Chemosensitisation effect of verapamil and cyclosporin A in vitro is reduced under acidic pH conditions.
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Colonic Neoplasms↗
Biomedical subjects
T Koperna
Publications and source records attributed to T Koperna.
The termination of the vein of "Labbé" and its microsurgical significance.
Information about the termination of the inferior anastomotic vein of Labbé is of crucial importance in the subtemporal neurosurgical approach and its modifications. An intradural course has been observed in all cases. The vein of Labbé reaches in 3/4th the anterior third of the transverse sinus, in 73% of all cases tracing a so-called tentorial sinus. By dissecting the vein of Labbé out of its dural bed and shifting its fixation point, microsurgical access is facilitated considerably.
Cerebral Veins↗
[Spinal meningoceles. Diagnosis--microsurgery--long-term results].
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Adolescent↗
[Anatomical aspects of the arteria inferior posterior cerebelli for posterior fossa surgery].
As the arteria inferior posterior cerebelli sometimes causes surprises of grave consequence at surgical approaches, its origin and course had to be described in detail. For this aim, we especially considered the local relationships of this artery with the medulla oblongata and the cranial nerves of the posterior fossa. Branches of the a. inferior posterior cerebelli supplying the medulla oblongata have been noticed in relation to the arterial supply of the medulla oblongata by corresponding vessels and the aa. spinales lateralis and posterior with special reference to all the possible collateralizations.
Arteries↗
Laparoscopic versus open treatment of patients with acute cholecystitis.
BACKGROUND/AIMS: The studies published so far mention a high rate of complication and conversion in laparoscopic surgical treatment of acute cholecystitis. Considering the relatively high conversion rate in cases of acute cholecystitis, it is necessary to pre-operatively estimate the chance of successful laparoscopic cholecystectomy. One of the aims of this study was to determine the factors that influence the chance of success of this technique. Another aim was to define possible advantages of the method. METHODOLOGY: From 1991 through to 1995, a total of 295 patients in whom acute cholecystitis had been diagnosed on the basis of clinical examination, laboratory data, ultrasonography and pathohistological examination, underwent operative therapy. The laparoscopic approach was attempted in 49 of these patients. Since the patients who underwent primary open surgery were markedly handicapped with regard to severity of inflammation and co-morbid factors, we identified a sub-group of these patients who were comparable to those who underwent laparoscopic cholecystectomy in accordance of the above-mentioned criteria. RESULTS: The rate of conversion (44.9%) correlated with the severity of inflammation, which was determined on the basis of leukocytosis > 10 x 10(9)/l (p = 0.004) and the pathohistological diagnosis (p = 0.005). Hence, the rate of conversion was 71.4% in cases of empyema of the gallbladder but only 29.2% in cases of edematous cholecystitis. In patients whose leukocyte count decreased within 4 days of conservative treatment, a successful laparoscopic cholecystectomy (LC) was performed in 91.7% (11/12) of cases, while 8 patients whose leukocyte count increased or showed no reduction during this time required conversion to open cholecystectomy (p = 0.0001). In cases of acute cholecystitis, the complication rate after LC is lesser in respect of wound infection (p = 0.07) and pneumonia (p = 0.04). In all patients, obesity was a risk factor for wound infection (p = 0.04). Injury to the small intestine was registered in 1 case but in no case was LC associated with injury to the bile duct. CONCLUSIONS: The degree of inflammation and its response to conservative treatment, which are determined on the basis of leukocytosis and clinical improvement, are clear indications of the chance of successful delayed laparoscopic cholecystectomy within the first week. Hence, all patients whose leukocyte count does not decrease after antibiotic treatment should be treated with open cholecystectomy (OC). The complication rate following LC is less than that following OC. Although no injury to the bile duct has been observed in cases of acute cholecystitis, major complications are possible and should not be excluded.
Acute Disease↗
Diagnosis and treatment of bleeding colonic diverticula.
