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Biomedical subjects

G Marconi

Publications and source records attributed to G Marconi.

At least 19 recordsLinked to original sources

Opioid-related side-effects after intrathecal morphine: a prospective, randomized, double-blind dose-response study.

BACKGROUND AND OBJECTIVE: The aim of this prospective, randomized, double-blind investigation was to assess the dose-effect characteristics of postoperative nausea and vomiting after intrathecal administration of small doses of morphine (from 0.015 to 0.25 mg) in opioid-naïve, non-surgical patients. METHODS: With Ethic Committee approval and written informed consent 144 opioid-naïve patients suffering from non-cancerous chronic back-pain, and receiving intrathecal morphine as diagnostic test for their chronic pain, were randomly allocated to receive intrathecal injection of 0.015 mg (Group I, n=25), 0.03 mg (Group II, n=30), 0.06 mg (Group III, n=31) or 0.25 mg (Group IV, n=33) morphine. The control group consisted in 25 further patients not included in the dose-effect study and receiving a placebo injection of normal saline in the interspinous ligament. A blinded observer recorded the occurrence of pruritus, nausea, vomiting, urinary retention and respiratory depression (respiratory rate<6 bpm) at 2, 4 and 24 h after injection. RESULTS: Clinically significant pain relief was observed in all patients receiving intrathecal morphine but only six patients (25%) of the control group (P=0.0005). The incidence of pruritus was lower in patients of Groups III (6%) and IV (3%) than in Groups I (12%) and II (20%) (P=0.002). The incidence of nausea and vomiting was higher at 2- and 4-h observation times, and decreased 24 h after intrathecal injection. Surprisingly, nausea was more frequent in Groups I (56%) and II (50%) than in Groups III (33%) and IV (24%) (P=0.0005). Vomiting was higher in patients receiving morphine than in control group, but without differences among the four doses. No urinary retention was observed in the control group, while 2 h after intrathecal injection urinary retention was observed in 20-40% of cases, and decreased to less than 10% 24 h after spinal injection without differences among the four doses. CONCLUSIONS: The onset and incidence of minor opioid-related side-effects after intrathecal morphine administration do not depend on its dose, occurring with even very small doses of morphine. Accordingly, they can be considered as a patient-dependent effect of the drug, suggesting the presence of a primary dose-independent excitatory component that might be related to the theory of the bimodal activation of opioid receptors. The very low incidence major respiratory depression prevents us from drawing any conclusion about the dose-effect relationship for this side-effect, and further properly powered studies should be advocated to evaluate major respiratory depression after spinal morphine.

Aged↗

Living donor liver transplantation and management of portal venous pressure.

Small-for-size syndrome occurs in the presence of a reduced mass of liver that is insufficient to maintain normal liver function. It has been speculated that this dysfunction is principally associated with graft exposure to excessive portal perfusion. The aim of these cases was to evaluate the efficacy of octreotide, a splanchnic vasoconstrictor, and esmolol, a selective beta-blocker, to modify the portal perfusion in the postoperative phase after left living related liver transplantation (LRLT). Four patients who underwent left LRLT with graft-to-recipient weight ratios of 0.60 +/- 0.24 were studied with a catheter placed in a jejunal vein. We observed high basal values of hepatic venous pressure gradient (HVPG) and portal vein flow (PVF). Octreotide infusion decreased HVPG, an effect that was more pronounced when it was combined with esmolol. The administration of both drugs was also associated with an improvement in portal vein oxygen saturation. Despite variation in PVF, the plasma disappearance rate of indocyanin green did not change during the infusion of the two drugs. In conclusion, octreotide and esmolol infusion allowed a manipulation of portal vein pressure that should be measured in left LRLT using a small-for-size graft.

Blood Pressure↗

Radiolytically induced one-electron reduction of artemisinin in H2O/ethanol (1:1 v/v) solution: a pulse radiolysis study.

