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Biomedical subjects

D Jocham

Publications and source records attributed to D Jocham.

At least 109 records · Page 6Linked to original sources
PubMed1993

Dissecting the immunobiological effects of Bacillus Calmette-Guérin (BCG) in vitro: evidence of a distinct BCG-activated killer (BAK) cell phenomenon.

Several immunobiological effects of intravesical bacillus Calmette-Guérin (BCG) during immunotherapy of superficial bladder cancer have been suggested as possible mediators of the mode of action. In an attempt to elucidate which of these effects is relevant to tumoricidal activity, an in vitro cytotoxicity assay was employed in which the direct effects of BCG and of cytokines against four transitional carcinoma cell lines were studied. Furthermore, peripheral blood mononuclear cells (PBMNC) were analyzed for their cytotoxic potential against these target cells. We found that none of the cytokines interleukin-1, interleukin-2, interferon-gamma, tumor necrosis factor alpha, lymphotoxin, or BCG alone were cytotoxic against the bladder carcinoma cell lines. However, a pronounced cytotoxicity against these targets resistant to natural killer cells could be induced in PBMNC by coincubation with viable BCG. We termed this the BCG-activated killer (BAK) cell phenomenon. In contrast to lymphokine-activated (LAK) cells, these BAK cells needed prolonged activation for 7 days and did not enhance the cytotoxicity against K562 target cells sensitive to natural killer cells. Nonviable, heat-inactivated BCG was significantly less effective, and sonificated fractions of BCG were not effective in stimulating PBMNC towards BAK cell activity. In vitro dissection of effects observed during BCG intravesical therapy may give more insight into the mode of action of BCG and may help to separate primary tumoricidal effector mechanisms from secondary concomitant phenomena. Further characterization of the BAK cell may result in an improvement of intravesical BCG immunotherapy.

BCG Vaccine↗
PubMed1993

Tumour localisation kinetics of photofrin and three synthetic porphyrinoids in an amelanotic melanoma of the hamster.

In this study the localisation of porphyrinoid photosensitizers in tumours was investigated. To determine if tumour selectivity results from a preferential uptake or prolonged retention of photosensitizers, intravital fluorescence microscopy and chemical extraction were used. Amelanotic melanoma (A-Mel-3) were implanted in a skin fold chamber in Syrian Golden hamsters. Distribution of the porphyrin mixture Photofrin and three porphycenes, pure porphyrinoid model compounds, was studied quantitatively by intravital fluorescence microscopy. Extraction of tissue and blood samples was performed to verify and supplement intravital microscopic results. Photofrin accumulated in melanomas reaching a maximum tumour:skin tissue ratio of 1.7:1. Localisation of the different porphycenes was found to be highly tumour selective (3.2:1), anti-tumour selective (0.2:1), and non-selective (1:1) with increasing polarity of the porphycenes. The two non-tumour selective porphycenes had distinctly accelerated serum and tissue kinetics; serum halflife times being as short as 1 min. The specific localisation of the slowly distributed, tumour selective photosensitizers, occurred exclusively during the distribution from serum and uptake into tissues. For the most selective porphycene, the tumour selection process had a halflife of 260 +/- 150 min and led to a strongly fluorescent tumour edge edema. Accumulation of porphyrines by the amelanotic melanoma (A-Mel-3) can be attributed to an enhanced uptake rate for lipophilic molecules in this subcutaneously growing neoplasm. The slow distribution of the two tumour specific photosensitizers and the strong fluorescence of these hydrophobic molecules in the tumour compartment with a high water content indicate a carrier role of serum proteins in the selection process. Enhanced permeability of the tumour vasculature to macromolecules appears to be the most probable reason for the tumour selectivity of these two sensitisers.

Animals↗
PubMed1992

Clinical evidence of systemic persistence of bacillus Calmette-Guerin: long-term pulmonary bacillus Calmette-Guerin infection after intravesical therapy for bladder cancer and subsequent cystectomy.

A patient with urothelial bladder carcinoma is reported who suffered from culture proved pulmonary bacillus Calmette-Guerin (BCG) infection 14 months after a single course of intravesical BCG and 11 months after subsequent radical cystectomy for progressive cancer. This unusual case raises the question of the ultimate fate of intravesically instilled BCG and the possible persistence of these mycobacteria in remote organs. Systemic spread and dormant survival at least in some cases are suggested, and therapeutic and diagnostic consequences are discussed.