BACKGROUND/AIMS: Colonic diverticula are the most frequent cause of major lower intestinal bleeding and pose a diagnostic and therapeutic challenge to the attending physician. Emergency surgical resection is associated with a high mortality and morbidity and patients who will stop bleeding spontaneously cannot be distinguished from those who will continue to bleed. Our aim was to evaluate the efficacy of barium enema as a sole less invasive treatment option for severe diverticular bleeding. METHODOLOGY: We evaluated 102 patients admitted with colonic diverticular bleeding, from 1993 to 1997, who needed transfusion of 2 or more units of blood. We compared the clinical efficacy of surgical resection, conservative treatment, and therapeutic barium enema with regard to the cessation of bleeding, morbidity, mortality, and rebleeding rate. The therapeutic strategies used after further episodes of bleeding were also registered. RESULTS: Transfusion requirements were highest in patients who underwent surgical treatment, while the least amount of blood was required by the barium enema group (6.9 +/- 3.1 vs. 3.6 +/- 1.5 units of blood). However, the quantity of transfused blood did not correlate with the initial hemoglobin level, which was highest in the conservative treatment group and lowest in the operative group (9.0 +/- 1.2 vs. 8.1 +/- 1.3 g/dL). These data support the fact that the most severe bleeding would necessitate surgical resection and that therapeutic barium enema may be considered more effective than conservative treatments. With regard to the outcome of treatment, conservative treatment led to a rebleeding rate of 43.3%, which differed significantly from a 15.9% rebleeding rate after therapeutic barium enema (P = 0.009). No rebleeding was registered in surgically treated patients. Sixty percent of patients in whom therapeutic barium enema failed were treated by colonic resection without mortality, while 77% of patients who had rebleeding after conservative treatment were successfully treated with barium enema. Overall, barium enema was the most frequently applied second-line treatment (56.5%). The mortality after surgery was significantly higher than that after other treatment modalities (33% vs. 1%; P = 0.0001). CONCLUSIONS: If diverticular bleeding is clinically suspected as the cause of major lower intestinal hemorrhage, barium enema is a more promising alternative than conservative treatment because of diagnostic and therapeutic importance in the long-term. In the event of urgent secondary surgery following the failure of barium enema to stop bleeding, we recommend a sigmoidoscopy and, optionally, an angiography before surgery in order to first localize the bleeding. We conclude that therapeutic barium enema is the treatment of choice for the first bleeding episode, while surgical resection should be performed if rebleeding occurs.
Aged↗
Innovative chemotherapies for stage III colon cancer: a cost-effectiveness study.
BACKGROUND/AIMS: The lower mortality rate associated with Oxaliplatin or Irinotecan added to Fluorouracil chemotherapy for stage III colon cancer should outweigh significantly higher costs of these therapies. While efficacy data currently are lacking, our aim was to generate cost-effectiveness data about a range of potential benefits to define the increase in mortality reduction required for the future acceptance of these new chemotherapies. METHODOLOGY: Estimates of efficacy were derived from the literature. Forty-seven of our patients treated with Oxaliplatin or Fluorouracil/Leucovorin alone were evaluated for cost-analysis. RESULTS: Three scenarios for Oxaliplatin chemotherapies were constructed with a 20% to 50% increase of mortality reduction at 5 years after surgery when compared to Fluorouracil chemotherapy. The associated increase of cost-effectiveness ratio to Fluorouacil chemotherapy was 92% to 36%. A sensitivity analysis for various key input parameters demonstrated the robustness of the model overall. Only the choice of another chemotherapy schedule may significantly alter cost-effective ratios (p < 0.001). CONCLUSIONS: Even the most conservative scenario showed a discounted cost-effectiveness ratio of only 12,485 per life year gained, when compared to best supportive care and therefore met strict cost-effectiveness standards. Oxaliplatin chemotherapy should be accepted for all patients with stage III colon cancer if the required 20% increase in mortality reduction is achieved. Because of the high impact on cost-effectiveness each more expensive chemo-therapy schedule with higher overall dosage should first prove its superior clinical efficacy.
Aged↗
The multidrug-resistance modifiers verapamil, cyclosporine A and tamoxifen induce an intracellular acidification in colon carcinoma cell lines in vitro.
In this study we have investigated the effects of the multidrug-resistance (MDR) modifiers verapamil (VPM), cyclosporin A (CsA) and tamoxifen (TMX) on the intracellular pH(pHi) of four colon carcinoma-derived cell lines with low P-glycoprotein expression (CaCo-2, HT-29, SW 620 and SW 480). Addition of VPM (1 mu M), CsA (1 microgram/ml) or TMX (2 microM) in HEPES- or bicarbonate/CO2-buffered Ringer's solution was followed by dose-dependent and reversible decreases of the pHi (0.1-0.3 units) of all cell lines, as measured ratiometrically by the changes in the pH-dependent fluorescence of bis(carboxyethyl)carboxyfluorescein (BCECF). Testing the effects of the resistance modifiers on the Na+/H+ antiporter and bicarbonate trans-porters under appropriate buffer conditions and addition of inhibitors (amiloride, DIDS) revealed that the chemomodulator-induced acidification does not interfere with the function of these major pHi-regulating acid-base transporters. The induction of changes in pHi shows no correlation with MDR-reversing activity of the drugs and our data do not support the P-gp-inhibition-mediated accumulation of acidic substrates as underlying mechanism. In addition to the P-gp-directed MDR-reversal, chemomodulator-induced intracellular acidification may enhance the chemosensitivity of the cells especially under alkaline extracellular conditions, and contribute to the decreased efficacy of MDR-modifiers in acidic extracellular environments and to the chemosensitising effect of VPM in P-gp-negative cell lines.
ATP Binding Cassette Transporter, Subfamily B, Mem↗