Osteoscopy for assessment of blood supply to the femoral head: a preliminary study.

OBJECTIVES: The aim of our study was to develop a minimally invasive endoscopic procedure (osteoscopy), which is capable of visualizing blood supply and quantitatively assessing circulation to the femoral head at the time of definitive surgery. METHODS: The new diagnostic technique was developed in animal experiments (four piglets) and was subsequently tested in nine consecutive patients requiring surgery for a femoral neck fracture. The direct visualization of the femoral head circulation was performed in the mortise prepared for the implant. The osteoscope optic fiber was placed at the orifice of the cavity created by the custom-made drill bit. The "mortise-sleeve-optic" system was connected to a manometer and a saline reservoir. The bleeding from the wall of bony cavity was observed, meanwhile the inner pressure of the "mortise-sleeve-optic" system was changed gradually. The pressure measurement at the first appearance of bleeding and the intraosseal pressure was recorded. RESULTS: The animal investigations demonstrated that the osteoscopy readily distinguished among diffuse bleeding, pulsatile bleeding, and the absence of bleeding in the femoral head. The human experiments proved that a different quality of the femoral head circulation can be observed during osteoscopy. CONCLUSIONS: Preliminary findings indicate that clinical osteoscopy may be a useful tool in the assessment of blood circulation to the femoral head.

Application of platysma-based transpositional flap for through-and-through facial defect when the facial artery circulation is blocked or compromised.

PURPOSE: A novel use of site-limited platysma-based transpositional flap is demonstrated and discussed for the reconstruction of facial defects. MATERIALS AND METHODS: Between January 1985 and January 2001, 342 patients were operated on for advanced oral-oropharyngeal and orofacial cancers. In 6 cases, a platysma-based transpositional flap was used for external closure of facial through-and-through defects. Internally, the saved oral mucosa was used in 4 patients and fasciocutaneous forearm free flaps in 2 patients. The facial artery was blocked in all cases. RESULTS: The postoperative course was uneventful except in 1 case, when partial loss of the flap was observed intraorally. The externally used transpositional platysma-based flap showed cosmetic and functional advantages: its consistency, color, and texture were similar to those of the original facial tissues, the area of operation was the same, and the donor site was closed primarily. CONCLUSION: The site-limited platysma-based myocutaneous transpositional flap is usable and safe even in those cases in which circulation of the facial artery is damaged or local vascular compromise has occurred and the facial through-and-through defect is extended. The facial reconstruction described is one of several applicable reconstructive methods that may be chosen for special facial defects. The method is not applicable when the neck is radically operated on (radical neck dissection) and/or irradiated. No similar use of platysma-based transpositional flaps has been reported thus far.

Neoadjuvant chemotherapy: does it have benefits for the surgeon in the treatment of advanced squamous cell cancer of the oral cavity?

The purpose of this clinicopathological study was to evaluate the effects and efficiency of combined neoadjuvant chemotherapy related to surgical margin. 100 consecutively treated squamous cell cancer patients receiving a combined neoadjuvant therapy were selected (Bleomycin-Vincristin-Methotrexate (BVM) or BVM + Mitolactol or BVM + Cisplatin). After three courses of chemotherapy, the patients were operated on. The largest diameter of the primary tumors was compared before and after chemotherapy. In the surgical specimen, the involvement of surgical margin was assessed. The largest diameter before chemotherapy was: T2 30%; T3 55%; T4A 15%. After chemotherapy, the rest tumor was assessed in the surgical specimen as: no rest 11%; <2 cm 57%; 2-4 cm 28%; 4-6 cm 4%. The no rest and <2 cm (optimal operability) tumor was observed in T2: 94%; in T3: 73%; in the T4A: 0%. Severe side effects (Grade III-IV) were not observed. There was a significant decrease in size (P < 0.0001). Of the 100 surgical specimens, 83% had clear-, 9% close- and 8% involved margins. From T4A, there was a 40% (6 patients) involved margin. Based on the significantly better size and operability of primary T2-3, the mild side effects and the high (83%) percentage of clear surgical margins, that is better than other (without preoperative chemotherapy) results, sought the use of chemotherapy is recommended before surgery. Due to the 40% involved margin, we don't suggest surgery in T4A.

