PubMed Health⌕ Search

Biomedical subjects

V Pavone

Publications and source records attributed to V Pavone.

At least 55 records · Page 3Linked to original sources
PubMed1998

Reflex sympathetic dystrophy associated with deep peroneal nerve entrapment.

Reflex sympathetic dystrophy (RSD or causalgia) has been rarely reported in children. We now report a 10-year-old boy with RSD in whom we performed extensive ancillary investigations including thermography, bone scintigraphy and dermo-echography. The clinical, laboratory and ancillary studies reported here highlight the profound focal acquired autonomic disturbance in this disorder. The patient presented a compression of the deep peroneal nerve at the inferior extensor retinaculum in the affected limb. Surgical decompression lead to rapid improvement of the patient's condition. Peripheral nerve decompression should be considered as a possible treatment of RSD in children, particularly those that are refractory to conservative maneuvers.

Causalgia↗
PubMed1998

Involvement of ovarian steroids in the opioid-mediated reduction of insulin secretion in hyperinsulinemic patients with polycystic ovary syndrome.

To evaluate the possible involvement of ovarian steroids on the opioid-mediated disorders of insulin in patients affected by polycystic ovary syndrome (PCOS), we studied 40 PCOS women. All patients underwent an oral glucose tolerance test (OGTT; 75 g) and basal hormone assay; based on the insulin response to OGTT, 26 women were classified as hyperinsulinemic and continued the study protocol. Patients were randomly divided into three groups characterized by different treatments: group A (nine patients) was treated with GnRH analog (one ampule every 28 days for 2 months), group B (eight patients) was treated with naltrexone (an oral opioid antagonist, 50 mg/day, orally) for 8 weeks, and group C (nine patients) was treated with GnRH analog plus naltrexone for 2 months. After continuation of treatment, all patients repeated the basal study in a second hospitalization. Naltrexone treatment significantly reduced the insulin response to OGTT, whereas GnRH analogue administration did not significantly change the insulin secretion after the glucose load. The GnRH analog/ naltrexone cotreatment was not able to influence the insulin secretory pattern; in fact, the insulin area under the curve was superimposable before and after therapy. These data could lead to the hypothesis that the opioidergic regulation of insulin secretion requires a normal steroidogenic pattern, thus suggesting that ovarian steroids modulate opioid activity also at peripheric districts.

Adult↗
PubMed1998

Familial osteoma of the cranial vault.

A case of solitary osteoma of the parietal skull is described in a mother and her 12-year-old son. There were no other craniofacial or dysmorphic features and there was no history of previous cranial trauma or inflammatory process and no radiographic evidence of other skeletal lesions in both patients. Family history was otherwise unremarkable. Gardner syndrome was ruled out by excluding other associated clinical abnormalities and by family history. The clinical and radiological features of the patients' osteomas were different from those of Albright hereditary osteodystrophy, fibrodysplasia ossificans progressiva, progressive osseous heteroplasia and familial ectopic ossification. To the author's knowledge this is the first case of the familial presentation of osteomas.

Adolescent↗
PubMed1997

Familial broad terminal phalanges with one individual showing additional anomalies.

We describe a family with four relatives showing broad terminal phalanges (BTP) of the fingers and toes. One also had mental retardation, an unusual facial appearance, cleft palate with bifid uvula, and gingival hyperplasia. The BTP anomaly in this family seems to be transmitted as an autosomal dominant trait.

Abnormalities, Multiple↗
PubMed1997

Autosomal dominant and sporadic radio-ulnar synostosis.

We report on seven cases of congenital radio-ulnar synostosis (RUS). Five were found in the same family and two were sporadic. In six the synostosis was bilateral and consistently involved the proximal end of the radius and ulna. In the familial cases the anomaly was inherited as an autosomal dominant trait and was associated with a Dubois sign and relative shortness of metacarpals number 4 and 5 in two patients, and of number 2 in another patient, and of all phalanges of the 5th fingers. These observations suggest involvement of an ulnar developmental field. RUS does not seem to be rare in the Sicilian population.

