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Biomedical subjects

M Baldassarre

Publications and source records attributed to M Baldassarre.

At least 19 recordsLinked to original sources

Composition and seasonal variation of soluble cuticular waxes in Actinidia deliciosa leaves.

This research examines the annual evolution and composition of soluble cuticular waxes of Actinidia deliciosa Chev. cv Hayward leaves. Soluble cuticular waxes of foliar blade were extracted in chloroform and analysed by GC-MS. The seasonal weighted mean of the wax coverage was about 24 microg cm(-2). The alkyl alkanoates were the main class of components (10 microg cm(-2)) followed by hydrocarbons (6 microg cm(-2)), terpenes (3 microg cm(-2)), alkanols (1 microg cm(-2)), ketones (1 microg cm(-2)), alkanoic acids (1 microg cm(-2)), alkanals (0.7 microg cm(-2)), and sterols (0.6 microg cm(-2)). The concentration of the soluble cuticular components reached a peak (43 microg cm(-2)) on the 83rd day after bud break. Different causes were proposed to explicate the seasonal evolution of the leaf waxes: biosynthesis of the waxes prevalently during rapid leaf growth; natural wax erosion and evaporation; progressive reduction in the extractability of the intracuticular free compounds due to the slow polymerization of the cutin matrix.

Actinidia↗

Burden of first-ever ischemic stroke in the oldest old: evidence from a population-based study.

OBJECTIVE: To evaluate the contribution of subjects 80 years old or older to the burden of ischemic stroke as compared with subjects younger than 80 years. METHODS: All first-ever ischemic strokes occurring in a 5-year period (1994 to 1998) in the population-based L'Aquila registry were traced. Incidence, total health care utilization, disability, and mortality were assessed in patients 80 years old or older, and differences with those younger than 80 years were assessed by univariate and survival analyses. RESULTS: One thousand three hundred sixteen of 3,594 first-ever ischemic strokes (36.6%) occurred in patients 80 years old or older, accounting on average for one-third of health care utilization. The crude annual incidence rate was 21.54 per 1,000 (95% CI 20.42 to 22.72). At the 1-year follow-up, 27.7% of patients had mild or no disability, 20.7% had severe disability, and 51.6% had died. With respect to patients under 80 years of age, older patients showed a higher proportion of women (61.3 vs 47.7%), atrial fibrillation (30.2 vs 20.7%), coronary heart disease (31.0 vs 23.4%), and peripheral arterial disease (14.6 vs 10.8%) and a lower proportion of cigarette smoking (15.3 vs 29.2%) and hypercholesterolemia (20.4 vs 29.4%). Thirty-day (34.6 vs 13.4%) and 1-year (51.6 vs 22.3%) mortality were higher in patients 80 years old or older than in those younger than 80, mostly in the presence of atrial fibrillation (hazard ratio [HR] was 1.39 for 30-day mortality and 1.37 for 1-year mortality) and diabetes mellitus (HR was 1.39 for 30-day mortality and 1.31 for 1-year mortality). CONCLUSION: The burden of ischemic stroke is high in subjects 80 years old or older, contributing about one-third of health care utilization and 59.8% of deaths within 30 days.

Age Distribution↗

Urinary pharmacokinetics and theoretical pharmacodynamics of intravenous levofloxacin in intensive care unit patients treated with 500 mg b.i.d. for ventilator-associated pneumonia.