The aim was to obtain information on the one-electron reduction of the antimalarial natural drug artemisinin (ART). The pulse radiolysis of ART in H(2)O/ethanol (EtOH) (1:1 v/v) solution was studied in the absence and presence of the so-called redox indicators N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD), Fe(CN)6(4-), 1,1'-dimethyl-4,4'-bipyridinium dichloride (methyl viologen, MV(2+)) and Fe(CN)6(3-). In an argon-purged solution, ART reacts with solvated electrons (es(-)) with k=4.4 x 10(9) dm(3) mol(-1) s(-1) generating an absorption band rising in the ultraviolet region similar to the spectrum of the CH3(*)CHOH radical. The species originating from the reaction between ART and es(-) do not show any appreciable reactivity toward Fe(CN)6(4-), TMPD, MV(2+) and Fe(CN)6(3-). The experiments performed in the presence of ART and MV(2+) have provided strong support to the idea that the first species obtained from the addition of the electron, which is believed to occur at the endoperoxide group level, undergoes a rapid (k on the order of 10(8) s(-1) or higher) intramolecular rearrangement to give species, most likely carbon-centred radicals, that show some reactivity towards the methyl viologen radical cation (MV(*+)).

Artemisinins↗

Pure quadriceps myopathy in two sisters.

The authors carried out a clinical, laboratory and muscle computed tomographgy CT follow-up study of 18-21 years on two sisters affected by quadriceps myopathy (QM). The onset in the fourth decade was a weakness in the thighs. During the follow-up study, the patients showed only vasti muscles involvement, normal creatine kinase (CK) levels, myopathic muscle biopsy and electromyography (EMG) and normal membrane protein expression on immunocytochemical analysis. Therefore, all muscle pathologies known to have quadriceps involvement as a leading feature have been ruled out. We conclude that our patients have pure QM with probable autosomal recessive inheritance.

Biopsy↗

Development of S-SAP markers based on an LTR-like sequence from Medicago sativa L.

The Sequence-Specific Amplification Polymorphism (S-SAP) method, recently derived from the Amplified Fragment Length Polymorphism (AFLP) technique, produces amplified fragments containing a retrotransposon LTR sequence at one end and a host restriction site at the other. We report the application of this procedure to the LTR of the Tms1 element from Medicago sativa L. Genomic dot-blot analysis indicated that Tms1 LTRs represent about 0.056% of the M. sativa genome, corresponding to 16 x 10(3) copies per haploid genome. An average of 66 markers were amplified for each primer combination. Overall 49 polymorphic fragments were reliably scored and mapped in a F(1) population obtained by crossing diploid M. falcata with M. coerulea. The utility of the LTR S-SAP markers was higher than that of AFLP or SAMPL (Selective Amplification of Microsatellite Polymorphic Loci) markers. The efficiency index of the LTR S-SAP assay was 28.3, whereas the corresponding values for AFLP and SAMPL markers were 21.1 and 16.7, respectively. The marker index for S-SAP was 13.1, compared to 8.8 for AFLP and 9.5 for SAMPL. Application of the Tms1 LTR-based S-SAP to double-stranded cDNA resulted in a complex banding pattern, demonstrating the presence of Tms1 LTRs within exons. As the technique was successfully applied to other species of the genus Medicago, it should prove suitable for studying genetic diversity within, and relatedness between, alfalfa species.

DNA, Complementary↗

Axial myopathy--an unrecognised entity.

Axial myopathy (AM) is a rare neuromuscular disorder characterised by selective involvement of the spinal muscles with a bent spine and/or drooping head as leading clinical features. We here report the results of clinical, histopathological, MRI, molecular genetics and electrophysiological investigations carried out on six patients affected by pure axial myopathy. Symptoms appeared within an age range of 35 to 56 years. The first symptoms were difficulty in keeping the trunk and head in an upright position. Both bent spine and dropped head were reduced in a supine position. The disease was slowly progressive. Muscle strength examination and muscle imaging revealed involvement of the spinal and neck extensor muscles only. Serum CK was normal to slightly increased. EMG and muscle biopsy specimens obtained from spinal muscles showed an advanced chronic myopathic pattern. We conclude that axial myopathy may be much more common than previously thought, because gradual progression of cervical kyphosis may often be explained as a feature of normal ageing or as an associated sign of several neurological disorders and vertebral degeneration diseases.

