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L Locatelli

Publications and source records attributed to L Locatelli.

At least 19 recordsLinked to original sources
PubMed2005

Long-term effects of intravenous high dose methylprednisolone pulses on bone mineral density in patients with multiple sclerosis.

To determine the effects of high dose methylprednisolone (HDMP) pulses on bone mineral density (BMD) in patients with multiple sclerosis (MS), we studied 25 MS patients who received regular pulses of HDMP as well as pulses of HDMP for relapses, 18 MS patients who received HDMP at the same dose schedule only for relapses, and 61 healthy controls. We measured BMDs at lumbar spine and femoral neck and we assessed biochemical markers of bone metabolism and turnover. The average lifetime dosage of MP was 75.4 (SD 11.9) g in the pulsed HDMP group and 28.6 (SD 18.3) g in the HDMP for relapses group (P < 0.0001). Two MS patients (4.7%) and four controls (6.6%) had osteoporosis (P = NS), whereas 25 patients with MS (58.1%) and 21 controls (34.4%) had osteopenia (P = 0.016). BMDs measured at lumbar spine and femoral neck and biochemical indices of bone metabolism did not differ in MS patients and controls. BMD measures were not associated with lifetime methylprednisolone dosage. In partial correlation analysis, controlling for age, gender and menopausal status there was a significant inverse correlation between BMD at femoral neck and Expanded Disability Status Scale (EDSS) score (r = -0.31, P = 0.05). In conclusion, treatment with repeated HDMP pulses was not associated with osteoporosis in patients with MS who participated in a trial of methylprednisolone. However, osteopenia was observed more frequently in MS patients than healthy controls. Our data are reassuring, as them suggest that repeated pulses of methylprednisolone do not result in substantially increased risk of osteoporosis in MS patients. Moreover, osteopenia was found only in patients treated for relapses, who had a significantly higher EDSS score than patients in the HDMP group, suggesting that decreased mobility may contribute to bone loss more than corticosteroid use. BMD should be monitored in patients with MS, regardless of the use of methylprednisolone.

Adult↗
PubMed2003

Risk factors of multiple sclerosis: a case-control study.

We assessed the risk of multiple sclerosis (MS) associated with a series of putative risk factors. We studied 140 patients (90 women) with MS (mean age, 42.1 years; SD= 10.2 years; disease duration, 10.9 years, SD= 7.5 years) and 131 sex-and age-matched controls. Using a structured questionnaire, we collected information related to demographic data, socio-economic status, education, ethnicity, changes of domiciles, migration, occupation, environmental, nutritional and hormonal factors, exposure to various bacterial and viral agents, vaccinations, and family history of diseases. In multiple logistic regression analysis, we found independent risk factors of MS to be: familiarity for MS (OR= 12.1; 95% CI, 1.3-110.7), autoimmune diseases (OR= 3.8; 95% CI, 2.0-7.1) and migraine (OR= 8.7; 95% CI, 1.0-75.4); comorbidity with autoimmune disease (OR= 6.8; 95% CI, 1.4-32.0) and migraine (OR= 13.5; 95% CI, 1.5-116.6); and vaccination against measles (OR= 92.2; 95%, 12.1-700.2). Familial susceptibility to MS, autoimmune diseases and migraine, and vaccination to measles are associated with an increased risk of MS. The data collected in this study are confirmatory and support the hypothesis that etiology of MS constitutes the effect of interplay between genetic and environmental risk factors. However, the relatively small number of cases and controls prevents firm conclusions.

Adolescent↗
PubMed2003

Correlation of sexual dysfunction and brain magnetic resonance imaging in multiple sclerosis.

Sixty-two patients (40 women and 22 men) with multiple sclerosis (MS) were examined with 1.5 tesla magnetic resonance imaging (MRI) of the brain. Information on sexual and sphincteric disturbances has been collected, and data on disability, independence, cognitive performances and psychological functioning have been assessed. Calculations of T1- and T2-lesion load (LL) of total brain, frontal lobes and pons have been performed using a reproducible semiautomated technique. Whole brain, frontal and pontine atrophies were estimated using a normalized measure, the brain parenchymal fraction (BPF), obtained with a computerized interactive program. When comparing patients with and without sexual dysfunction (SD), there were no differences in total brain, frontal and pontine T1- and T2-LL, as well as in measures of whole brain and frontal atrophy. The only significant difference was in the pontine BPF (P = 0.026). In linear multiple regression analysis, SD was associated with depression (R = 0.56, P < 0.001) and, after adjusting for depression and anxiety, with bladder dysfunction (R = 0.43, P = 0.003) and pontine BPF (R = 0.56, P < 0.001). No association between SD and any of the measures of T1- and T2-LL was found. The findings showed a relationship between SD and pontine atrophy, confirmed the correlation of SD with bladder dysfunction and highlighted the role of psychological factors in determining SD.

Adult↗
PubMed1997

Extended lymph node dissection for gastric cancer: results of a prospective, multi-centre analysis of morbidity and mortality in 118 consecutive cases.

This study reports interim data on post-operative morbidity, hospital mortality and duration of hospital stay of Italian patients undergoing extended lymph-node dissection combined with a pancreas-preserving technique for gastric cancer. Of the 218 patients admitted to one of eight general and/or university hospitals in North Italy, 118 were enrolled in the trial. Eligible patients presented with proven primary adenocarcinoma of the stomach without clinical evidence of distant, peritoneal and/or liver metastasis, or metastasis in para-aortic and retropancreatic nodes at intraoperative biopsy. Patients underwent the extended procedure as described by the Japanese Research Society for the Study of Gastric Cancer, following the Maruyama pancreas-preserving technique. A strict quality control system was used to ensure the performance of a standard surgical treatment. A surgeon of the reference centre (M.D.), who stayed at the National Cancer Center Hospital in Tokyo to learn the D2 technique from a specialist Japanese surgeon, became the trial supervisor and assisted each surgeon in all the Italian participating centres. The patients were staged according both to the TNM system and to the General Rules for the Gastric Cancer Study in Surgery and Pathology. Post-operative surgical complications developed in 21 patients (17.8%). The non-surgical complication rate was 2.5%. Reoperation was necessary in six patients (5%), all of whom survived. The 30-day mortality rate for the eligible group was 2.5%. The overall hospital mortality was the same. Total gastrectomy was associated with a slightly higher operative mortality (4.5% vs 1.3%). Only one patient died from an anastomotic leak. The rate of leakages was higher after total than after distal gastrectomy (15.9 vs 5.4%); the association of splenectomy and pancreatectomy worsened the morbidity rate. D2 lymphadenectomy with pancreas-preserving technique, when performed at experienced centres, seems a feasible and safe technique for the radical treatment of gastric cancer in selected Western patients.

Adenocarcinoma↗
PubMed1997

Effect of nucleoside analogs on neurite regeneration and mitochondrial DNA synthesis in PC-12 cells.

The effects of several anti-human immunodeficiency virus nucleoside analogs were examined on neurite regeneration and mitochondrial DNA (mtDNA) synthesis in nerve growth factor-primed PC-12 cells. Under pharmacologically relevant concentrations, the exposure of cells to 2',3'-dideoxyinosine (ddI), 2',3'-dideoxycytidine (ddC) and 2',3'-didehydro-3'-deoxythymidine (d4T) led to a marked dose-dependent inhibition of neurite regeneration with a 50% inhibitory concentration approximating 1, 5 and 15 microM, respectively. In contrast, 3'-azido-3'-deoxythymidine (AZT) and beta-L-2',3'-dideoxy-3'-thiacytidine (3TC) had no effect on neurite regeneration. Inhibition of mtDNA synthesis by ddI was dose dependent, and ddC at a concentration of 10 microM strongly reduced mtDNA content by >75%. However, no inhibition of mtDNA synthesis was detected in cells exposed to 10 microM 3TC or d4T and to 25 microM AZT, suggesting a lack of definite correlation between mtDNA depletion and blockage of neurite regeneration. High performance liquid chromatographic analysis demonstrated that AZT, ddC, 3TC and d4T were anabolized to their respective monophosphate, diphosphate and triphosphate derivatives in the PC-12 cells. In addition, d4T was phosphorylated to form its monophosphate, diphosphate and triphosphate derivatives in isolated mitochondria, whereas ddC was metabolized only to its monophosphate form and no phosphorylated metabolites of 3TC were detected under the same conditions. In summary, the peripheral neuropathy induced by ddC and ddI in patients with acquired immune deficiency syndrome may be accounted for by the depletion of mtDNA content in the neurons. As for d4T, some other mechanism(s) may be involved in its clinical neurotoxicity. Both AZT and 3TC lacked any substantial toxicity in our in vitro model, which is in agreement with the clinical action of these drugs.

Animals↗
PubMed1996

Clinical findings in a family with familial adenomatous polyposis and a missense mutation of the adenomatous polyposis coli gene.

BACKGROUND: More than 100 different mutations in the adenomatous polyposis coli (APC) gene have been identified; virtually all lead to the production of a truncated protein. Clinical details of patients with missense mutations undoubtedly cosegregating with the disease have not been reported and may be relevant in understanding the APC protein function. METHODS: In one family with familial adenomatous polyposis (FAP) the APC gene was analyzed by SSCP and sequencing of the aberrant SSCP band. RESULTS: A missense mutation in exon 15 at nucleotide 4921 segregating with the disease was observed. This predicts a tryptophan instead of an arginine at amino acid 1641 of the APC protein. No such mutation was present in 100 control subjects. CONCLUSIONS: In this family the colonic manifestations are as expected for classical FAP. However, the occurrence of congenital hypertrophy of the retinal pigment epithelium is unusual, owing to the inconsistency of this manifestation between family members and because congenital hypertrophy of the retinal pigment epithelium is generally absent when mutations are after codon 1387.

Adenomatous Polyposis Coli↗
PubMed1995

[Factors affecting recurrence after surgical treatment of Crohn disease].

Surgery does not cure Crohn's disease, but only its complications, as the recurrence rate that requires a new intervention is 6% per year. The resections performed by the surgeon should be as limited as possible, in order to avoid the consequent malabsorption. The identification of two forms of Crohn's disease, with different aggressiveness, has found that the stricturoplastic is an encouraging way of treatment for those forms with a prevalent stenotic component. A lot of studies have evaluated the relationships between recurrences and resections on margins microscopically free or affected by the disease. The aim of this study was a retrospective verification of the influence of any possible microscopical residue of the disease on the recurrence rate, evaluating whether the two different forms of aggressiveness of the disease (presence of stenosis or fistula) can influence the rate and precocity of the recurrence onset. In 37 patients operated for the first time of ileal or ileocolic resection, the overall recurrence rate was 18.9%; neither the presence of microscopically affected margins nor the presence of fistulas or stenosis has showed to have an influence on the onset of the recurrences. The only data that emerged is a greater precocity of the onset of recurrence in those patients whose disease was characterised by the presence of enteric fistulas. The forms in which fistulas and perforations were evident showed a recurrence rate not significantly higher than that of forms with stenosis only, but the period of time free from the disease was notably longer for the latter. In the end, patients in which typical granulomas were present showed a recurrence rate of just 9%, compared to 23% of patients in which granulomas were absent. MATERIALS AND METHODS. From 1980 through 1992, 61 patients affected by Crohn's disease were operated. There were 39 men and 22 women (mean age: 40.4 years). The mean length of the follow-up was 55.5 months. It was the first operation for 43 patients, while 9 had already undergone surgery in other hospitals; 9 patients showed anorectal complications. The operations performed on the patients for the first time have been ileal resection in the following localizations: duodenum-jejunum 4, jejunum and ileal 34, colic 5; the recurrences treated have been ileal-jejunum in 7 cases and colic in 2. In 2 cases of recurrence a stricturoplastic has been performed. RESULTS. The operative mortality was of 3 patients: 2 due to sepsis for anastomotic dehiscence and 1 to systemic mycosis. Four postoperative fistulas were observed. Recurrence of the disease occurred in 13 patients (26.5%), specifically in 21.4% of the patients operated for the first time and in 57.1% of those that were operated for recurrences. DISCUSSION AND CONCLUSIONS. In the treatment of Crohn's disease, it is important to identify any possible group with high risk of recurrence in order to undertake an appropriate medical prophylaxis. The results concerning the presence of microscopical disease on the resection margins are today still controversial. Some groups of authors prefer wide resection margins, some others are in favour of restricted resections. Our considerations let us assert that in those patients in which the resections have been performed on margins with microscopic presence of the disease, the interval before the recurrence occurs is not significantly shorter than that of patients with free margins. But the patients suffering from Crohn's disease with fistulae, probably need medical post-operative therapy to delay recurrences onset.

Adolescent↗
PubMed1995

[Surgical treatment of rectal cancer: prognostic factors for long-term survival].

The aim of our retrospective study was to verify the results of surgical treatment of rectal cancer in a homogeneous case series, evaluating the various factors that can influence the prognosis and long-term results. The prognostic factors taken into consideration were: Duke's stage; grading; colloid component; location of tumour; type of surgical intervention; age; sex; duration of the symptoms; length of normal rectum below the lower border of the tumour correlated to stage and grading. One hundred and sixty-five patients were operated with a radical approach: 50 abdominoperineal resections (APR) and 115 sphincter-saving resections (SSR) were performed. There were 90 males and 75 females. The mean age was 63 years. Total survival was 61.7% after 5 years and 50% after 10 years. In our study neither the age nor the sex, duration of symptoms or location of the tumours proved to have an influence on survival; while Duke's state turned out to be decisive for survival; also the colloid tumour component proved to have a worse prognosis. The 5-10-year survival rate was respectively 53.6% and 49% in the APR and 65.7% and 50.9% in the SSR (p = n.s.). The data we have collected show that APR and SSR operations have analogous efficiency.

Adult↗
PubMed1995

Ultrasonographic cross-sectional area and mean echogenicity of the superficial and deep digital flexor tendons in 50 trained thoroughbred racehorses.

Fifty Thoroughbred horses were examined. All horses had been in race training for a minimum of 4 months before examination and had worked at racing speed; 24 horses had raced. All horses were clinically sound at the time of examination. Ultrasonography was performed, using a 7.5-MHz transducer with built-in fluid offset. Videotaped images of the palmar soft tissue structures were obtained at 4, 8, 12, 16, 20 and 24 cm distal to the base of the accessory carpal bone (DACB). Images were digitized, and each image was calibrated. Values for cross-sectional area (CSA) and mean echogenicity (ME) were then determined from the cross-sectional images of the superficial digital flexor (SDF) and the deep digital flexor (DDF) tendons, using an image-analysis program. The SDF tendons were compared between right and left forelimbs at each level, and from proximal to distal on each limb, as were the DDF tendons. The relation between the SDF and DDF tendons for the same forelimb was determined at each level. There were no significant differences in CSA or ME at equivalent levels of the left and right SDF tendons. Mean (+/- SD) CSA was 1.01 +/- 0.12) cm2 at 4 cm DACB, 0.95 (+/- 0.14) cm2 at 12 cm DACB, and 1.12 (+/- 0.15) cm2 at 24 cm DACB. Adjusted ME was 2.34 (+/- 0.34) at 4 cm DACB, 2.03 (-/+- 0.38) at 12 cm DACB, and 2.04 (+/- 0.35) at 24 cm DACB. The left and right DDF tendons did not have significant differences in CSA or ME at any level. Cross-sectional area was 1.13 (+/- 0.18) cm2 at 4 cm DACB, 1.01 (+/- 0.12) cm2 at 12 cm DACB, and 1.75 (+/- 0.29) cm 2 at 24 cm DACB. Adjusted ME was 2.60 (+/-0.46) at 4 cm DACB, 2.49 (+/- 0.49) at 12 cm DACB, and 2.50 (+/- 0.44) at 24 cm DACB. At all levels, the left and right SDF tendons were smaller and less echoic than the DDF tendons of the same limb. The SDF and DDF tendons had an hour glass shape, with smallest CSA at 12 cm DACB. Mean echogenicity generally decreased for the SDF and DDF tendons from proximal to distal on the limb. These results indicate that for clinically normal trained Thoroughbred racehorses, there should be no significant difference in CSA or echogenicity between the left and right SDF tendons at equivalent distances DACB. There should be no significant differences in the left and right DDF tendons at equivalent levels DACB. The SDF tendon is usually smaller and less echoic than the corresponding DDF tendon at each level.

Animals↗
PubMed1994

Beta-endorphin concentrations in brain areas and peritoneal macrophages in rats susceptible and resistant to experimental allergic encephalomyelitis: a possible relationship between tumor necrosis factor alpha and opioids in the disease.

Since the central nervous system and neuropeptides modulate immune functions, we investigated whether the different susceptibility of Lewis and Brown Norway rats to experimental allergic encephalomyelitis could also reflect differences in beta-endorphin and substance P concentrations in brain areas and macrophages during the development of the disease. We show that beta-endorphin concentrations increase much more in the hypothalamus and macrophages of Lewis rats during the development of the disease, while the increase is much lower or absent in Brown Norway rats. Tumor necrosis factor-alpha seems to play an important role in this difference. The administration of the opiate receptor antagonist naltrexone worsens the development of the disease, suggesting that the increase of the opioid beta-endorphin might represent a mechanism to downregulate the immune response. In both strains, the concentrations of substance P do not change.

Animals↗
PubMed1993

Evidence for an opioid inhibitory effect on T cell proliferation.

