Anterior dislocation of the hip associated with intertrochanteric fracture of the femur - Case presentation.

Dislocations of the hip usually occur following high energy trauma, the coxo-femoral joint being inherently stable, and can be associated with acetabular fractures or fractures of the head, neck or shaft of femur. However, the combination between the anterior hip dislocation and the ipsilateral intertrochanteric fracture is extremely rare, the literature offering only scarce information. We present the case of a patient, aged 44, victim of a trauma by precipitation from height (12m), diagnosed with left hip anterior dislocation and intertrochanteric fracture of the ipsilateral femur. An emergency surgical treatment was applied in less than 3 hours after trauma. The hip dislocation was reduced under general anesthesia and the intertrochanteric fracture was also reduced and internally fixed with a dynamic hip screw. Radiological and functional evaluation at 6 months after surgery, using the modified Merle D'Aubigne hip score was good. The clinical outcome of such a case depends on the quick evaluation and treatment. Providing a stable reduction of the dislocation and a stable internal fixation of the fracture as soon as possible (within the first 6 hours) will allow an early physical rehabilitation and decrease the risk of complications.

Histopathological examination in evaluation of long-term results after osteocartilaginous transplantation.

OBJECTIVE: To assess long-term outcomes of osteocartilaginous transplantation for non-degenerative lesions of hyaline articular cartilage in the knee, by performing minibiopsies from the transplanted area and examining them histopathologically. PATIENTS AND METHODS: Forty-four patients with post-traumatic cartilage injuries of the bearing surfaces of the knee were enrolled in a prospective study, that included treatment with autologous osteocartilaginous grafts at the level of the lesion, "second look" arthroscopy and targeted minibiopsies at one year and five years postoperatively (six minibiopsies per patient). The collected tissue fragments were examined by optic microscopy. In order to integrate the histopathological findings in the clinical context, the function of the knee was also quantified by calculation of the International Cartilage Repair Society Score preoperatively, at one year and at five years postoperatively. RESULTS: Five years post-transplant the outcomes for 36 patients were available. One year post-transplant, the histopathological examination revealed the presence of hyaline cartilage in 165 of the 216 (76.39%) tissue samples collected and fibrocartilage in 51 (23.61%) respectively. Five years after surgery, the proportions of these findings were 159/216 (73.61%) for hyaline cartilage and 57/216 (26.39%) for fibrocartilage. The difference was not statistically significant (p>0.1).The evolution of the ICRS clinical score was from 38.57±3.42 preoperatively to 80.31±3.85 (p<0.0001) after one year and to 81.35±4.57, respectively at five years after surgery. CONCLUSIONS: Autologous osteocartilaginous transplantation brings hyaline articular cartilage at the level of the injured area. Approximately three quarters of the surface lesion remains covered by high quality hyaline cartilage that maintains its macroscopic structure and architecture for a long period of time.

Giant-cell tumor of the bone (GCTOB): clinical case.

Giant-cell tumor of the bone is a benign tumor, but with high local aggressiveness, even with risk of distant metastasis. From an epidemiological standpoint, giant-cell tumor of the bone accounts for 4-5% of primary bone tumors and ~20% of benign bone tumors; commonly affects adults between 20-40 years, slightly more common in females. We present the case of a 57-year-old woman, without significant pathological history, which, after clinical, imagistic and anatomopathological investigations, is diagnosed with giant cell tumor of the right distal radius. The patient underwent surgery and segmental resection of the tumor in oncological limits was performed, replacing the remaining bone defect with fibular autograft. The results were good, according to Mayo functional assessment score. This way, the wrist joint mobility and the carpal cartilage were preserved, providing a barrier against distal migration of any remaining tumoral cells, as well. In conclusion, we can state that in aggressive giant cell tumors located at the distal radius, the best therapeutic option is en bloc resection of the formation (lesion) with fibular autograft replacement of the bone defect.

Primary total knee arthroplasty in severe valgus knee.

AIM: Outcome of primary total arthroplasty for osteoarthritis of the knee with valgus deformity. MATERIALS AND METHODS: Between 2005 and 2007, 28 primary total knee replacements were performed for osteoarthritis of the knee with valgus deformity. 21 cases were women and 7 men with a mean age of 66.6 years (extremes 54-81). The clinical and radiological evaluations were done considering the knee range of motion, Knee Society Score (KSS) and femorotibial angle measured on the frontal standing long leg X-rays. Preoperatively, the knee valgus deformity angle was 6 to 15 degrees in 14 cases, 15 to 25 degrees in 10 cases and over 25 degrees in 4 cases. RESULTS: After a mean follow-up time of 14 months (extremes 7-29), the knee range of motion improved from a mean of 71 degrees (extremes 52-87) preoperatively to a mean of 95 degrees (extremes 78-110) postoperatively. The KSS value improved from 21.3 points (extremes 1-33) preoperatively to 80.7 points (extremes 70-92) postoperatively and the frontal femorotibial angle from a mean value of 21 degrees (extremes 11-39) of valgus before surgery, to a mean of 9 degrees (extremes 0-12) of valgus after surgery. CONCLUSIONS: Long leg AP view X-ray examination in standing position is mandatory. The standard medial parapatellar approach is appropriate in this type of arthroplasty even if significant knee valgus deviations are present because it avoids the lateral approach complications. Postoperatively, one can get an aligned and stable knee if a judicious and progressive periarticular soft tissues balancing is achieved, in both flexion and extension position.