This study assessed the urinary pharmacokinetics and theoretical pharmacodynamics of levofloxacin in ICU patients treated with 500 mg b.i.d. i.v. for ventilator associated pneumonia to evaluate if this high dosage regimen might ensure appropriate exposure in the treatment of severe UTIs in ICU patients. Nineteen patients (11M, 8F; age, 52 +/- 21 years; weight, 75 +/- 16 kg) presenting with normal renal function (estimated creatinine clearance, 1.83 +/- 0.61 ml/min/kg; diuresis, 1709 +/- 643ml / 24h) were assessed. In steady-state conditions, urine samples were collected at 0-2h, 2-4h, 4-8h and 8-12h during a dosing interval, and urinary concentrations of levofloxacin were assayed by HPLC. Mean (+/- SD) levofloxacin urinary concentrations were 329.1 +/- 159.9, 388.6 +/- 143.5, 266.0 +/- 102.8 and 168.1 +/- 93.3mg/L at 0-2h, 2-4h, 4-8h and 8-12h, respectively, with urinary AUC0-tau of 3171.4 +/- 1192.1mg/L x h. Mean (+/- SD) levofloxacin excretion rates were 44.1 +/- 20.7, 42.8 +/- 8.2, 31.7 +/- 5.8 and 19.8 +/- 4.2 mg/h during the 0-2h, 2-4, 4-8h and 8-12h interval, respectively. Our findings suggest that, consistently with levofloxacin showing high renal excretion as unmodified drug, 500mg b.i.d. i.v. of levofloxacin ensure and maintain urinary concentrations at least 50-fold higher than the MIC90 of most sensitive uropathogens during the overall dosing interval in ICU patients with normal renal function. Considering the major pharmacodynamic determinants for the concentration-dependent bactericidal activity of levofloxacin as applicable at the urinary level (CU/MIC of >12.2 and/or AUC24h U /MIC of >125h), this high dosage regimen may ensure optimal exposure for the treatment of catheter-related and severe lower UTIs not only against sensitive microorganisms, but probably also whenever microorganisms usually considered as intermediate susceptible or resistant to levofloxacin may be involved.

Adult↗

Determination of cerebral water content by magnetic resonance imaging after small volume infusion of 18% hypertonic saline solution in a patient with refractory intracranial hypertension.

Hypertonic saline solution (HSS) has been investigated in the treatment of intracranial hypertension (ICH) in a limited number of studies, usually after failure of conventional treatment. HSS, used in concentrations that vary from 3% to 23.4%, seems to be effective in reducing refractory ICH and to be devoid of adverse effects. We treated a patient with refractory ICH with a small-volume infusion of 18% HSS, and performed magnetic resonance imaging (MRI) before and after HSS infusion. MRI showed a marked reduction in cerebral water content 1 h after the infusion. To our knowledge, this is the first MRI study in a patient with brain injury to evaluate the effect of HSS on brain water content. Further studies are necessary to test HSS efficacy and to identify, through MRI or computed tomography (CT) scan imaging, a subgroup of patients with brain injury who would be best treated with HSS.

Accidents, Traffic↗

Proportion of older people in the community as a predictor of increasing stroke incidence.

OBJECTIVES: To compare stroke incidence rates among comparable registries and to make correlations with aging of the resident populations. METHODS: This correlation study included all comparable stroke registries maintained in industrialized countries (Italy, France, United Kingdom, Denmark, Norway, United States, and Australia). Eleven community-based stroke registries with similar high proportions of radiologically confirmed diagnoses based on standard definitions were identified. Incidence rates of first-ever stroke from the prospective L'Aquila registry and from the other registries were compared after age and sex standardization to the 1996 European population. The rates were then correlated with the proportion of individuals aged 65 and over in the corresponding resident populations by means of the Poisson regression analysis. RESULTS: In the L'Aquila registry, the crude annual incidence of first-ever stroke was 281/100,000 (95% confidence interval 271-293) based on 2,515 patients included during a 3-year period. The rate standardized to the European population was 249/100,000. Standardized incidence ratios indicated a significant excess of first-ever strokes in the L'Aquila registry up to 51% with respect to most of the compared studies. A significant correlation was also found between crude (p < 0.0001) and standardized (p = 0.0012) stroke incidence rates and proportions of individuals aged 65 and over in the different populations. CONCLUSIONS: The L'Aquila experience suggests that any further aging of a population will increase the stroke occurrence for both the reasons of a direct and predictable effect of the growing proportion of elderly individuals within that population and a disproportionately increased stroke risk in the older age groups.

Adolescent↗

Stroke in young adults in the community-based L'Aquila registry: incidence and prognosis.