Administration, Intravesical↗
PubMed1992

Pharmacokinetics of fluorescent polyporphyrin Photofrin II in normal rat tissue and rat bladder tumor.

The transient behavior of the molecular components responsible for fluorescence emission of the photosensitizing polyporphyrin Photofrin II has been studied quantitatively in the liver, small intestines, bladder and muscles of rats. Relative concentrations of the substance were determined fluorometrically in vivo using a Kr(+)-laser (wavelength = 406.7 nm) and a mercury arc lamp (wavelength = 405 or 550 nm) for fluorescence excitation of Photofrin II. Fluorescence was detected at the maxima of the emission bands, at 630 or 690 nm. The results of the experiments show that Photofrin II can be clearly detected by its fluorescence in all the organs investigated from 3 h up to at least 28 days after systemic application of the substance. Within this investigational period the fluorescing components of Photofrin II are released continuously from the organs. In all the tissues examined, an initial decrease with time constants between 2 and 42 h followed by a slow decay with time constants between about 300 and 600 h can be observed. In addition the pharmacokinetics of the fluorescent components of Photofrin II in chemically induced rat bladder tumors with different stages of malignancy were compared to healthy rat bladder tissue. In a time range of 2-10 days after intravenous injection Photofrin II shows a fluorescence 2-5 times brighter in rat bladder tumors than in healthy bladder tissue.

Animals↗
PubMed1992

Long-term immunobiological effects of intravesical bacillus Calmette-Guérin against bladder carcinoma recurrences.

Intravesical bacillus Calmette-Guérin is a highly effective therapy against superficial bladder cancer recurrences and urothelial carcinoma in situ, the antitumoral effects of which seem to be linked to immunological effector mechanisms. To characterize further these mechanisms which contribute to the long-term effectiveness of BCG therapy, the local mononuclear cell subsets as well as the local cytokine production were assessed in the bladder wall of patients receiving intravesical BCG immunotherapy with special regard to long-term persisting changes, using immuno-enzymatical staining methods. All patients exhibited a significant increase after BCG in the local mononuclear cell population, with a predominance of the helper T-cell subset. Immunocompetent cells expressed activation markers for a prolonged period. Furthermore, a significant increase in the local cytokine production after the initial course of BCG was demonstrable, which persisted even after 12 to 21 months. These changes suggest that the BCG-induced activation of the local immune system persists over a long period after an initial course of intravesical therapy.

Administration, Intravesical↗
PubMed1992

[Ureterorenoscopy as a diagnostic procedure in the upper urinary tract].

Ureteropyeloscopy has become a valuable asset in the diagnosis and treatment in the upper urinary tract. From 1984 to 1991 we performed 1635 ureteropyeloscopies, 180 procedures in a diagnostic intention. Rigid ureteropyeloscopes permit endoscopic access into the ureter and the upper calix, actively deflectable instruments are necessary to visualize the middle and lower calix.

Biopsy↗
PubMed1991

[Therapy of superficial bladder carcinoma].

Topical therapy is administered after transurethral resection (TUR) for superficial cancer to reduce the frequency of recurrence, to avoid local tumor progression and to increase the survival rate. However, the results of prospective randomized studies on topical chemotherapy show that successful reduction of tumor recurrence is limited to a small group of patients. Topical immunotherapy with BCG seems to be more efficient, but prospective multicenter studies have not confirmed the superiority of BCG treatment. At present neither chemotherapy nor immunotherapy can influence progression or survival rate. It therefore seems advisable to continue to enroll patients with superficial bladder tumors in prospective studies to obtain more information on treatment schedules and their side-effects and therapeutic activity. The following information may be helpful in deciding on individual treatment schedules for patients with superficial bladder cancer: (1) Carcinoma in situ is the only therapeutic indication for topical therapy, and BCG may be more potent than chemotherapy. (2) Patients with pTaG1 tumor should be excluded from topical therapy. (3) Topical therapy may not be indicated at all for pT1G3 tumors. The rate of local progression and distant metastasis is high and cannot be influenced by this form of adjuvant treatment. (4) At present no drug of first choice is known. (5) Early application of intravesical chemotherapy immediately after TUR has no advantage over delayed treatment. (6) Long-term chemoprophylaxis is equivalent to short-term prophylaxis (6-24 months) in effect. (7) Immunotherapy with BCG can be limited to a period of 6 months.

