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M Lotti

Publications and source records attributed to M Lotti.

104 records · Page 6Linked to original sources

Neuropathy target esterase in human lymphocytes.

Measurement of neuropathy target esterase activity (NTE) in blood lymphocytes has been suggested as a possible biomonitor for organophosphate-induced delayed polyneuropathy. Human lymphocyte NTE was characterized in vitro according to the sensitivity to several organophosphate inhibitors, which was found similar to that of the nervous system enzyme. Methods for collection, storage, and processing of blood and the NTE assay are described (averaged coefficient of variation of the method is 8%). The mean (+/- SD) value of lymphocyte NTE activity in a caucasian population (108 healthy subjects) was 11.5 +/- 2.5 nMoles/min X mg of protein. No sex or age differences were detected. The averaged intraindividual coefficient of variation was 10.1%. These results suggest the feasibility of the test in clinical conditions, a sufficient reproducibility of the test, and a large interindividual variation. Appropriate baseline values are advisable when using the test to evaluate the effects of an occupational exposure to organophosphorus esters which may cause delayed polyneuropathy.

Adult↗

Toxicologic studies in a fatal overdose of 2,4-D, MCPP, and chlorpyrifos.

A death due to ingestion of 2,4-dichlorophenoxyacetic acid (2,4-D), 2-(2-methyl-4-chlorophenoxy) propionic acid (MCPP), and phosphorothioic acid O,O-diethyl O-(3,5,6-trichloro-2-pyridinyl)ester (chlorpyrifos) is reported. The clinical course, dose ingested, and plasma levels of the chemicals were compatible with previous fatalities due to the chlorophenoxyacetic acids. Chlorpyrifos concentrations and tissue cholinesterase and in esterase inhibitions indicated the presence of the organophosphate and its biochemical effect, but few cholinergic signs were observed clinically. Lymphocytic neurotoxic esterase activity was decreased for a limited period of time after ingestion. Postmortem nervous tissue neurotoxic esterase was also decreased. This association has not been demonstrated before in man. HPLC and GC/NPD methods for measuring chlorophenoxy acetic acids and chlorpyrifos, respectively, are presented.

2,4-Dichlorophenoxyacetic Acid↗

Promotion of peripheral axonopathies by certain esterase inhibitors.

Certain esterase inhibitors were found to exacerbate the clinical signs of polyneuropathy caused by various neurotoxic compounds and to delay the recovery from nerve crush. This phenomenon is referred to as promotion of axonopathies. The molecular target of promotion has not yet been identified. However, all known promoters are also inhibitors of neuropathy target esterase (NTE), the putative target of organophosphate neuropathy, but it has been shown that the target of promotion is unlikely to be NTE. Available data suggest that promoters might affect a target and a mechanism present in the nervous system that is not activated by axonal lesions. Promotion may be important to understand the physiological mechanism of nerve damage and repair. This finding also implies a changing perspective for the risk assessment of exposures to esterase inhibitors, some of which are used as pesticides and might be promoters.

Animals↗

Flexible sigmoidoscopy as a colorectal cancer screening test in the general population: recruitment phase results of a randomized controlled trial in Lombardia, Italy.

UNLABELLED: A two arm multicentre randomized controlled trial is in progress to evaluate the efficacy of flexible sigmoidoscopy (FS) as a screening test for colorectal cancer in the general population. AIMS: To determine the acceptance rate and feasibility of FS as a colorectal cancer screening test in average-risk asymptomatic volunteers. Average-risk, asymptomatic subjects, aged 55-64 years and assisted by 244 general practitioners (GPs) in Lombardy, Italy, were invited by postal questionnaire (PQ) to enter a study for the prevention of colorectal cancer and asked to indicate their interest in, and willingness to undergo, screening: those responding positively were randomized to the intervention or control arms. GPs were trained in colorectal cancer screening and proposed free FS to their patients randomized to the intervention arm. All sigmoidoscopies were performed by experienced endoscopists. Small polyps were removed at FS. Colonoscopy was indicated for high risk polyps (size more than 5 mm, more than two adenomas, villous histology, severe dysplasia or malignancy). 40,945 subjects were invited. 667 PQs were returned undelivered due to postal failure. 7,892 (19.59%) subjects responded, 2,116 of whom (26.81%) were not included, presenting 1 or more exclusion criteria. We randomized 5,778 volunteers and performed 1,582 sigmoidoscopies out of 2,885 subjects in the intervention arm (54.84% acceptance rate). Although the screening procedure had a good attendance rate in the intervention group, involvement of the people invited was lower than expected. Future FS screening programmes will require a keener focus on recruitment strategies, mainly with participation of GPs.