Adult↗
PubMed1997

Aplastic anemia in a young coke plant worker.

The objective of this study was to make a contribution to the debate on the cause-effect relationship between low-dose exposure to benzene and onset of hemopathies. We report the case of a coke plant worker suffering from aplastic anemia. Before being hired at the coke plant, he underwent a medical examination including a blood cell count: no disease or abnormalities of the blood crasis were found. For 3 years the patient was then exposed to gas containing-as measured in environmental investigation carried out at the coke plant-concentrations of benzene lower than TLV-TWA ACGIH (measured values 21-109 micrograms/m3). In the absence from the patient's history of any exposure to other myelotoxic agents and of any earlier pathology causing aplastic anemia, we assume there is a relationship between exposure to low levels of benzene and onset of the disease. However, it is very important to consider that exposure to low levels of benzene could promote myelotoxic reactions when the working environment contains other substances that may act synergistically or compete for the same metabolism sites, or when carcinogenic substances are present in the working environment.

Adult↗
PubMed1997

Impact of long-term naltrexone treatment on growth hormone and insulin secretion in hyperandrogenic and normal obese patients.

The growth hormone (GH) response to stimulation tests is impaired in obesity. Moreover, obese patients exhibit a "paradoxical" increase of GH to GH-releasing hormone (GHRH) stimulation after food ingestion; this paradoxical response is reversed by naloxone infusion. On the other hand, beta-endorphin seems to exert profound effects on insulin release. Recent studies also demonstrated an impairment of GH response to several stimuli in polycystic ovary syndrome (PCOS), a condition associated with obesity, hyperinsulinism, and insulin resistance. Chronic inhibition of opioid tone by the opioid antagonist naltrexone (NTX) is able to reduce the insulin response to an oral glucose tolerance test (OGTT) in hyperinsulinemic PCOS patients. Since insulin and GH may reciprocally influence their secretion and the opioid system may have a role in the pathogenesis of hyperinsulinemia and reduced GH secretion, we have explored the involvement of these neuroendocrine mechanisms in essential obesity and in obesity associated with hyperandrogenism by a long-term treatment with an opiate antagonist. We tested seven obese patients affected by PCOS, seven matched women with essential obesity (EO), and five non-obese control subjects. All patients, in the follicular phase, underwent an OGTT (75 g) and basal hormone assay. Two days later, patients were subjected to a GHRH test. The patients then had 4 weeks of treatment with NTX 50 mg/d. Following continuation of the treatment, OGTT and GHRH tests were repeated. Insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) plasma concentrations were also determined in the basal condition before and after NTX treatment. NTX treatment reduced fasting insulin levels in patients with EO (P < .05) and restored a normal GH response to GHRH without affecting IGF-1 and IGFBP-3 levels. In PCOS subjects, NTX reduced the insulin response to a glucose load and failed to modify the blunted GH response to GHRH. Our data suggest a significant difference in opioid system function in PCOS and EO subjects, indicating a particular form of obesity in PCOS. The opiate antagonist treatment in EO may act through the reduction of negative insulin feedback on GH secretion. In PCOS patients, the failure to improve GH secretion in obese hyperandrogenized patients may be related to a high opioidergic tone or to the inhibitory predominance of other neurotransmitters.

Adult↗
PubMed1997

Heterogeneity in beta cell activity, hepatic insulin clearance and peripheral insulin sensitivity in women with polycystic ovary syndrome.

