MRI in acute simple elbow dislocations: correlation of preoperative imaging and intraoperative findings of collateral ligaments and associated soft tissue injuries.

PURPOSE: The aim of our study was the evaluation of correspondence among collateral ligaments and other soft tissue injuries detected by MRI and by intraoperative findings in a consecutive series of patients treated for simple elbow dislocation. METHODS: After clinical and MRI examination, 16 out of 59 consecutive patients with moderate or severe instability after simple elbow dislocation were addressed to surgical treatment. There were 14 men and 2 women. The mean age was 39.6 years (range 16-69 years). RESULTS: MRI showed full-thickness lesion of MCL in 9/16 patients (53.3%) and partial lesion in 6/16 patients (40%), and in 1 case, the MCL was considered intact. On the lateral side, MRI showed complete injury of LCL in 7/16 patients (46.6%) and partial injury in 7/16 patients (40%). No lesions of LCL were observed in 2 patients (13.4%). MCL was surgically explored in all the patients. We observed 10/16 full-thickness lesions (62.5%) and 6/16 partial lesions (37.5%). LCL was surgically explored in 11/16 patients. We observed 6/11 full-thickness lesions (54.6%) and 5/11 partial lesions (45.4%). In 3 cases, associated soft tissue injuries were detected. The rate of concordance between MRI and surgical findings was 87.5% (14/16 cases) on the medial side and 90.9% (10/11 cases) on the lateral side. CONCLUSION: Our study demonstrated that MRI is a reliable and useful tool to investigate collateral ligaments and soft tissue injuries around the elbow and to plan the most adequate surgical treatment.

Bone marrow-derived cell mobilization by G-CSF to enhance osseointegration of bone substitute in high tibial osteotomy.

PURPOSE: To evaluate granulocyte colony-stimulating factor (G-CSF) efficacy in accelerating bone regeneration following opening-wedge high tibial valgus osteotomy for genu varum. METHODS: A phase II trial was conducted for evaluating the preoperative administration of G-CSF given at 10 µg/kg/day for 3 consecutive days with an additional half-dose 4 h before the opening-wedge high tibial valgus osteotomy. Overall, 12 patients (Group A) received G-CSF treatment, and the subsequent 12 patients (Group B) underwent surgery without G-CSF. The osteotomy gap was filled by a bone graft substitute. Bone marrow cell (BMC) mobilization was monitored by CD34+ve cell and clonogenic progenitor cell analysis. All patients underwent a clinical (Lysholm Knee Scale and SF-36) and radiographic evaluation preoperatively, as well as at given intervals postsurgery. RESULTS: All patients completed the treatment program without major side effects; G-CSF was well tolerated. BMC mobilization occurred in all Group A patients, with median peak values of circulating CD34+ve cells of 110/µL (range 29-256). Circulating clonogenic progenitors paralleled CD34+ve cell levels. A significant improvement in Lysholm Knee Scale was recorded at follow-up in Group A compared to Group B. At the radiographic evaluation, there was a significant increase in osseointegration at the bone-graft junction in Group A at 1, 2, 3 and 6 months postsurgery compared to Group B. The computerized tomography scan of the grafted area at 2 months postsurgery showed no significant difference in the quality of the newly formed bone between the two Groups. CONCLUSIONS: Although the limited number of patients does not allow firm conclusions, the study suggests that G-CSF can be safely administered preoperatively in subjects undergoing opening-wedge high tibial valgus osteotomy; in addition, the clinical, radiographic and CT monitoring indicate that G-CSF and/or mobilized BMCs may hasten bone graft substitute osseointegration. LEVEL OF EVIDENCE: I.

The effects of diminishing albumin binding to some Endothelin receptor antagonists.

As a pharmacological class, Endothelin-A receptor (ET(A)) antagonists are highly bound (>98%) to serum albumin. In the presence of physiological concentrations of albumin, their affinities for ET(A) decrease 10 to 100 fold. We have prepared ET(A) antagonists which exhibit lower degrees of binding to albumin, while maintaining potency and selectivity for the ET(A) receptor. The protein induced IC50 shift is reduced or eliminated in this new series of compounds. The compounds also display altered in vivo and pharmacokinetic profiles which may be consistent with their lower degree of protein binding.

Synthesis of 9-deoxo-4''-deoxy-6,9-epoxyerythromycin derivatives: novel and acid-stable motilides.

