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Biomedical subjects

T Kocher

Publications and source records attributed to T Kocher.

At least 91 records · Page 5Linked to original sources

Peptide-specific CTL in tumor infiltrating lymphocytes from metastatic melanomas expressing MART-1/Melan-A, gp100 and Tyrosinase genes: a study in an unselected group of HLA-A2.1-positive patients.

Peptide specificity of cultured tumor-infiltrating lymphocytes (TIL) was systematically investigated in a group of HLA-A2.1+ metastatic melanoma patients consecutively referred to our department for surgical treatment. Seven samples from 6 patients were studied. All surgical specimens showed evidence of gp 100, MART-1/Melan-A and Tyrosinase gene expression as detectable by reverse PCR (rPCR). Cultured TIL from 2 patients displayed cytotoxic activity against autologous or HLA-matched EBV-transformed cells previously pulsed with MART-1/Melan-A27-35 peptide. In contrast, no CTL activity against gp100(280-288) or tyrosinase1-9 peptides could be observed. TIL were then repeatedly stimulated in vitro with the same peptides. After 6 restimulation courses at weekly intervals, specific recognition of gp100(280-288) and MART-1/Melan-A peptides was detectable in 3 and 5 TIL populations, respectively. In one case Tyrosinase1-9-specific CTL could be demonstrated. Two TIL populations from metastases resected from a melanoma patient at 6 months' distance showed a different peptide specificity pattern, and no specific CTL could be generated from simultaneously sampled peripheral blood mononuclear cells (PBMC). All peptide-specific CTL populations also displayed significant cytotoxic activity against HLA-A2.1 matched melanoma cell lines expressing the antigens under investigation. Our data indicate that CTL specific for MART-Melan-A27-35, gp100(280-288) or Tyrosinase1-9 peptides could be expanded with varying frequency from TIL derived from 4 out of 6 HLA-A2.1+ patients whose tumors expressed the genes encoding these tumor-associated antigens (TAA).

Adult↗

[Laparoscopic adrenalectomy in pheochromocytoma].

Standard adrenalectomy for pheochromocytoma was until recently performed via the transperitoneal open approach. The disadvantage of the open procedure is a more painful and longer recovery. With good surgical experience in laparoscopic techniques and in endocrine surgery, laparoscopic adrenalectomy can be performed safely without complications. The advantage of the laparoscopic technique is excellent vision of the operative field with magnification even of very small vessels. The first two cases of laparoscopic right adrenalectomy at our institution are described.

Adrenal Gland Neoplasms↗

Identification and intracellular location of MAGE-3 gene product.

The human MAGE-3 gene encodes a melanoma antigenic epitope recognized by specific cytotoxic T lymphocytes, but its gene product has not been identified thus far. We produced a recombinant MAGE-3 gene product by expression cloning of the entire reading frame in the context of a fusion protein characterized by a 10-histidine tail, allowing purification by metal chelation on a nickel Sepharose column. The semipurified product was used to generate MAGE-3-specific monoclonal antibodies. One reagent could identify by immunoblotting the native MAGE-3 gene product as a M(r) 48,000 protein in lysates of cell lines showing evidence of MAGE-3 gene expression. No apparent cross-reactivity with recombinant or native MAGE-1 gene product was observed. Immunohistochemistry shows that, closely resembling the MAGE-1 gene product, MAGE-3 is a cytoplasmic protein.

Animals↗

Tyrosine kinase-dependent and -independent events induced by interleukin-2 stimulation: interleukin-2-mediated NO production required for the induction of lymphokine-activated killer cell activity in rat splenocytes is tyrosine kinase independent.