Aged↗

Synthesis and electronic properties of covalent assemblies of oligophenylenevinylene units arising from a calix.

Assemblies of four oligophenylenevinylene moieties arising from a calix[4]arene core, i.e., calix[4]oligophenylenevinylenes, have been prepared by Heck-type cross-coupling reactions of styrene derivatives with a tetraiodinated cone-calix[4]arene precursor. Photophysical studies in solution have revealed that there are electronic ground state interactions between the covalently bonded OPV moieties. The absorption spectra of the calix[4]oligophenylenevinylenes are significantly different from those obtained by summing the spectra of four model units and their emission is red-shifted when compared to the corresponding model compounds. Electrochemical studies have shown that the redox processes of the four OPV subunits do not take place at the same potentials indicating also a strong electronic interaction among them in the calix[4]oligophenylenevinylenes.

Journal Article↗

Co-conformational variability of cyclodextrin complexes studied by induced circular dichroism of azoalkanes.

The solution structures of the beta-cyclodextrin complexes between 2,3-diazabicyclo[2.2.2]oct-2-ene (1) and its 1-isopropyl-4-methyl derivative 2 have been investigated by means of induced circular dichroism (ICD) and MM3-92 force-field calculations, which considered the effect of solvation within a continuum approximation. Of primary interest was the so-called co-conformation of the host-guest complex, i.e., the relative orientation of the guest within the host. A pool of low-energy complex structures, which were located by means of a Monte Carlo simulated annealing routine, was generated to evaluate the dynamic co-conformational variability of the complexes. The ICD effects were calculated for the computed low-energy structures by applying a semiempirical method. The experimental and theoretical ICD as well as the calculated low-energy complex geometries suggest solution co-conformations in which the parent compound 1 adapts a lateral arrangement with the ethano bridge of the guest penetrating deepest into the cavity and the azo group aligning parallel to the plane of the upper rim. In contrast, the alkyl derivative 2 prefers a frontal co-conformation with the isopropyl group penetrating deepest into the cavity and the azo group aligning perpendicular to the plane of the upper rim. The validity of the predictions of the Harata rule regarding the sign and the intensity of the ICD signals for the n(-)pi, n(+)pi, and pipi transition of the azo chromophore in dependence on the complex co-conformation are discussed. With respect to the co-conformational variability of the complexes of the two azoalkanes, it was observed that the nearly spherical guest 1 forms a geometrically better defined complex than the sterically biased, alkyl-substituted derivative 2. This dichotomy is attributed to the largely different modes of binding for azoalkanes 1 and 2. It is concluded that the goodness-of-fit in a host-guest complex cannot be directly related to the "tightness-of-fit".

Journal Article↗

Dysferlinopathy (LGMD2B): a 23-year follow-up study of 10 patients homozygous for the same frameshifting dysferlin mutations.

The limb-girdle muscular dystrophies are a group of inherited neuromuscular disorders which are clinically and genetically heterogeneous. We have been able to carry out a follow-up study on 10 patients from a large Palestinian family with a confirmed mutation in the dysferlin gene. These patients have been followed for more than 23 years since the onset of the disease. They all had normal developmental milestones. The onset of the disease was usually in the second decade, more rarely in the third and fourth decades. The first symptoms were difficulty with running and climbing stairs. Patients showed a distinct type of gait due to the unique pattern of muscle involvement which was characterised by early involvement of the posterior muscle compartment of the thighs and legs (hamstrings, adductors, gastrocnemius and soleus). The shoulder and upper limb musculature became involved later, especially supra and infraspinatus and biceps. In the early stages of disease these patients may clinically show only proximal lower limb-girdle muscle weakness; however, the use of muscle imaging techniques were very important, always detecting in these patients also distal lower limb muscle involvement, so that the pattern of muscle involvement found in dysferlin deficiency may not strictly conform to the definition of limb-girdle muscular dystrophy. The pattern of muscular dystrophy is essentially uniform and has clearly distinct features (involving mainly the initial pattern of muscle involvement and the mode of gait) which differ significantly from the well reported clinical features associated with sarcoglycanopathy, calpainopathy and Miyoshi myopathy.

