recent studies do not provide information associating specific exposures with cancer risk. The preventive measures taken in the rubber industry in recent years may decrease risks, but this has not been documented yet in epidemiological studies.

Case-Control Studies↗

[Screening for colorectal cancer in Catalonia. Results of a population survey].

BACKGROUND: In recent years, the usefulness of programs for the prevention of colorectal cancer has been demonstrated in the general population as well as on specific risk groups. However, its implantation rate is unknown in our area. This study was aimed at evaluating the level of introduction of colorectal cancer screening. METHOD: A telephonic survey has been carried out using a pre-established questionnaire to find out if the interviewed had undergone a fecal occult blood test, digital rectal examination, barium enema and/or colorectal endoscopy with the final aim of colorectal cancer prevention. Moreover, the knowledge of both above mentioned explorations and the colorectal cancer clinical manifestations have also been evaluated. Individual characteristics determining these aspects have also been investigated. RESULTS: Only two (0.8%) of the 250 subjects included had undergone a screening procedure (digital rectal examination). In contrast, in female population, 142 women (82%) had been included in a surveillance program to detect early signs of breast or gynecological cancer. In addition, a low level of knowledge of these explorations has been observed (digital rectal examination: 58%; colorectal endoscopy: 56%; barium enema: 44%; fecal occult blood test: 41%). This low level was also observed regarding to clinical manifestations associated with colorectal cancer. CONCLUSIONS: In contrast with gynecological cancer, colorectal cancer screening has not yet been introduced in Catalonia. Moreover, the knowledge of the available information regarding to preventive strategies is very low.

Adult↗

Polydeoxyribonucleotide (defibrotide) protects against post-ischemic behavioral, electroencephalographic and neuronal damage in the gerbil.

The effectiveness of defibrotide, a single-stranded polydeoxyribonucleotide compound, in preventing damage caused by cerebral ischemia was studied. Global ischemia was induced in anesthetized gerbils by bilateral carotid artery occlusion for 10 min. Defibrotide (100 mg/kg) or saline was injected, i.v., immediately after reperfusion. The following parameters were evaluated simultaneously: (1) electroencephalographic (EEG) spectral power, recorded before, during and after the ischemic period; (2) body temperature, monitored with a rectal thermistor probe after reperfusion for 120 min; (3) spontaneous motility, evaluated through a photocell system and quantified in terms of total distance travelled in 30 min, 1 h after recirculation and at periods over 15 days; (4) mnemonic functions assessed by passive avoidance test from 3 to 15 days after ischemia; (5) histological examination, 7 days after reperfusion, counting CA1 hippocampal neuronal cells. The ischemia-induced complete flattening of spectral power was significantly reversed (P < 0.01) by post-ischemic treatment with defibrotide between 30 and 90 min after ischemia. A complete recovery of total EEG spectral power was seen in the defibrotide group at 6 h and the saline ischemic group at 1 day. Seven days after bilateral carotid occlusion, there was a significant decrease in spectral power (-70% +/- 6) together with a loss of the number of CA1 cells in the saline ischemic group (-64%). Treatment with defibrotide significantly protected against the decrease in spectral power (-30% +/- 7) and cell loss (-9%). Finally, the number of animals found to be protected against the ischemia-induced flattening was significantly larger for defibrotide-treated gerbils than for saline-treated animals throughout the experiment except for the third day. Body temperature was significantly decreased only at 30 min after reperfusion in both ischemic and sham-operated groups. Defibrotide reduced ischemia-induced hypermotility but only 6 h after the insult. The ischemia-induced impairment of memory was partially reversed within 3 days in the defibrotide-treated animals and fully reversed within 7 days in the defibrotide group and 15 days in the saline group. Our results demonstrate that defibrotide, even when administered after the post-ischemic period, possesses anti-ischemic properties. The mechanism by which defibrotide protects the ischemic reperfused brain is still largely unknown. However, a neuroprotection via adenosine A1 and A2 subtype receptor interaction can be put forward.

Animals↗

Ultrasonography-detected macroregenerative nodules in cirrhosis: a prospective study.

BACKGROUND & AIMS: The preneoplastic role of macroregenerative nodules in cirrhosis is still debated. Thirty-two consecutive ultrasonography-detected macronodules were followed up to evaluate whether and which lesions are the actual precursors of hepatocellular carcinoma, if histology can identify preneoplastic macronodules, and whether additional parameters are related to neoplastic evolution. METHODS: Macroregenerative nodule classification was based on recently proposed histological criteria. Extranodular liver cell dysplasia was also evaluated. The follow-up included ultrasonography and serum alpha-fetoprotein level determination every 3 months. RESULTS: Twenty-two macronodules (78%) were classified as typical and 7 (22%) as atypical. Twenty-one were hypoechoic, and 11 were hyperechoic. Extranodular dysplasia was more frequently associated with atypical than typical macronodules (5 of 7 vs. 6 of 22). After 28 +/- 15 months, neoplastic transformation occurred in 8 macronodules (25%) and was more frequent in atypical than in typical (5 of 7 vs. 3 of 25), in hyperechoic than in hypoechoic (5 of 11 vs. 3 of 21), and in extranodular dysplasia-associated macronodules than in extranodular dysplasia-free macronodules (5 of 11 vs. 2 of 18). Five hepatocellular carcinomas appeared outside the original macronodule. CONCLUSIONS: Atypical macroregenerative nodules can be considered precursors of hepatocellular carcinoma. Histology is useful in identifying preneoplastic macronodules, and hyperechoic pattern and extranodular dysplasia are additional risk factors for neoplastic transformation.