The aim of this study was to evaluate the impact of reduced peripheral insulin sensitivity, beta cell hypersecretion and reduced hepatic insulin clearance in the hyper-insulinaemia of lean and obese PCOS patients. A total of 35 women with polycystic ovary syndrome (PCOS) and 10 lean normo-ovulatory controls underwent an oral glucose tolerance test and an euglycaemic-hyper-insulinaemic clamp study. PCOS patients were classified into four groups according to their BMI and insulin secretion (normo-lean; normo-obese; hyper-lean; hyper-obese), and results were compared between groups and with the controls. All the PCOS groups showed significantly higher insulin secretion than controls; there were no differences in insulin response to glucose load between lean and obese normo- and hyper-insulinaemic patients. Secretion of c-peptide was greater in PCOS groups than controls. All the hyper-insulinaemic PCOS patients had lower values of hepatic insulin clearance, independent of BMI, when compared either with controls (P < 0.001) or with PCOS normo-insulinaemic women (P < 0.01). Normo- and hyper-insulinaemic obese patients had similar total body glucose utilization (M value), which was lower than in lean PCOS subjects and controls. Our results suggest that evaluation of insulin resistance alone does not fully characterize the PCOS population; differences in liver metabolism of insulin are present in obese insulin resistant subjects and in lean patients with normal insulin sensitivity when divided into normo- and hyper-insulinaemic subgroups. Insulin resistance and hyper-insulinaemia may represent two distinct features of the insulin disorder in PCOS: the former appear to reflect the presence of obesity, while the latter may be a primary feature of PCOS.

Adolescent↗
PubMed1997

Craniofacial anomalies, severe cerebellar hypoplasia, psychomotor and growth delay in a child with congenital hypothyroidism.

We describe a 4-year-old boy affected by congenital hypothyroidism (CH) with the unusual association of brachycephaly, large and poorly structured ears, bilateral convergent strabismus, pectus carinatum and slight scoliosis, psychomotor delay, growth retardation and a severe hypoplasia of the right cerebellar hemisphere and vermis. Given the finding of unilateral cerebellar pathology this unusual association might be explained by an insult in utero--more environmental than genetic. However, to the best of our knowledge, a relationship between CH and cerebellar anomalies has not been previously reported.

Cerebellum↗
PubMed1997

Tuberculosis of the ankle in childhood: clinical, roentgenographic and computed tomography findings.

We report on three Italian children who presented with unilateral ankle tuberculosis (TB) consecutively during a short time period and in the same geographical area. A 6-year-old-girl with a family history of TB had limited mobility of the right leg at age 9 months; Mantoux test and radiographs at that age yielded normal findings. When severe right tibiotarsal swelling, reddening, pain and restriction of motion became apparent at age 4.6 years, the typical lesions of TB were evident on radiographs and computed tomographic (CT) scans. Mantoux test and synovial biopsy confirmed TB. A three-drug regimen of treatment proved useless: articular cartilage destruction and diffuse osteosclerosis ensued. Only a four-drug prolonged regimen of treatment proved to be somewhat effective. A 5-year-old girl had a 6-month history of painless swelling and limited mobility of the ankle; radiographs and CT showed osteopenia with marginal erosion of cartilages. A 14-month-old boy presented with a 2-week history of painless swelling ankle. Radiographs showed decreased bone density of talocalcanear bones. Mantoux test and synovial biopsy confirmed TB in both patients; treatment with a three-drug regimen greatly reduced symptoms. A careful suspicion of the diagnosis of tuberculosis is paramount in children with chronic or subacute monoarticular arthritis, even in absence of a positive tuberculin test or abnormalities on chest radiograph. When negative early on, the tuberculin test should be repeated after 6 weeks of arthritis, and a needle biopsy of the synovium is required in those children with monoarticular arthritis and a positive tuberculin test. Careful therapy is necessary to avoid sequelae that may lead to severe osteoarticular damage.

Ankle Joint↗
PubMed1997

The impact of insulin secretion on the ovarian response to exogenous gonadotropins in polycystic ovary syndrome.

