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Biomedical subjects

M Francesconi

Publications and source records attributed to M Francesconi.

At least 19 recordsLinked to original sources
PubMed2006

Modì: a new mobile instrument for in situ double-pulse LIBS analysis.

Laser-induced breakdown spectroscopy (LIBS) is a promising technique for in situ elemental analysis. A new mobile instrument for LIBS analysis, developed in a collaboration between Marwan Technology s.r.l. and the Applied Laser Spectroscopy Laboratory in Pisa, is presented, and some applications of it and results from it are outlined. The innovative experimental set-up, based on the use of two suitably retarded laser pulses and a standardless analysis procedure, which overcomes problems related to matrix effects, greatly improves the potential of this technique for accurate quantitative analysis.

Journal Article↗
PubMed2004

Impact of a new dosing regimen of epoetin alfa on quality of life and anemia in patients with low-risk myelodysplastic syndrome.

This study evaluated the impact of a new epoetin alfa dosing regimen on quality of life (QOL), transfusion requirements, and hemoglobin (Hb) levels in 133 patients with low-risk myelodysplastic syndrome (MDS) and Hb < or =10 g/dl. Epoetin alfa 40,000 IU was given subcutaneously twice weekly; after 4 weeks, the dose could be reduced to 40,000 IU weekly in patients achieving erythroid response. QOL was assessed using the functional assessment of cancer therapy-anemia (FACT-An) questionnaire. FACT-An scores increased on average by 7.5 after 4 weeks and by 8.8 after 8 weeks compared with baseline. FACT-An scores were positively associated with Hb values (r=0.53, P<0.01). The mean FACT-An score increase at week 8 was 10.2 in responders and 5.6 in nonresponders. The overall erythroid response rate at week 8 was 68%: 74% in transfusion-independent patients and 59% in transfusion-dependent patients. Of all responders at week 8, response was maintained in 86% at week 12, 71% at week 16, 65% at week 20, and 54% at week 24. Treatment was generally well tolerated. Our data provide new and encouraging results regarding the benefits of 40,000 IU biweekly induction doses followed by 40,000 IU weekly in improving QOL, correcting anemia, and reducing transfusion requirements in low-risk MDS patients.

Adult↗
PubMed2004

Outcome of conservative therapy of patients with severe intermittent claudication.

BACKGROUND: Intermittent claudication due to peripheral artery disease (PAD) can be treated conservatively, or by revascularization. OBJECTIVES: To assess the short-term outcome of conservatively-treated claudicants, and determine predictors for clinical improvement. Design. A retrospective cohort study. METHODS: We evaluated Fontaine stage, walking distance and ankle brachial index (ABI) at baseline and after median 9 months (interquartile range (IQR) 6-24) in 181 patients with severe claudication. RESULTS: We found clinical improvement by at least one Fontaine stage in 38 patients (21%) with an increased walking distance from baseline median 100 m (IQR 50-150) to follow-up median 650 m (IQR 300 to unlimited; p<0.001), but without changes in ABI (median 0.57, IQR 0.48-0.73 vs. median 0.54, IQR 0.45-0.81; p=0.10). One hundred and thirty-eight patients (76%) remained clinically and hemodynamically stable. A worsening of the clinical stage but without amputation was recorded in five patients (3%). Female gender (hazard ratio (HR) 0.51, p=0.052), diabetes (HR 0.35, p=0.020), and baseline ABI below 0.44 (HR 0.31, p=0.019) were associated with a reduced probability of clinical improvement. CONCLUSION: Certain patients with intermittent claudication show substantial clinical improvement with conservative medical therapy, despite any lack of hemodynamic improvement. Given the low number of patients with clinical deterioration in the short term, primarily conservative therapy should be the preferred initial option for most claudicants.

Aged↗
PubMed2004

Antiviral profile of HIV inhibitors in macrophages: implications for therapy.