Administration, Intravesical↗
PubMed1990

Clinical experience with the integral photodynamic therapy of bladder carcinoma.

Photodynamic therapy (PDT) was given to 20 patients who had recurring superficial tumours after unsuccessful application of other treatments. The phototherapeutic results were evaluated by check-ups at 3 month intervals (endoscopy, cytology, bladder mapping, renal ultrasonography) and computed tomography (CT) examination at 8-13 month intervals. In six patients treated with PDT no tumour recurrence was found over the whole observation period up to nearly 5 years. Four patients remained free of tumour (12 and 14 months) after repeated transurethral resection (TUR) and Nd:YAG laser therapy following PDT. Due to an initial application of insufficient irradiation, four patients required a second photodynamic treatment. In one of these cases a circumscribed dysplasia which appeared at the left ostium 26 months following PDT was treated successfully using the Nd:YAG laser following TUR. In six patients slight mucosal atypia persisted for a period of at least 2.5 years. One cystectomy had to be performed because of bladder shrinkage. The dissected bladder was free of tumour. According to these preliminary results, PDT with strict patient selection (worst case situation with recommended cystectomy) is justified in the case of recurrent superficial TIS bladder carcinoma.

Antineoplastic Agents↗
PubMed1990

[NMR tomography of vena cava thrombi: clinical significance in the differential diagnosis and therapy].

31 patients with advanced renal cell carcinoma underwent abdominal MRI which were examined by an independent experienced radiologist and compared with the intraoperative findings. 12 of 13 vena caval tumor thrombi were diagnosed correctly, 1 small tumor thrombus in a case with large retroperitoneal lymph nodes compressing the vena cava could not be detected. The extension of the tumor in the vena cava could exactly be described in topographic relation to liver, diaphragm and right atrium which is important for planning the operative procedure.

Carcinoma, Renal Cell↗
PubMed1990

[Photodynamic therapy of bronchial cancer].

Photodynamic therapy (PDT) with porphyrin derivatives (haematoporphyrin and dihaematoporphyrin äther/ester) and laser light of the wavelength 640 nm, is a new procedure for the treatment of carcinomas. This form of therapy is selective, can be applied through the bronchoscope, and is aimed at accomplishing curative elimination of central tumours of the lung. To date, we have successfully applied PDT in four selected patients. Our first patient was treated in April, 1987. The irradiation modalities and the clinical course are described.

Adenocarcinoma↗
PubMed1989

Long-term experience with integral photodynamic therapy of TIS bladder carcinoma.

Fifteen patients in whom superficial bladder tumours (TIS GII-III) recurred after the unsuccessful application of other treatments were treated by photodynamic therapy (PDT) and observed for 24-54 months. The results of therapy were evaluated by regular three-monthly check-ups (endoscopy, cytology, bladder mapping, renal ultrasonography) as well as by computed tomography (CT) examination at 8- to 13-month intervals. In nine patients treated by PDT no tumour recurrence has been found over the whole observation period. Two patients have remained free of tumour (12 and 14 months) after repeated transurethral resection (TUR) and Nd-YAG laser therapy after PDT. Two patients required a second application of PDT before the treatment goal was achieved. In one of these cases a circumscribed dysplasia which appeared at the left ostium 26 months after PDT was treated by TUR and Nd-YAG laser. Further observations showed it had been successfully removed. In six patients slight mucosal atypia persisted for at least 2.5 years. In the short-term course of further cases (n = 12) one cystectomy has to be performed because of bladder shrinkage. According to these preliminary results, PDT (with strict patient selection--worst-case situation with recommended cystectomy) is justified for recurrent superficial TIS bladder carcinoma.

Carcinoma in Situ↗
PubMed1989

Bronchoscopic photodynamic therapy of bronchial carcinoma.

Photodynamic therapy with photosensitizers is a new method of treating malignant tumors. In the area of bronchoscopy it is employed for the selective therapy of early carcinomas at central localizations. We report on our first attempts at treatment with hematoporphyrin derivative in an inoperable patient. The modalities of irradiation and the recurrence-free progress of, to date, 2.5 years, are described.