Aged↗

Naltrexone, naltrindole, and CTOP block cocaine-induced sensitization to seizures and death.

I.c.v. injection for 9 days of either naltexone (NTX) (5, 10, 20, 40 micrograms/rat) or a selective mu peptide (CTOP) (0.125, 0.25, 0.5, 1, 3, 6 micrograms/rat) or delta (naltrindole) (NLT) (5, 10, 20 micrograms/rat) subtype opioid receptor antagonist affected sensitization to cocaine (COC) (50 mg/kg, i.p.) administered 10 min after. NTX (5 and 40 micrograms/rat), NLT (10 and 20 micrograms/rat), and the peptide CTOP (0.25-0.5 microgram/rat) attenuated seizure parameters (percent of animals showing seizures, mean score and latency) in a day-related manner. The DD50 (days to reach 50% of death) value for COC was 2.69, whereas it was 9.67 and 7.27 for NTX 5 and 40 micrograms/rat, 8.59 for NLT (10 micrograms/rat), and 6.11, 5.95, and 4.30 for CTOP (0.25, 0.5, and 1 microgram/rat respectively). These findings suggest a concurrent involvement of mu- and delta-opioid receptor subtype in COC-induced sensitization to toxic effects.

Animals↗

Effect of nedocromil sodium on bronchial hyperreactivity in children with nonatopic asthma.

BACKGROUND AND OBJECTIVES: Although cromones inhibit immediate bronchial responses to both allergen and nonspecific challenge, their effectiveness in treating nonatopic childhood asthma is unknown. We therefore investigated a possible effect of nedocromil sodium on bronchial hyperreactivity and asthmatic symptoms in a group of children receiving this drug for nonatopic asthma. STUDY DESIGN AND METHODS: A double-blind, placebo-controlled, randomized trial of two parallel groups was carried out in our pediatric respiratory disease clinic. Twenty children with mild, nonatopic asthma hyperreactive to fog-induced challenge were treated with inhaled nedocromil sodium 16 mg each day for 6 weeks (group N) or with a placebo (group P). Five girls and five boys (7 to 13 years of age) were randomly assigned to group N, and three girls and seven boys (aged 6 to 16 years) to group P. Symptoms and bronchodilator use were reported on diary cards. Ultrasonic nebulized distilled water PD10 was measured administering increasing doses of nebulized distilled water (2.5, 5, 10, 20, and 40 L). RESULTS: Symptom scores were significantly affected by the active treatment. Baseline lung function was normal and remained unaltered after treatment with nedocromil sodium. Nonspecific reactivity was significantly reduced over time only in the active treatment group. CONCLUSIONS: Nedocromil sodium can reduce the severity of asthmatic symptoms and nonspecific bronchial hyperreactivity at fog-induced challenge in children with stable, nonatopic asthma.

Adolescent↗

Metabolism of hexachlorobenzene in humans: association between serum levels and urinary metabolites in a highly exposed population.

Serum and urine from 100 subjects of a general population highly exposed to airborne hexachlorobenzene (HCB) were analyzed to obtain new insights into the metabolism of this ubiquitous compound. HCB was detected in all serum samples with concentrations ranging between 1.1 and 953 ng/ml. The major known metabolites of HCB were investigated in urine collected over 24 hr. Pentachlorophenol (PCP) was detected in all urines with values ranging between 0.58 and 13.9 micrograms excreted in 24 hr [mean +/- standard deviation (SD), 2.52 +/- 2.05; geometric mean, 2.05]. A sulfur derivative that, after hydrolysis, yielded pentachlorobenzenethiol (PCBT) could also be identified and quantified in all the urines with values ranging between 0.18 and 84.0 micrograms of PCBT excreted in 24 hr (mean +/- SD, 3.47 +/- 10.8; geometric mean, 1.39). The sulfur derivative assessed as PCBT appeared to be the main metabolite, with urinary concentrations surpassing those of PCP in the subjects with higher HCB accumulation (HCB in serum > 32 ng/ml). PCBT concentration in urine collected over 24 hr showed a very strong association with HCB concentration in serum; the association was stronger in males than in females. An increase of 1 ng/ml of HCB in serum led to an increase of 2.12 micrograms of PCBT excreted in urine collected over 24 hr in males (95% CI, 1.82-2.44) and to an increase of 0.67 microgram of PCBT in females (CI, 0.33-1.09). A weaker association was found between PCP in urine and HCB in serum, which was only statistically significant in males (an increase of 1 ng/ml of HCB in serum led to an increase of 0.63 microgram of PCP excreted in urine collected over 24 hr; (CI, 0.34-0.95). These results show that the formation of the cysteine conjugate is a quantitatively more important metabolic pathway in humans than the formation of PCP. Moreover, the association found suggests that PCBT is a good urinary marker of HCB internal dose and glutathione-mediated metabolism.

