[Giant cell tumor of the tendon sheath: characteristic findings of the bone scintigraphy and correlation with MRI]. / Tumor de células gigantes de la vaina tendinosa: hallazgos característicos de la gammagrafía ósea y correlación con la RMN.

We report 3 cases of an unusual tumor, that is, the giant cell tumor of the tendon sheath. The patients consulted due to the appearance of a well-defined, painless, soft tissue mass with mild-to-moderate inflammation located in the thumbs or toes. These clinical data, together with the bone scan findings, oriented the diagnostic suspicion that was confirmed by a pathology study of the tumor after resection. This work has aimed to review the characteristics of the bone scan (BS) image of this tumor and its correlation with the conventional X-ray imaging and magnetic resonance imaging (MRI).

Tumor de células gigantes de la vaina tendinosa: hallazgos característicos de la gammagrafía ósea y correlación con la RMN / Giant cell tumor of the tendon sheath: characteristic findings of the bone scintigraphy and correlation with MRI

Presentamos 3 casos de un tumor poco usual: el tumor de células gigantes de la vaina tendinosa. Los pacientes consultaron por la aparición de una masa de partes blandas, delimitada y no dolorosa, acompañada de leve-moderada inflamación, localizada en un dedo de la mano o el pie. Estos datos clínicos junto con las características gammagráficas orientaron la sospecha diagnóstica, que se confirmó mediante el estudio anatomopatológico de la lesión tras su exéresis quirúrgica. El objetivo del trabajo es revisar las características de la imagen gammagráfica ósea de este tumor y su correlación con la radiografía convencional y la resonancia magnética nuclear(AU)

We report 3 cases of an unusual tumor, that is, the giant cell tumor of the tendon sheath. The patients consulted due to the appearance of a well-defined, painless, soft tissue mass with mild-to-moderate inflammation located in the thumbs or toes. These clinical data, together with the bone scan findings, oriented the diagnostic suspicion that was confirmed by a pathology study of the tumor after resection. This work has aimed to review the characteristics of the bone scan (BS) image of this tumor and its correlation with the conventional X-ray imaging and magnetic resonance imaging (MRI)(AU)

[Analysis of work accidents during the years 1999-2006 in a hospital company in Lombardia]. / Analisi del fenomeno infortunistico 1999-2006 in un'Azienda Ospedaliera Lombarda.

This study describe accidents occurred in the period between 1999 and 2006 in the Hospital of Cremona, in which about 2400 subjects operate. The analysis of Accident Register showed a reduction of about 30% of the total number of accidents during the examined period and a non homogeneous distribution of the various types of accidents. The most frequent accidents were prick (25.8%), trauma (22.9%) and "in itinere" accidents (7.8%). One type of accident has been little considered up to now: the aggressions. Professional nurses were the most frequently involved and the most affected units were those that belong to the Internal Medicine Department. "In itinere" accidents had the longest average prognosis (11.6 days). The repetition of accidents occurred to the same operator hasn't been analysed before now: a professional nurse had nine accidents (of various type) in the seven years considered. Probably the reduction of accident must be attributed to the effectiveness of the prevention activities undertaken during the reviewed period. Biological accidents, for which it was possible to implement prevention programs, have been markedly reduced; it was not the same for "In Itinere" accidents, that depend significantly on external factors that are not easily dismissed.

Use of simulated blood cultures for antibiotic effect on time to detection of the two blood culture systems BacT/ALERT and BACTEC 9240.

To avoid the influence of pre-analytical steps, this study was performed using sterile blood spiked with defined loads of microorganisms as inoculum. Time-to-Detection (TTD) was evaluated for the most frequently encountered bacteria comparing two commercially available blood culture systems, BD BACTEC 9240 (Becton Dickinson) and BacT/ALERT (Organon Teknika). The effect of the most widely used antibiotics on TTD was evaluated on both systems. TTD was measured with antibiotics at their trough and at increasing concentrations. The results show that the BACTEC PLUS system recovers more pathogens with shorter time to detection than the BacT/ALERT FAN system when beta-lactam antibiotics (Ampicillin, Cefotaxime) are present at their respective trough concentration corresponding to parenteral therapy. The two systems seem to be equally efficient when Gentamicin, Ciprofloxacin and Trimethoprim/sulfamethoxazole are used; in the case of Vancomycin, BACTEC seems more effective than BacT/ALERT.