Macrophages (M/M) are identified as the second cellular target of HIV and a crucial virus reservoir. M/M are persistently infected cells and not susceptible to the HIV cytophatic effects typical of infected CD4+ T-lymphocytes. HIV replication in M/M is a crucial pathogenetic event during the whole course of the disease. Moreover, the dynamics of HIV-1 replication and cumulative virus production is quite different in M/M and CD4+ T-lymphocytes in the presence or in the absence of antiviral drugs. Thus, for their unique cellular characteristics, the activity of anti-HIV compounds could be different in M/M than in CD4+ T-lymphocytes. Indeed, nucleoside analogues inhibitors of HIV-reverse transcriptase (NRTIs) show potent antiviral activity in macrophages, although the limited penetration of these compounds in sequestered body compartments and the scarce phosphorylation ability of macrophages, suggest that a phosphate group linked to NRTIs may confer a greater anti-HIV activity in such cells. The antiviral activity of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in macrophages is similar to that found in CD4-lymphocytes. Interestingly, protease inhibitors (PIs), acting at post-integrational stages of virus replication, are the only drugs able to interfere with virus production and release from macrophages with established and persistent HIV infection. For these reasons, a careful analysis of the distribution of antiviral drugs, and the assessment of their activity in cells of macrophage lineage, represent key factors in the development of therapeutic strategies aimed to the treatment of the HIV-infected patients.

Anti-HIV Agents↗
PubMed2002

An estimate of the current risk of transmitting blood-borne infections through blood transfusion in Italy.

We conducted a retrospective cohort study to estimate the incidence of major blood-borne agents among Italian blood donors and calculated the risk of infection among blood recipients using the 'incidence/window period model'. The study was conducted among 46 180 blood donors enrolled in six blood centres between 1994 and 1999. During follow-up, seven new infections were confirmed: three donors seroconverted for anti-human immunodeficiency virus (HIV); two for anti-hepatitis C virus (HCV); and two showed hepatitis B surface antigen (HBsAg) reactivity; no cases of syphilis were observed. The incidence rates per 100 000 person/years were: 4.06 (95% CI: 0.82-11.85) for HIV; 2.41 (95% CI: 0.29-8.70) for HCV; and 2.70 (95% CI: 0.32-9.77) for HBsAg; the incidence for total hepatitis B virus (HBV) infection was 9.77 per 100 000 person/years (95% CI: 1.16-35.36). The estimated risk of an infectious blood unit not being detected was: 2.45 (95% CI: 0.13-12.33) per 1 million units for HIV; 4.35 (95% CI: 0.30-22.39) for HCV; and 15.78 (95% CI: 1.16-84.23) for HBV. Overall, an estimated 22.58 per 1 million units are infected. In Italy, the risk of transfusion-transmitted infections is low and is similar to that in other western countries. The introduction of new more sensitive screening tests could reduce the residual risk of transfusion-transmitted infection by 40-80%.

Adolescent↗
PubMed2002

[Demographic and metabolic data of persons with different risk for diabetes mellitus based on "random" blood glucose values].

Four risk-categories for diabetes probability where defined by measured random-blood glucose values: minimum risk (random blood glucose < or = 95 mg/dl), low (96-139 mg/dl), moderate (140-199 mg/dl), and high (> or = 200 mg/dl). Using these risk categories and other risk factors as age, sex, BMI, and cholesterol, further data analysis were made. Among high-risk patients, male sex was represented two fold compared to female sex. In +65 year old subjects the diabetes risk increased from 8.2% for the whole study cohort up to 12.1%. An increase of body weight was paralleled by an increased risk for diabetes, whereas in the highest diabetes risk-group, obese subjects (BMI subgroup 4) were twice as frequent as in the next lower risk category. Additionally, 62% of subjects with a high diabetes risk had elevated cholesterol levels.

Adult↗
PubMed2001

Health related quality of life in patients with long-standing insulin dependent (type 1) diabetes mellitus: benefits of regular physical training.