Nitric oxide (NO) has recently been shown to be an indispensable co-factor in the generation of lymphokine-activated killer (LAK) cells induced by interleukin-2 (IL-2). Upon stimulation with IL-2, cells endowed with specific receptors undergo phosphorylation of substrates mediated by protein tyrosine kinases (PTK). In this work we utilized a well-characterized PTK inhibitor, genistein (GEN), to address the role of PTK on NO-dependent LAK cell generation. The effects of GEN were tested on the expression of the inducible NO synthase (iNOS) gene, proliferation, generation of cytotoxic activity and production of NO upon IL-2 stimulation of rat splenocytes. We report here that GEN displays profound inhibitory effects on recombinant (r)IL-2 induced proliferation and on LAK cell generation, while only marginally affecting NO production, measured as NO2-. In contrast, a specific inhibitor of the NO synthetic pathway (NG-monomethyl-L-arginine; NMMA) blocked generation of LAK cells and NO production without affecting cell proliferation. If added directly to the cytotoxicity tests, GEN exerted minor inhibitory effects, not exceeding 25% of control tests, while NMMA was completely ineffective. Sodium nitroprusside (SNP), a non-enzymatic NO-releasing substance, restored LAK cell generation in cultures performed in the presence of NMMA, but not in those performed in the presence of GEN. These results indicate that IL-2-induced NO production is a PTK-independent event. IL-2-stimulated LAK cell generation obligatorily requires the concurrent activation of PTK dependent and independent signal transduction pathways.

Animals↗

[Surgery in pheochromocytoma. 12-year development].

Hypertension (sustained and/or paroxysmal) is the most common symptom of pheochromocytoma. Correct evaluation nearly always leads to the diagnosis, and complete surgical excision is the definitive treatment. Our study deals with preoperative evaluation, operative morbidity and long-term results after surgery. During the 12-year period (1981-1992) 31 patients (48 years, 25-85) with pheochromocytoma were treated at our institution. The selected preoperative management was reviewed on the basis of patient records. Long-term follow-up was carried out consecutively and personally. All patients received alpha-adrenergic blockers to achieve preoperative normotension and volume repletion. All resections were performed by laparotomy; two of the early cases were extended into the chest. 27 of 29 patients (93.1%) had elevated levels of urinary vanillylmandelic acid; a similar sensitivity was noted in the urinary catecholamines (24/26 = 92.3%). In anatomical localization CT-scan was accurate in 100% (27/27). MIGB scintigraphy was of help in 21 of 23 (91.3%) and, in the most recent patients, MRI was helpful in 3 of 3 (100%). No patient died during the first 30 days after surgery. One patient developed an anaphylactic reaction after cephalosporin administration (morbidity: 3.2%). 2 patients (6.4%) with malignant pheochromocytoma developed a recurrent tumor during the follow-up period. Resection of pheochromocytomas by laparotomy has a low perioperative morbidity and mortality after standardized preparation. A positive MIBG scintigraphy allows extra-adrenal localization. Better resolution and multiplanar imaging are the advantages of MRI. Perioperative management and new imaging techniques--eliminating arteriography and venous sampling among others--have simplified surgical treatment and improved its safety.

Adrenal Gland Neoplasms↗

[Cholecystectomy today. A prospective study].

Between 13 June 1990 and 12 June 1993, we performed 1145 consecutive cholecystectomies. 127 patients who had undergone additional surgery were excluded from the prospective study. Of the remaining 1018 patients, 806 (78.2%) underwent laparoscopic cholecystectomy. The conversion rate to open procedure was 11.2% (90/806). The operative morbidity associated with laparoscopic cholecystectomy was 2.1% (17/806) and with open surgery 1.9% (4/212); mortality was 0.12% (1/806) and 0.47% (1/212) respectively. The reoperation rate after laparoscopic cholecystectomy was 0.6% (5/806). Reoperation was performed for lesions of the common bile duct, bleeding, and abscess formation. If the indications for open cholecystectomy are respected the morbidity and mortality were low for both laparoscopic and conventional cholecystectomy.

Adolescent↗

Treatment of subgingival implant surfaces with Teflon-coated sonic and ultrasonic scaler tips and various implant curettes. An in vitro study.

