PubMed Health⌕ Search

Biomedical subjects

S Cacciaguerra

Publications and source records attributed to S Cacciaguerra.

At least 19 recordsLinked to original sources
PubMed2004

Current outcome of antenally diagnosed cystic lung disease.

BACKGROUND/PURPOSE: The natural history of parenchymal lung lesions such as congenital cystic adenomatoid malformation (CCAM) and pulmonary sequestration (PS) has been altered by the advent of antenatal ultrasonography. Initial reports were characterized by a high (about 30%) incidence of adverse features (eg, hydrops) and a poor outcome and did not accord with our recent experience. The authors have reviewed the outcome of fetuses that had been diagnosed in a large tertiary referral fetal medicine unit with the aim of delineating current experience. The term cystic lung disease was used throughout to avoid unjustifiable histologic precision. METHODS: The scans of all fetuses that had been diagnosed with cystic lung disease between January 1995 and July 2001 were reviewed. The outcome of each pregnancy was established, and, where possible, all infants underwent appropriate investigations, including thoracic computed tomography (CT) scans. RESULTS: Sixty-seven fetuses had a cystic lung abnormality diagnosed from January 1995 to July 2001. The median (range) age at diagnosis was 21 (19 to 28) weeks. The lesion was right sided in 29 (43%), left in 36 (54%), and bilateral in 2 (3%); it was characterized as dominantly macrocystic in 27 (40%), microcystic in 35 (52%), and mixed in 5 (8%). Mediastinal shift was present in 30 fetuses (45%). Severe signs of fetal distress (eg, hydrops) were present in 5 fetuses (7%). Antenatal intervention was performed in 4 fetuses (thoraco-amniotic shunts [n = 3] and percutaneous intrauterine laser therapy [n = 1]). Sixty-four (96%) of the fetuses were born alive. There was 1 termination of pregnancy and 2 intrauterine deaths (all severe microcystic lesions). Forty-two infants (63%) underwent thoracotomy and appropriate excisional surgery at a median of 7.5 months (range, 1 day to 34 months). Two infants (which included the fetus having intrauterine laser therapy) died early in the postnatal period. Both were large microcystic lesions and had antenatal features of severe fetal distress. Twelve infants were investigated in the postnatal period but did not undergo surgery. Ten infants were not appropriately investigated or were lost to follow-up. Histologic examination showed definitive diagnostic features of CCAM (n = 25) or PS (n = 6). Other lesions with hybrid features of both were also seen (n = 11). There was a degree of correlation between antenatal ultrasound features (size of cyst [P =.03], in-utero behavior [P =.06], mediastinal shift [P = 0.05]) and the need for surgery but not with the final histologic diagnosis. Surgical excision was required in 45% of lesions showing late-gestation "resolution." CONCLUSIONS: Antenatally diagnosed "cystic lung disease" has an excellent prognosis in the absence of signs of severe fetal distress. The need for surgery should be based on appropriate postnatal investigations (eg, CT scans), rather than on antenatal behavior.

Abortion, Therapeutic↗
PubMed2001

Analysis of the muscarinic receptor subtype mediating inhibition of the neurogenic contractions in rabbit isolated vas deferens by a series of polymethylene tetra-amines.