Proposed interaction between angiotensinogen and retinoblastoma tumor suppressor protein: Potential molecular origin of hypertension.

Hypertension ranks among the most important disease challenges on a global scale. Here, a novel hypothesis is presented which implicates angiotensinogen, i.e. the precursor protein for the hypertensive peptide angiotensin II, as a key culprit in the pathogenesis of hypertension. This hypothesis more precisely entails that intracellular angiotensinogen binds and thereby inactivates the retinoblastoma tumor suppressor protein (RB), consequently leading to an inflammatory and hyperproliferative state that significantly contributes to pathologically increasing blood pressure. Accordingly, a conceivable antihypertensive strategy could comprise RB-derived compounds that neutralize angiotensinogen.

Acroplate--a modern solution for the treatment of acromioclavicular joint dislocation.

Two main ways to fix the reduction were imposed in surgical treatment of the acromioclavicular joint dislocations: fixation with trans acromioclavicular pin (Phemister method) and fixation with plate and screws type acroplate. The purpose of the present paper work is to compare immediate and later postoperative results between the two types of surgical interventions. During 2005-2007, 37 surgical reductions and fixation of acromioclavicular joint dislocations were performed in the Orthopedic-Traumatology Clinic of SUUB. In 17 cases a fixation with screws and plates type acroplate has been performed and in 20 cases with pins using the Phemister method. Sex ratio: 31 men and 8 women. Patients were aged between 17 and 56 years old. Follow up at 6 weeks, 3, 6, 12 and 18 post-operatory months. Osteosintesis material removing was done postoperatively, at 4 weeks in case of acroplate's and at 6 weeks in case of the pins. All patients treated of fixation with plate and screws acroplate type had a favorable evolution/development, starting with the shoulder joint mobilization at 24 hours postoperatively, with a complete recovery 4 weeks after the operation, at the same time with the ablation, and without immediate other late complications. As far as the patients treated by using the Phemister method are concerned, they were applied an immobilization, postoperatively. Desault bandage or the scarf for a period between 1 and 3 weeks, beginning with the shoulder joint mobilization later on and a full recovery after a minimum of 6 weeks. However, 3 of the cases showed a migration of one or both pins. Following the study, a more rapid recovery resulted, complete, and without complications of mobility in the shoulder joint, when using plate type acroplate vs pin.

The development of xenograft glioblastoma implants in nude mice brain.

The inefficacity of the actual therapies for glioblastoma multiformis stimulates the researchers to search for new and innovative therapies. Therefore, the development of in vivo model for glioblastoma is an essential step during these researches, being a link between cells cultures studies and the first phases of clinical trials. In this paper, we present several procedures which have been performed for the first time in our country, such as: the cultivation and manipulation of U87MG line, the manipulation of athymic knock-out mice (NUDE Crl: CD-1 Foxn 1), the stereotactic inoculation of glioblastoma cells and finally the development of glioblastoma xenograft in the brain of inoculated nude mice. These results, which offer to the researchers from our country an in vivo model for glioblastoma, could be the start point for several projects oriented to the development of new therapies in glioblastoma, and could raise the performance of our scientific research to the European level.

Potent in vivo antineoplastic activity of MCR peptides MCR-4 and MCR-14 against chemotherapy-resistant human small cell lung cancer.

Previous studies have shown that MCR peptides possessing the retinoblastoma protein (RB) fragment LFYKKV as the active site are able to inhibit the proliferation of human non-small cell lung cancer (NSCLC) cells in vitro and in vivo. The goal of the present study was to test these compounds against human small cell lung cancer (SCLC) in vivo since this tumor is notoriously resistant to conventional therapy or, respectively, is characterized by rapid relapse after initially successful treatment. We herein report that the MCR peptides MCR-4 and MCR-14 display potent antiproliferative activity against RB-negative H82 SCLC xenograft tumors in nude mice, whereas the chemotherapeutic agent VP-16 tested in parallel in a clinically relevant dose had no anti-tumor effect. These encouraging results warrant accelerating the introduction of MCR peptides into clinical trials in patients with RB-negative tumors such as SCLC in the near future.