Protein tyrosine phosphatase gene C1858T allele confers risk for rheumatoid arthritis in Hungarian subjects.

The C1858T allele of the PTPN22 gene has been reported to confer risk for RA; but in some reports, the effect was restricted to RF- and/or anti-CCP-seropositive patients. Hungarian RA patients and matched controls were genotyped. The 1858T allele showed an increased prevalence in RA patients compared to controls. The 1858T allele represents a risk factor in the whole RA population (P = 0.001); an association was found both in RF-seropositive (P = 0.001) and anti-CCP-seropositive patients (P = 0.001), and in subjects with the combination of these factors (P = 0.002). In TT homozygotes, the estimated susceptibility to RA was more than double (OR = 5.04) of that seen in TC heterozygotes (OR = 1.89); the same gene dosage effect was observed in all seropositive RA subgroups. Our data show that the Hungarian RA patients belong to the populations in which the 1858T allele represents a susceptibility factor both in the RF- and/or anti-CCP-seropositive subjects, and the association exhibit a gene dosage dependency.

Detailed analyses of antibodies recognizing mitochondrial antigens suggest similar or identical mechanism for production of natural antibodies and natural autoantibodies.

Because of their endosymbiotic evolutionary origin, proteins compartmentalized into mitochondria represent an interesting transition from prokaryotic foreign to essential self molecules. We investigated the presence of naturally occurring antibodies (nAbs) recognizing mitochondrial inner membrane enzymes. Epitope mapping analysis of a mitochondrial inner membrane enzyme, citrate synthase (CS) by synthetic overlapping peptides and phage display libraries using sera from healthy individuals and from patients having systemic autoimmune disease revealed CS recognizing nAbs with IgM isotype. We analyzed cross-reactive epitopes on human CS, bacterial CS, and various standard autoantigens. We have found that the fine epitope pattern on CS is different under physiological and pathological conditions. Moreover sera affinity purified on CS cross reacts with nucleosome antigen, which cross-reactivity could be mapped to a short epitope on human CS. These data indicate that in theory, nAbs "specific" for a given self antigen could fulfill the function of participating in innate defense mechanisms and at the same time recognize a target antigen in a systemic autoimmune disease. Thus, at the level of recognized epitopes there is a possible link between the innate like part and the adaptive-autoimmune arm of the humoral immune system.

[Submandibular sialolith: case report and review of the literature]. / Nagyméretü submandibularis nyálkö és sialo-oralis fistula Esetismertetés és irodalmi áttekintés.

Sialolithiasis is a common disease of the salivary glands and a major cause of salivary gland dysfunction. The dominance of submandibular sialoliths is widely investigated. Giant stones (>15 mm) are rare, approximately every tenth or twelfth of the stones belong to this category. Sialo-oral or sialo-cutaneous fistula formation promotes the growth of an excessive size. In their presentation, the authors would like to introduce the diagnostic and therapeutic process of a giant (27 mm) submandibular sialolith and give a review of the literature.

Submental endotracheal intubation in concurrent orthognathic surgery: a technical note.

INTRODUCTION: Achieving the necessary occlusion for orthognathic surgery is not possible with conventional oral intubation since the tube interferes with the occluding teeth. Sometimes nasotracheal intubation is impossible due to developmental malformations requiring repair. Also, the oral or nasotracheal tube may interfere with the operation or may be damaged during the procedure. In 1986, Hernandez Altemir described a method of submental endotracheal intubation. His intentions were to avoid tracheostomy in maxillofacial trauma cases where short-term intermaxillary fixation was required. PATIENTS: Between January 2000 and May 2003, 13 patients were operated on, using submental intubation. Eight of these (three females and five males) had surgery for orthognathic malformations. METHODS: The Hernandez Altemir technique was modified to ease the procedure: a sterile nylon guiding tube and the '222 rule' incision were introduced. Eight cases with concurrent complex orthognathic surgery, using this modified technique are reported in this paper. RESULTS: There were no operative or postoperative complications related to the procedure. CONCLUSION: The technique is easy to use, rapid and free of complications compared to 'alternative' intubation methods (tracheostomy, retromolar location of tube, etc.). Submental scarring is acceptable. It is recommended for orthognathic procedures in selected cases.