BACKGROUND AND AIMS: Regular exercise is recommended to diabetic patients in addition to dietary restrictions and drug therapy. We have studied whether health related quality of life (HRQOL) can be improved by a regular physical training program. METHODS: 23 otherwise healthy patients with history of type 1 diabetes for 20 +/- 10 years were included. 15 patients (age: 41 +/- 2 years) participated in an aerobic physical training program over 4 months and 8 patients (33 +/- 11 years) served as a control group. HRQOL was assessed by a validated questionnaire (MOS SF-36). Tests were carried out at baseline and after 4 months. RESULTS: Physical training increased peak oxygen uptake (VO2max) by 27 +/- 13% after 4 months (p = 0.04) in the training group. There was no significant change in hand or leg isometric muscle strength. All HRQOL scales improved in the training group with significantly higher (p < 0.04) Social Functioning and Vitality scores, respectively. Moreover, insulin requirements decreased during physical training program (p < 0.05). CONCLUSIONS: Our data indicate that physical exercise training in patients with type I diabetes mellitus improves metabolic control and various aspects of HRQOL. Besides enhanced cardiorespiratory capacity, this is an important subjective benefit in patients with longstanding insulin dependent (type 1) diabetes mellitus.

Adult↗
PubMed2001

Postprandial impairment of resistance vessel function in insulin treated patients with diabetes mellitus type-2.

Reduced postischaemic reactive hyperaemia, is considered a marker of impaired resistance vessel function. Acute postprandial hyperlipidaemia has been shown to induce vascular dysfunction. In the present study, the impact of postprandial hyperglycaemia on resistance vessel reactivity was investigated in insulin treated type-2 diabetic patients. The study was performed in 16 insulin treated type-2 diabetics (eight male/eight female, age 47 +/- 3 years, HbA1c 7.2 +/- 0.2) and 16 controls. Reactive hyperaemia was measured in the forearm by venous occlusion plethysmography after 5 min of ischaemia in the fasting state and 90 min after a test meal. In diabetics, blood glucose increased from 8.7 +/- 1.1 to 15.3 +/- 1.0 mmol l-1 (P<0.001) postprandially. This resulted in (i) a significant increase of resting blood flow (3.4 +/- 0.3 to 4.8 +/- 0.4 ml min-1 100 ml-1, P<0.01) and (ii) in a reduced peak reactive hyperaemia (52.3 +/- 7.4 to 36.8 +/- 4.3 ml min-1 100 ml-1, P<0.005). In controls, a similar effect of the meal on resting flow was observed but reactive hyperaemia was unaltered. In the absence of a test meal, basal flow as well as peak reactive hyperaemia remained unchanged in diabetic as well as in non-diabetic subjects. Our data provide evidence that in the postprandial state resistance vessel reactivity becomes reduced in insulin treated type-2 diabetic patients.

Adult↗
PubMed2000

Adrenaline potentiates type 2B von Willebrand factor-induced activation of human platelets by enhancing both the formation and action of thromboxanes.

Von Willebrand factor (vWF) is a large plasma glycoprotein that mediates platelet adhesion at sites of vascular injury. We have previously reported that the pathological type 2B (formerly named type IIB) variant of vWF promotes platelet activation through phospholipase A(2)-mediated release of arachidonic acid. The present report shows that adrenaline (1 microM) potentiates type 2B vWF-induced platelet aggregation, serotonin secretion, rise in cytosolic Ca(2+) concentration, and pleckstrin phosphorylation, as well as thromboxane B(2) production. The hormone also increases the partially inhibited release of serotonin observed in platelets pretreated with the anti-GPIIb-IIIa antibody LJCP8 but does remove the total inhibition on the secretion caused by the anti-GPIb antibody LJIB1. Adrenaline also increases type 2B vWF-elicited tyrosine phosphorylation of proteins with apparent molecular masses of 60 and 80 kDa. Furthermore, adrenaline potentiates the rise in cytosolic Ca(2+) and the release of thromboxane B(2) in platelets stimulated with arachidonic acid (2 microM) as well as the increase in Ca(2+) induced by the thromboxane mimetic U46619 (0.3 microM). Platelet pretreatment with yohimbine or 13-azaprostanoic acid, which are antagonists of the alpha(2)-adrenergic and thromboxane receptors, respectively, or with acetylsalicylate and indomethacin, both of which act as inhibitors of thromboxane formation, abolishes the potentiating effect of adrenaline. These observations lead to the conclusion that the potentiating action of adrenaline on type 2B vWF-promoted platelet responses is due to an increase in both the formation and activating action of thromboxanes.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2000

On the mechanism of the spermine-exerted inhibition on alpha-thrombin-induced platelet activation.

