Combination of flavone acetic acid (FAA) with adriamycin,cis-platinum and difluoromethylornithine (DFMO) in vitro against human colon cancer cells

Summary Unresectable solid tumors in the metastatic stage are quite resistant to current chemotherapy and radiation therapy regimens. Flavone acetic acid (FAA) is a novel antitumor agent which appears to work through a different mechanism than the conventional chemotherapeutic agents. In preclinical studies it has shown effectiveness against a variety of transplantable murine and human tumors and appears to be solid tumor selective. It also has non-overlapping toxicities as compared to conventional agents. We therefore investigated FAA in vitro against human colon cancer cells and explored whether its effectiveness could be enhanced in combination with other agents such as adriamycin (ADR), cis-platinum (CP) and difluoromethyornithine (DFMO) — an inhibitor of polyamine biosynthesis. Addition of FAA for 24 hours in liquid media produced dose dependent growth inhibition. Using soft agar colony assay, growth was inhibited by 58% by 3mM FAA and only 1.4% by 0.375mM FAA. The combination of FAA and cis-platinum produced synergism at the lower doses tested. The combination of FAA and adriamycin produced antagonism at all doses tested and the combination of FAA with DFMO did not produce results significantly different from DFMO alone. We conclude that enhancement of FAA activity can be achieved in combination with conventional antitumor agents, but may be drug and dose specific.     

Dupuytren disease of the sole]

The authors discuss the essence of Dupuytren disease occurring in the plantar aponeurosis with literary surveys. They briefly outline the essence of the well-known different theories which endeavour to explain the causes of the development of this disease of unknown etiology. In their article, they deal with its clinical manifestation, histological changes and therapeutical possibilities in connection with the 5 cases treated by them.     

Management of lung and bone metastases from thyroid cancers of differentiated structures

During a period of thirty years (1959-1989) 374 patients underwent surgery for differentiated thyroid carcinoma at the 1st Department of Surgery of the University Medical School in Debrecen. Distant metastases were found in the lungs or bones in 36 patients (9.6%). In 20 patients the first clinical sign of the primary disease was the distant metastasis. The aspects of surgical treatment depended on whether the metastases were solitary or multiple, capable or uncapable of radioiodine uptake. Whereas the majority of pulmonary metastases respond well to 131I-treatment the therapy of bone metastases is multidisciplinary. The 5-year survival rate was 47%, the 10-year one 19%.     

Mycobacterium marinum infection of the hand and wrist. Results of conservative treatment in twenty-four cases

Inadequate débridement, extensive scarring, and breakdown of the wound have been commonly encountered after surgical débridement has been employed as the initial treatment of infection with Mycobacterium marinum involving the deep structures of the hand. Because of our disappointment with the results of this form of treatment, from 1982 to 1986 we treated twenty-four patients who had such an infection with rifampicin and ethambutol after a diagnostic biopsy was done. Surgical treatment was deferred until it was determined that the infection had not been controlled by the chemotherapy. The clinical outcome for these patients could be divided into three patterns: eleven patients (Group I) had a good result with no complications, three patients (Group II) had delayed healing of the wound, and ten patients (Group III) did not have a good response to conservative treatment and required one or more surgical débridements. Complications were sometimes associated with use of the drugs, and loss of visual acuity was a concern in three patients. In twenty-one (87 per cent) of the patients, at follow-up the function of the treated hand was equal to that of the other hand. Persistent pain, a discharging sinus, and previous local injection of steroids were unfavorable prognostic factors. If these factors are present, surgical débridement is advised.     

The mechanism of cytolytic and cytostatic activity of benfluron

Benfluron at concentrations of 0.26 and 0.52 mumol l-1 inhibited the formation of V79 colonies in a concentration-dependent way. Diminution of the size of colonies of the treated cells was accompanied by a decrease in protein content per cell. At the same time an increase in metabolic activity was observed. Benfluron blocked the V79 cells in S and G2 phases of the cell cycle and at higher concentrations induced cell lysis documented by alterations in cell membrane permeability and morphology. The in vitro membrane effect of benfluron involved a biphasic modulation of the cardiac sarcolemmal (Na+ + K+)-ATPase activity.     

A randomised controlled study comparing conventional and magnetic guidewires in a two-dimensional branching tortuous phantom simulating angulated coronary vessels.

