Biomedical subjects
Publications and source records attributed to P Kessler.
We describe the rare entity of an intraosseous meningioma arising in the mandible. The meningioma was found incidentally in an asymptomatic adult patient on dental radiography, mimicking other cystic-appearing jaw masses. The CT and MR imaging features of mandibular meningioma are reviewed with reference to prior published descriptions of this unusual entity.
In light of recent epidemiological studies that associate diabetes mellitus with increased risk for oral cancer, we investigated in diabetic (type I) and normal rats with induced oral squamous cell carcinoma whether the molecular basis for that putative association involves insulin receptor substrate-1 (IRS-1) and focal adhesion kinase (FAK). Fourteen diabetic and 12 normal rats developed cancer after 4-nitroquinoline-N-oxide treatment, while six diabetic and six normal animals were used as controls. Oral sections were studied using monoclonal antibodies against IRS-1 and FAK proteins. Expression of IRS-1 was significantly higher in diabetic than normal rats, but it decreased in diabetic animals with tumor, especially in more advanced stages. FAK expression was significantly higher in rats with cancer in comparison to the ones without it, regardless the diabetes status. These data suggest that the IRS-1/FAK pathway is altered by diabetes resulting in reduced cell adhesion and possibly increasing risk for oral cancer.
In light of the recently observed contribution of thrombosis-related factors to carcinogenesis, we investigated the possible association of plasminogen activator inhibitor-1 (PAI-1) with increased risk for oral cancer. In DNA samples of 104 patients with oral squamous cell carcinoma and 106 healthy controls of comparable ethnicity, age and sex, we studied the 4G/5G polymorphism in the PAI-1 gene, which affects its expression. The mutant 4G allele and carrier frequencies were significantly increased in patients compared to controls (65.9% versus 49.5%; 88.5% versus 69.8% respectively, P<0.01). That increase was even higher in patients with a positive family history for thrombophilia or without one for cancer (P<0.001). Interestingly, significant difference from controls was observed only in patients with cancer stages I and II. These findings suggest that the 4G allele, by resulting in higher PAI-1 expression, is a major contributing factor in early stages of oral oncogenesis. Possibly, increased PAI-1 promotes initial development of oral cancer through regulation of cell detachment and delays further tumor progression by inhibiting vascularization.
AIMS: In light to association of increased platelet glycoprotein Ia (GPIa) expression with tumor invasion and metastasis in several types of cancer, we investigated the possible contribution of a common polymorphism (C807/T807), affecting the GPIa gene expression, in the development of oral cancer. METHODS: DNA samples of 110 patients with oral cancer and 114 healthy controls were examined by allele-specific polymerase chain reaction followed by electrophoretic analysis. RESULTS: The mutant T807 allele homozygotes were significantly increased in the group of patients compared to the control group (P < 0.001). Furthermore, significantly increased frequency of mutant alleles compared to controls was observed in the subgroup of patients with a positive history for cancer (P < 0.01). CONCLUSIONS: The obtained results indicate that the C807/T807 polymorphism is indeed a genetic predisposing factor which contributes to increased risk for oral cancer.
This article summarizes the published data on the prevention of venous thromboembolism. Routine thromboprophylaxis is the best way to lower the risk. It is recommended to sort patients according the thrombosis risk and to make use of the standard prophylactic modes. In low risk patients, no specific thromboprophylaxis is needed. Patients with moderate risk levels are candidates for administration of subcutaneous low molecular weight heparin (LMWH) at doses under 3 400 anti-Xa units a day and patients with increased risk at doses higher than 3400 anti-Xa units a day during the period of higher risk. In order to decrease the risk of bleeding, a half dose 2 hours prior or 4-6 hours after the operation can be administered. Under the highest risk conditions, there is a recommendation to combine LMWH over 3 400 anti-Xa units with elastic panty-hose or, alternatively, with intermittent pneumatic compression. At moderate risk levels, subcutaneous administration of unfractionated heparin at the doses of 5 000 units twice a day is also possible and at increased risk levels, a TID administration over the increased risk period. In patients with a significant bleeding risk, the physical method of thromboprophylaxis can be used and pharmacological prophylaxis can set in after the risk of bleeding has passed. Fondaparinux is the alternative to LMWH in people after major orthopaedic surgeries and with a history of heparin induced thrombocytopenia over the past three months. An alternative to the administration of LMWH even after the end of the hospitalization can be warfarin in certain situations. The sole use of acetylsalicylic acid or Rheodextran is not recommended. While undertaking epidural anaesthesia or analgesia, it is necessary to follow strictly the guidelines of the use of pharmacological thromboprophylaxis.