The pharmacological characteristics of the presynaptic muscarinic receptor subtype, which mediates inhibition of the neurogenic contractions in the prostatic portion of rabbit vas deferens, have been investigated by using a series of polymethylene tetra-amines, which were selected for their ability to differentiate among muscarinic receptor subtypes. It was found that all tetra-amines antagonized McN-A-343-induced inhibition in electrically stimulated rabbit vas deferens in a competitive manner and with affinity values (pA:(2)) ranging between 6.27+/-0.09 (spirotramine) and 8.51+/-0.02 (AM170). Competition radioligand binding studies, using native muscarinic receptors from rat tissues (M(1), cortex; M(2), heart; M(3), submaxillary gland) or from NG 108-15 cells (M(4)) and human cloned muscarinic M(1)-M(4) receptors expressed in CHO-K1 cells, were undertaken with the same tetra-amines employed in functional assays. All antagonists indicated a one-site fit. The affinity estimates (pK:(i)) of tetra-amines calculated in binding assays using native receptors were similar to those obtained using cloned receptors. Among these compounds some displayed selectivity between muscarinic receptor subtypes, indicating that they may be valuable tools in receptor characterization. Spirotramine was selective for M(1) receptors versus all other subtypes (pK:(i) native: M(1), 7.32+/-0.10; M(2), 6.50+/-0.11; M(3), 6.02+/-0.13; M(4), 6.28+/-0.16; pK:(i) cloned: M(1), 7.69+/-0.08; M(2), 6.22+/-0.14; M(3), 6.11+/-0.16; 6.35+/-0.11) whereas CC8 is highly selective for M(2) receptors versus the other subtypes (pK:(i) native: M(1), 7.50+/-0.04; M(2), 9.01+/-0.12; M(3), 6.70+/-0.08; M(4), 7.56+/-0.04; pK:(i) cloned: M(1), 7.90+/-0.20; M(2), 9.04+/-0.08; M(3), 6.40+/-0.07; M(4), 7.40+/-0.04). Furthermore, particularly relevant for this investigation were tetra-amines dipitramine and AM172 for their ability to significantly differentiate M(1) and M(4) receptors. The apparent affinity values (pA:(2)) obtained for tetra-amines in functional studies using the prostatic portion of rabbit vas deferens correlated most closely with the values (pK:(i)) obtained at either native or human recombinant muscarinic M(4) receptors. This supports the view that the muscarinic receptor mediating inhibition of neurogenic contractions of rabbit vas deferens may not belong to the M(1) type but rather appears to be of the M(4) subtype.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed2001

Neonatal diaphragmatic hemangioma.

The first neonatal case of a hemangioma of the diaphragm in a neonate is reported. After 25 months the patient is well with no signs of recurrence. Diaphragmatic tumors should be considered in the differential diagnosis of neonatal thoracic masses.

Diaphragm↗
PubMed2000

Striated muscle cells in non-neoplastic lung tissue: a clinicopathologic study.

This study was performed to study the prevalence, origin, and clinical implication of striated muscle cells in congenital non-neoplastic lung abnormalities. Five cases of striated muscle cell proliferation within congenital non-neoplastic pulmonary abnormalities were identified from a series of 31 (16%) resected specimens obtained at King's College Hospital, London, during the period 1992 to 1998. Lung tissue was also obtained from 48 normal human fetuses and serial sections stained for the presence of striated muscle. A histologic and immunohistochemical study of the clinical cases and the fetal material was performed by using phosphotungstic acid hematoxylin staining and immunostaining for myoglobin and desmin. Striated muscle cells were identified either as a diffuse or a focal proliferation within the lung interstitia of five infants. The congenital lung anomalies were intra-abdominal pulmonary sequestration associated with congenital cystic adenomatoid malformation (CCAM), intrathoracic sequestration again with features of CCAM, an intrathoracic sequestration associated with a congenital diaphragmatic hernia, and 2 Stocker type II intrathoracic CCAMs. Striated muscle cells were not identified in any section of lung tissue derived from the fetal series. Striated muscle cells proliferation in non-neoplastic lung tissue is more common than usually reported. Although the exact origin of such cells is speculative, because it is always detected within pulmonary anomalies, a wide morphogenetic error is likely. The clinical implication of its presence has to be further defined. HUM PATHOL 31:1477-1481.

Adult↗
PubMed1999

Characterization of a putative calcitonin receptor in IMR 32 human neuroblastoma cells.