Bronchoscopy↗
PubMed1989

[Laser light-induced cytotoxicity of cultivated squamous cell cancer cells of the head and neck following photosensitization].

Photodynamic therapy, which involves the action of light-activated dyes on biological tissues, has been attempted to treat tumors. In order to achieve effective tumor cell destruction in head and neck cancer, the direct photodynamic effects on in vitro cultured squamous carcinoma cell lines were analyzed. Without light no tumor cell killing was observed after photosensitization up to 6 hrs with dihematoporphyrinester/-ether (DHE) concentrations of 5 micrograms/ml. With longer incubation times and higher light irradiation dosages, however, an increasing cytotoxicity could be observed. Optimal intervals for photosensitization were 48 hours. Squamous cell carcinoma lines of the head and neck from different locations did not differ in their photodynamic behaviour with respect to photodynamic treatment. With the results presented, it will be appropriate to complete in vivo studies to inspire photodynamic tumor cell destruction in the treatment of head and neck cancer as a new approach besides the classical therapeutic modalities.

Carcinoma, Squamous Cell↗
PubMed1989

Adjuvant laser treatment of bladder cancer: 8 years' experience with the Nd-YAG laser 1064 nm.

Following the development of suitable equipment for the endoscopic application of an Nd-YAG laser in this department, the laser has been used routinely in the management of bladder cancer since 1978. To evaluate side effects and efficiency, 252 consecutive laser treatments were evaluated with a minimum follow-up of 12 months. Side effects were few (0.3% perforation) and patients tolerated the treatment very well. The general recurrence rate of T1 tumours varied from 33% for primary carcinomas to 54% for recurrent tumours, but the incidence of local recurrence was only 7%. The long-term results of laser treatment showed a decrease in the local recurrence rate when compared with the results of conservative electocautery resection, but there was no significant influence on the total recurrence rate.

Aged↗
PubMed1989

[Fluorescence diagnosis of porphyrin-marked urothelial tumors. Status of experimental development].

On the basis of selective storage of fluorescing hematoporphyrin derivative (HpD) in tumors, a method has been developed that enables the endoscopic detection of early-stage cancer by monitoring fluorescent images. The contrast-reducing portion of the superposed tissue autofluorescence is suppressed by the use of two-wavelength excitation and subsequent image processing in realtime. The amount of photosensitizing HpD necessary for diagnostic purposes is considerably reduced by means of sensitive detection devices. A clear distinction between benign and malignant bladder tissue seems possible according to the results of animal studies.

Animals↗
PubMed1989

[Prevalence and incidence of arterial hypertension in patients with kidney calculi treated by extracorporeal shock wave lithotripsy].

Follow-up studies were conducted on 806 patients to investigate the question of whether or not arterial hypertension can develop subsequent to ESWL. First of all, it was determined that 509 of 518 patients who were subjected to ESWL treatment from December 1985 to December 1986 still had normotension (n = 410) or hypertension (RR greater than or equal to, 160/95, n = 99) prior to and on an average of 9.3 months after ESWL. Six hypertensive patients became normotensive subsequent to ESWL. Only 1 patient developed hypertension following ESWL. Secondly, the 288 patients who were subjected to ESWL treatment from May 1982 to May 1984 revealed a 3.1% incidence of arterial hypertension within a period of 3.6 years following ESWL. This incidence, however, only illustrates that there was a pronounced age-related increase in the prevalence of hypertension (0.8% per year) in these study groups.

Adult↗
PubMed1989

[Long-term experiences following extracorporeal shockwave lithotripsy in patients with urinary calculi].

A report is given on the experience we have had over a period of up to 7 years following ESWL treatment in urinary stone patients. 131I-hippuran clearance studies were conducted on 19 patients prior to and 6.6 years subsequent to ESWL. There was no evidence of any degree of deterioration in total renal function or of any form of dysfunction in the kidney treated. Follow-up examinations on 247 patients showed a 7% recurrent stone rate within a period of 3.6 years following ESWL. In 16% of the cases, residual concretions were found 6 months after ESWL, only 4% of which were larger than 5 mm in diameter. In 22%, concretions were discovered 3.6 years after ESWL 36% of which were larger than 5 mm. This size increase in the fragments accounts for the stone growth.

Adult↗