Previous reports have shown that various amines inhibited platelet activation, but no definitive conclusions on their action mechanism were drawn. We have further investigated the action of spermine on platelet responses evoked by alpha-thrombin and other agonists. Spermine inhibited in a concentration-dependent manner (1-10 mM), and more efficiently than spermidine and putrescine, the alpha-thrombin-induced (1.5 nM) platelet activation. Spermine added at a concentration that inhibited completely aggregation only partially affected the thrombin-induced increase in cytosolic Ca(2+) concentration, protein phosphorylation, and ATP secretion. The polyamine had little effect on the morphology of resting platelets, as measured by electron microscopy, thrombin hydrolytic activity, and fibrinogen clotting capacity but decreased the thrombin binding to platelets and isolated glycocalicin. Spermine partially inhibited the aggregation elicited by ADP, vasopressin, platelet-activating factor, thrombin receptor-activating peptide, fluoroaluminate, ionomycin, and dioctanoylglycerol but did not affect the cytosolic Ca(2+) increase induced by these agonists. The polyamine bound to both glycocalicin and platelets, and it inhibited the fibrinogen binding to stimulated platelets. The amount of 14C-spermine bound to resting cells decreased in the presence of the glycoprotein GPIb-antibody LJIB1, whereas the polyamine bound to activated platelets, which was higher than that tied to resting cells, was markedly reduced by LJCP8 or decorsin, a GPIIb/IIIa antibody and antagonist-peptide, respectively. These results indicate that spermine specifically inhibits the thrombin binding to GPIb of resting platelets and the fibrinogen binding to GPIIb/IIIa (integrin alpha(IIb)beta(3)) of activated platelets.

Adenosine Triphosphate↗
PubMed1999

Determinants of post-ischaemic reactive hyperaemia in patients with diabetes mellitus type II.

Dysfunction of resistance arteries is thought to be an early reversible stage in the development of atherosclerosis. Dynamics of post-ischaemic reactive hyperaemia are believed to constitute a useful tool for monitoring resistance vessel function. Patient characteristics influencing reactive hyperaemia, however, need to be defined more precisely. Since reactive hyperaemia is a dynamic process, yielding submaximal peak values after 5 min of ischaemia, this period was chosen to investigate the determinants of reactive hyperaemia in 100 type II diabetic patients as well as in 61 control subjects. Reactive hyperaemia was measured by venous-occlusion plethysmography; clinical and laboratory data were acquired by routine methods. Statistical comparison was performed with SYSTAT 5.0 for Apple Macintosh. Overall, no significant differences between diabetic patients and controls were observed by group comparison. In control subjects, only gender showed an influence on peak reactive hyperaemia (females 40.5 +/- 15.3; males 51.8 +/- 17.7 ml min-1 100 ml-1, P < 0.01). In diabetic patients, in addition to gender, actual blood glucose (r = 0.377, P < 0.05) and meal intake (non-fasting 42.8 +/- 19.2; fasting 51.2 +/- 19.5 ml min-1 100 ml-1, P < 0.05) were found to influence reactive hyperaemia. Further investigation revealed a loss of the correlation between peak reactive hyperaemia and actual blood glucose observed in the fasting state (P < 0.001) in non-fasting diabetic patients, indicating an influence of meal intake on resistance vessel reactivity. Our results suggest that, in diabetic subjects, in addition to gender actual blood glucose and the postprandial situation impacts on peak reactive hyperaemia.

Diabetes Mellitus, Type 2↗
PubMed1999

Cisapride versus placebo for 8 weeks on glycemic control and gastric emptying in insulin-dependent diabetes: a double blind cross-over trial.