The lateral flow card test: an alternative method for the detection of Trichinella infection in swine.

A novel lateral flow card (TS-Card pork) test was developed for the serological detection of Trichinella infected pigs. Based on extensive studies performed in Romania during 1999-2000 this test proved to be highly specific sensitive, rapid (3-12 minutes) and easy to use (no need for laboratory facilities). It can be used both for the detection of Trichinella infection in carcasses and for epizooliological studies using a variety of samples including whole or dried blood, serum, or tissue fluids. The TS-Card pork test, used as a screening test, can be the foundation of an on-farm or field based inspection system to significantly improve food safety in countries with a high prevalence of Trichinella in pigs or other food animal species. The results presented are also promising for application of the test in an on-line laboratory based inspection system since the speed of the test allows sufficient time to rail out suspected hog carcasses during the slaughter process.

Nuclear colocalization and complex formation of insulin with retinoblastoma protein in HepG2 human hepatoma cells.

Previous structural and biochemical evidence had suggested that insulin may bind to the nuclear tumor suppressor retinoblastoma protein (RB). The present study is now the first to unravel the physical and functional interaction between a growth factor and an anti-oncoprotein, specifically demonstrating the association between insulin and RB in living cells and finding that this complex formation is relevant for cell division. Our immunofluorescence microscopy data suggest that insulin colocalizes with RB in the cell nuclei of HepG2 human hepatoma cells and that contacts the B-region of the RB pocket. Furthermore, these events were found to correlate with an enhancement of cell proliferation. These results are in line with the initial structure-based predictions and, moreover, provide a suitable starting point for the further understanding as well as the pharmacological modulation of nucleocrine interactions between growth factors and tumor suppressors, in physiology and disease.

Selective inhibition of human lung cancer cell growth by peptides derived from retinoblastoma protein.

Peptides containing retinoblastoma protein (RB) fragment 649-654 (LFYKKV) were tested for their ability to block the proliferation of RB-negative and RB-positive human non-small cell lung cancer (NSCLC) cells. These peptides potently restrained the growth of both types of tumor cells, as measured by metabolic (MTT) and cellular viability (trypan blue exclusion) assays. As such, and remarkably, the peptides were able to overcome the resistance of RB-positive cells usually observed with RB gene or protein replacement therapy. Compared to the overall performance of conventional chemotherapy tested in parallel, the peptides were more cytotoxic against RB-negative neoplastic cells and equipotent toward RB-positive tumor cells, yet less toxic toward normal human cells. Thus, these new molecules hold great promise to evolve into an efficient therapy for human lung cancer, a common malignancy still defying treatment and holding a poor prognosis, as well as for other human neoplasias.

Nuclear localization of insulin-like growth factor binding protein 3 in a lung cancer cell line.

Considerable evidence exists that lung cancer cell lines produce large amounts of insulin-like growth factor-binding proteins (IGFBPs). In addition, these cells are subject to an autocrine or paracrine growth control by insulin-like growth factors (IGFs). We now demonstrate by immunocytochemistry with IGFBP-3 antibodies that nuclei of a lung cancer cell line distinctly immunostain for IGFBP-3. This finding led us to investigate in more detail the localization of this protein that, to date, had only been known to occur extracellularly. Ligand blotting revealed that purified nuclear extracts contain a 43,000-Da IGFBP which can bind [I125]IGF-I. By Western blot this protein was identified as IGFBP-3. Thus, our data are consistent with the results of a previous structural study predicting a nuclear localization for IGFBP-3. Moreover, our findings raise the possibility that nuclear IGFBP-3 is functional and involved in the pathogenesis of lung cancer.

Prion function and dysfunction: a structure-based scenario.

Prion diseases are transmissible, neurodegenerative disorders associated with as yet incompletely defined isoforms of a cellular protein termed prion protein (PrP). We have now identified in PrP structural information compatible with nucleotide- and nucleic acid-binding. As such, PrP contains a putative nicotinamide adenine dinucleotide (NADH)-binding site. Moreover, the PrP octarepeats reveal homology to the nucleic acid-binding and strand-annealing octarepeats of mammalian heterogeneous ribonucleoprotein (RNP) A1. Therefore, PrP may have NADH-dependent oxidoreductase activity as well as A1-like functions such as nucleic acid annealing and splicing. Moreover, we propose that infectious prions are propagated through a dynamic molecular symbiosis between a ribozyme-like nucleic acid and a conformational isomer of the RNP-like prion protein. Thus, our model has important implications for the understanding and treatment of prion diseases.

Insulin receptor alpha-subunit: a putative gene regulatory molecule.