In our quest toward the discovery of highly potent and acid-stable motilides, novel 4"-deoxy derivatives of 9-deoxo-6, 9-epoxyerythromycin were designed, synthesized, and evaluated for their gastrointestinal prokinetic activities. These compounds, in their 9R configuration, were more potent than their 6,9-enol ether homologues in inducing well-coordinated smooth muscle contractions in an in vitro rabbit duodenal assay: e.g., (9R), (8S)-9-deoxo-4"-deoxy-3'-N-desmethyl-3'-N-ethyl-6, 9-epoxyerythromycin A (10) and (9R), (8S)-9-deoxo-4"-deoxy-3'-N-desmethyl-3'-N-ethanol-6, 9-epoxyerythromycin A (15) had a pED50 of 8.54 and 8.11 compared to a pED50 of 7.22 for compound 2 (ABT-229). Reduction of the 6,9-enol ether, which was aimed at improving the acid stability, afforded the most stable motilides to date with t1/2 of 5.5 h for 10 and 15. Compounds 10 and 15 bind specifically to rabbit antral smooth muscle motilin receptors with pIC50 values of 8.52 and 8.70.

c-Myc inactivation by mutant Max alters growth and morphology of NCI-H-630 colon cancer cells.

The myc gene family has been implicated in multiple cell processes including proliferation, differentiation, tumorigenesis, and apoptosis. For its cellular growth promoting function, Myc must heterodimerize with Max. To study the effect of Myc inactivation on the growth and differentiation properties of epithelial tumor cells, we transfected the H-630 human colon cancer cell line with bm-max, a mutant Max protein in which DNA-binding activity has been abolished. Cells expressing high levels of bm-Max grow poorly, and the morphology of both colonies and single cells is altered. Moreover, increased bm-Max expression results in a prolonged G alpha/G1 phase accompanied by induced expression of p21 (WAF1/CIP1), elevated levels of alkaline phosphatase (ALP) activity, and accumulation of large fat granuli within the cells. These distinctive cell characteristics are associated with differentiation processes in numerous malignant cell lines. The results of this study support a model in which sequestering of endogenous Myc and Max proteins into "basic mutant" dimers lacking DNA-binding activity is sufficient both to inhibit proliferation and to induce changes in cell behavior consistent with differentiation.

Identification of in vivo target RNA sequences bound by thymidylate synthase.

We developed an immunoprecipitation-RNA-random PCR (rPCR) method to isolate cellular RNA sequences that bind to the folate-dependent enzyme thymidylate synthase (TS). Using this approach, nine different cellular RNAs that formed a ribonucleoprotein (RNP) complex with thymidylate synthase (TS) in human colon cancer cells were identified. RNA binding experiments revealed that seven of these RNAs bound TS with relatively high affinity (IC50 values ranging from 1.5 to 6 nM). One of the RNAs was shown to encode the interferon (IFN)-induced 15 kDa protein. Western immunoblot analyses demonstrated that the level of IFN-induced 15 kDa protein was significantly decreased in human colon cancer H630-R10 cells compared with parent H630 cells. While the level of IFN-induced 15 kDa mRNA expression was the same in parent and TS-overexpressing cell lines, the level of IFN-induced 15 kDa RNA bound to TS in the form of a RNP complex was markedly higher in H630-R10 cells relative to parent H630 cells. These studies begin to define a number of cellular target RNA sequences with which TS interacts and suggest that these TS protein-cellular RNA interactions may have a biological role.

Method to estimate the rate and extent of intestinal absorption in conscious rats using an absorption probe and portal blood sampling.

PURPOSE: A variety of methods exist which determine the rate and extent of intestinal absorption. The method described here employs an internal absorption reference probe and portal blood sampling in unanesthetized rat. METHODS: Theophylline and tritiated water were selected as absorption reference probes since they are quantitatively absorbed in conscious rat. The fraction of an intestinal dose which reaches portal blood was determined from the resulting portal-systemic blood concentration gradients of the drug relative to the absorption probe. The absorption probes provide a means to calculate the drug mass reaching portal blood without the need of measuring the portal blood flow rate. The technique was evaluated with verapamil and a well-absorbed 5-lipoxygenase inhibitor, A-79035. RESULTS: The fraction of an intrajejunal dose of A-79035 reaching the portal vein (FG) was 0.86 using theophylline as the absorption probe. Verapamil, which is susceptible to extensive hepatic first-pass elimination, was completely absorbed (FG = 0.98) within 1 hour, but was only 21.4% bioavailable. Absorption rate constants, estimated from initial appearance rates in portal blood, were used to monitor factors that affect drug absorption. For example, with a dose solution containing 30% PEG-400, the absorption rate constants of theophylline and A-79035 were significantly reduced. Anesthesia reduced the absorption rate constant for theophylline in rats by 40% compared to conscious animals. CONCLUSIONS: The technique detailed here allows reliable, direct measurement of intestinal absorption which may assist in characterizing oral dosing for novel therapeutic agents.