In insulin-dependent diabetes mellitus, slow gastric emptying may make absorption unpredictable and foster glycemic instability. Cisapride accelerates emptying, but controlled long term studies are scarce, and effects on glycemic control unknown. We investigated, in patients with insulin-dependent diabetes mellitus and unstable glycemia, the effects of 10 mg cisapride 4 times daily for 8 weeks vs. placebo on glycemic control and gastric emptying under random, cross-over, double blind conditions. In 14 patients with delayed and 9 with nondelayed emptying, blood glucose variability over 28-week treatment periods separated by a 4-week wash-out and gastric emptying of a semisolid 1168-kJ meal immediately after the treatment periods were assessed. Cisapride did not affect glycemic control [SD of within-patient mean blood glucose, 4.2 mmol/L +/-0.1 (+/- SEM) vs. 4.0+/-0.1 mmol/L after placebo; hemoglobin A1c, 8.3+/-0.2% vs. 8.5+/-0.2%]. Emptying was faster after cisapride than after placebo in 8 of 14 patients with delayed vs. 7 of 9 with nondelayed emptying (P = NS) and in 11 of 15 without vs. 4 of 8 with cardiovascular autonomic neuropathy (P = NS). Autonomic neuropathy prevailed in 7 of 14 patients with delayed and 1 of 9 with nondelayed emptying. Blood glucose immediately before and during assessment of emptying was unrelated to the emptying rate, whereas blood glucose increases over fasting levels were greater with faster emptying (P<0.002). In conclusion, cisapride's effects were not different from those of placebo on glycemic control and gastric emptying, it did not differently affect patients with delayed vs. nondelayed emptying, and it slightly accelerated emptying (P = NS) in patients without, but not in those with, cardiovascular autonomic neuropathy. Blood glucose levels before and during assessment of emptying did not affect emptying, but the glucose rise over fasting levels was greater with faster emptying.

Adult↗
PubMed1998

Clinical implications of HIV dynamics and drug resistance in macrophages.

Macrophages are widely recognized as the second major target of HIV in the body. The cellular characteristics of such resting cells markedly affect the dynamics of virus lifecycle, that is slower but far more prolonged that in lymphocytes. In addition, the limited concentrations of endogenous nucleotide pools in macrophages downregulate the enzymatic activity of reverse transcriptase. As a consequence, both the anti-HIV activity and the development of resistance to antiviral drugs in macrophages are substantially different than those found in activated lymphocytes. These peculiar characteristics of virus replication and efficacy of antiviral drugs in macrophages have a natural in vivo counterpart in extralymphoid tissues, where macrophages account for the majority of cells infected by HIV. Furthermore, the replication of HIV in macrophages of testis and central nervous system is far less affected by antiviral drugs than in lymph nodes, because of the presence of natural barriers that markedly diminish the concentration of such drugs. For all these reasons, HIV infection of macrophages should be taken into account in therapeutic strategies aimed to achieve an optimal therapeutic effect in all tissue compartments where the virus hides and replicates.

Anti-HIV Agents↗
PubMed1997

Inhibition of replication of HIV in primary monocyte/macrophages by different antiviral drugs and comparative efficacy in lymphocytes.

Several anti-HIV drugs acting on different steps of virus replication were tested in our experimental model of primary monocyte/macrophages; the results were compared with the activity found in lymphocytes. Nucleoside analogues (AZT, ddI, ddC, d4T, PMEA, 3TC etc.) show greater activity in macrophages (M/M) than in lymphocytes. In particular, the EC50 of AZT, ddC, and ddI in M/M is 2- to 100-fold lower than that found in lymphocytes. This greater efficacy of nucleoside analogues in M/M depends on the enhancement of their chain-terminating activity by the low levels of endogenous deoxynucleoside-triphosphates (dNTP) usually found in resting cells such as M/M. Non-nucleoside reverse transcriptase inhibitors (NNRTI) do not act as chain terminators (thus their antiviral effect is not related to the intracellular concentrations of dNTP); as a consequence the activity of TSAO, HEPT, TIBO, and other NNRTI tested in M/M is similar to that found in lymphocytes. Regarding inhibitors of binding and fusion of HIV, we found that their anti-HIV activity is markedly decreased (or even nullified) when M/M are treated with cytokine activators of M/M function and enhancers of HIV replication. More relevant from a clinical standpoint, protease inhibitors are able to inhibit HIV replication in chronically infected macrophages (i.e., cells carrying the proviral genome already integrated in the host genome). All other inhibitors of late stage of virus life cycle tested (antisense-rev, anti-tat, interferon-alpha and -gamma, phosphorothioate analogues, GLQ-223, etc.) were totally inactive in chronically infected macrophages. The different effects of various classes of HIV inhibitors in lymphocytes and macrophages suggests that AIDS therapy should consider all aspects of the pathogenesis of HIV infection and must be restricted to drugs, or combinations of drugs, active against both lymphocytes and M/M in all body compartments where the virus hides and replicates.