The aim of the study was to evaluate the influence of insulin level on the ovarian response to FSH when inducing ovulation in patients affected by polycystic ovarian syndrome (PCOS). To evaluate the presence of hyperinsulinemia, 34 patients affected by PCOS were studied by an oral glucose tolerance test, then patients were stimulated for 52 cycles using FSH to induce ovulation. The ovarian response to therapy was evaluated by ultrasounds and as estradiol (E2) and androstenedione (A) plasma level determinations. On the basis of the insulinemic response to the glucose challenge, 20 patients were considered to be hyperinsulinemic and 14 normoinsulinemic. The hormonal features of each group were similar. The ovulation rate was similar in hyperinsulinemic and normoinsulinemic subjects, whereas the incidence of ovarian hyperstimulation was significantly higher in the hyperinsulinemic group. The increase in ovarian dimensions observed in hyperinsulinemic subjects after gonadotropin stimulation was more marked than that observed in normoinsulinemic ones. This was caused by the development of a larger number of immature follicles. E2 levels gradually increased after gonadotropin stimulation in both groups of subjects; however, higher levels were observed in hyperinsulinemic patients. During stimulation, the higher E2/A ratio suggests the presence of a greater aromatization activity in hyper-insulinemic patients. In conclusion, the present study suggests that, in PCOS, the insulinemic pattern may influence the ovarian response to gonadotropin administration; thus, hyperinsulinemic subjects may be at greater risk of ovarian hyperstimulation syndrome than normoinsulinemic subjects.

Adult↗
PubMed1996

A review of the design, synthesis and biological activity of the bicyclic hexapeptide tachykinin NK2 antagonist MEN 10627.

We review the reported data on the design, the conformational features and the pharmacological properties of the bicyclic peptide tachykinin NK2 receptor antagonist MEN 10,627 or cyclo(Met-Asp-Trp-Phe-Dap-Leu)cyclo(2 beta-5 beta). MEN 10,627 possesses a highly constrained structure characterized by two consecutive beta-turns, as confirmed by the almost coincident results of NMR and X-ray analyses. The compound has been efficiently synthesized by solid-phase methodology using either Boc or Fmoc strategies. It is quite stable to metabolic degradation and is endowed with high affinity and selectivity for NK2 receptor expressed in various species. At the hamster NK2 receptor MEN 10,627 is about 30-fold more potent than the nonpeptide NK2 receptor antagonist, SR 48,968, while the converse is true for the rabbit NK2 receptor. MEN 10,627 and SR 48,968 show comparable affinities for the human NK2 receptor. MEN 10,627 produces a long lasting inhibition of the response to the selective NK2 receptor agonist [beta Ala8]NKA(4-10) in the rat urinary bladder in vivo after intravenous, intranasal and intraduodenal administration. Therefore different administration routes are possible for this compound that overcomes the usual drawbacks for the application of peptides as drugs.

Animals↗
PubMed1996

Rational design of true hirudin mimetics: synthesis and characterization of multisite-directed alpha-thrombin inhibitors.

We describe here the design, synthesis, and activity of a novel class of alpha-thrombin inhibitors named hirunorms. They were rationally designed to interact through their N-terminal end with the alpha-thrombin active site in a nonsubstrate mode and to specifically bind the fibrinogen recognition exosite. An appropriate spacer that is able to properly orient the N-terminal end in the active site was also selected. This spacer allowed the size of the inhibitors to be reduced to about one-third of the amino acid residues in the hirudin sequence. Hirunorms specifically inhibit the amidolytic action of human alpha-thrombin toward a small chromogenic substrate. The most active compounds of the series, hirunorms IV and V, inhibit alpha-thrombin catalyzed hydrolysis of Tos-Gly-Pro-Arg-p-nitroanilide with K(i) = 0.09 and K(i) = 0.21 nM, respectively. Comparison of the anticoagulant properties of hirunorms, natural hirudin from the European leech Hirudo medicinalis, and the synthetic analog hirulog-1 revealed that hirunorm IV is about 10-fold and 3-fold more active, on a molar base, than hirudin and hirulog-1 in increasing the aPTT, PT, and TT of normal human plasma. The peculiar structure of hirunorms makes them stable to the amidolytic action of thrombin without the introduction of any peptide bond modification. These molecules display long-lasting activity in human plasma, due to the presence of several unnatural amino acids in susceptible positions. Hirunorms are potential candidates for injectable anticoagulants, due to their potency, specificity of action, long-lasting activity, and safety profiles.