Removal of plaque and calculus by means of sonic and ultrasonic scalers causes considerable damage to implants. With a view to avoiding the aggressive effects of these instruments, an experimental study was carried out for which conventional sonic and ultrasonic scalers were coated with Teflon. The effects of these instruments on implant surfaces was then compared with that of plastic and metal implant curettes. Stereo-microscopy, scanning electron microscopy and surface profilometry were used to detect and record damage to implant surfaces and changes in surface roughness. Generation and propagation of heat in subgingival simulation of use of sonic and ultrasonic scalers were also recorded by means of temperature measurements at the implant surface. The results revealed that no discernible damage was caused by Teflon-coated sonic and ultrasonic scalers or implant curettes made of plastic on smooth titanium surfaces. Instrument material residues were found on rough implant surfaces. It was not the intention of this study to provide an analysis of the prerequisites for the cleaning of rough implant surfaces, but rather to determine what type of damage is to be expected when contact is made with smooth and rough surfaces unintentionally. Temperature measurements during the subgingival use of sonic and ultrasonic scalers indicated satisfactory functioning of the cooling system. Coating of sonic and ultrasonic scaler tips with Teflon thus facilitates the use of high-frequency instruments to achieve professional cleaning of implants.

Dental Implants↗

Periodontal manifestation of hypophosphatasia. A family case report.

Hypophosphatasia is a rare inherited disease, the 1st clinical sign of which is often a premature loss of deciduous teeth. We describe clinical, histological and SEM findings of 2 cases of hypophosphatasia from a single family and discuss the pathological mechanisms with reference to the literature.

Alkaline Phosphatase↗

[Laparoscopic and open cholecystectomy in 954 patients. A prospective evaluation].

In 2 1/2 years we performed at the St. Clara Hospital in Basel 954 cholecystectomies; 661 were done laparoscopically. In the laparoscopic group we observed a morbidity of 2.3%, a reoperation rate of 0.6% and a mortality of 0.15%. In the group with open cholecystectomy the morbidity was 9.9% and the mortality 1.3%. In all 954 patients who had a cholecystectomy the morbidity was 4.6%, reoperation rate 0.4% and mortality 0.5%. Because of negative patient selection a comparison with the open cholecystectomy in our series is not possible. In summary we can say that the laparoscopic procedure has a low morbidity and low mortality. With the lesser operative trauma it allows a shorter hospital stay. We believe that laparoscopic cholecystectomy with good indication will replace open cholecystectomy as the gold standard therapy of symptomatic gallstone disease.

Adult↗

[Hemorrhage from pseudocysts caused by pseudoaneurysms in chronic pancreatitis. Diagnosis and management].

Bleeding pseudocysts respectively pseudoaneurysms represents a seldom complication of chronic pancreatitis in owing to erosion of pancreatic or peripancreatic arteries. The potential rupture into neighbouring organs or in the peritoneal cavity is accompanied with paramount life-threatening risks. During the last years we observed 3 patients with acute intestinal bleeding caused by pseudocysts converted to pseudoaneurysms. The goal of our report is to analyze the diagnostic tools and the management of patients with bleeding pancreatic pseudocysts, also well establish the clinical constellation, which is typical for this complication, the best diagnostic tool and the modalities to immediate control of the acute bleeding situation. All three patients suffered from chronic pancreatitis and alcohol abuse. The first patient had a known pancreatic pseudocyst, which penetrated through the gastric wall and caused a life-threatening bleeding. The second patient was admitted in owing to melena. The examinations yielded a pancreatic pseudocyst with hematosuccus pancreatis. The third patient suffered from abdominal pain and vertigo caused by anemia. With endoscopy, Cat and celiacography a pancreatic pseudocyst with cysto-colic fistula has been identified. The color-doppler ultrasound revealed a pseudoaneurysm supplied from a splenic artery branch. With management of these patients with hemorrhagic complications of pancreatic pseudocysts we acquired the following findings: 1. Patients with known chronic pancreatitis and abdominal tumor, especially when accompanied by epigastric pain and anemia, are highly suspicious for pancreatic pseudoaneurysms. 2. The color-doppler ultrasound is the best diagnostic tool, since this investigation can establish the pseudoaneurysm and identify the source.