In this study we characterized calcitonin (CT) receptors in human neuroblastoma IMR 32 cells. Saturation binding assays indicated that [125I]-human CT bound with high affinity to IMR 32 cell membranes (K(d) = 253.6 pM; Bmax = 3.84 fmol/ mg protein). In competition binding studies, human adrenomedullin displayed high affinity for these sites (IC50 = 30 nM) whereas human alpha calcitonin-gene related peptide (alphaCGRP; IC50 = 145 nM) and human amylin (IC50 = 415 nM) showed lower affinity. These peptides increased cAMP levels in viable cells; the relative potencies were: human CT > human adrenomedullin > human cCGRP > or = human amylin. The expression of mRNA coding for the published sequences of the human calcitonin receptor and of the human calcitonin receptor-like receptorwas evaluated by reverse transcriptase-polymerase chain reaction. Electrophoretic analysis did not confirm the occurrence of mRNA coding for the above mentioned receptors in these cells. This study suggests the presence of a novel, putative CT receptor in IMR 32 cells.

Adrenomedullin↗
PubMed1999

Sigma1 recognition sites in rabbit iris-ciliary body: topical sigma1-site agonists lower intraocular pressure.

In this study, we examined the presence of sigma1 and sigma2 sites in the rabbit iris-ciliary body by receptor binding and investigated their effects on intraocular pressure (IOP) in albino rabbits. The iris-ciliary body has binding sites for the sigma1-site agonist [3H](+)-pentazocine (Kd = 4.6 nM; Bmax = 212 fmol/mg protein) and sigma2 sites labeled with [3H]1,3-di-o-tolylguanidine (DTG) (Kd = 8. 2 nM; Bmax = 1120 fmol/mg protein). In competition binding studies, (+)-pentazocine and the sigma antagonist NE-100 displayed high affinity for sigma1 sites (Ki = 2.1 and 2.4 nM, respectively), whereas (+)-N-allylnormetazocine (NANM) was less potent (Ki = 178 nM). Unilateral topical (+)-pentazocine (0.01-0.1%) caused a significant dose-related reduction of IOP in ocular normotensive rabbits and in the alpha-chymotrypsin model of ocular hypertension. (+)-NANM was less potent than (+)-pentazocine. Neither compound altered the IOP of the contralateral eye, and their hypotensive activity was blocked by NE-100 that, by itself, had no effect on IOP. (-)-Pentazocine, (-)-NANM, and DTG had no effect on IOP. DTG prevented the hypotensive effect of (+)-pentazocine, suggesting that it acts as a sigma1-site antagonist. sigma-Site ligands did not affect pupil diameter or cause ocular inflammation. Topical [3H](+)-pentazocine reaches the intraocular tissues within 30 min, and its uptake in the iris-ciliary body and retina was significantly reduced by topical pretreatment with NE-100, as expected for a receptor-specific agent. Reverse-phase HPLC confirmed the presence of intact (+)-pentazocine in iris-ciliary body homogenates. sigma1-Site agonists may offer a novel class of agents potentially effective in the control of ocular hypertension.

Animals↗
PubMed1998

Universal template approach to drug design: polyamines as selective muscarinic receptor antagonists.

The concept that polyamines may represent a universal template in the receptor recognition process is embodied in the design of new selective muscarinic ligands. Tetraamines 4-7 and 16-20 and diamine diamides 8-15 were synthesized, and their pharmacological profiles at muscarinic receptor subtypes were assessed by functional experiments in isolated guinea pig left atrium (M2) and ileum (M3) and by binding assays in rat cortex (M1), heart (M2), submaxillary gland (M3), and NG 108-15 cells (M4). It has been confirmed that appropriate substituents on the terminal nitrogens of a tetraamine template can tune both affinity and selectivity for muscarinic receptors. The novel tetraamine C-tripitramine (17) was able to discriminate significantly M1 and M2 receptors versus the other subtypes, and in addition it was 100-fold more lipophilic than the lead compound tripitramine. Compound 14 (tripinamide), in which the tetraamine backbone was transformed into a diamine diamide one, retained high affinity for muscarinic subtypes, displaying a binding affinity profile (M2 > M1 > M4 > M3) qualitatively similar to that of tripitramine. Both these ligands, owing to their improved lipophilicity relative to tripitramine and methoctramine, could serve as tools in investigating cholinergic functions in the central nervous system. Furthermore, notwithstanding the fact that the highest affinity was always associated with muscarinic M2 receptors, for the first time polyamines were shown to display high pA2 values also toward muscarinic M3 receptors.