Antihypertensive compounds that modulate the Na-K pump.

A primary impairment of the kidney sodium excretion has been documented both in hypertensive patients (EH) and genetic animal models (Milan hypertensive rat [MHS]) carrying mutations of the cytoskeletal protein adducin and/or increased plasma levels of endogenous ouabain (EO). Ouabain (OU) itself induces hypertension in rats and both OU and mutated adducin activate the renal Na/K-ATPase function both in vivo and in cultured renal cells (NRK). A new antihypertensive agent, PST 2238, able to selectively interact with these alterations has been developed. PST lowers blood pressure (BP) by normalizing the expression and activity of the renal Na-K pump selectively in those rat models carrying the adducin mutation (MHS) and/or increased EO levels (OS) at oral doses of 0.1-10 micro g/kg. In NRK cells either transfected with mutated adducin or incubated with 10(-9) M OU, PST normalizes the Na-K pump activity. Recently, an association between EO and cardiac complications has been observed in both EH and rat models consistent with a prohypertrophic activity of OU. OS rats showed a 10% increase of left ventricle and kidney weights as compared with controls, and PST 2238 (1 micro g/kg OS) prevented both ventricle and renal hypertrophy. This effect was associated with the ability of PST to antagonize the OU-dependent activation of growth-related genes, in the membrane subdomains of caveolae. In conclusion, PST is a new antihypertensive agent that may prevent cardiovascular complications associated with hypertension through the selective modulation of the Na-K pump function.

Pharmacological profile of the novel inotropic agent (E,Z)-3-((2-aminoethoxy)imino)androstane-6,17-dione hydrochloride (PST2744).

The novel Na(+)/K(+)-ATPase inhibitor (E,Z)-3-((2-aminoethoxy)imino)androstane-6,17-dione hydrochloride (PST2744) was characterized for its inotropic and toxic properties. Inhibition potency on dog kidney Na(+)/K(+)-ATPase was comparable (0.43 microM) to that of digoxin (0.45 microM). PST2744 concentration-dependently increased force of contraction in guinea pig atria and twitch amplitude in isolated guinea pig myocytes; in the latter, aftercontractions developed significantly less than with digoxin. Intravenous infusion of 0.2 mg/kg/min PST2744 in anesthetized guinea pigs exerted an immediate and long-lasting inotropic effect (ED(80) of 1.89 +/- 0.37 mg/kg) without causing lethal arrhythmias up to a cumulative dose of 18 mg/kg. Conversely, an equieffective infusion of digoxin (0.016 mg/kg/min; ED(80) of 0.32 mg/kg) caused lethal arrhythmias at a cumulative dose of 0.81 mg/kg. At a higher rate (0.4 mg/kg/min), PST2744 induced lethal arrhythmias, with a lethal dose/ED(80) ratio significantly greater than digoxin (20.2 +/- 6.3 versus 3.23 +/- 0.55, p < 0.05). Decay of the inotropic effect (t(1/2), min) was significantly faster for PST2744 (6.0 +/- 0.39) than for digoxin (18.3 +/- 4.5, p < 0.05). In anesthetized dogs, PST2744 dose-dependently increased maximum velocity of pressure rise (+dP/dt(max)) in the range 32 to 500 microg/kg i.v. and was safer than digoxin. In conscious dogs with a healed myocardial infarction, PST2744 significantly increased resting values of +dP/dt(max), left ventricular pressure, and SPB, and increased +dP/dt(max) throughout treadmill exercise while reverting the increase in left ventricular end diastolic pressure seen in control animals. Digoxin significantly decreased basal heart rate, while not affecting the hemodynamic response to exercise. Thus, PST2744 represents a new class of Na(+)/K(+)-ATPase inhibitors endowed with inotropic activity comparable with that of digitalis but having greater safety.

17 alpha-O-(aminoalkyl)oxime derivatives of 3 beta,14 beta-dihydroxy-5 beta-androstane and 3 beta-hydroxy-14-oxoseco-D-5 beta-androstane as inhibitors of Na(+),K(+)-ATPase at the digitalis receptor.