Amides↗
PubMed1996

Bicyclic peptides as type I/type II beta-turn scaffolds.

We recently reported the rational design, synthetics, and structural characterization of the most potent and selective peptide-based neurokinin A antagonist thus far described: cyclo(Met1-Asp2-Trp3-Phe4-Dap5-Leu6)cyclo(2 beta-5 beta). Its bicyclic structure is characterized by a type I and a type II two beta-turn around Trp3-Phe4 and Leu6-Met1, respectively. In order to understand whether the two different beta-turned structures are determined by the bicyclic structure or by the amino acid type at the corner positions, we have synthesized the pseudo-symmetrical analogue cyclo(Phe1-Asp2-Trp3-Phe4-Dap5-Trp6)cyclo(2 beta-5 beta). The structural characterization in the crystal state and in solution, here reported, gives an experimental evidence that the backbone of the bicyclic structure is a rigid scaffold that can be used to build both a type I and type II beta-turn independently from the amino acid composition.

Crystallography, X-Ray↗
PubMed1996

Solvent-mediated conformational transition in beta-alanine containing cyclic peptides. VIII.

In the present paper we describe the solution nmr structural analysis and restrained molecular dynamic simulation of the cyclic pentapeptide cyclo-(Pro-Phe-Phe-beta-Ala-beta-Ala). The conformational analysis carried out in CD3CN and dimethylsulfoxide (DMSO) solutions by nmr spectroscopy was based on interproton distances derived from rotating frame nuclear Overhauser effect spectroscopy spectra and homonuclear coupling constants. A restrained molecular dynamic simulation in vacuo was also performed to build refined molecular models. The molecule is present in both solvent systems as two slowly interconverting conformers, characterized by a cis-trans isomerism around the beta-Ala5-Pro1 peptide bond. In CD3CN solution, the conformer with a ci5 peptide bond is quite similar to that observed in the solid state, while the conformer containing all trans peptide bonds is characterized by an intramolecular hydrogen bond stabilizing a C10- and a C13-ring structure. In DMSO solution, the trans isomer is partly similar to that observed in CD3CN solution while the cis isomer is different from that observed in the solid state. The effect of the solvent in stabilizing different conformations was also investigated in DMSO-CD3CN solvent mixtures.

Amino Acid Sequence↗
PubMed1996

Discovering protein secondary structures: classification and description of isolated alpha-turns.

Irregular protein secondary structures are believed to be important structural domains involved in molecular recognition processes between proteins, in interactions between peptide substrates and receptors, and in protein folding. In these respects tight turns are being studied in detail. They also represent template structures for the design of new molecules such as drugs, pesticides, or antigens. Isolated alpha-turns, not participating in alpha-helical structures, have received little attention due to the overwhelming presence of other types of tight turns in peptide and protein structures. The growing number of protein X-ray structures allowed us to undertake a systematic search into the Protein Data Bank of this uncharacterized protein secondary structure. A classification of isolated alpha-turns into different types, based on conformational similarity, is reported here. A preliminary analysis on the occurrence of some particular amino acids in certain positions of the turned structure is also presented.

Amino Acid Sequence↗
PubMed1996

Unusual conformational preferences of beta-alanine containing cyclic peptides. VII.

In the present paper we describe the synthesis, purification, and single crystal x-ray analysis of the cyclic pentapeptide cyclo-(Pro-Phe-Phe-beta-Ala-beta-Ala). This compound crystallizes in the orthorhombic space group P2I2I2I from methanol and adopts in the solid state an unusual conformation characterized by a cis beta-Ala5-Pro1 peptide bond and by an intramolecular hydrogen bond stabilizing a C11-and a C12-ring structure. The C11 structure contains the Phe3 and the beta-Ala4 at the corner position of the turn; it is the first observation of a type II beta-turn enlargement due to the insertion of an extra methylene group of the beta-alanine residue. The rest of the molecule participates in a newly characterized C12-ring structure, which incorporates a beta-Ala residue at position i of the turn.

Amino Acid Sequence↗