There are significant differences among patients treated with warfarin in the dosage volumes necessary to reach an optimum therapeutic effect. Apart from the external influences (interactions with drugs and food), genetic predispositions play an important role. Polymorphysms of the P 450 2C9 cytochrome bear upon the speed ofbreaking down S-warfarin, polymorfysms VKORC1 bear on the volume and quality of epoxide reductase--an enzyme whose blockade is the crux of the mechanism how cumarin anticoagulants act. These two genes are responsible for at least 50% of the warfarin effect variability. Warfarin's effect is further determined by the genetic variants of gamma-carboxylase, prothrombin, factors VII and IX. In near future, further results of pharmacogenetic research and clinical studies can be expected. They study the impact of the findings in clinical practice.
The incidence of venous thromboembolism in orthopaedic patients is high and its prevention deserves special attention. In patients with total hip and knee replacements and with the proximal femur fractures, low molecular weight heparin should be administered at higher prophylactic dosages. Following its approval, pentasaccharide (fondaparinux) should become the drug of choice, especially in patients with proximal femur fractures. Pharmacological prophylaxis should take at least 10 days in case of total knee replacements and longer in patients with increased risk of venous thromboembolism. In patients with total hip replacements or with proximal femur fractures, LMWH or pentasaccharide prophylaxis is indicated over a period of 28-35 days. Under the conditions of well working infrastructure for anticoagulation treatment, there is an alternative of warfarin treatment, lasting consequently 6-8 weeks. In patients with proximal femur fracture that bleed or are in a very increased risk of bleeding, a possible alternative is represented by intermittent pneumatic compression and shift to antithrombotic treatment after bleeding stops. In patients with knee arthroscopies displaying no risk factors of venous thromboembolism where tourniquet was used no longer than 60 minutes, pharmacological prophylaxis is not necessary. Only timely mobilisation is recommended. In patients displaying risk factors of venous thromboembolism or with tourniquet use surpassing 60 minutes, it is advisable to administer low molecular weight heparin in lower prophylactic dosage. In patients with lower extremity fractures treated with osteosynthesis, LMWH administration of 7-10 days is indicated. In patients with lower extremity injuries requiring plaster casting or other type of fixation reaching below the knee, LMWH administration is indicated over the whole period of fixation in persons with higher risk (people with venous thromboembolism in their histories, in direct relative's histories, people with thrombophilic conditions including poeple with malignancies, women using hormonal contraceptives or their substitutions). Aspirin is not a suitable drug for separate administration in the prophylaxis of venous thromboembolism in orthopaedic patients.
Bleeding is probably the major complication of anticoagulant treatment with vitamin K antagonists represented nowadays mostly by warfarin in the Czech Republic. The main risk factors in hemorrhagic complications of warfarinisation are the intensity and instability of the anticoagulant treatment, individual patient characteristics, warfarin interactions with other drugs and the length of the anticoagulant therapy. Severe bleeding in warfarin patients is most effectively brought about by a fast and complete undoing of the anticoagulation effect of the drug employing the prothrombin complex concentrate and slow i.v. vitamin K1 infusion regardless of the reason for the anticoagulation. This approach can secure the minimalisation of the bleeding's negative consequences. A less severe bleeding or asymptomatic increase in the international normalized ratio can be treated effectively by skipping or decreasing of the warfarin dosage and/or oral administration of vitamin K1 (i.v. administration only in selected higher risk cases) that does result only in a partial consolidation of coagulopathy but of such type that the risk of thrombotic event requires. The article's goal is to contribute to the treatment standardization in patients with warfarin overdose and/or with hemorrhagic complications due to warfarin treatment and it is available at www.thrombosis.cz. The guidelines include a ready-reference chart whose objective is immediate and quick crash course in the clinical practice.
