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Biomedical subjects

D Jocham

Publications and source records attributed to D Jocham.

At least 73 records · Page 4Linked to original sources
PubMed2000

Technology evaluation: CN-706, Calydon Inc.

CN-706, an engineered adenovirus containing the prostate tissue-specific enhancer (PSE) gene is under development by Calydon as a potential treatment for prostate cancer. The company is collaborating with the Johns Hopkins Hospital, which has agreed to sponsor clinical trials [274956]. Phase I trials in patients with advanced and recurring prostate cancer began during 1998 at the Johns Hopkins Brady Urological Institute and the Oncology Center [283946], [296857], and the results of phase I/II trials were reported in 2000 [386879]. The US Patent Office issued three patents in October 1998 [301251] related to Calydon's technology for engineering viruses to replicate and kill prostate cancer cells [US-05648478], [US-05698443], [US-05783435]. In June 1999, Calydon was issued two further patents [US-05871726], [US-05830686], [327511].

Adenoviridae↗
PubMed2000

Technology evaluation: Abarelix, Praecis pharmaceuticals.

Abarelix (PPI-149) is a luteinizing hormone-releasing hormone (LHRH) receptor antagonist under development by Praecis, