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Biomedical subjects

M Fiore

Publications and source records attributed to M Fiore.

At least 19 recordsLinked to original sources

What are subcutaneous adipocytes really good for?

Our acute awareness of the cosmetic, psychosocial and sexual importance of subcutaneous adipose tissue contrasts dramatically with how poorly we have understood the biology of this massive, enigmatic, often ignored and much-abused skin compartment. Therefore, it is timely to recall the exciting, steadily growing, yet underappreciated body of evidence that subcutaneous adipocytes are so much more than just 'fat guys', hanging around passively to conspire, at most, against your desperate attempts to maintain ideal weight. Although the subcutis, quantitatively, tends to represent the dominant architectural component of human skin, conventional wisdom confines its biological key functions to those of energy storage, physical buffer, thermoregulation and thermoinsulation. However, already the distribution of human superficial adipose tissue, by itself, questions how justified the popular belief is that 'skin fat' (which actually may be more diverse than often assumed) serves primarily thermoinsulatory purposes. And although the metabolic complications of obesity are well appreciated, our understanding of how exactly subcutaneous adipocytes contribute to extracutaneous disease - and even influence important immune and brain functions! - is far from complete. The increasing insights recently won into subcutaneous adipose tissue as a cytokine depot that regulates innate immunity and cell growth exemplarily serve to illustrate the vast open research expanses that remain to be fully explored in the subcutis. The following public debate carries you from the evolutionary origins and the key functional purposes of adipose tissue, via adipose-derived stem cells and adipokines straight to the neuroendocrine, immunomodulatory and central nervous effects of signals that originate in the subcutis - perhaps, the most underestimated tissue of the human body. The editors are confident that, at the end, you shall agree: No basic scientist and no doctor with a serious interest in skin, and hardly anyone else in the life sciences, can afford to ignore the subcutaneous adipocyte - beyond its ample impact on beauty, benessence and body mass.

Adipocytes↗

Space-charge effects in the current-filamentation or Weibel instability.

We consider how an unmagnetized plasma responds to an incoming flux of energetic electrons. We assume a return current is present and allow for the incoming electrons to have a different transverse temperature than the return current. To analyze this configuration we present a nonrelativistic theory of the current-filamentation or Weibel instability for rigorously current-neutral and nonseparable distribution functions, f(0)(p(x), p(y), p(z)) is not equal to f(x)(p(x))f(y)(p(y))f(z)(p(z)). We find that such distribution functions lead to lower growth rates because of space-charge forces that arise when the forward-going electrons pinch to a lesser degree than the colder, backward-flowing electrons. We verify the growth rate, range of unstable wave numbers, and the formation of the density filaments using particle-in-cell simulations.

Journal Article↗

[Reservoirs and transmission of Pseudomonas aeruginosa in intensive care unit].

OBJECTIVE: The authors had for aim to study reservoirs and transmission of Pseudomonas aeruginosa in an intensive care unit. DESIGN: A 6-month prospective descriptive study was made on water samples, samples from hands of health care workers, and clinical samples. P. aeruginosa strains were compared by pulsed-field gel electrophoresis. RESULTS: Among the 211 patients hospitalized during the study, 14 (6.6%) were infected by P. aeruginosa. Out of 494 water samples, 80 were contaminated by P. aeruginosa. The regularly disinfected water taps were more rarely contaminated than the others (P<10(-5)). Out of 140 hand samples, one showed contamination from an infected patient. CONCLUSIONS: aeruginosa cross transmission was observed during this study. We should follow strict hygienic precautions such as wearing gloves and performing thorough alcoholic rub disinfection. Water taps are often contaminated and require regular disinfection.

Cross Infection↗

Status of surgical margins and prognosis in adult soft tissue sarcomas of the extremities: a series of patients treated at a single institution.

PURPOSE: To explore the prognostic effect of microscopic marginal status after surgery for extremity soft tissue sarcomas. PATIENTS AND METHODS: We analyzed 911 consecutive patients surgically treated throughout a 20-year span at a single referral center. Six hundred forty-two were first seen with a primary tumor, and 269, with a locally recurrent tumor. All patients underwent macroscopically complete resection. Microscopic marginal status was negative (tumor size > 1 mm) in 748 patients and positive (</= 1 mm) in 163 patients. Median follow-up was 107 months. RESULTS: Patients with primary disease had a lower disease-specific mortality in comparison to those first examined for recurrence (25% v 37%, respectively, at 10 years). Size, malignancy grade, depth, histotype, and local recurrence had a statistically significant prognostic effect at multivariable analysis, while microscopically positive surgical margins had not, though a trend in favor of negative margins was observed. However, an extra risk was observed for patients with positive margins after 3 to 5 years (hazard ratio, 1.8 after 5 years v 0.8 before 5 years). In patients treated for a local recurrence, the prognostic impact of positive margins was higher (hazard ratio, 1.6). CONCLUSION: Positive surgical margins had a weak adverse prognostic effect, which was more pronounced for those patients escaping an early relapse. This would seem to justify a policy of surgical adequacy in adult soft tissue sarcomas, though clinical decision making in borderline presentations for conservative surgery might be reasonably flexible and shared with the patient. Once a local relapse has occurred, the impact of local treatments seems more critical.

Adult↗

Exposure to rizatriptan during pregnancy: post-marketing experience up to 30 June 2004.

Merck & Co., Inc. evaluates outcomes of the use of rizatriptan during pregnancy through a Pregnancy Registry in the United States (US) and spontaneous reports for pregnancies reported from sources outside the US. Review of the outcomes of 25 prospective pregnancy reports in the Pregnancy Registry and reports from other sources does not suggest that treatment with rizatriptan predisposes patients to spontaneous abortions or congenital anomalies. However, the number of reports is small. Healthcare providers in the United States are encouraged to report any prenatal exposure to rizatriptan by calling the Pregnancy Registry at +1 (800) 986 8999 or visiting the Registry's website at http://www.merckpregnancyregistries.com.

Abnormalities, Drug-Induced↗

Atypical pleomorphic epithelioid angiomyolipoma localized to the pelvis: a case report and review of the literature.

AIMS: Angiomyolipoma is the most common mesenchymal tumour of the kidney. It has been reported in several other sites outside the kidney, mainly in the liver. We report the first case of atypical pleomorphic angiomyolipoma in a man, arising from the pouch of Douglas and extending to the entire abdominal cavity. METHODS: A 17-year-old man underwent a complete resection of a giant abdominopelvic mass. The tissue was formalin fixed and paraffin embedded and 4 micro m thick histological sections were stained with haematoxylin-eosin. Immunohistochemical stains for HMB-45, smooth muscle actin, vimentin, calponin, S100 and desmin were performed. Sections for electron microscopy were also prepared. RESULTS: Microscopic examination revealed a neoplasm composed of pleomorphic epithelioid cells with atypical features, immunoreactive for HMB-45, MART-1, actin, vimentin and calponin, while S100 protein and desmin stains were negative. Ultrastructurally, the tumour cells showed prominent nucleoli, vacuolated cytoplasm, and some premelanosomes. A diagnosis of atypical pleomorphic epithelioid angiomyolipoma was then made. CONCLUSIONS: To date five patients with abdominal epithelioid angiomyolipoma have been described in the literature. All were women. Three of the five patients reported developed metastasis, while our patient is still free of disease at 16 months of follow-up. Clear prognostic pathological features have not been identified.

Adolescent↗

Quality of surgery and outcome in extra-abdominal aggressive fibromatosis: a series of patients surgically treated at a single institution.

PURPOSE: To explore prognostic factors in surgically treated aggressive fibromatosis (extra-abdominal desmoid tumor). PATIENTS AND METHODS: A total of 203 consecutive patients treated with surgery over a 35-year period at a single referral center were retrospectively reviewed. One hundred twenty-eight were first seen at our institution with primary disease, whereas 75 had a recurrent tumor. All patients underwent macroscopically complete resection. Margins were rated as negative in 146 (97 with primary tumors, 49 with recurrences) and positive in 57 (31 in primary, 26 in recurrences) patients. Median follow-up was 135 months. RESULTS: Patients with primary disease had a better disease-free survival rate than those with recurrence (76% v 59% at 10 years). Presenting with a recurrence was also the strongest predictor of local failure in the multivariate analysis. In patients first treated for primary disease, size and site had prognostic significance, whereas microscopically positive surgical margins did not. In contrast, in patients with recurrence, there was a trend toward better prognosis if margins were negative (although this was not significant at multivariate analysis). CONCLUSION: Presence of microscopic disease does not necessarily affect long-term disease-free survival in patients with primary presentation of extra-abdominal desmoid tumors. Thus, function-sparing surgery may be a reasonable choice when feasible without leaving macroscopic residual disease. In patients with recurrences, positive margins may more clearly affect prognosis, potentially necessitating adjuvant radiation in selected cases.