Previous studies have demonstrated the presence of the insulin receptor in the cell nucleus. Recently, it was shown that the insulin receptor also exhibits nuclear tyrosine kinase activity. In the present investigation, I have searched for structural correlates to a nuclear localization of the insulin receptor as well as to other potential nuclear actions of this molecule. Interestingly, this analysis yielded that the insulin receptor (alpha-subunit) contains a bipartite nuclear localization signal (consistent with the preceding experimental data), several zinc finger-like motifs and an RGG box. These findings have intriguing implications with regard to a presumable role of the insulin receptor (alpha-subunit) as a gene regulatory molecule.

Antibody constant region: potential to bind metal and nucleic acid.

Environmental challenges appear to elicit similar patterns of cellular responses such as positive autoregulation and autoamplification whether one considers the generation of antibodies with identical antigen specificity or the accumulation of host-protective transcription factors. Therefore, I analyzed the structure of immunoglobulins (Ig) for motifs commonly found in transcription factors. Specifically, the well-known abundance and periodic location of cysteine residues in immunoglobulin chains prompted me to check antibody constant regions for the presence of putative metal-binding domains and zinc finger-like sequences. The constant regions of Ig light and heavy chains were found to harbor one or several copies, respectively, of a short cysteine- and histidine-containing sequence. Moreover, all four IgG subclasses were detected to comprise zinc finger-like motifs in their heavy chain constant and hinge domains. Yet another finding is the occurrence of several sequences of the form serine-proline-X-X and/or threonine-proline-X-X in the hinge sections of IgA and IgG3. These results suggest that antibody constant regions, as a fragment and/or embedded in a full-length immunoglobulin chain, may complex metal, thus acquiring conformations conducive to dimerization and nucleic acid binding. As such, my study provides a putative structural basis for the known requirement of divalent metal cations, particularly of zinc ions, for a normal immune response, and warrants further investigations, both theoretical and experimental, into the potential of antibody constant regions for metal binding and gene regulation. Moreover, future testing of the proposed zinc finger peptides from Ig constant domains should yield information relevant to zinc finger design with potentially wide applications in research and clinical medicine.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding of the LXCXE insulin motif to a hexapeptide derived from retinoblastoma protein.

Peptides corresponding to retinoblastoma protein (RB) fragment 649-654 (LFYKKV) were tested for their ability to recognize the LXCXE sequence motif in human papilloma virus type 16E7 protein (HPV-16E7) encompassing E7 residues 21-26 (DLYCYE) and an identical motif in human insulin comprising insulin B-chain residues 16-21 (YLVCGE), respectively. Interaction between these complementary peptide sequences was observed by several approaches, including direct and competitive ELISA as well as affinity chromatography. Moreover, we demonstrated that immobilized RB649-654 displays specific recognition properties towards full-length insulin. Hence, this study provides a first experimental support for the previously anticipated complex formation between insulin and RB.

The 'LXCXE' hydropathic superfamily of ligands for retinoblastoma protein: a proposal.

The present study reports structural similarities between viral oncoproteins, growth factors belonging to the insulin family, members of the steroid/thyroid receptor superfamily, a D-type cyclin, the Elf-1 transcription factor and Bcl oncoproteins in regions that have been shown or proposed to mediate complex formation of these proteins with the tumor suppressor retinoblastoma protein (RB). This relationship predicts a common intracellular pathway for mitogenic signals and molecules promoting cell survival. Conversely, the structural evidence described here suggests that RB may play a central role both at the boundary between negative and positive cell growth regulation as well as in developmental decisions between cell death and cell survival.

Synthetic inducible biological response amplifiers (SIBRAs): rational peptides at the crossroads between molecular evolution and structure-based drug design.

The present study proposes a novel type of synthetic chimaeric polypeptides potentially useful in the therapy of various diseases. The prototype peptide termed 'synthetic inducible biological response amplifier' (SIBRA) would comprise a ligand-binding site, a DNA-binding region, a trans-activating domain as well as strings of residues ensuring bioavailability and targeting to specific compartments such as the cell nucleus. These domains would be selected from cellular proteins, artificially tailored to a SIBRA and further modified towards a molecule with both in vivo and intracellular activity. Since proposed to resemble a host molecule with autoregulatory properties, a SIBRA would be activated upon exposure to a defined environmental stimulus and amplify host responses appropriate for this stimulus. Proteins would accumulate that share functional domains with the administered SIBRA and have a positive autoregulatory capacity. The latter may involve the interaction of the induced protein with the promoter of its gene resulting in a direct positive autoregulatory loop or require the induction of intermediary proteins that eventually upregulate the production of SIBRA-like host proteins. Since the ligand-binding site of a SIBRA is rationally designed to target a pathogenic protein, SIBRAs could be regarded as the product of an artificial acceleration and refinement of strategies intrinsic to the immune system.