PURPOSE: We investigated whether the mutant methylenetetrahydrofolate reductase (MTHFR) increases risk for oral cancer. The common germ-line mutation C677T in the MTHFR gene significantly diminishes specific activity of the enzyme, which is responsible for the circulating form of folate. Folate deficiency is associated with increased risk for thrombosis, as well as for several types of cancer, through disruption of DNA methylation, DNA synthesis and deficient DNA repair. METHODS: We searched for the C677T mutation by restriction fragment analysis of PCR products in DNA samples of 110 patients with oral squamous cell carcinoma and 120 healthy controls of comparable ethnicity, age and sex. RESULTS: The number of heterozygotes was significantly different in the two groups (P<0.005), as well as in subgroups of patients with or without a positive family history for cancer, compared to normal controls (P<0.01 and P<0.005, respectively). Furthermore, the subgroup of patients with a positive family history for thrombophilia had a significant increase both in the frequencies of mutant alleles (P<0.01) and heterozygotes (P<0.001) in comparison to normal controls. CONCLUSIONS: The obtained results suggest that the MTHFR mutation is a minor contributing factor in oncogenesis in the oral region, in conjunction with low dietary uptake of folate.
We have investigated the feasibility of an exclusively endoscopic approach to the submandibular region in four pigs, four cadavers and two women. We inflated the subplatysmal space with carbon dioxide at low pressure. The submandibular gland and the jugulodigastric region were easy to identify once the correct anatomical space had been dissected and inflated. Four endoscopic resections of the submandibular gland were done successfully.
In 1998 we harvested a total of 127 bone grafts from the iliac crest of 65 male and 53 female patients aged 8-80 years. We measured the quantity of bone obtained, the operating time and the donor site morbidity of the anterior approach (n=81) compared with the posterior approach (n=46). The mean volume of bone harvested was 15 cm(3) (range: 9-25.5) of monocorticocancellous- or bicortico-cancellous bone chips or those from a trephine bur. The mean operating time for the anterior approach was 35 min (range: 22-48), for the posterior approach 40 min (range: 32-55). There were 15 complications, which were limited to those in whom the volume of bone exceeded 17 cm(3). The posterior approach caused less morbidity, notably in the form of significantly less pain and irregularity of gait. The patient has, however, to be repositioned during operation, which added to its total duration.
The rate and frequency of distraction have a decisive influence on the regenerative process. We tested a newly developed hydraulic osteodistractor in 12 pigs, which were assigned to have continuous and intermittent osteodistraction of the mandible after osteotomy. The forces necessary to distract the mandible were recorded during intermittent distraction. These data were then used for continuous distraction of the bone. Continuous osteodistraction resulted in intramembranous regeneration of bone, whereas intermittent osteodistraction caused chondroid ossification in the regeneration of the bone. Continuous osteodistraction caused speedier regeneration, and distraction forces were lower than with intermittent distraction.
Current options for minimally invasive surgical treatment of single-vessel coronary artery disease include beating heart procedures without cardiopulmonary bypass (CPB) via mini-thoracotomy (MIDCAB) and totally endoscopic robot-assisted techniques (TECAB) with CPB. Both procedures are associated with potential myocardial stress before revascularization, such as single-lung ventilation (SLV), temporary coronary artery occlusion, cardiac luxation, intrathoracic carbon dioxide insufflation, and extended CPB and operating time. In this echocardiographic study we sought to evaluate the extent of intraoperative segmental wall motion abnormalities (SWMA) during MIDCAB and TECAB surgery and to identify factors affecting SWMA. Forty-six patients with single-vessel coronary artery disease were studied. Sixteen patients were operated using the MIDCAB technique and 30 patients with TECAB. In both groups sequential transesophageal echocardiograms were recorded during the entire procedure. Hemodynamic data and oxygenation variables were acquired simultaneously. In both groups, mild but obvious perioperative SWMA were identified and noted to increase during the course of the operation. These SWMA were more pronounced in the TECAB group. Independent of operating time, these changes disappeared completely after revascularization. No significant hemodynamic compromise was observed. We conclude that MIDCAB and TECAB techniques are associated with significant perioperative SWMA. The appearance of more profound SWMA in the TECAB group compared with the MIDCAB patients might have been the result of intrathoracic CO(2) insufflation, as SLV was used in both groups. No persistent SWMA or post-CPB SWMA were apparent in either group. More extensive intraoperative ventricular SWMA was detected in the TECAB group, suggesting that a more frequent risk for right ventricular dysfunction may exist during TECAB procedures.
