Biomedical subjects
Publications and source records attributed to D Nardi.
Primary localization of hydatidosis in the musculoskeletal system is a quite rare occurrence. We report a case of a 67 year old man with an infestation of the coracobrachialis muscle. We discuss several instrumental and serologic diagnosis methods and the hypothesis of a primary muscular localization.
Continuous intraoperative somatosensory-evoked potential monitoring during scoliosis surgery, along with improved instrumentation techniques, has contributed to the reduction of neurologic injury from 4-6.9% to 0-0.7%. To assess whether somatosensory-evoked potential monitoring might play a similar role in cervical surgery, the authors compared the morbidity and mortality rates associated with 218 patients who were not monitored and were operated on between 1985-1989 with those found in 100 consecutive somatosensory-evoked potential monitored procedures done from 1989-1991. The cervical procedures were conducted for disc disease, stenosis, spondylosis, and ossification of the posterior longitudinal ligament. Eight of 218 unmonitored patients became quadriplegic (3.7%) and 1 died (0.5%); no instances of quadriplegia and no deaths were encountered among the 100 monitored patients. The reduction of neurologic deficit was attributed in part to early somatosensory-evoked potential detection of vascular or mechanical compromise of the spinal cord or nerve roots and to the immediate alteration of anesthetic or surgical technique in response to somatosensory-evoked potential changes, i.e., reversal of systemic or "relative" hypotension, adjustment of operative position, release of distraction, and cessation of manipulation. Continuous intraoperative somatosensory-evoked potential monitoring also was a practical tool in monitoring cervical surgery.
Laparoscopic surgery represents a real innovation with respect to the traditional laparotomic way of access, owing to its undeniable advantages, both intraoperative and postoperative. This new technique reduces the complications connected with the surgical wound and with forced allerement. Therefore it allows the patient's fast recovery. Laparoscopic surgery application ground get's wider and wider every day: in fact, the authors report two medical cases, one of elective surgery (treatment of a hidatid cyst of the liver) and the other in emergency surgery (peritonitis due to perforated duodenal ulcer), both obtaining a positive result about the clinical and the postoperative timing of recovery.
In order to obtain new analogs of flavoxate endowed with higher stability and possibly higher potency, a new series of basic esters of 2-phenyl-3-methyl-4-oxo-4H-1-benzopyran-8-carboxylic acid (MFCA) has been prepared and investigated. Derivatives in which the structure of flavoxate was modified by branching and lengthening of the estereal alkyl chain were synthesized, together with the conformationally restricted N-piperidinyl derivatives. Esters containing in their structure various alicyclic tertiary amines which are present in natural or synthetic drugs endowed with spasmolytic properties, mainly of anticholinergic nature, were also prepared. The stability in aqueous solution, acute toxicity in mouse, and in vitro spasmolytic properties of the new compounds were investigated in comparison with flavoxate. Based on the results obtained from this screening procedure, 3 compounds were selected for further investigation. In this phase, further pharmacological and stability testing as well as preliminary animal pharmacokinetic investigations were carried out. The obtained results suggested the choice of 1,1-dimethyl-2-(1-piperidinyl)ethyl 2-phenyl-3-methyl-4-oxo-4H-1-benzopyran-8-carboxylate HCl (Rec 151 2053, terflavoxate, CAS 86433-39-8) as a candidate for preclinical development. The deeper pharmacological characterization of this compound, carried out mainly in comparison with flavoxate, terodiline, and oxybutynin confirmed its good spasmolytic activity.
Data are reported on the structural characterization of 3-methyl-4-oxo-2-phenyl-4H-1-benzopyran-8-carboxylic acid 1,1-dimethyl-2-(N-piperidinyl)ethyl ester hydrochloride (terflavoxate-HCl, Rec 15/2053, CAS 86433-39-8), a new antispasmodic for the lower urinary tract. UV, IR, NMR and MS spectra fully confirmed the structure. The X-ray crystal structure determination revealed that the molecular structure consists of a rigid platform, formed by the chromone system, with two arms, the phenyl group at C(2) and the ester chain at C(8). The ester chain conformation generates a small hollow where two oxygen atoms face.