A randomized study to assess the effectiveness of orally administered pilocarpine during and after radiotherapy of head and neck cancer.

BACKGROUND: This prospective randomized study was undertaken to assess the effectiveness of oral pilocarpine chloratum (Salagen) during and after radiotherapy. PATIENTS AND METHODS: Between October 1999 and December 2003, 66 patients received 60 Gy of irradiation to their head and neck cancer. Half of the patients received 5 mg oral pilocarpine 3 times a day from the beginning of radiotherapy over a period of 12 weeks. The control group received similar doses of pilocarpine only in the second 6 weeks following irradiation. Patient saliva secretion was recorded, and a visual analog scale measuring overall and daily xerostomia, difficulty in sleeping, speaking, eating and wearing dentures was employed. RESULTS: Pilocarpine, given concomitantly with radiotherapy, statistically improved the salivary flow and induced better patient comfort by the end of radiotherapy. Patient comfort and symptoms related to xerostomia greatly decreased compared to patients receiving pilocarpine after irradiation in the second 6-week period of therapy. The patients' quality of life, saliva production and symptoms related to xerostomia showed significant progress by the end of the 12 weeks. CONCLUSION: The results suggest that stimulated salivary glands suffer less decrease in saliva production during radiotherapy. The stimulated saliva flow reduced the side-effects of irradiation.

Comprehensive regression analysis of hepatitis B virus X antigen level and anti-HBx antibody titer in the sera of patients with HBV infection.

Although the pathogenetic significance of hepatitis B virus x protein (HBxAg) in chronic hepatitis, liver cirrhosis, and primary hepatocellular carcinoma has already been studied, the comparative analyses of both the actual serum HBxAg levels and antibody production against various HBx epitopes have been examined to lesser extent. We have simultaneously investigated the relationship between antibody production (IgG and IgM) against the HBxAg fragments and HBxAg level in the sera of patients with acute (14) or chronic hepatitis (80) and symptomless carriers (12). A recently developed sandwich-type ELISA was used for the quantitative measurements of HBxAg. Overlapping recombinant and synthetic antigens were used to map the fine epitope specificities of circulating anti-HBx antibodies. In acute hepatitis, we have found high and homogenous correlation in the IgM type immune responses against all the examined HBxAg regions. Moreover, strong correlation has been observed between IgG type immune responses to a characteristic C-terminal region (C1: 79-117) and the longest fragment (X: 10-143). Moderate correlation has been found between HBxAg concentration and the IgG type anti-HBx antibody levels against C-terminus of HBxAg in patients with chronic hepatitis. In the case of symptomless carriers, there were also demonstrable associations in the immune responses against the C-terminal sequences; however, significant correlations were found for antibody production against the N-terminal region as well. The examinations show that the C-terminal sequence, responsible for transactivation, promotes an efficient IgG antibody response in all three groups of patients, whereas the negative regulator N-terminal part of the HBxAg molecule for the most part does not trigger antibody production. This suggests that the immune responses against various - biologically active - epitopes of the HBxAg may have a different role in the pathogenesis of hepatitis and may be used as prognostic markers in human HBV infections.

A possible new bridge between innate and adaptive immunity: Are the anti-mitochondrial citrate synthase autoantibodies components of the natural antibody network?

Natural antibody (nAb) producing B-1 B cells are considered an intermediate stage of evolution between innate and adaptive immunity. nAbs are immunoglobulins that are produced without antigen priming. nAbs can recognize foreign targets and may serve in the first line of immune defense during an infection. Natural autoantibodies (nAAbs) present in the serum of both healthy humans and patients suffering from systemic autoimmune diseases recognize a set of evolutionarily conserved self-structures. Because of their endosymbiotic evolutionary origin, proteins compartmentalized into mitochondria represent an interesting transition from prokaryotic foreign (non-self) to essential (self) molecules. We investigated the possible overlap in recognized epitopes of innate and self-reactive nAbs and surveyed changes in physiological autoreactivity under pathological autoimmune conditions. Epitope mapping analysis of a mitochondrial inner membrane enzyme, citrate synthase (CS) (EC 2.3.3.1) by synthetic overlapping peptides and phage display libraries using sera from healthy individuals and from patients having systemic autoimmune disease revealed CS recognizing nAAbs with IgM isotype. We analyzed cross reactive epitopes on human CS, bacterial CS, and various standard autoantigens. The anti-CS nAAbs by participating in the nAb network, could function in innate defense mechanisms and at the same time recognize a target antigen (nucleosome) in a systemic autoimmune disease. Thus, at the level of recognized epitopes there is a possible new link between the innate like component and the adaptive-autoimmune arm of the humoral immune system.

[Age estimation of children in south-western Hungary using the modified Demirjian method]. / Dél-dunántúli gyermekek kormeghatározáisa a módosított demirjian-módszer alapján.

The biological age of a child, in contrast to his or her chronological age, may be described in terms of skeletal or dental maturity, the development of secondary sex characters etc. These factors can be applied separately or together to assess the degree of physiological maturity of a growing child. The determination of this physiological age and its correlation to the chronological age is of importance within many fields, such as archaeology, forensic medicine, endocrinology, orthodontics etc. Dental maturity was studied on 203 panoramic radiographs, taken between 1985 and 1995, of healthy Hungarian children aged 2.9 to 17.5 years from the south-west Transdanubian part of Hungary. The revised method of Demirjian was used for determination of the maturity score of each individual. For each tooth a score (on a scale A-H) was given according to the radiographic development, from first appearance of calcification to the closure of the apex. This score was then transformed into a self-weighted maturity score for the dental stages (0-19.3) as presented in the paper. The individual scores were then added giving a total maturity score (0-100). This total maturity score represents the biological maturity of the child and may then be compared with the known chronological age. The total maturity scores of the Hungarian population was plotted against the chronological (real) age, and a curve was fitted using the Lowess method of locally weighted least-square method. Our results show that each population needs its own standards. Hungarian boys and girls are approximately 1 year ahead of their French-Canadian counterparts at the age of 6-8. At older ages, the difference decreases. Similar to other studies, we found high individual variance up to 2 years, in tooth development, in the Hungarian population.

Sandwich type ELISA and a fluorescent cytometric microbead assay for quantitative determination of hepatitis B virus X antigen level in human sera.

The hepatitis B virus X protein (HBxAg) is responsible for severe complications of HBV infections including primary hepatocellular carcinoma. A sandwich type ELISA and a flow cytometric microbead assay for quantitative determination of serum levels of Hbx-Ag are introduced. We have previously developed monoclonal antibody families against well-conserved epitopes on HbxAg, characterized by different immunohistochemical and immunoserological techniques. Special selection of the antibody pairs provided highly sensitive and highly specific tools for quantitative immunoassay development. The resulting assays were tested on human sera (208 samples) collected from patients suffering from different clinical forms of HBV infection. The sensitivity range of the sandwich type ELISA was between 4 and 2000 ng/ml as measured on both the recombinant antigen and the sera of chronic hepatitis patients. A further flow cytometric microbead assay was established and tested in parallel with the ELISA. The quantitative results of these two immunoserological techniques were in strong correlation and they were found to be highly specific and sensitive on clinical samples. The HBxAg ELISA technique is applicable for routine clinical laboratory measurements, and our HBxAg microbead technique is recommended for complex multiparametric measurements combined with other markers.

[In vitro comparison of root canal preparation with step-back technique and GT rotary file--a nickel-titanium engine driven rotary instrument system]. / Step-back technikával és GT rotary file nikkel-titanium gépi forgómuszerrel végzett gyökércsatorna-elokészítés in vitro vizsgálata.