OBJECTIVES: To directly compare the magnetic navigation system (MNS) guidewires with conventional guidewires in branching tortuous phantoms with operators of varying MNS and percutaneous coronary intervention experience. BACKGROUND: Vessel tortuosity, angulation, and side branches remain limiting factors in coronary interventions. The MNS addresses these limitations by precisely directing the tip of a magnetised guidewire in vivo aided by two permanent adjustable external magnets. METHODS: Crossing and fluoroscopy times of six operators were evaluated in five tortuous Perspex(R) phantom vessels in three consecutive attempts. Standard guidewire (SG) usage was unrestricted. Two 2nd generation magnetic guidewires (MG) were used. Failure was noted if the cross was unsuccessful within 5 min. RESULTS: The magnetic navigation was vastly superior to SG techniques with increasingly tortuous phantoms. It dramatically decreased both the crossing and fluoroscopy times with maximal reduction from 201.7 +/- 111 to 36.4 +/- 13 sec, P < 0.001 and 204.7 +/- 24 to 47.2 +/- 19 sec, P < 0.001, respectively. The MNS had a 98.8% procedural success rate compared to 68% with SG techniques. Moreover it considerably limited the amount of wire usage from 5.5 to 1.3. Operators with prior MG experience performed significantly better than those without, except in the simplest phantom where the difference was nonsignificant (33.8 +/- 13 sec vs. 41.7 +/- 17 sec, P = 0.2). CONCLUSION: MNS significantly reduces both the crossing and fluoroscopy times in tortuous coronary phantom models achieving excellent success rates with dramatic reductions in guidewire usage. Operators with prior MNS experience had an advantage over the inexperienced.     

The Maillard reaction in demineralized dentin in vitro

The Maillard reaction between carbohydrate and protein has been proposed as a cause of the browning of carious lesions. The aim of the present investigation was to determine the occurrence of this reaction in bovine dentin collagen in vitro and to establish the effect of the reaction on the proteolytic degradation of bovine dentin collagen in vitro. Slices of demineralized bovine dentin were incubated with 0.2 M glucose or buffer for 10 weeks at 37°C. The formation of initial (furosine) and advanced (pentosidine) products of the Maillard reaction in dentin exposed to glucose was confirmed by HPLC. After reduction with NaBH₄ to prevent intermediate Maillard products from further reaction, slices were either degraded with collagenase for fluorescence measurement or incubated with trypsin or pepsin to assess enzymatic degradation. Fluorescence characteristic for the Maillard reaction increased in glucose-exposed slices. Degradation of collagen by pepsin, but not by trypsin, was greatly depressed following glucose pretreatment. This may indicate an altered sensitivity to proteolytic degradation; the Maillard reaction thus has a potential role in caries arrestment.     

Late results after repair of partial atrioventricular septal defect in adolescents and adults

From January 1966 through December 1985, 29 adolescents and adults underwent surgical repair of a partial atrioventricular septal defect at our institution. The patients included 20 females and 9 males, whose ages ranged from 16 to 47 years (mean, 27.6 +/- 10.1 years). Preoperatively, 24 patients were in New York Heart Association functional class I or II, and 5 were in class III. The pulmonary artery systolic pressure ranged from 22 to 62 mmHg (mean, 38.3 +/- 12.7 mmHg). The pulmonary-to-systemic flow ratio ranged from 1.4 to 2.9 (mean, 2.3 +/- 0.5). Upon left ventriculography, regurgitation through the left atrioventricular valve was trivial or nonexistent in 4 patients (13.8%), mild in 14 (48.3%), moderate in 10 (34.5%), and severe in 1 patient (3.4%). All patients underwent patch closure of the ostium primum defect, and all but 2 underwent partial or complete suturing of the septal commissure. One patient died within 30 days, for a hospital mortality of 3.4%. The follow-up period ranged from 7 to 25 years (mean, 15.2 +/- 5.3 years). Postoperatively, all patients were evaluated with 2-dimensional and Doppler echocardiography. One patient underwent early implantation of a permanent pacemaker for persistent complete heart block. Three patients succumbed to late death 10, 15, and 21 years after operation. Among the 25 long-term survivors, 1 patient required late valve replacement because of severe left atrioventricular valve regurgitation. Nine (37.5%) of the other 24 long-term survivors had little or no regurgitation. Of the 11 patients with moderate-to-severe preoperative left atrioventricular valve regurgitation, 4 had moderate postoperative regurgitation. Seventeen patients had a moderate or severe persistent apical systolic murmur. At the latest follow-up in 1991, 5 (20%) of the 25 long-term survivors had significant arrhythmias. At 25 years, the actuarial survival rate was 78.9% +/- 25.6%. All 25 surviving patients were in New York Heart Association class I or II. The rate of freedom from reoperation was 77.7% +/- 25.9%. We conclude that, in adolescents and adults, correction of a partial atrioventricular septal defect entails little risk and is likely to improve the patient's functional status. Repair of the left atrioventricular valve yields good results, even at long-term follow-up.