This study examined hospital-based nursing interventions used for the problem of drug exposure in newborns and their mothers. Although there are few published reports of treatment services for this at-risk population, there is a consensus among health care providers on the need for treatment and the type of services that a treatment program should offer. A questionnaire measured use of assessment tools for newborn drug exposure and maternal drug use, patterns of referral, and use of aftercare and community treatment programs. The mean number of policies was 2.5, and the mean number of services offered was 1.042, consisting mostly of referral to community programs after discharge. Results can be used to develop quality assurance programs to address this issue and provide a more comprehensive response to the problem.
The relationship between peak-systolic/end-diastolic ratio of the umbilical artery waveform and fetal biometry was studied in 127 uncomplicated pregnancies with established dates between 20 and 40 weeks' gestation. At each ultrasonographic examination fetal biometry included measurement of the biparietal diameter, head circumference, abdominal circumference, and femur length. The peak-systolic/end-diastolic ratio was measured by either a continuous or a pulsed-wave method. There were significant linear negative correlations between all the biometric parameters, as well as between the ultrasonographically estimated fetal weight and peak-systolic/end-diastolic ratio. Of the individual ultrasonographic parameters the femur length (for gestations less than 30 weeks) and the abdominal circumference (for gestations greater than or equal to 30 weeks) were found to be best correlated with the peak-systolic/end-diastolic ratio. Regression curves, including the 10th and the 90th percentile, were developed between each biometric parameter (biparietal diameter, head circumference, abdominal circumference, and femur length), as well as between estimated fetal weight and peak-systolic/end-diastolic ratio. The estimated fetal weight nomogram had the best sensitivity (48%) in predicting intrauterine growth retardation. These nomograms should prove most useful in assessing downstream placental vascular resistance in high-risk patients with unknown dates.
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In a prospective study of 162 patients, measurements of the transverse cerebellar diameter (TCD) and abdominal circumference (AC) were obtained between 15-38 weeks' gestation. A ratio between the TCD and AC was calculated after each examination. This ratio remained constant during gestation. The mean ratio was 13.7% (fifth and 95th percentiles of 11.9 and 15.9%, respectively); the median ratio was 13.6%. Forty-two patients had repeat measurements and the ratio did not change. This ratio is gestational age-independent; however, further investigation is needed to determine its application in the assessment of fetal growth abnormalities.
A number of new 1,2-diphenylethane derivatives were synthesized and tested for anticonvulsant activity. Their structure was designed on the basis of the potential metabolic degradation of the imidazole ring present in denzimol ( ( +/- )-N-[2-[4-(beta-phenylethyl)phenyl]-2-hydroxethyl]imidazole), a potent anticonvulsant. The compounds which inhibited the electroshock-induced seizures (MES) in mice, namely N-[4-(beta-phenylethyl)phenacyl]formamide (VII) and N-[2-[4-(beta-phenylethyl)phenyl]-2-hydroxyethyl]formamide (IX), proved active also as inhibitors of the pentylenetetrazole-induced tonic seizures. The results of the pharmacological screening were evaluated in relation to the lipophilicity of the compounds.
The new flavone derivative REC 15/2053, a compound with spasmolytic activity on the lower urinary tract, was examined for its in vitro interaction with alpha- and beta-noradrenergic receptors, dopaminergic, muscarinic, serotoninergic, and opiate receptors, and calcium-channel binding sites labeled with 1,4-dihydropyridines from normal rat brain. All the investigated receptors are directly or indirectly involved in the nervous control of the lower urinary tract functions. The activity of REC 15/2053 on these receptors was studied in comparison to the most common drugs used in the management of urinary bladder disorders such as flavoxate, emepronium bromide, oxybutynin, terodiline, and imipramine. REC 15/2053 showed only weak binding to [3H]nitrendipine sites (IC50 = 14 microM) and muscarinic receptors (IC50 = 18 microM), whereas flavoxate was slightly active only at muscarinic receptors (IC50 = 12.2 microM). Emepronium bromide, oxybutynin, and terodiline were active only at muscarinic receptors, with IC50 values of 236, 5.4, and 588 nM, respectively. Oxybutynin showed a weak affinity to [3H]nitrendipine binding sites (IC50 = 44.4 microM). Imipramine was active at alpha 1-adrenergic and muscarinic receptors (IC50 = 248 and 653 nM, respectively). The activity of REC 15/2053 at muscarinic receptors and 1,4-dihydropyridine binding sites seems too low to account for its mechanism of action.