Animals↗
PubMed1998

(+)-cis-N-ethyleneamino-N-normetazocine derivatives. Novel and selective sigma ligands with antagonist properties.

A series of (+)-cis-N-normetazocine derivatives has been described, and their affinities for sigma1, sigma2, and phencyclidine (PCP) sites and opioid, muscarinic (M2), dopamine (D2), and serotonin (5-HT2) receptors were evaluated. The effect of the N-substitution with a substituted ethylamino spacer was investigated. Compounds 8c-11c displayed high affinities for sigma1 sites and for opioid receptors. Substitution of the second basic nitrogen either with alkyl or cycloalkyl substituents give compounds (1a-6a) with high affinity and selectivity for sigma1 binding sites. Compounds 1a-5a were further characterized in vivo, and their agonist/antagonist activity was evaluated. In mouse, compound 1a and 2a as well as haloperidol suppressed in a dose-related manner the stereotyped behavior induced by (+)-SKF 10,047. Compounds 3a-5a and (+)-pentazocine do not affect the stereotyped behavior induced by ip injection of (+)-SKF 10,047. Therefore, from this series of compounds we identified potent and selective sigma1 ligands which might prove useful to unveil the functional role of sigma1 sites.

Animals↗
PubMed1998

Synthesis and anticonvulsant activity of 2(3H)-benzoxazolone and 2(3H)-benzothiazolone derivatives.

A series of 2(3H)-benzoxazolone and 2(3H)-benzothiazolone derivatives were synthesized and evaluated for anticonvulsant activity. The compounds were assayed, intraperitoneally in mice and per os in rats, against seizures induced by maximal electroshock (MES) and pentylenetetrazole (scMet). Neurologic deficit was evaluated by the rotarod test. The compounds were prepared to determine the relationship between the 2(3H)-benzoxazolone and 2(3H)-benzothiazolone derivatives' structures and anticonvulsant activity. Several of these compounds showed significant anticonvulsant activity. Compounds 43 and 45 were the most active of the series against MES-induced seizures with ED50 values of 8.7 and 7.6 mg/kg, respectively. Compound 45 displayed good protection against MES-induced seizures and low toxicity in rats with an oral ED50 of 18.6 mg/kg and a protective index (PI = TD50/ED50) of < 26.9. In vitro receptor binding studies revealed that compounds 43 and 45 bind to sigma 1 receptors with nanomolar affinities.

Animals↗
PubMed1998

The importance of detailed diagnostic assessment in a case of partial situs inversus.

Partial situs inversus is not necessarily symptomatic; however, recent experience with a child affected by this condition and polysplenia led us to reconsider the approach to such cases. The collection of as much pre operative information as possible is desirable in order to delineate a correct surgical approach. In particular, the presence of gastrointestinal anomalies, e.g., duodenal dilatation, should be assessed individually, since they are virtually always pathological and not necessarily related to the situs inversus. At laparotomy all of the intra-abdominal contents should be carefully assessed.

Abnormalities, Multiple↗
PubMed1998

Tracheal ring-graft reinforcement in lieu of tracheostomy for tracheomalacia.