The synthesis and binding affinities to the digitalis Na(+),K(+)-ATPase receptor of a series of 3 beta,14 beta-dihydroxy-5 beta-androstane and 3 beta-hydroxy-14-oxoseco-D-5 beta-androstane derivatives bearing a 17 alpha-(aminoalkoxy)imino chain are reported; some derivatives were also studied for their inotropic activity. Our recently proposed model of interaction of molecules with the digitalis receptor was used to design these compounds. On that basis, the possibility to design novel potent inhibitors of Na(+),K(+)-ATPase without being constrained by the stereochemistry of the classical digitalis skeleton in the D-ring region was predicted. The binding affinities of the most potent compounds in the two series, (EZ)-17 alpha-[2-[(2-aminoethoxy)imino]ethyl]-5 beta-androstane-3 beta,14 beta-diol (6f) and (EZ)-3 beta-hydroxy-17 alpha-[2-[(2-aminoethoxy)imino]ethyl]-14,15-seco-5 beta-androstan-14-one (24c) are higher than that of the potent natural compound digitoxigenin, despite the unusual alpha-exit of the substituent in position 17 of 6f or the disruption of the D-ring in 24c. These results further support the validity of our recently proposed model of binding at the digitalis receptor. Results of the inotropic tests on guinea pig atrium deserve further investigation on the pharmacological profile of these derivatives.

17beta-O-Aminoalkyloximes of 5beta-androstane-3beta,14beta-diol with digitalis-like activity: synthesis, cardiotonic activity, structure-activity relationships, and molecular modeling of the Na(+),K(+)-ATPase receptor.

A series of digitalis-like compounds with a 17-aminoalkoxyiminoalkyl or -alkenyl substituent was synthesized and evaluated for inhibition of Na(+),K(+)-ATPase and for inotropic activity. The highest inhibition was found with compounds having the substituent in configuration 17beta and the amino group at a distance of 6 or 7 bonds from C(17) of the digitoxigenin skeleton. The presence of the oxime function strengthens the interaction with the receptor, more if alpha,beta-unsaturated, thus mimicking the electronic situation of the unsaturated lactone in natural digitalis compounds. The most active compounds showed Na(+),K(+)-ATPase inhibitory potencies (IC(50)) 17-25 times higher than the standards digitoxigenin and digoxin and 3-11 times higher inotropic potencies (EC(50)) in isolated guinea pig left atria. These features are supported by a molecular model suggesting the possible interactions of the groups described above with particular amino acid residues in the H1-H2 domains of Na(+),K(+)-ATPase. Some interactions are the classical ones already described in the literature; a new, very strong interaction of the basic group with the Cys138 was found and adds new possibilities to design compounds interacting with this region of the receptor. The most interesting compounds were also studied in vivo in the anesthetized guinea pig for evaluating their inotropic effect versus the lethal dose. Compounds 9 and 12 showed a slightly higher safety ratio than digoxin and deserve further evaluation.

PST 2238: A new antihypertensive compound that modulates Na,K-ATPase in genetic hypertension.

A genetic alteration in the adducin genes is associated with hypertension and up-regulation of the expression of renal Na, K-ATPase in Milan-hypertensive (MHS) rats, in which increased ouabain-like factor (OLF) levels are also observed. PST 2238, a new antihypertensive compound that antagonizes the pressor effect of ouabain in vivo and normalizes ouabain-dependent up-regulation of the renal Na-K pump, was evaluated for its ability to lower blood pressure and regulate renal Na,K-ATPase activity in MHS genetic hypertension. In this study, we show that PST 2238, given orally at very low doses (1 and 10 microg/kg for 5-6 weeks), reduced the development of hypertension in MHS rats and normalized the increased renal Na,K-ATPase activity and mRNA levels, whereas it did not affect either blood pressure or Na,K-ATPase in Milan-normotensive (MNS) rats. In addition, a similar antihypertensive effect was observed in adult MHS rats after a short-term treatment. In cultured rat renal cells with increased Na-K pump activity at Vmax due to overexpression of the hypertensive variant of adducin, 5 days of incubation with PST 2238 (10(-10-)-10(-9) M) lowered the pump rate to the level of normal wild-type cells, which in turn were not affected by the drug. In conclusion, PST 2238 is a very potent compound that in MHS rats reduces blood pressure and normalizes Na-K pump alterations caused by a genetic alteration of the cytoskeletal adducin. Because adducin gene mutations have been associated with human essential hypertension, it is suggested that PST 2238 may display greater antihypertensive activity in those patients carrying such a genetic alteration.

Synthesis and biological evaluation of 2-hydroxy derivatives of digitoxigenin and 3-epidigitoxigenin.