BACKGROUND AND PURPOSE: Stroke type in the young may influence the outcome and may have a dramatic impact on the quality of life in survivors. This study aimed to evaluate the incidence and prognosis of first-ever stroke in the young and to make comparisons with older patients within a well-defined population. METHODS: All first-ever strokes occurring in the L'Aquila district, central Italy, were traced by active monitoring of inpatient and outpatient health services. Incidence rates were standardized to the 1996 European population according to the direct method. Long-term survival was estimated by the Kaplan-Meier method; outcome in survivors was evaluated by the modified Rankin scale. RESULTS: Of 4353 patients who had a first-ever stroke, 89 patients <45 years of age (55 men and 34 women) (2%) were identified in a 5-year period. Mean age+/-SD was 36.1+/-8.1 years. Twenty patients (22.5%) had a subarachnoid hemorrhage, 18 (20.2%) an intracerebral hemorrhage, and 51 (57.3%) a cerebral infarction. The corresponding proportions in patients >45 years of age were 2.4%, 13.3%, and 83.1%. Neuroimaging studies of the brain detected 14 intracranial aneurysms and 6 arteriovenous malformations in 20 of 38 patients (52.6%) with either subarachnoid (n=17) or intracerebral (n=3) hemorrhage. The crude annual incidence rate was 10.18/100,000 (95% CI, 8.14 to 12.57) and 10.23/100,000 when standardized to the 1996 European population. The 30-day case-fatality rate was 11.2% (95% CI, 6.2 to 19.4). Patients with subarachnoid hemorrhage had the highest proportion of good recovery (60%), patients with intracerebral hemorrhage had the highest mortality (44%), and patients with cerebral infarction had the highest proportion of severe disability (47%). CONCLUSIONS: Stroke patients <45 years of age showed a disproportionate cumulative high prevalence (42.7%) of subarachnoid and intracerebral hemorrhage with respect to older patients (15.7%), mainly (52.6%) due to aneurysms and arteriovenous malformations. Therefore, screening procedures and preventive strategies in the young should also be addressed to subjects at risk of subarachnoid and intracerebral hemorrhage.

Adult↗

The lysosomal protease cathepsin D is efficiently sorted to and secreted from regulated secretory compartments in the rat basophilic/mast cell line RBL.

Basophils and mast cells contain a peculiar class of inflammatory granules that discharge their content upon antigen-mediated crosslinking of IgE-membrane receptors. The pathways for granule biogenesis and exocytosis in these cells are still largely obscure. In this study we employed the rat basophilic leukemia (RBL)/mast cell line to verify the hypothesis that inflammatory granules share common bioactive molecules and functional properties with lysosomes. We demonstrate that inflammatory granules, as identified by the monoclonal 5G10 antibody (which recognises an integral membrane protein) or by Toluidine Blue staining, have an intralumenal acidic pH, possess lysosomal enzymes and are accessible by fluid-phase and membrane endocytosis markers. In addition, we studied the targeting, subcellular localisation and regulated secretion of the lysosomal aspartic protease cathepsin D (CD) as affected by IgE receptor stimulation in order to obtain information on the pathways for granule biogenesis and exocytosis. Stimulation with DNP-BSA of specific IgE-primed RBL cells led to a prompt release of processed forms of CD, along with other mature lysosomal hydrolases. This release could be prevented by addition of EGTA, indicating that it was dependent on extracellular calcium influx. Antigen stimulation also induced exocytosis of immature CD forms accumulated by ammonium chloride, suggesting the existence of an intermediate station in the pathway for granule biogenesis still sensitive to regulated exocytosis. The targeting of molecules to secretory granules may occur via either a mannose-6-phosphate-dependent or mannose-6-phosphate-independent pathway. We conclude that endosomes and lysosomes in basophils/mast cells can act as regulated secretory granules or actually identify with them.

Animals↗

Regulation of protein sorting at the TGN by plasma membrane receptor activation.

We show that in the rat basophilic leukemia cell line RBL, the physiological stimulation of the IgE receptor or direct activation of PKC leads to the missorting of proteins to the plasma membrane, diverting them from their normal intracellular destination. This is demonstrated for two classes of proteins that are normally targeted to the secretory lysosomes via completely different mechanisms, i.e. proteoglycans and the aspartic protease cathepsin D. In the latter case, normal processing of the enzyme is also affected, leading to secretion of the immature form of cathepsin. The present study shows how completely different sorting mechanisms, such as those for delivering proteoglycans and cathepsin D to secretory lysosomes, might share common regulatory signals and are similarly affected when the levels of these signals are perturbed. Finally, protein kinase C appears to be a major player in the signal transduction pathways, leading to proteoglycan and cathepsin D missorting.