The pharmacological properties of 3-methylflavone-8-carboxylic acid (MFCA), the main metabolite of flavoxate, have been studied in vitro and in vivo. MFCA did not display antispasmodic activity on isolated organs contractions induced by histamine, acetylcholine or CaCl2, nor did it exhibit significant affinity for the rat brain alpha- and beta-adrenergic, serotoninic, muscarinic, D2, opiate and Ca2+ receptors. However, it showed a remarkable phosphodiesterase (PDE) inhibiting activity. Moreover in vivo studies indicate an interesting activity of MFCA which inhibited the rat urinary bladder voiding contractions, increased bladder volume capacity and decreased micturition pressure in the rat cystometric recordings. The activity of MFCA in the two in vivo experimental models, probably related to cAMP-PDE inhibitory properties, suggests that flavoxate's therapeutical potential might be partially sustained by its main metabolite.
New 1-(2-pyridinyl)piperazine derivatives were synthesized and tested as inhibitors of the reaginic passive cutaneous anaphylaxis in the rat (PCA), of the histamine-induced bronchospasm in the guinea pig, and of the rat mesenteric mast cell degranulation induced by compound 48/80. On the basis of test results, a series of N-(substituted phenyl)-omega-[4-(2-pyridinyl)-1-piperazinyl]alkanamides was prepared. The nature of substituents at the anilide ring strongly influenced mast cell stabilizing activity, whereas it was less determining in the case of the other two tests. No clear correlation between the most common physicochemical parameters (pi, sigma, Vw volume) of substituents and activity could be detected. With regard to the position of substituents at the anilide ring, the rank order of potency, in the PCA and bronchoconstriction tests, was para greater than meta greater than ortho. Introduction of substituents in the 1-(2-pyridinyl)piperazinyl moiety of the N-(substituted phenyl)propanamide derivatives hardly affected activity, or the effect was deleterious. Some of the new compounds exhibited a simultaneous remarkable activity in all the three assays employed.
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New 2,4-dibromo-6-(N-cyclohexyl-N-methyl)aminomethylanilides of N-acetylcysteine and N-acetyl-S-carboxymethylcisteine derivatives, N-benzyloxycarbonylcysteine and N,N'-bisbenzyloxycarbonylcystine were synthesized. The compounds were tested for the expectorant activity in rabbit and mouse. N,N'-Bisbenzyloxycarbonylcystin-bis [2,4-dibromo-6-(N-cyclohexyl-N-methyl)aminomethyl]anilide (XIX) was selected for further investigations.
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N-[2-(7-Dimethylaminomethyl-5-methyl-2-benzofuranmethylthio)ethyl]-N'-methyl-2-nitro-1,1-ethenediamine (III) and N-cyano-N'-[2-(7-dimethylaminomethyl-5-methyl-2-benzofuranmethylthio)ethyl]-N"-methylguanidine (IV) were synthesized. The direct transformation of 2,2-dicarbethoxy-3-hydroxy-5-methyl-7-dimethylaminomethylcoumaran (VII) and of 2,2-dicarbethoxy-3-hydroxycoumaran (XVI) to the corresponding ethyl 2-benzofurancarboxylates (IX) and (XV) is also reported. A mechanism for this reaction is proposed. Compounds (III) and (IV) showed hystamine H2 receptor antagonist activity, but were less potent than cimetidine and ranitidine.