[Ultrasonographic study of the patellar tendon following bone-tendon-bone anterior cruciate ligament reconstruction arthroscopy]. / Studio ecotomografico del tendine rotuleo dopo prelievo osso-tendine-osso per ricostruzione artroscopica del legamento crociato anteriore.

The arthroscopic reconstruction of the anterior cruciate ligament requires the partial removal of the patellar tendon. US potentials in the assessment of residual patellar tendon after bone-tendon-bone removal were compared with those of CT and clinics. Mechanical resistance reduction of the residual tendon may be caused by removal modalities and size. This work was aimed at investigating the morphologic US patterns indicating "stability" of the operated tendon, which is mandatory for a risk-free functional recovery. Twenty patients were submitted to US of the operated tendon with contralateral comparison. In each patient tendon thickness and structure in the site of removal were studied, especially aiming at demonstrating diffuse or focal alterations of echogenicity. Middle third thickness and new tissue echostructure are fundamental US variables to define residual tendon "stability". The authors describe some US patterns of the surgical tendon to be considered as normal and not abnormal findings, provided that US be performed at least two months after surgery.

Type II interleukin-1 receptor is not expressed in cultured endothelial cells and is not involved in endothelial cell activation.

Interleukin-1 (IL-1) profoundly affects a number of functions of endothelial cells (EC). It was previously shown that EC express the type I 80-Kd IL-1 receptor (IL-1 RI). In this study we define the expression and functional significance of the type II IL-1R (IL-1 RII) in EC. Human umbilical vein EC did not express appreciable levels of IL-1 RII mRNA as assessed by Northern analysis or reverse transcription and polymerase chain reaction. Exposure to various cytokines (including IL-4, which augments IL-1 RII in neutrophils) failed to induce IL-1 RII mRNA. The binding of radiolabeled IL-1 beta to EC was blocked by antitype I (M4) but not by antitype II (M22) monoclonal antibodies (MoAbs). MoAbs directed against the IL-1 RI (M1 and M4) inhibited the induction of IL-6 and adhesion molecules in EC by IL-1, whereas an anti-IL-1 RII (M22) was inactive. The human IL-1 receptor antagonist (IL-1ra) preferentially interacts with IL-1 RI versus IL-1 RII in the mouse. IL-1 ra inhibited the response of mouse endothelial cells to IL-1. We conclude that EC selectively express the IL-1 RI and that this is involved in the response of this cell type to IL-1.

[Pneumothorax in multiple trauma. Radiologic and CT study]. / Pneumotorace nei politraumi. Studio radiologico e TC.

This study was aimed at evaluating the necessity to perform chest Computerized Tomography (CT) in multiple traumatized patients to diagnose pleuropulmonary lesions and, particularly, pneumothorax: the correct identification of this condition, although minimal, is important especially in prevision of long anesthesias and/or positive end-expiratory pressure (PEEP) therapy. This assisted respiratory technique improves arterial oxygenation but causes a barotrauma which may cause some complications; particularly, a small undetected pneumothorax can suddenly increase so as to cause pulmonary collapse with sometimes dramatic symptoms. Chest X-ray films and CT scans, performed in rapid succession on patient's admission in Emergency Ward, were compared in 21 subjects. CT is indispensable in case of severe chest parietal lesions which can mask the radiological evidence of pulmonary or pleural conditions, as it occurred in 3 of our cases. Moreover, CT resulted more reliable than chest X-rays (18 versus 10 correct diagnoses) especially in the detection of small antero-inferior pneumothorax flaps, in which direct radiological signs cannot be identified, in default of radio-geometrical assumptions. Indirect radiological signs of pneumothorax must be recognized but critically considered in order to avoid over-staging.

Expression of a monocyte chemotactic cytokine by human mononuclear phagocytes.

The present study was designed to investigate the capacity of human mononuclear phagocytes to produce a cytokine chemotactic for monocytes (monocyte chemotactic protein (MCP), alternative acronyms JE, monocyte chemotactic and activating factor, MCP-1, and tumor-derived chemotactic factor). Human PBMC exposed in vitro to bacterial LPS expressed high levels of MCP transcripts. Monocyte-depleted lymphoid cells were not induced to express MCP by LPS. Percoll-gradient purified monocytes were able to express high levels of MCP transcripts. In an effort to exclude a role of contaminating non-monocytic cells, mononuclear phagocytes were separated by flow cytometry and sorting: CD14+ cells exposed to LPS showed high levels of MCP mRNA. LPS-stimulated monocytes released chemotactic activity for monocytes that could be inhibited by absorption with anti-MCP antibodies. IL-1, TNF, IFN-gamma, granulocyte-macrophage-CSF and, to a lesser extent, macrophage-CSF, as well as inactivated streptococci, also induced MCP gene expression. Actinomycin D experiments indicated that induction of MCP in monocytes was gene transcription-dependent. The protein synthesis inhibitor cycloheximide (Cy) blocked IL-1-, TNF-, or LPS-induced MCP gene expression in monocytes. In contrast, expression of the structurally related chemotactic cytokine IL-8 was superinduced by Cy. Moreover, Cy superinduced MCP gene expression in cells other than monocytes, including endothelial cells, smooth muscle cell and fibrosarcoma cells, indicating different mechanisms of regulation in mononuclear phagocytes vs cells of other lineages. The capacity of cells of the monocyte-macrophage lineage to produce a cytokine that recruits and activates circulating monocytes may be of considerable importance in inflammatory and immunologic reactions. Thus, the mononuclear phagocyte system can autonomously regulate the extravasation and activation of immature elements of the same lineage, a key event in inflammation and immunity.

Interleukin 4 amplifies monocyte chemotactic protein and interleukin 6 production by endothelial cells.

Upon exposure to interleukin 4 (IL-4), human umbilical vein endothelial cells (EC) produced low amounts of IL-6 and expressed low levels of IL-6 transcripts. While being a weak stimulus for IL-6 production, IL-4 amplified the release and mRNA expression of this cytokine in response to optimal concentrations of IL-1. IL-4 also induced low levels of monocyte chemotactic protein but amplified the expression of this chemoattractant in response to inflammatory signals. Thus IL-4, by amplifying at the level of the vascular endothelium the expression of vascular cell adhesion molecule 1 selectively, as well as that of chemoattractants and IL-6, may favour the selective recruitment and activation of lymphoid and monocytic elements crucial for subacute/chronic inflammation and immune reactions.

[Ultrasonography in diseases of lymph nodes and soft tissues of the neck]. / L'ecotomografia nelle affezioni dei linfonodi e dei tessuti molli del collo.

A study of 55 patients affected by neoplasia of the head and neck or clinically evident laterocervical swellings was carried out in order to evaluate the diagnostic value of ultrasonography in the study of cervical lymph nodes and soft tissues, excluding thyroid or salivary pathologies. The analysis of results confirmed that, in line with previously published findings, ultrasonography is a reliable method of diagnosing lesions and correctly identifying the affected organ, but then it is considerably less reliable in defining the type of lesion. In view of this, it is reasonable to propose a more widespread use of ultrasonographically guided needle biopsy which, in addition to being a rapid and non-traumatic method, would allow precisely target samples to be taken from those lesions with a doubtful or unusual clinical or ultrasonic appearance.

[The clinical prognostic importance of routine study of the aorta during abdominal echotomography in the elderly patient]. / Significato clinico-prognostico dello studio "di routine" dell'aorta in corso di ecotomografia addominale nel paziente anziano.

Aneurysm of the abdominal aorta (AAA) is encountered with increasing frequency and is often observed at fixation or rupture, events which can be treated surgically but suffer from high operative mortality. Given the current tendency to extend the surgical indication to increasing sectors of patients, the clinico-prognostic significance of routine study of the abdominal aorta with echotomography has been investigated. This examination is reliable in all elderly patients who undergo ultrasound examination for different clinical indications. In the 147 patients considered, aged more than 60 and of both sexes, 12 AAA not suspected clinically were observed. For this the surgical indication or echotomographic monitoring was discussed in relation to age and clinical condition and with due consideration for the morphologic volumetry of the lesion. The finding of the 12 cases of AAA is an indicator of the usefulness of a routine study of the aorta in elderly patients, for awareness of the lesion means that the best therapeutic decisions can be taken and makes it possible to act effectively in emergency situations such as fixation, rupture and distal embolism.