BACKGROUND: This study was designed to investigate the impact of bispectral index (BIS) or A-line AAI index (based on middle-latency auditory evoked potential) monitoring on recovery times and drug consumption when compared with standard anaesthetic practice during desflurane-remifentanil anaesthesia. METHODS: After having obtained approval from the institutional review board and written informed consent, 200 adult patients undergoing minor surgical procedures were randomized to receive a desflurane-remifentanil anaesthetic controlled either solely by clinical parameters or by BIS or AAI to the following target values: during maintenance of anaesthesia to a value of '50' (BIS) or '30' (AAI), 15 min before the end of surgery to '60' (BIS) or '45' (AAI). Recovery times and drug consumption were recorded by a blinded investigator. RESULTS: Compared with standard practice, patients with BIS or AAI monitoring needed similar desflurane concentrations (standard practice 2.9 [0.5] vol%, BIS 3.3 [0.9] vol%, AAI 2.6 [0.5] vol%), and had similar recovery times (open eyes 5.6 [2.5] min, 5.9 [3.4] min, 5.0 [3.1] min; extubation 6.3 [2.4] min, 6.6 [3.5] min, 5.6 [3.0] min; stating name 7.3 [2.4] min, 7.6 [3.5] min, 7.3 [6.6] min). CONCLUSIONS: Compared with standard anaesthetic practice BIS and AAI guided titration to the used target ranges did not result in a reduction of desflurane consumption or recovery times during minor surgery with use of remifentanil.
INTRODUCTION: In patients with oral cancer the treatment has a strong impact on the quality of life. In recent years different therapeutic concepts have been developed, which include preoperative simultaneous 'neoadjuvant' radiochemotherapy (RCT) and one-stage surgery with tumour ablation and reconstruction. Consideration of long-term survival rates yields substantial evidence that mixed-modality treatment including neoadjuvant RCT is superior to adjuvant therapy concepts based on a surgical approach with postoperative radiation. PATIENTS AND METHODS: In this nonrandomised longitudinal prospective study quality of life was evaluated in two groups made up of a total of 53 patients with squamous cell carcinoma of the oral cavity, 26 of whom underwent neoadjuvant radiochemotherapy with subsequent surgical resection while the remaining 27 received surgical treatment first and then postoperative radiotherapy. The quality-of-life core questionnaire (QLQ C-30) and the head and neck cancer module (H&N 35) of the European Organisation for Research and Treatment of Cancer (EORTC) were used. Long-term survival was estimated according to the Kaplan-Meier test. RESULTS: Postoperatively both groups showed a marked reduction in quality of life, especially in restricted chewing, swallowing and speaking. One year later their quality of life had improved substantially, though without quite reaching the preoperative quality-of-life scores. Both groups showed specific impairments in the symptom scales. With adjustment for the fact that the patients were not randomised, long-term survival was 78% in the neoadjuvant treatment group and 50% in the adjuvant treatment group. CONCLUSION: Temporary limitations in the quality of life can be expected after tumour treatment of the kinds presented here for oral cancer. Neoadjuvant therapy concept is more aggressive and might result in longer disease-free survival. The primary goal should be eradication of the tumour. Nevertheless preservation or reconstruction of a maximum of function is essential for a high level of quality of life. Combined-modality treatments seem to be superior to any kind of monotherapy and should therefore be preferred.