The four stereoisomers of the 2-hydroxy derivatives of digitoxigenin and 3-epidigitoxigenin have been synthesized, their structures established by NMR, and their binding affinity for the digitalis receptor on Na+, K(+)-ATPase evaluated. These derivatives showed lower affinities than the parent compounds. The hydrophilic hydroxy groups in the alpha position are more detrimental to the affinity than hydroxy groups in the beta position.

A new approach to the design of novel inhibitors of Na+,K+-ATPase: 17alpha-substituted seco-D 5beta-androstane as cassaine analogues.

A new three-dimensional model for the relative binding mode of cassaine 1 and digitoxigenin 2 at the digitalis receptor site is proposed on the basis of the structural and conformational similarities among 1, 2 and its 14,15-seco analogues 3 and 4. Accordingly, the speculation that also 17alpha-substituted derivatives of the digitalis 5beta,14beta-androstane skeleton could efficiently bind to the Na+,K+-ATPase receptor is put forward and verified through the synthesis of some related compounds. The binding affinity shown by 2-(N,N-dimethylamino)ethyl 3beta, 14-dihydroxy-5beta,14beta-androstane-17alpha-acrylate 6 (IC50 = 5.89 microM) and, much more significantly, by the corresponding 14, 15-seco-14-oxo derivative 9 (IC50 = 0.12 microM) substantiates the new hypothesis and opens new prospects to the design of novel inhibitors of Na+,K+-ATPase as potential positive inotropic compounds.

PST2238: a new antihypertensive compound that antagonizes the long-term pressor effect of ouabain.

The inhibition of the long-term pressor effect of ouabain may be useful for the therapy of essential hypertension. Here, for the first time, a selective inhibitor of the ouabain pressor effect is described. In vitro, 17beta-(3-furyl)-5beta-androstane-3beta, 14beta, 17alpha-triol (PST 2238) displaced ouabain from its binding sites on purified sodium, potassium ATPase enzyme (Na-K ATPase) (IC50 1.7 x 10(-6) M) without interacting with other receptors involved in blood pressure regulation or hormonal control. In cultured renal cells, incubation with ouabain (10(-10) to 10(-8) M) for 5 days stimulated the Na-K pump at Vmax, whereas PST 2238 showed the same effect at micromolar concentration. The ouabain-dependent increase in the Na-K pump rate was abolished by PST 2238 at concentrations from 10(-14) to 10(-9) M. In rats made hypertensive by chronic infusion of 50 microg/kg/day of ouabain, PST 2238 given p.o at very low doses (0.1-1 microg/kg/day for 4 weeks) abolished the increase in blood pressure and renal Na-K ATPase activity caused by ouabain. PST 2238 did not affect either blood pressure or renal Na-K ATPase activity in normotensive rats. In conclusion, PST 2238 is a very potent compound that normalizes both blood pressure and alterations in the Na-K pump caused by ouabain. Thus it represents the prototype of a new class of antihypertensive drugs that could be effective in forms of hypertension sustained by the concomitant increase of endogenous ouabain levels and alterations in the Na-K pump.

Synthesis, cardiotonic activity, and structure-activity relationships of 17 beta-guanylhydrazone derivatives of 5 beta-androstane-3 beta, 14 beta-diol acting on the Na+,K(+)-ATPase receptor.

A series of digitalis-like compounds, with the lactone ring shifted from the original position through a spacer or replaced by a series of guanylhydrazone substituent-bearing chains, was synthesized and evaluated for inhibition of Na+,K(+)-ATPase and for inotropic activity. The highest Na+,K(+)-ATPase inhibition (IC50) and inotropic activity (EC50) were reached with the vinylogous guanylhydrazone 5 where a cardenolide-like polarized alpha,beta-unsaturated system and a basic guanidino group were both present at the 17 beta-position; for this compound IC50 and EC50 values were comparable to or higher than those of Thomas' parent guanylhydrazone 1, digitoxigenin, and digoxin. A substantial improvement of the desired positive inotropic activity versus the toxic arrhythmogenic concentration was not reached within this series; only a slightly better therapeutic index can be envisaged for compounds 5 and 4, even though, for the latter, to the detriment of potency, presumably because of a weaker interaction with the receptor, due to the lack of a cardenolide-like polarized system.

Diagnostic imaging of tibial periosteal ganglion.