Adolescent↗

Unusual response to second-line single-agent gemcitabine in locally advanced primary leiomyosarcoma of the lung: a case report.

Primary leiomyosarcomas (LMSs) of the lung are extremely rare malignancies that have been the subject of single or small series of case reports. Today, the gold standard of treatment in patients with locally advanced and metastatic disease includes one of the many possible regimens containing an anthracycline and/or ifosfamide. Few chemotherapy agents are active in the second-line setting. In particular, gemcitabine is considered quite ineffective in the treatment of first- as well as second-line chemotherapy of soft tissue sarcoma and responses to this agent are seldom reported. In this paper, we report a single patient with primary LMS of the lung previously treated with a combination of epirubicin and ifosfamide. The patient responded to second-line chemotherapy with gemcitabine 1250 mg/m2 given as a 30-minute infusion on days 1, 8, and 15 of a 28-day cycle and showed an 8-month response duration and negligible toxicity. Gemcitabine may represent an alternative to the best supportive care in patients affected with soft tissue sarcoma who fail first-line chemotherapy.

Antimetabolites, Antineoplastic↗

Chordoma: natural history and results in 28 patients treated at a single institution.

BACKGROUND: The natural history of chordoma is characterized by a high failure rate and a poor functional outcome. The purpose of this study was to review the long-term outcome of our institutional experience. METHODS: The clinical features, type of treatment, pathologic assessment, and follow-up of 56 consecutive patients with chordoma were reviewed. RESULTS: Fifty sacral and six mobile spine chordomas (median size, 13 cm; range, 2-30 cm) were treated at our center between January 1933 and December 2000. Twenty-eight patients affected by sacrococcygeal chordoma and operated on after 1977 form the basis of our study. Surgical margins were rated as wide in 11 cases, marginal in 13 cases, and intralesional in 4 cases. The median follow-up was 71 months (range, 15-200 months). Seventeen patients' disease recurred. Ten patients died as a result of disease. Nine patients remained continuously free of disease. The estimated 5- and 10-year overall survival was, respectively, 87.8% and 48.9%; disease-free survival was 60.6% and 24.2%. Radiotherapy was considered for marginal and intralesional resections. CONCLUSIONS: High sacral amputation can achieve a good rate of wide-margin resections for sacrococcygeal chordomas. Adjuvant radiotherapy may offset the negative effect in the prognosis of marginal resections.

Adult↗

Stress and nerve growth factor: findings in animal models and humans.

Stress is elicited by environmental, social or pathological conditions occurring during the life of animals and humans that determine changes in the nervous, endocrine and immune systems. In the present review, we present data supporting the hypothesis that stress-related events both in animal models and humans are characterized by modifications of endogenous nerve growth factor (NGF) synthesis and/or utilization. Stress inducing alteration in NGF synthesis and/or utilization appears to be more severe during neurogenesis and in early postnatal life. However, NGF endogenously released during stress may promote remodeling of damaged tissues following acute and/or chronic stressful events.

Animals↗

Bromodeoxyuridine and methylazoxymethanol exposure during brain development affects behavior in rats: consideration for a role of nerve growth factor and brain derived neurotrophic factor.

Rats prenatally exposed to the neurotoxins methylazoxymethanol (MAM) or 5-Bromo-2'-deoxyuridine (BrdU) are used as animal models of brain maldevelopment. We administered in rats MAM (20 mg/kg), or BrdU (100 mg/kg) or both at gestational day 11. Locomotion was not affected by any prenatal treatment whereas learning was delayed in the Morris maze in MAM animals. BrdU induced decreased NGF and BDNF levels in the hippocampus. In the parietal cortex prenatal BrdU administration induced NGF potentation associated with decreased BDNF. Animals treated with both MAM and BrdU showed also an increased immunopositivity for choline acetyltransferase (ChAT) and low affinity neurotrophins' receptor (p75) in the septum and Meynert's nuclei. These findings suggest that embryonic exposure to MAM and/or BrdU may be useful for studying mechanisms associated with neurodegenerative diseases affecting brain morphology and behavior.