Animals↗

Morphological and biochemical analysis of the secretory pathway in melanoma cells with distinct metastatic potential.

In this report, we have investigated whether alterations of the morphological and functional aspects of the biosecretory membrane system are associated with the metastatic potential of tumor cells. To this end, we have analyzed the morphology of the Golgi complex, the cytoskeleton organization and membrane trafficking steps of the secretory pathway in two human melanoma A375 cell line variants with low (A375-P) and high metastatic (A375-MM) potential. Immunofluorescence analysis showed that in A375-P cells, the Golgi complex showed a collapsed morphology. Conversely, in A375-MM cells, the Golgi complex presented a reticular and extended morphology. At the ultrastructural level, the Golgi complex of A375-P cells was fragmented and cisternae were swollen. When the cytoskeleton was analyzed, the microtubular network appeared normal in both cell variants, whereas actin stress fibers were largely absent in A375-P, but not in A375-MM cells. In addition, the F-actin content in A375-P cells was significantly lower than in A375-MM cells. These morphological differences in A375-P cells were accompanied by acceleration and an increase in the endoplasmic reticulum to Golgi and the trans-Golgi network to cell surface membrane transport, respectively. Our results indicate that in human A375 melanoma cells, metastatic potential correlates with a well-structured morphofunctional organization of the Golgi complex and actin cytoskeleton.

Biological Transport↗

Spontaneous rupture of the iliac vein.

Two unusual cases of iliac vein spontaneous rupture into the retroperitoneum are presented together with 18 cases reported by the literature. In one patient of ours, entrapment of clots in an IVC filter and proximal iliac vein involvement into the scar tissue surrounding the left limb of an aortoiliac bifurcation graft might have caused flow disturbances and subsequent predisposition to rupture of the thrombosed external iliac vein. Inflammatory parietal changes, including infiltration of macrophages, T and B lymphocytes producing elastin degradation by means of cytokines, may have led ultimately to vein disruption. Despite clinical features and CT scan findings, the physician's awareness of this disease remains the most important factor for the early treatment.

Aged↗

Procollagen traverses the Golgi stack without leaving the lumen of cisternae: evidence for cisternal maturation.

Newly synthesized procollagen type I (PC) assembles into 300 nm rigid, rod-like triple helices in the lumen of the endoplasmic reticulum. This oligomeric complex moves to the Golgi and forms large electron-dense aggregates. We have monitored the transport of PC along the secretory pathway. We show that PC moves across the Golgi stacks without ever leaving the lumen of the Golgi cisternae. During transport from the endoplasmic reticulum to the Golgi, PC is found within tubular-saccular structures greater than 300 nm in length. Thus, supermolecular cargoes such as PC do not utilize the conventional vesicle-mediated transport to traverse the Golgi stacks. Our results imply that PC moves in the anterograde direction across the Golgi complex by a process involving progressive maturation of Golgi cisternae.

2,2'-Dipyridyl↗

[High prevalence of hepatitis C virus infection in patients with non-Hodgkin's lymphoma at the onset. Preliminary results of an Italian multicenter study].

143 patients with non-Hodgkin lymphoma (NHL) at the onset entered this perspective study on NHL-associated risk factors. They were 87 males and 56 females with a mean age of 52.3 years (range 14.6-82.3). An associated hepatitis C virus (HCV) infection was found in 16 of the 143 NHL cases (11.2%; 95% CI 6.5-17.5). They were 11 males and 5 females [mean age 59.9] year with disseminated (13/16) or localized NHL disease (3/16)]. The NHL histological subgroup was low grade (6/16), intermediate grade (2/16) or high grade (8/16). The cell origin was B in 15/16 cases and B cell-T cell rich in 1/16. The discovery of HCV infection was contemporary to lymphoma diagnosis in 6/16 cases but preceded the NHL onset in the other 10 patients. In these 10 patients the median time between HCV infection diagnosis and NHL onset was 3.6 years (range 1-14.5). These data confirm that in Italy the prevalence of HCV infection in patients with NHL (11.2%) is significantly higher than expected in the general population (1.3-3.2%). The finding that, in most cases, HCV infection was definitely antecedent to NHL onset, usually by years, adds evidence to the possible causative role of the HCV in lymphomagenesis.