Colorectal Neoplasms↗

Neuropathy target esterase is not reduced in neural tissues of diabetic rats.

Marked (greater than 70%) reduction of the neuropathy target enzyme (NTE) shortly after exposure to organophosphorus compounds heralds the onset of delayed neuropathic damage in animals and humans. One previous study reported that lymphocyte NTE from diabetic patients was depressed by greater than 70%; such a reduction was considered to be a biological marker of diabetic polyneuropathy. To ascertain whether NTE from target tissues might be involved in diabetic neuropathy, we measured NTE activity in the brain, spinal cord and peripheral nerves of streptozotocin-diabetic rats. No reduction in NTE activity was detected in these neural specimens. Therefore, it is concluded that NTE is not involved in diabetic nerve damage and that the meaning of low NTE activity in peripheral lymphocytes of diabetic patients remains unclear.

Animals↗

[Biological monitoring and risk assessment].

Risk assessment in occupational medicine is the part of risk analysis where physicians also contribute. A risk is the probability of an adverse health effect and derives from the hazard posed by a given chemical and from exposure characteristics. Due to the complexity of this process, models are used in occupational medicine, where risk factors are identified and exposure estimated, combined with an understanding of the severity of possible effects. Theoretically, the advantages of biological monitoring are obvious. However, the paucity of available data on biological monitoring limits its uses. Moreover, the utilization of data on biological monitoring requires evaluation of their significance. Examples are discussed to highlight advantages and limitations of biological monitoring data in both hazard and risk assessments. They include exposure to polycyclic aromatic hydrocarbons, benzene, other carcinogens, paraquat and polychlorinated biphenyls.

Benzene↗

[Feasibility of exeresis. Controversial aspects in the surgery of carcinoma of the pancreas].

Pancreatic cancer has a dismal prognosis also after resection with a 5 years' survival of about 5% in operated patients. The main clinical issue in patients with a malignant tumour is to identify the ones that would benefit from a surgical treatment. Resectability of pancreatic cancer has not an absolute value and the possible advantages in terms of prognosis and quality of life should be balanced with surgical mortality and morbidity. For this reason the management of this disease involves a multidisciplinary approach and the surgeon should join with the other specialists in experienced oncology centers. En exhaustive evaluation of the following prognostic factors should be made pre and intra-operatively to better define life expectancy with or without resection: Histotype: endocrine tumours and cystadenocarcinoma have, in general, a better prognosis, Staging: JPS classification has a better prognostic value if compared to the UICC. Completeness of the resection. Biological characteristics of the tumour. The main variables to be considered for the exeresis are: Size and local growth of the tumour (also considering the involvement of vessels, retroperitoneum and pancreatic capsule). Liver or peritoneal metastases: for this laparoscopy has a key role for staging. Histologic confirmation: differential diagnosis with chronic pancreatitis is sometimes difficult and every attempt should be made to have a pre-operative histology. Vascular invasion is one of the main contraindications to surgery and an exhaustive evaluation of vascular involvement should be considered mandatory. Lymph nodal involvement, in general, represents a negative prognostic factor even if Japanese authors claim that a radical resection can be performed in case of positive nodes in the peripancreatic area, if a complete lymphadenectomy is carried out.

Carcinoma↗