Air Pollutants↗

Effects of nedocromil sodium on the oxidative burst of polymorphonuclear leukocytes: comparison with salbutamol.

The effects of nedocromil sodium and of salbutamol on the generation of oxygen-derived free radicals in human polymorphonuclear leukocytes (PMNs) were compared in vitro by the luminol-amplified-chemiluminescence (LACL) assay induced by both particulate (Candida albicans) and soluble formyl-methionyl-leucyl-phenylalanine (fMLP) stimulants. Inhibitory dose-effect linear regressions were observed from 10(-3) to 10(-8) M for nedocromil and salbutamol after a 3' period of incubation with either C. albicans or fMLP. There was a linear regression with nedocromil sodium after 30' incubation, but desensitization was observed with salbutamol after this longer period of incubation. The generation of oxygen-derived free radicals was significantly greater for asthmatic patients than for normal subjects; therefore antiasthmatic drugs with this inhibitory activity could be an extra pharmacological benefit in the treatment of asthmatic patients.

Albuterol↗

[Clinical response and survival in metastatic renal carcinoma during subcutaneous administration of interleukin-2 alone. Subcutaneous Il-2 in renal carcinoma].

Several clinical studies have demonstrated the efficacy of subcutaneous immunotherapy with Il-2 alone in metastatic renal cell carcinoma (RCC). In an attempt to better define the clinical parameters which may predict the efficacy of treatment, the present study shows the results obtained with subcutaneous Il-2 alone in 91 evaluable metastatic RCC patients. IL-2 was injected subcutaneously at 3 million IU twice/day for 5 days/week for 6 weeks, corresponding to one immunotherapeutic cycle. In nonprogressing patients, a second cycle was given after 28-day rest period. A complete response (CR) was achieved in 2/91 patients. Moreover, 19/91 patients had a partial response (PR). Therefore, objective response (OR) rate was 21/91 (23%) patients. Stable disease (SD) was achieved in 41 patients, while the remaining 29 patients had a progressive disease (PD). OR rate was significantly higher in patients with a long disease-free survival than in patients with synchronous metastases, in nephrectomized patients than in the non-nephrectomized ones, and in patients with high than in those with low PS. The survival obtained in patients with CR or PA was significantly longer with respect to that found in patients with SD or PD. The toxicity was substantially low in all patients. This study confirms that the subcutaneous immunotherapy with IL-2 alone is an effective and well tolerated therapy of metastatic RCC.

Adult↗

Acute pancreatitis after long-term 5-aminosalicylic acid therapy.

Acute pancreatitis is a known, although rare, complication of mesalamine treatment. This complication typically appears within the first days or weeks after initiation of therapy. We describe two cases of acute pancreatitis that occurred after long term mesalamine therapy for ulcerative colitis. A rechallenge, performed in both patients, confirmed the diagnosis of mesalamine-induced pancreatitis. These case reports provide evidence that 5-aminosalicylic acid may induce acute pancreatitis after long term treatment.

Acute Disease↗

Impact of abomasal nematodes on roe deer and chamois body condition in an alpine environment.

Abomasal helminths were examined from 101 roe deer and 43 chamois, shot or found-dead, in the period July-November 1993-95, in the Parco Naturale Paneveggio Pale di San Martino (Italian Eastern Alps). Twelve helminth species were observed in both roe deer and chamois. For both host species, discriminant analysis, using the abundance of each parasite species in the hosts, failed to distinguish between subjects from each of the three study years. For 44 roe deer and 27 chamois data on body weight, body length, foot length, withers height, thoracic circumference and kidney fat index were also available. Principal Component Analysis was performed on the biometrical data in order to group related variables into a few compound variables. In both host species it was possible to identify two principal components, with an explained variance > 80%: the first component, led by body length, was an expression of skeletal development and the second, led by kidney fat index, of nutritional status. Parasite abundance and richness appeared to be negatively correlated with the scores of both skeletal and nutritional Components in the two host species, although only the correlation between parasite abundance and the scores of the nutritional component in roe deer was statistically significant (Spearman r = -0.411; p < 0.05). These results support the susceptibility of roe deer to abomasal helminths, which could be important considering the spatial and nutritional interspecific competition between domestic and wild ruminants often recorded in alpine environments.

Abomasum↗