Adolescent↗

Muscle CT in peripheral neuropathies.

We studied retrospectively the muscle CT scans of 60 acquired and 40 congenital motor peripheral neuropathies in order to define the diagnostic usefulness of muscle CT in these disorders. Fifty-five percent of the acquired and 72% of the congenital forms showed muscle CT pathological changes correlated to the clinical severity. The typical finding was pure muscle atrophy but several patients also revealed areas of hypodensity. In most of the acquired forms, muscle changes affected both the thighs and legs with a prevalent involvement of the posterior muscles. The congenital forms showed early involvement of the anterior leg muscles. Our study suggests that a CT scan might be useful in evaluating the severity of muscular atrophy, its evolution in time and the prognosis of motor function, in confirming the diagnosis of acquired or congenital neuropathies, and in some cases in defining the phenotypes of congenital forms.

Adolescent↗

Relationship of ovarian stimulation response with vascular endothelial growth factor and degree of granulosa cell apoptosis.

BACKGROUND: The aim of this study was to evaluate the concentration of vascular endothelial growth factor (VEGF) in follicular fluid and in granulosa cell cultures in relation to the degree of apoptosis in granulosa cells from patients with different types of ovarian response to controlled ovarian hyperstimulation. METHODS: We studied 30 women who underwent controlled ovarian hyperstimulation and oocyte retrieval. Group A comprised patients with 1-4 follicles (n = 10), group B patients with 5-14 follicles (n = 10) and group C patients with >15 follicles (n = 10). RESULTS: Mean (+/-SD) VEGF concentrations in follicular fluid were 1232 +/- 209, 813 +/- 198 and 396 +/- 103 pg/ml for groups A, B and C respectively (P > 0.01). Concentrations of VEGF in granulosa cell supernatant were 684 +/- 316, 1101 +/- 295 and 1596 +/- 227 pg/ml respectively (P < 0.05). Percentages of apoptotic cells in granulosa cells culture was 55.02 +/- 7.5, 23.98 +/- 4.4 and 14.2 +/- 2.3% respectively (A versus B, P < 0.01, A versus C, P < 0.006, B versus C, NS). CONCLUSIONS: Our findings showed that in patients with decreased ovarian response to controlled ovarian hyperstimulation, follicular fluid VEGF concentration is elevated, the concentration from granulosa cells culture supernatant is decreased and the percentage of apoptotic granulosa cells is increased, while opposite findings occurred in patients with normal or hyper-responses.

Adult↗

The photochemistry of flutamide and its inclusion complex with beta-cyclodextrin. Dramatic effect of the microenvironment on the nature and on the efficiency of the photodegradation pathways.

The photochemistry of the anticancer drug flutamide (FM), 2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide, in homogeneous media and in the beta-cyclodextrin (beta-CD) cavity has been investigated. The photoreactivity of the free molecule has been rationalized on the basis of an intramolecular nitro to nitrite rearrangement followed by cleavage of the nitrite intermediate. The twisted geometry of the nitro group with respect to the aromatic plane plays a key role in triggering such a photoprocess. Incorporation of FM in the beta-CD cavity leads to dramatic effects on both the efficiency and the nature of the photochemical deactivation pathways of the guest molecule. A 20-fold increase in the FM photodecomposition quantum yield and the formation of photoproducts originated by both reduction of the nitro group and cleavage of the amide bond were observed in the presence of the macrocycle. Such a behavior cannot be attributed exclusively to the micropolarity of beta-CD and/or to its role as a reactant. The induced circular dichroism spectra and the nature of the photoproducts formed in these experimental conditions provide indications that the photoreactivity in the beta-CD microenvironment could likely be mediated by structural changes of FM upon complexation.