[A possible role of magnetic resonance in the follow-up of renal transplants]. / Possibile ruolo della RM nel follow-up del trapianto renale.

The authors discuss the possible role of Magnetic Resonance Imaging (MRI) in the follow-up of renal transplants. Its diagnostic accuracy is compared with Ultrasounds (US), which is considered the method of choice in postoperative monitoring of renal transplants. Thirty-two patients (transplant life ranging from 5 days to 37 months) were examined in the same day with both MRI and US. Sonographic evaluation is based on a group of signs related to renal alterations and unanimously ascertained; the identification of MR patterns of normally functioning kidney or renal rejection might give way to more extensive clinical applications of the method, with the advantages of multiplanarity and no X-ray use. MR diagnostic accuracy in the diagnosis of normally functioning transplant or renal rejection was 82.7% (vs. US: 68.9%); even though specificity was the same (84.6%). MRI had higher sensibility than US (82.25% vs. 656.25%). MRI is more sensitive in demonstrating renal pathology in transplanted kidneys, and its diagnostic accuracy is superior. Still, US must be considered the methodology of choice in instrumental research when there is a clinical suspicion of renal rejection, due to its sufficient diagnostic accuracy, to its being easy to perform in continuous follow-up, to its low cost and to the short execution time. MRI is nevertheless suggested in the follow-up of renal transplants both in questionable cases and when biopsy cannot be performed.

[Ultrasonic evaluation of primary hyperparathyroidism]. / Valutazione ecotomografica dell'iperparatiroidismo primitivo.

The authors evaluated the diagnostic reliability of echotomography in detecting parathyroid masses: 37 patients were studied with primary hyperparathyroidism, in four cases recurrent. They all underwent surgical ablation of the mass, identification of all glands, and biopsy of an apparently normal parathyroid. Echotomography was accurate in 91.4% of cases: it identified 27 out of 39 pathological glands (sensibility 69.2%) and gave no false-positive results (specificity 100%). Since parathyroid is often ectopic, oblique scans are suggested, i.e. of jugulum while the patient is swallowing. Such scans were always used in our study, in order to identify lesions even in case of "difficult" locations, such as the superior mediastinum.

[Disorders of heart rhythm during urography studied with Holter monitoring. Comparison of ionic and non-ionic contrast media]. / Le turbe del ritmo cardiaco in corso di urografia studiate con monitoraggio Holter. Raffronto tra mdc ionico e non ionico.

Given the disagreements in the literature over the extent of cardiac complications during urography it was decided to assess any arrhythmias following the injection of ionic and non-ionic contrast media and a placebo by means of 24 hours dynamic Holter monitoring. The results were subjected to meticulous statistical analysis and showed no connection between electrocardiographic alterations and the substance injected. The absence of statistical significance and the variability of the results suggest that alterations in the physiological parameters and/or arrhythmias arising during the administration of contrast media should be assessed with extreme caution.

[Diagnostic accuracy of sequential angio-urography with the spot-camera in clinical practice]. / Accuratezza diagnostica dell'angiourografia sequenziale (AUS) con spot-camera nella practica clinica.

In this perspective study the authors examined 57 patients to evaluate diagnostic accuracy of sequential angiourography (AUS) using spot-camera and image subtraction for the visualization of the vascular phase of the renal arteries. All the subjects underwent surgery or follow-up with other clinical and radiological methods. The results obtained with this technique, of low cost and simple execution, were satisfactory: accuracy 98%, sensitivity 100%, specificity 98%.

Use of the thyroid 99Tcm scintiscan with lead-shield on the hot nodule in the diagnosis of autonomous adenoma.

Eighteen patients bearing a hot nodule, imaged by basal 99Tcm scintiscan and toxic in eight of them, were studied. All patients underwent 99Tcm thyroid scintiscan in basal conditions and after placing a lead-shield on the hot thyroid nodule, without other radioisotope administration. In eight cases the thyroid scintiscan after lead-shield overlapping the hot nodule, was compared to a second 99Tcm thyroid scintiscan after thyrotrophic hormone stimulation, TSH. This technique of nodule shielding was able to show the extranodular tissue in 15 patients; in the remaining three cases neither this approach nor the scintiscan after exogenous TSH were able to demonstrate any remainder thyroid parenchyma. Thus, this scintigraphic method can be considered excellent in the diagnosis of autonomous adenoma: it needs, in fact, a single radioisotope administration and does not present the adverse effects frequently induced by exogenous TSH.