Adult↗

[Laparoscopic cholecystectomy. Initial experiences and results in 278 patients].

Of 467 cholecystectomies (performed between 13. 6. 1990 and 12. 9. 1991) 278 were done by laparoscopy (196 women, 82 men; mean age 53 [18-86] years). Contraindications to a laparoscopic procedure were acute cholecystitis, severe chronic cholecystitis with adhesions, abnormal clotting and suspected gallbladder carcinoma. In 31 patients (11.1%) the initial laparoscopic cholecystectomy was continued as a conventional cholecystectomy, usually because of unclear conditions in severe chronic cholecystitis. Mean duration of hospital stay was 6.3 days for the laparoscopic procedure compared with 11.5 days for the conventional one. Complications occurred in four patients (in 12 with the conventional method): one occlusion (by clip) of the common bile duct, one bile leak, one bleeding and one pneumothorax, requiring re-operation in three patients. There were no deaths (compared with two in the conventional group). Assuming correct indications, laparoscopic cholecystectomy is a sparing method for the treatment of cholecystolithiasis.

Adolescent↗

[Laparoscopic cholecystectomy--experiences and results with a new surgical technique].

Laparoscopic cholecystectomy is a genuine alternative to open cholecystectomy. Acute cholecystitis, chronic cholecystitis with adhesions and gallbladder cancer are absolute, and bile duct stones in rare situations and previous surgery relative contraindications. Ultrasound and intravenous cholecysto-cholangio-tomography are obligatory preoperative investigations. Over 14 months we performed 253 laparoscopic cholecystectomies. Mortality was 0%. Relaparotomy was necessary in 3 of 4 complications (injury of the common bile duct, bile leak and hemorrhage), the reoperation rate is 1.18%. The fourth complication was a pneumothorax after injury of the diaphragm with the electrohook. Conversion to open cholecystectomy was necessary in 10.7%, usually after severe chronic cholecystitis with adhesions. The length of hospitalization was 11 days after open cholecystectomy and could be reduced to 6.5 days after laparoscopic cholecystectomy. With similar results concerning mortality and reoperation rate, the advantages of laparoscopic cholecystectomy are reduced postoperative pain, a shorter recovery time, shorter hospitalization and a better cosmetic result.

Adolescent↗

[Long-term study on the effects of the width of keratinized gingiva on the localization of the gingival margin].

In a 5-year longitudinal study we assessed the amount and frequency of gingival recessions in relation to the width of the keratinized gingiva and the already existing recessions in two groups (each n = 15). Group I (dental students) had nearly no recessions and group II (patients) had exposed roots on 24% of their teeth. In both groups there existed no correlation between the width of the keratinized gingiva or, respectively the existing recessions and the recessions occurring. Only 36 sites had a recession greater than or equal to 1 mm, these were accumulated in just a few probands.

Adult↗

[Guided tissue regeneration for the treatment of different periodontal defects. A clinical study].

In 31 patients we implanted a teflon membrane (Gore-Tex) during flap operation for a duration of 6 weeks. The periodontal situation was assessed clinically and radiographically 1-1.5 years after surgery. The study comprised 18 upper and lower molars with furcation involvement and 15 single-rooted teeth with a 2-wall-, 3-wall- or combined bony defect. Clinical gain of attachment only occurred in furcation class II lesions (upper molars + 2.3 mm, lower molars + 2.5 mm), whereas the attachment level was unchanged in "through and through" furcation defects in the upper jaw and loss of attachment was observed at lower molars with class III furcations. In single-rooted teeth the gain of attachment varied between 0.5 and 8.5 mm, depending on the proportions of the defect and the number of the surrounding bony walls.

Adult↗

[Root surface instrumentation].

The present status of root surface debridement is reviewed. Recently it was shown that the influence of root surface roughness and endotoxin-contaminated cementum was overestimated. The method of instrumentation (i.e., hand instrument, sonic or ultrasonic scaler) does not influence wound healing after periodontal surgery. The operator's technique is of utmost importance.

Dental Scaling↗