Animals↗

Effect of hypergravity on the mouse basal expression of NGF and BDNF in the retina, visual cortex and geniculate nucleus: correlative aspects with NPY immunoreactivity.

We investigated the effect of hypergravitation on Nerve growth factor (NGF) and Brain-derived-neurotrophic factor (BDNF) expression in the visual cortex, geniculate nucleus (GN), and retina of adult male mice. The results showed that altered gravity causes an increase in NGF and BDNF in the visual cortex and GN which resulted to be associated with an up-regulation of cells immunoreactive to neuropeptide Y (NPY) in the visual cortex and GN. We also found a decrease in NGF, BDNF, and NPY in the mouse retina exposed to hypergravity. These findings suggest that alteration in gravitational environment differentially affects local neurotrophic factors and NPY expression. The possible functional significance of these observations is discussed.

Animals↗

Nerve growth factor levels and mast cell distribution in human coronary atherosclerosis.

Nerve growth factor (NGF), in addition to its neurotrophic function, acts on a variety of non-neuronal cells including immune cells and vascular smooth muscle cells. The aim of the present study was to determine the NGF levels and the distribution of NGF and low-affinity NGF receptor (p75NGFR) and mast cells (MC) in human atherosclerotic coronary arteries. Specimens of human coronary arteries obtained from autopsy cases (n=12, subjects with atherosclerotic lesions; n=9, subjects without atherosclerotic lesions/controls) were used. The present study showed that in the atherosclerosis-lesioned arteries, the amount of NGF decreased, whereas the expression of p75NGFR immunoreactivity and the number, both of MC and vasa vasorum, particularly in the adventitia, significantly increased, compared with the control arteries. Cumulatively, our findings help to set the neurotrophic theory and its currently extended neuroimmune framework into the context of pathobiology of atherosclerosis, suggesting that altered presence of NGF, p75NGFR, and MC may play a role in neuroimmune mechanisms of human coronary atherosclerosis.

Adult↗

NGF, BDNF, leptin, and mast cells in human coronary atherosclerosis and metabolic syndrome.

While multiple growth factor, cytokines, and immune cells are identified in atherosclerotic lesions, as well as an essential nonneuronal function of neurotrophins implicated in cardiovascular tissue development and in lipid and glucose metabolism, the role of the neurotrophins NGF and BDNF and also the adipokine leptin in human coronary atherosclerosis and related disorders, such as metabolic syndrome, remains unclear. Here we report that (i) both the amount and the immunoreactivity of NGF was reduced and the expression of p75NGF receptor and the number of mast cell increased in human atherosclerotic coronary arteries (n = 12) compared with control specimens (n = 9) obtained from autopsy cases, and (ii) NGF and BDNF plasma levels were reduced in patients with metabolic syndrome (n = 23) compared with control subjects (n = 10). Also, in metabolic syndrome patients, a positive correlation between the plasma leptin levels and the number of adipose tissue mast cells was found, suggesting that leptin may be a novel adipoimmune mediator. Altogether, the results provide the first correlative evidence for the potential involvement of NGF, BDNF, leptin, and mast cells in human coronary atherosclerosis and metabolic syndrome, implying neuroimmune and adipoimmune pathways in the pathobiology of these cardiovascular disorders.

Brain-Derived Neurotrophic Factor↗

Neuroinflammatory implication of Schistosoma mansoni infection in the mouse.

Schistosomiasis is a parasitic disease due to Schistosoma mansoni. Schistosome infection is known to induce granulomas not only in the spleen, bladder, liver and intestine but also in the brain and spinal cord resulting in severe neuropathological and psychiatric disorders though the interaction between Schistosoma mansoni infection and the nervous system has received on the whole little attention. In the present review it has been discussed recent findings from experimental Schistosoma mansoni infection in mouse nervous system. We show that brain granulomas are associated with a significant alteration in the constitutive levels of nerve growth factor (NGF), a trophic factor playing an essential role in nerve growth and differentiation and in preventing neuronal damages. Animals infected with schistosomes suffered also of increased pain sensitivity which was inhibited by TNF-alpha antibody injections and not by anti-NGF. These findings suggest that the neuropathological dysfunctions in neuroschistosomiasis may be linked to changes in the basal levels and/or activity of neurotrophic factors caused by local formation of granulomas.

Animals↗