Adolescent↗

Neutrophil extracted lipocortin inhibits corticotropin secretion in the AtT-20 D16:16 clonal mouse pituitary cell line. Lipocortin inhibition of ACTH release in vitro.

The mechanism of short-term glucocorticoid (GC) inhibition of the hypothalamic-pituitary-adrenal axis is not well understood. The direct anti-inflammatory activities of lipocortins (LCs) have suggested a role for them as extra- and intracellular mediators of the biological effects of GCs. It has been reported that recombinant human (rh) LC1 inhibits corticotropin (ACTH) release from pituitary tissue in vitro but not from AtT-20 D16:16 corticotrophs. Using the same cell line we have tested whether other exogenous rhLCs or native LC extracted from polymorphonucleate neutrophils (neLC), likely LC1, have an effect on ACTH secretion. It is shown that: (1) basal release was not affected by a short-term incubation with neLC; (2) secretion induced by corticotropin-releasing factor (CRF) and other secretagogues (phorbol ester, potassium ion or calcium ionophore) was inhibited by neLC; (3) GC inhibition of CRF-stimulated release was reverted by a monoclonal anti-neLC antibody; (4) rhLC2, rhLC5 and the fragment 212-234 of rhLC5 were without effect. Thus, only neLC is effective on AtT-20 D16:16 cells, suggesting for this annexin a role in the early phase GC inhibition of ACTH secretion.

Adrenocorticotropic Hormone↗

Role of pancreatic impairment in growth recovery during gluten-free diet in childhood celiac disease.

BACKGROUND & AIMS: Clinical significance and duration of insufficient release of pancreatic enzymes in childhood celiac disease have not been clarified. The aim of this study was to evaluate the role that pancreatic impairment plays in growth recovery and the duration of this impairment. METHODS: Forty-six patients with celiac disease who had a median age of 2.5 years were enrolled. Fecal chymotrypsin level was determined at diagnosis and then every 15 days after the beginning of a gluten-free diet in all patients. RESULTS: At diagnosis, 17 of 46 patients with celiac disease had subnormal fecal chymotrypsin values. During the gluten-free diet, a progressive reduction in the percentage of patients with subnormal fecal chymotrypsin values was observed: 12 of 46 patients after 30 days and 2 of 46 patients after 60 days. Weight increase after 2 months of gluten-free diet was significantly greater in patients with normal fecal chymotrypsin values at diagnosis than in patients with subnormal values, and a positive correlation was found between fecal chymotrypsin at diagnosis and weight increase (r = 0.56). CONCLUSIONS: A small percentage of patients with celiac disease still had subnormal chymotrypsin concentrations after 60 days of gluten-free diet. Fecal chymotrypsin is a predictive index of weight recovery in the first months after diagnosis of celiac disease; it could be used to select patients for enzyme supplementation therapy.

Body Weight↗

High stroke incidence in the prospective community-based L'Aquila registry (1994-1998). First year's results.

BACKGROUND AND PURPOSE: Changes in stroke incidence are likely to occur as a consequence of aging of the population, but evidence for this hypothesis is lacking. METHODS: A prospective community-based registry of first-ever strokes (1994 to 1998) classified according to the International Classification of Diseases, 9th Revision (ICD-9) was established in the L'Aquila district, central Italy, with a total population of 297,838 (1991 census). Patients were identified by active monitoring of multiple sources, including general practitioners. RESULTS: In 1994, 819 patients (398 men and 421 women; mean +/- SD age, 74.8 +/- 11.3 years) suffered from a first-ever stroke. Eighty-nine percent of the patients had neuroimaging studies of the brain and were reclassified with the recent Application of the International Classification of Diseases to Neurology (ICD-10 NA). The occurrence of subarachnoid hemorrhage, intracerebral hemorrhage, cerebral infarction, and ill-defined events was 2.9%, 14.9%, 80.2%, and 2.0%, respectively. Crude annual incidence of first-ever stroke was 2.75/1000 (95% confidence interval [CI], 2.57 to 2.94) and 24.23/1000 (95% CI, 21.65 to 27.10) in patients older than 80 years. Incidence rates were higher in men and steeply increased with age. The standardized rate was 2.37/1000 for the Italian and 2.28/1000 for the European population. The 30-day case-fatality rate was 25.6% (95% CI, 22.8% to 28.7%). The occurrence of death, disability, and full recovery at 1 year was 36.9%, 38.9%, and 24.2%, respectively. No differences were found in stroke incidence and case-fatality according to income and urban or rural residences. CONCLUSIONS: In our population-based study, we found a high stroke incidence notably in the older age subgroups, suggesting that rather than declining, stroke is only being postponed until later in life.