BACKGROUND: Giant cell lesions of the bone present similar histological features. The differential diagnosis comprises central giant cell granuloma, giant cell tumor of bone, and osteitis fibrosa cystica (brown tumor) in combination with hyperparathyroidism. Since these lesions may mimic metastatic bone disease in patients with a history of cancer, a malignant process has to be considered. Since the treatment and prognosis of these entities-benign versus malignant osteolytic bone processes-differ greatly, definitive differential diagnosis is of utmost importance. CASE REPORT: Two patients presenting with osteolytic lesions of the maxilla are reported here. In both cases a history of cancer (breast and prostate) suggested bone spreading of these malignant tumors. The clinical and histological findings were similar in both patients. One lesion was diagnosed as central giant cell granuloma, the other was found to be brown tumour in osteitis fibrosa cystica as an initial manifestation of hyperparathyroidism. DISCUSSION: The presented cases demonstrate the difficulties in establishing the correct diagnosis of patients found to have osteolytic lesions of the jawbones which is critical for the appropriate management of these patients. The article discusses the different entities of osteolytic lesions of the jawbones and the necessary diagnostic and therapeutic approach.
BACKGROUND: Extraperitoneal laparoscopic prostatectomy is an alternative to the intraperitoneal method. However, the effects of extraperitoneal carbon dioxide (CO2) insufflation on hemodynamics and respiratory data have not been adequately studied. This study compared the effects of prolonged intra- and extraperitoneal CO2 insufflation on hemodynamics and gas exchange. METHODS: For this study, 20 patients were assigned to receive totally endoscopic robot-assisted radical prostatectomy (TERP) via the intra- or extraperitoneal approach. Hemodynamic parameters and respiratory data were obtained during 8 h of insufflation and analyzed for statistical differences. RESULTS: With both insufflation methods, arterial CO2 pressure increased rapidly, reaching higher levels with extraperitoneal insufflation. Therefore, patients managed with extraperitoneal insufflation required a significantly higher minute ventilation. Heart rate and central venous pressure increased in both groups, whereas mean arterial blood pressure and pH decreased. CONCLUSIONS: Prolonged intra- and extraperitoneal CO2 insufflation for TERP resulted in significant, but mostly clinically unimportant, hemodynamic alterations. Carbon dioxide absorption was more pronounced with extraperitoneal insufflation.
BACKGROUND: The pharmacokinetics of remifentanil, an opioid analgesic metabolized by non-specific esterases, and its principal metabolite, remifentanil acid (RA), which is excreted via the kidneys, were assessed as part of an open-label safety study in intensive care unit (ICU) patients with varying degrees of renal impairment. METHODS: Forty adult ICU patients with normal/mildly impaired renal function (creatinine clearance [CL(cr)] 62.9 (sd) 14.5 ml min(-1); n=10) or moderate/severe renal impairment (CL(cr) 14.7 (15.7) ml min(-1); n=30) were included. Remifentanil was infused for up to 72 h, at a starting rate of 6-9 microg kg(-1) h(-1) titrated to achieve a target sedation level, with additional propofol (0.5 mg kg(-1) h(-1)) if required. Intensive arterial sampling was performed for up to 72 h after infusion. Pharmacokinetic parameters obtained by simultaneous modelling of remifentanil and RA data were statistically compared between the two groups. RESULTS: Remifentanil pharmacokinetics were not significantly affected by renal status. RA clearance in the moderate/severe group was reduced to about 25% that of the normal/mild group (41 (29) vs 176 (49) ml kg(-1) h(-1), P<0.0001). Metabolic ratio, a predictor of the ratio of RA to remifentanil concentrations at steady state, was approximately eight-fold higher in the moderate/severe group relative to the normal/mild group (116 (110) vs 15 (4), P<0.0001). Maximum RA levels approached 700 ng ml(-1) in the moderate/severe group. CONCLUSIONS: Although RA accumulates in patients with moderate/severe renal impairment, pharmacokinetic modelling predicts that RA concentrations during a 9 microg kg(-1) h(-1) remifentanil infusion for up to 15 days would not exceed those reported in the present study, for which no associated prolongation of mu-opioid effects was observed.