A case of a soft tissue tumor situated in the anterior surface of the proximal end of the tibia in an adult patient is demonstrated by conventional radiographs, CT, and MRI. The lesion was well defined with respect to the adjacent soft tissue. The CT exam showed a soft tissue mass with external cortical erosion and thick spicules by periosteal reaction. On T1-weighted images the mass was homogeneous and of low signal intensity, whereas on T2-weighted images it showed a high signal intensity, with some septa in the mass. The differential considerations include a periosteal chondroma, a lipoma, a subperiosteal hematoma, an inflammatory process, a giant cell tumor of tendon sheath, and a parosteal osteosarcoma. The CT and MR features of these entities are reviewed as an aid in differential diagnosis of the periosteal ganglion.

Digitalis-like compounds: synthesis and biological evaluation of seco-D and D-homo derivatives.

The synthesis of seco-D and D-homo digitalis derivatives, from the carda-14,20(22)-dienolide 1, is described. Selective ozonolysis gave the seco-D 14-ketoaldehyde 2a. Modification of the two carbonyl groups and of the alpha, beta-unsaturated lactone ring of the seco-D 14-ketoaldehyde 2a allowed preparation of derivatives with a broad range of binding affinity to the Na+, K(+)-ATPase receptor. Some of the seco-D derivatives (10, 11b, and 13b) showed a binding affinity similar to that of digitoxigenin, demonstrating that the D-ring is not essential for recognition by the digitalis receptor. In the class of D-homo derivatives the highest binding value, about 15 times lower than that of digitoxigenin, was that of the C/D cis compound 29b; the C/D trans analog 28b showed a 7-fold decrease in binding affinity, indicating that the C/D configuration plays an important role in D-homo derivatives as in the classical digitalis compounds.

Synthesis and quantitative structure-activity relationship of 17 beta-(hydrazonomethyl)-5 beta-androstane-3 beta,14 beta-diol derivatives that bind to Na+,K(+)-ATPase receptor.

A series of 17 beta-(hydrazonomethyl)-5 beta-androstane-3, beta,14 beta-diol derivatives was synthesized and evaluated in the displacement of [3H]ouabain binding from Na+,K(+)-ATPase. The data were explored with multiple linear regression and partial least-squares to find possible quantitatives structure-activity relationships. Good correlations were found between binding to the receptor and van der Waals volumes or molar refractivities of the 17 beta-hydrazonomethyl substituents and pKa values of the compounds. Equivalent results were obtained using the proton affinity (calculated using MOPAC) of the hydrazone residues instead of experimental pKa. As basicity or related electronic factors of the substituents explain a significant portion of the observed changes in the activity, an ion-pair interaction between a carboxylate residue of the enzyme and the protonated 17 beta-hydrazonomethyl group, as postulated by Thomas, plays an important role in the interaction of the ligand to the Na+,K(+)-ATPase receptor.

Elastofibroma dorsi: a chest wall pseudotumor. Computed tomography and magnetic resonance imaging diagnosis.

"Elastofibroma dorsi" is a benign soft tissue mass usually arising between the chest wall and the inferior and medial aspects of the scapula. This lesion is not a true neoplasm but rather a reactive hyperplasia of elastic fibers. We present a case report of a woman with a subscapular mass, which was studied by computed tomography and magnetic resonance imaging. These are the methods of choice to study a soft tissue mass in order to define the inner structures and limits Computed tomography is helpful to guide a percutaneous biopsy, avoiding lesions to adjacent structures. Biopsy is recommended even when the imaging presentation seems typical of elastofibroma. The pathologic findings are diagnostic. No treatment is necessary in the asymptomatic patient. The treatment of choice for a symptomatic elastofibroma is local excison. There have been no reported cases of malignant transformation.

New 2-substituted 2,3,3a,4-tetrahydro-1H-imidazo[5,1-c] [1,4]benzoxazin-1-ones as alpha 2-adrenoceptor antagonists.

The synthesis of new 2-imidazol(in)yl-alkyl derivatives of 2,3,3a,4-tetrahydro-1H-imidazo[5,1-c][1,4]benzoxazin-1-one is reported. Some compounds of the series have shown high affinity for alpha 2 receptors, high alpha 2/alpha 1 selectivity and alpha 2 antagonism in vitro (vas deferens). Owing to their selective alpha 2-antagonism associated to a novel structure, compounds 8 and 20 have been selected for further biological investigation as potential antidepressants.