The proliferative response of human or rat T lymphocytes to phytohemagglutinin (PHA) or concanavalin A (ConA) was measured after acute (30 min) or chronic (8 days) treatment with the opiate receptor antagonists naloxone or naltrexone. Both in the rat and in the human, proliferation was significantly enhanced by acute treatment with the opiate receptor antagonists. In contrast, after chronic treatment proliferation always decreased. The sudden removal of an opioid inhibitory tone might be the basis for the increased proliferative responses observed after acute treatment. The decrease after chronic treatment could be ascribed to the amplification of the inhibitory effect of endogenous opioids due to the up-regulation of opiate receptors that follows chronic antagonist administration. Receptor binding studies of beta-endorphin receptors on splenocytes of chronically naloxone treated rats confirmed this hypothesis: a higher number of beta-endorphin receptors were expressed on splenocytes of naloxone-treated rats compared to controls (Bmax = 9.8 x 10(-12) vs. 1.16 x 10(-12), respectively).

Adult↗
PubMed1993

Effect of ibuprofen and diclofenac on the chemotaxis induced by substance P and transforming growth factor-beta on human monocytes and polymorphonuclear cells.

The neuropeptide substance P and the cytokine transforming growth factor-beta are potent chemotactic factors for monocytes or polymorphonuclear cells. They are present in synovial fluid of arthritic patients, and participate in the pathogenesis of arthritis. We investigated, in vitro, the effect of two non-steroidal anti-inflammatory drugs, ibuprofen and diclofenac, on the chemotactic effect of substance P and transforming growth factor-beta at concentrations that can be present in the synovial fluid of arthritic patients. Both drugs decrease the chemotaxis induced by substance P and transforming growth factor-beta, at concentrations that can be easily reached in the synovial fluid during therapy. This event could be involved in the effect of some non-steroidal anti-inflammatory drugs on the development and progress of arthritic disease.

Arthritis↗
PubMed1993

Inhibitory effect of NSAIDs on the chemotaxis induced by substance P on human monocytes and polymorphonuclear cells.

Substance P is involved in the modulation of arthritic pain, and more recently it has been suggested that substance P might be involved also in the immunological aspects of arthritic diseases. Substance P is present in the synovial fluid of arthritic patients, where it can induce the chemotaxis of polymorphonuclear cells (PMN) and monocytes, and the synthesis of cytokines. We thought it worthwhile to investigate the effect of non steroidal anti-inflammatory drugs (NSAIDs) on the chemotactic effect of substance P on PMN and monocytes. We evaluated the effects of NSAIDs on the chemotactic effect of two concentrations of substance P that are well within those reached by the neuropeptide in arthritic diseases. The different NSAIDs inhibit the chemotactic response of PMN with different patterns, while the effect on the chemotaxis of monocytes is much weaker. The data we present suggest that the effect of NSAIDs on the development and progress of arthritic disease could involve their capacity of blocking the chemotactic activity of substance P, and with mechanism interfere with the self-feeding pathological circle of substance P. It remains to be determined whether the effect is mediated by the block of cyclooxygenase or other less specific effects of NSAIDs on PMN and monocyte membranes.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Corticotropin releasing hormone, interleukin-1 alpha, and tumor necrosis factor-alpha share characteristics of stress mediators.

Interleukin-1 alpha and tumor necrosis factor-alpha induce an increase in pain thresholds in the rat. We now show that also the corticotropin releasing hormone induces an analgesic effect that, similarly to what is observed with the two cytokines, is not reversible by naloxone. Moreover, we also show that after the administration of interleukin-1 alpha, tumor necrosis factor-alpha, and corticotropin releasing hormone, naloxone becomes analgesic itself. A similar observation was also made in the human and the experimental animal after exposure to stressful conditions. The results obtained suggest that the two cytokines share with corticotropin releasing hormone some characteristics of stress mediators.

Analgesia↗
PubMed1991

Pharmacological modulation of neuropeptides in peripheral mononuclear cells.

The concentrations of beta-endorphin and cholecystokinin were measured in fresh resting peripheral mononuclear cells obtained from rats and human subjects in basal conditions and after different pharmacological treatments. Both in the human and the rat, beta-endorphin concentrations in mononuclear cells, increased after treatment with serotoninergic agonists, decreased after dopaminergic or GABAergic drugs, while the respective antagonists exerted the opposite effect. In vitro, serotoninergic and GABAergic compounds confirmed their roles in the modulation of beta-endorphin in mononuclear cells. Cholecystokinin was never affected by the pharmacological treatments.

Animals↗