The aim of the authors' study was to compare the remaining root canal wall thickness and the preparation time of root canals, prepared either with step-back technique, or with GT Rotary File, an engine driven nickel-titanium rotary instrument system. Twenty extracted molars were decoronated. Teeth were divided in two groups. In Group 1 root canals were prepared with step-back technique. In Group 2 GT Rotary File System was utilized. Preoperative vestibulo-oral X-ray pictures were taken from all teeth with radiovisiograph (RVG). The final preparations at the mesiobuccal canals (MB) were performed with size #30 and palatinal/distal canals with size #40 instruments. Postoperative RVG pictures were taken ensuring the preoperative positioning. The working time was measured in seconds during each preparation. The authors also assessed the remaining root canal wall thickness at 3, 6 and 9 mm from the radiological apex, comparing the width of the canal walls of the vestibulo-oral projections on pre- and postoperative RVG pictures both mesially and buccally. The ratios of the residual and preoperative root canal wall thickness were calculated and compared. The largest difference was found at the MB canals of the coronal and middle third level of the root, measured on the distal canal wall. The ratio of the remaining dentin wall thickness at the coronal and the middle level in the case of step-back preparation was 0.605 and 0.754, and 0.824 and 0.895 in the cases of GT files respectively. The preparation time needed for GT Rotary File System was altogether 68.7% (MB) and 52.5% (D/P canals) of corresponding step-back preparation times. The use of GT Rotary File with comparison of standard step-back method resulted in a shortened preparation time and excessive damage of the coronal part of the root canal could be avoided.

Detection of citrate synthase-reacting autoantibodies after heart transplantation: an epitope mapping study.

Autoimmune mechanisms play an important role in the pathogenesis of allograft vasculopathy following heart transplantation, but the autoantigens involved have been only sparsely studied. Citrate synthase (CS) enzyme is a conserved molecule, and, as an important mitochondrial autoantigen, it is protected by the "immunological homunculus". Tissue destruction and alteration of the immune regulatory mechanisms can induce pathological immune response against CS in other autoimmune diseases. In our present study we aimed to detect CS-specific autoantibodies in heart transplant patients, therefore, prospective, randomised clinical tests were conducted on 33 heart transplant patients and compared with 130 healthy blood donors. The level and isotype of CS antibodies were detected by simple binding indirect enzyme-linked immunosorbent assay (ELISA). The epitope specificities of the autoantibodies were measured on synthetic overlapping peptide sequences of CS enzyme by an indirect multi-pin ELISA method. Mainly IgM isotype CS autoantibodies were found in healthy controls, while IgG was found at higher levels and frequency (four-times higher) in heart transplant patients. Autoantibodies of IgG isotype recognise different epitopes than do autoantibodies of IgM isotype, even within the same group and individual. New epitope-specific IgG and IgM isotype autoantibodies appeared in heart transplant patients when compared with the controls. Our findings suggest a possible role of CS-specific autoantibodies in the pathomechanism of allograft vasculopathy.

Failure of alkylating agents to improve induction chemotherapy of oropharyngeal squamous cell cancer.

BACKGROUND: This prospective semi-randomized study was undertaken to assess the effects and effectiveness of alkylating drugs in a preoperative setting. PATIENTS AND METHODS: During a 6-year period preceding February 2000, 80 patients with Stage II-IVa (AJCC 2002) squamous cell cancer of the oral cavity were treated. Thirty patients (Group N) received a combination of bleomycin, vincristine and methotrexate (BVM). In the alkylating group, thirty patients (Group A/M) received BVM and mitolactol (dibromodulcitol), while twenty patients (Group A/C) received BVM and cisplatin. Patients underwent surgery within 3 weeks after chemotherapy. Clinical response rate and tumour-free survival were investigated. RESULTS: Clinical complete response was 30%-36% (Group N-A). Partial response was 57%-56% (Group N-A). Side-effects were moderate and reversible. Nausea, anaemia and leucopenia were observed in the alkylating (A) group, while other side-effects (alopecia, mucositis, gastritis) were similar in both groups. The observation time was 36 months. Regional disease-free survival showed a significant difference, favouring the non-alkylating (N) group (p=0.03). A higher metastasis rate was observed in the alkylating (A) group. CONCLUSION: Cisplatin and mitolactol in combination with BVM showed higher local control and lower disease-free survival than BVM alone. That was mostly due to a higher rate of regional metastatis formation in the alkylating-treated patients. This may be a late side-effect caused by the immunosuppressive and myelosuppressive effect of alkylating agents.