Antineoplastic Agents, Hormonal↗

Interaction of 4-hydroxybiphenyl with cyclodextrins: effect of complex structure on spectroscopic and photophysical properties.

The structures, spectroscopic and photophysical properties of the inclusion complexes between 4-OH-biphenyl and cyclodextrins (CD) in water were studied theoretically and experimentally. The complex structures were predicted using a dynamic Monte Carlo procedure including solvation effects and analyzed via computed and experimentally determined circular dichroism. The interpretation of the induced circular dichroism spectra indicated the formation of stable 2:2 complexes between the probe and alpha-CD, while 1:1 structures account for the circular dichroism induced by beta- and gamma-CD. Fluorescence emission quantum yields and lifetimes, measured as a function of the CD concentration, confirmed the formation of this higher order complex with alpha-CD. Prototropic equilibration in the singlet excited state was found to be depressed in 2:2 complexes due to the hydrophobic environment of the OH groups, while it remained unperturbed in 1:1 complexes, where the substituent is exposed to the aqueous environment. Triplet-triplet absorption and triplet quenching data supported this interpretation. The photophysical properties of both the 1:1 and the 2:2 complexes are characterized by a significant reduction of the nonradiative decay rates.

Biphenyl Compounds↗

Charge-transfer interactions in face-to-face porphyrin-fullerene systems: solvent-dependent luminescence in the infrared spectral region

The cyclophane-type molecular dyads 1 x 2H and 1 x Zn, in which a doubly bridged porphyrin donor adopts a close, tangential orientation relative to the surface of a fullerene acceptor, were prepared by Bingel macrocylization. The porphyrin derivatives 2 x 2H and 2 x Zn with two appended, singly linked C60 moieties were also formed as side products. NMR investigations revealed that the latter compounds strongly prefer conformations with one of the carbon spheres nesting on the porphyrin surface, thereby taking a similar orientation to that of the fullerene moiety in the doubly bridged systems. Cyclic voltammetric measurements showed that the mutual electronic effects exerted by the fullerene on the porphyrin and vice versa are only small in all four dyads, despite the close proximity of the donor and acceptor components. The steady-state and time-resolved absorption and luminescence properties of 1 x Zn and 2 x Zn were investigated in toluene solution and it was shown that, upon light excitation, both the porphyrin- and the fullerene-centered excited states are deactivated to a lower-lying CT state, emitting in the IR spectral region (lambda max = 890 and 800 nm at 298 and 77 K, respectively). In the more polar solvent benzonitrile, this CT state is still detected but, owing to its very low energy (below 1.4 eV), is not luminescent and shorter-lived than in toluene. The remarkable observation of similar photophysical behavior of 1 x Zn and 2 x Zn suggests that a tight donor-acceptor distance cannot only be established in doubly bridged cyclophane-type structures but also in singly bridged dyads, by taking advantage of favourable fullerene-porphyrin ground-state interactions.

Journal Article↗

Photodecarboxylation of ketoprofen in aqueous solution. A time-resolved laser-induced optoacoustic study.