Anti-HIV Agents↗
PubMed1997

Slow gastric emptying in type I diabetes: relation to autonomic and peripheral neuropathy, blood glucose, and glycemic control.

OBJECTIVE: To investigate whether autonomic neuropathy or hyperglycemia plays a crucial etiological role in gastric retention of ingesta frequently found in type I diabetic patients. RESEARCH DESIGN AND METHODS: We investigated the gastric emptying of a radiolabeled semisolid 1,168 kJ meal in 38 female and 45 male patients (age 18-75 years; illness duration 3-46 years). None took drugs affecting gastrointestinal motility. Fasted patients underwent tests of cardiovascular autonomic and peripheral nerve function. Blood glucose levels were determined before and after the scintigraphic recording of gastric emptying. RESULTS: The percentage of meal remaining in the stomach at the end of the 50-min recording time was related significantly to the patients' degree of cardiovascular autonomic neuropathy [r (81) = 0.235, P < 0.028] but not to their degree of peripheral neuropathy, preprandial blood glucose level, HbA1c indicative of glycemic control, diabetes duration, and age. The patients' mean residual percentage of meal was significantly greater than that of 48 healthy subjects, that is, 71.1 +/- 15.1 vs. 53.5 +/- 13.1% [means +/- SD; t (129) = 6.48, P < 0.0001]. The healthy individuals' mean residual percentage + 2 SD was exceeded in 22 patients. CONCLUSIONS: Slow gastric emptying in patients with type I diabetes seems related to the degree of autonomic neuropathy but not to peripheral neuropathy, actual blood glucose, and glycemic control.

Adult↗
PubMed1996

Inhibitory effect of prostacyclin and nitroprusside on type IIB von Willebrand factor-promoted platelet activation.

Von Willebrand disease (vWD) of type IIB is a hereditary haemorrhagic disorder characterised by an excessive interaction of von Willebrand factor (vWF) with the platelet receptor GPIb which promotes platelet activation and aggregation through a phospholipase A2-mediated release of arachidonic acid. The present report shows that prostacyclin and nitroprusside, vasodilator-compounds that enhance the cAMP and cGMP concentration respectively, cause a drastic inhibition of the type IIB vWF-induced platelet responses including increase of cytosolic Ca2+ concentration, phosphorylation of pleckstrin (47 kDa) and myosin light chain (20 kDa), secretion of ATP and serotonin, and aggregation parallel to a decrease of arachidonic acid release. Type IIB vWF also elicits tyrosine phosphorylation of proteins with apparent molecular mass of 60, 74, 82 and 130 kDa. Prostacyclin, which induces per se tyrosine-phosphorylation of proteins of about 38 and 45 kDa, inhibits drastically the type IIB vWF-promoted tyrosine-phosphorylation of the 74 kDa protein while inhibits slightly that of 60 kDa band. The protein tyrosine-kinase inhibitor genistein causes a little decrease in the type IIB vWF-induced release of arachidonic acid. It is concluded that the inhibition exerted by prostacyclin and nitroprusside on type IIB vWF-elicited platelet activation seems to be largely ascribable to prevention of the phospholipase A2 activation with the ensuing decrease of the subsequent protein tyrosine phosphorylation.

Epoprostenol↗