Results and failures with or without cisplatin containing induction chemotherapy in the treatment of squamous cell carcinoma of the head and neck.

This prospective randomised study was undertaken to assess the effects and effectiveness of cisplatin in a pre-operative setting. Thirty-eight patients were treated with stage II-IVa (AJCC) squamous cell cancer of the oral cavity and oropharynx. Nineteen patients received a combination of bleomycin, vincristine, methotrexate (BVM; group I.), 19 received BVM and cisplatin (group II). Patients underwent surgery within 3 weeks after chemotherapy. Biopsy and surgical specimens were compared. A clinical complete response was seen in five patients in group I (26.3%) and in four patients in group II (21.1%). Partial response was noted in 11 patients in group I (57.8%) and in 13 patients in group II (68.4%). There was no statistical difference in clinical response between the two groups. Microscopic response was better in the cisplatin treated group. Median follow up of patients is 52 (36-70) months. Disease free survival showed a significant difference, favouring the no cisplatin group (P = 0.03). There was no significant difference in overall survival (P > 0.6). Cisplatin in combination with BVM showed significantly higher levels of microscopic response, but the lower disease free survival is mostly due to a higher rate of regional neck failure.

Determination of the fine epitope specificity of an anti-hepatitis B virus X protein monoclonal antibody using microanalytical and molecular biological methods.

The recombinant form of the 17kDa, highly hydrophobic and disulfide-bonded hepatitis B virus X protein (HBX) was used for developing a set of monoclonal antibodies (Mab). Our present goal was to determine the fine epitope specificity of our anti-HBX Mab. Based on computer analysis two sequences (amino acids 22-31 and 100-114) were predicted for possessing high immunogenity while the anti-HBX Mab did not recognized them. Limited proteolysis and mass spectroscopic analysis suggested another possible sequence (amino acids 14-26), which also proved to be negative using an immunoserological test. Subsequently, we performed a screen of a phage displayed random peptide library, by which we could localize the epitope to amino acids 88-93. This finding was confirmed using three overlapping fusion peptides spanning amino acids 77-142. Their testing in ELISA assigned the epitope to amino acids 77-95, which supports the result obtained by screening the phage displayed library. Our results suggest the necessity of a complex application of current molecular biological and immunological techniques in fine structure mapping. This approach will be useful to study the prognostic relevance of different antigenic sites on HBX during the development of chronic hepatitis and primary hepatocellular carcinoma.

Effect of cisplatin treatment on early activation of oncogenes in vivo.

The aim of the study was to monitor the early effect of cytostatics containing platinum on oncogenes in inbred CBA/Ca mice. In human head-neck tumors after treatment with the Cisplatin supplemented BVM (Bleomycin, Vincristine, Methotrexate) protocol, further surgeries are often necessary due to regional recurrence. Body weight equivalent amounts of human dose of Cisplatin were administered intraperitoneally to 6-8-week-old, inbred, female CBA/Ca mice. Twenty four 48 and 72 hours after the treatment RNA was isolated from the target organs and the quantitative expression of c-myc, Ha-ras and p53 genes was examined by dot-blotting in potential target tissues. Significant overexpression of Ha-ras and p53 genes was measured in the bone marrow. Regarding the expression of Ha-ras gene, a significant increase was also found in the lymph nodes after 48 hours. The p53 expression in the lungs was down-regulated compared to the control group. In the "short-term" in vivo test, 24-hour examination of gene expression and amplification is suitable for detecting the early effects of carcinogenetic exposure. Cisplatin-induced gene expression alterations call attention to its possible role in the development of regional recurrence in patients treated with cisplatin-containing regimens.