Three children with tracheomalacia had tracheal reinforcement with free three-quarter circumference ring grafts of autologous cartilage taken from the costal margin. A low cervical manubrium-splitting approach gave excellent access to the anterior mediastinum and the intrathoracic trachea in two children. The first child, a neonate with oesophageal atresia (OA) and tracheo-oesophageal fistula (TOF), had 11 grafts to support the whole of the trachea from the cricoid to the carina and never required a tracheostomy. For the first 5 years she had frequent pneumonic episodes and on one occasion bilateral pneumothoraces. These episodes and radiographic lung hyperinflation, attributed to distal bronchomalacia, have reduced spontaneously in frequency and severity. At 9 years of age she has a well-supported trachea with palpable cartilage rings in the cervical segment. The trachea has grown to approximately 75% of expected normal size for her age. Another child with tracheomalacia related to innominate-artery compression and who presented with 'dying episodes' was completely relieved and resumed a normal life without a tracheostomy following insertion of four grafts to the intrathoracic trachea. He remains well and symptom-free 8 months postoperatively. A third child had cartilage-graft reinforcement of the lower cervical trachea, including the tracheostomy site, to achieve tracheostomy closure at 16 months of age. Five years later he continues to have a well-supported trachea showing acceptable growth. However, he has ongoing evidence of tracheo-bronchomalacia presenting as expiratory wheezing, lung hyperinflation, and pneumonic episodes that are diminishing spontaneously with growth. Our experience, limited to three children, recommends primary tracheal reinforcement with autologous free costal-cartilage grafts for tracheomalacia in the neonate and young infant. This procedure and the anterior mediastinal approach are well-tolerated, providing instant tracheal support, removing the need for a tracheostomy, and allowing the child's rapid return to the family. Long-term follow-up, presently 9 and 5 years in two children originally presenting with OA and TOF, indicates adequate tracheal growth and an aesthetically acceptable appearance. It is relevant to prognosis that relief of the life-threatening tracheal component exposed the full extent of the bronchial cartilaginous weakness, which has significantly detracted from the quality of life for these two children with OA and TOF-related tracheomalacia.

Cartilage↗
PubMed1998

Gastric carcinoma with ovarian metastases in an adolescent.

Gastric carcinoma represents only 0.05% of malignant paediatric gastrointestinal tumours. This condition is associated with a poor prognosis because its rarity and non-specificity of the symptoms usually delay its diagnosis. The authors present a 16-year-old girl with a poorly differentiated gastric carcinoma (signet-ring-cell type) with bilateral ovarian metastases who died of peritoneal carcinomatosis despite extensive surgery and chemotherapy. The epidemiological, clinical, and pathological features of gastric carcinoma in childhood are discussed.

Adolescent↗
PubMed1998

Intra-abdominal pulmonary sequestration associated with congenital cystic adenomatoid malformation of the lung: just an unusual combination of rare pathologies?

A case of intra-abdominal pulmonary sequestration associated with histological features of congenital cystic adenomatoid malformation (CCAM) of the lung is reported. The lesion consisted of a Stocker type II CCAM in which numerous striated muscle cells were present. A review of the literature of this rare combination of congenital pulmonary anomalies is presented.

Adult↗
PubMed1998

Concepts and considerations for repair of a severe cloacal anomaly.

A 1.8 kg chromosomally normal child was suspected antenatally to have a cloacal anomaly and oligohydramnios. Both parents had a chromosome 9 inversion (inv [9] [p11 q13]). Postnatal study showed a high confluence of the urinary, genital and intestinal tracts. Because of prematurity, a right colostomy was performed on a short colon, but the genitourinary tract was not drained. Poor weight gain, urinary tract infection and septicaemia led to a one-stage reconstruction at 5 months of age and a weight of 3.2 kg. Follow-up although short at 15 months, is encouragingly suggestive of urinary and faecal continence. The vagina is patent. This paper considers concepts in cloacal management and submits for evaluation an alternative surgical plan to the presently almost exclusively accepted posterior sagittal approach of Peña and De Vries.

Cloaca↗
PubMed1998

Prenatal diagnosis of cloacal anomaly.

The authors present a case of prenatal diagnosis of cloacal anomaly, characterized by the presence of oligohydramnios and cystic pelvic mass with changing features during observation. Postnatal study confirmed the presence of a recto-cloacal fistula, with a high confluence of the urinary, genital and intestinal systems. Both parents had a chromosome 9 inversion (p11q13), but the child was chromosomally normal.

Adult↗