Adult↗

Combined vascular injuries and limb fractures.

Blunt arterial injuries secondary to bone fractures are frequently associated with nerve, vein and soft tissue lesions. A delayed diagnosis or treatment is the main cause of high amputation rate. Thirty-four patients presenting acute arterial occlusion (15 cases), false aneurysms (13 cases) or AVFs (6 cases) of the extremity were identified between 1983 and 1995. To repair injured arteries, ligation (3 cases), patch angioplasty (6 cases), autogenous vein (15 patients) or PTFE (4 cases) interposition or bypass grafting were made. Percutaneous embolization by coils was performed in 3 AVFs of small limb arteries. Associated venous lesions were treated in 9 patients. External fixation of long bone fractures was made in 29 patients, before vascular reconstruction, to prevent further injury during orthopedic stabilization. Fasciotomies were made in 6 patients to treat compartmental hypertension. Early reexplorations were necessary to correct technical defects in 4 patients. Hyperbaric oxygen therapy was applied in 7 patients to control bacterial contamination and improve wound healing. Primary (2 cases) or secondary (3 cases) amputations were carried out in unsalvageable limbs. Nerve or extensive muscle damage caused poor functional outcome in 4 patients. A multidisciplinary diagnostic and management strategy is required to improve limb and patient survival.

Adolescent↗

Late arteriovenous fistulas and pseudoaneurysms of the extremity secondary to civilian firearms.

To evaluate the treatment of late sequelae of penetrating arterial injuries associated with civilian firearms, such as false aneurysms and arteriovenous fistulas (AV-Fs) of the extremities, a retrospective clinical study was carried out. Whenever diagnosis or operative management is delayed because of local fibrosis or morphological and structural vessel changes, primary repair is not feasible and segmental resection is required. Twenty-four patients presenting late false aneurysms (14) and AV-Fs (11) of the extremities, caused by firearms (6 rifle wounds, and 18 pistol wounds), were identified between 1983 and 1995. Twenty-three patients were submitted to resection of pseudoaneurysms (13) or AV-Fs (8), while arterial patch angioplasty was applied in two patients. The venous lesions were repaired by an interposition graft (7) or lateral venorraphy (3). Saphenous vein (15) or PTFE (6) grafts were placed in injured arteries. Percutaneous embolization by coils was performed in two patients. Twenty-three out of 24 patients (95.8%) recovered; one patient (4.1%), affected by aneurysmal AV-Fs of a lower limb dating from 12 years, with enlarged and weakened artery, bled to death. No limb loss occurred. A better evaluation of minimal vascular injuries is required to avoid late sequelae of civilian firearms lesions, with significant blood loss, which need segmental excision of the injured vessels.

Adolescent↗

Popliteal artery entrapment syndrome: diagnosis and management.

A variety of anatomical abnormalities may product an external compression of the popliteal artery, resulting in a thrombotic occlusion. Between 1983 and 1995, 9 patients presented a popliteal artery entrapment syndrome, bilateral in two cases. Ultrasonography, Angio-CT scan and MRI showed the abnormal structures and position of the popliteal artery on popliteal fossa. Arteriography detected an arterial compression in 6 limbs and occlusion in 4 limbs as well as an associated popliteal aneurysm in one patient and distal embolism in four. The abnormal medial head of the gastrocnemius muscle was resected in 8 limbs, while fibrous membranes were resected in 3 limbs. Autogenous vein replacement was performed in 4 cases of popliteal artery occlusion and following resection of a popliteal artery aneurysm in one case. All patients recovered. In the followup period, the occlusion of the arterial reconstruction occurred after 28 months in one patient, with a mild claudication. Noninvasive vascular imaging techniques may allow early diagnosis and management of PAES, avoiding popliteal arterial wall lesions and its occlusion, with a better outcome.

Adolescent↗