The photodecarboxylation reaction of 2-(3-benzoylphenyl)propionate (ketoprofen anion, KP-) was studied in water and in 0.1 M phosphate buffer solutions in the pH range 5.7-11.0 by laser-induced optoacoustic spectroscopy (LIOAS, T range 9.5-31.6 degrees C). Upon exciting KP- with 355 nm laser pulses under anaerobic conditions, two components in the LIOAS signals with well-separated lifetimes were found (tau 1 < 20 ns; 250 < tau 2 < 500 ns) in the whole pH range, whereas a long-lived third component (4 < tau 3 < 10 microseconds) was only detected at pH < or = 6.1. The heat and structural volume changes accompanying the first step did not depend on pH or on the presence of buffer. The carbanion resulting from prompt decarboxylation within the nanosecond pulse (< 10 ns) drastically reduces its molar volume ([-18.9 +/- 2.0] cm3/mol) with respect to KP- and its enthalpy content is (256 +/- 10) kJ/mol. At acid pH (ca 6), a species is formed with a lifetime in the hundreds of ns. The enthalpy and structural volume change for this species with respect to KP- are (181 +/- 15) kJ/mol and (+0.6 +/- 2.0) cm3/mol, respectively. This species is most likely a neutral biradical formed by protonation of the decarboxylated carbanion, and decays to the final product 3-ethylbenzophenone in several microsecond. At basic pH (ca 11), direct formation of 3-ethylbenzophenone occurs in hundreds of ns involving a reaction with the solvent. The global decarboxylation reaction is endothermic ([45 +/- 15] kJ/mol) and shows an expansion of (+14.5 +/- 0.5) cm3/mol with respect to KP-. At low pH, the presence of buffer strongly affects the magnitude of the structural volume changes associated with intermolecular proton-transfer processes of the long-lived species due to reactions of the buffer anion with the decarboxylated ketoprofen anion.

Anti-Inflammatory Agents, Non-Steroidal↗

A Copper(I) Bis-phenanthroline Complex Buried in Fullerene-Functionalized Dendritic Black Boxes.

Virtual inaccessibility to external contact was revealed by electrochemical investigations for a bis(1,10-phenanthroline)copper(I) core embedded in dendrimers with up to 16 peripheral fullerene units (shown schematically). With increasing numbers of fullerene units, less and less light is available to the core, and the small quantity of light energy that reaches the central Cu(I) complex is returned to the external fullerenes by energy transfer-the central core is buried in a dendritic black box.

Journal Article↗

Merosin-positive congenital muscular dystrophy: a large inbred family.

Large families with congenital muscular dystrophy are rare. We report a clinical, histopathological, immunocytochemical, electrophysiological, radiological and genetic study of 10 cases affected by "pure" CMD belonging to two generations of a large inbred Palestinian family. The disease showed autosomal recessive inheritance. All patients had generalised muscular weakness and hypotonia at birth without arthrogryposis. They had a relatively benign clinical course with stabilisation of the clinical picture at different ages and at variable degrees of severity. The pattern of muscle weakness and wasting was more marked in the proximal upper limb-girdle and trunk muscles. Lower limb muscles were more mildly involved. Serum CK was normal or moderately increased. All patients had normal intelligence, normal computed tomography (CT) scans of the brain and normal somatosensory evoked potentials (SEP). Electromyography (EMG) and muscle biopsy showed morphological changes compatible with muscular dystrophy. Immunocytochemistry for dystrophin, laminin alpha 2 of merosin, and for alpha, beta, gamma sarcoglycans was normal. Linkage analysis excluded all the known loci for CMD, including laminin alpha 2 on chromosome 6q2, the Fukuyama congenital muscular dystrophy locus on 9q3, the integrin alpha 7 locus on chromosome 12q13 and the recently identified locus on 1p35-36. The family we present is clinically and genetically distinct from the already mapped forms of congenital muscular dystrophy. Genetic studies are in progress to localise the gene responsible for this condition.

Adolescent↗

A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 is mutated in limb-girdle muscular dystrophy type 2B.

The limb-girdle muscular dystrophies are a genetically heterogeneous group of inherited progressive muscle disorders that affect mainly the proximal musculature, with evidence for at least three autosomal dominant and eight autosomal recessive loci. The latter mostly involve mutations in genes encoding components of the dystrophin-associated complex; another form is caused by mutations in the gene for the muscle-specific protease calpain 3. Using a positional cloning approach, we have identified the gene for a form of limb-girdle muscular dystrophy that we previously mapped to chromosome 2p13 (LGMD2B). This gene shows no homology to any known mammalian gene, but its predicted product is related to the C. elegans spermatogenesis factor fer-1. We have identified two homozygous frameshift mutations in this gene, resulting in muscular dystrophy of either proximal or distal onset in nine families. The proposed name 'dysferlin' combines the role of the gene in producing muscular dystrophy with its C. elegans homology.

Adolescent↗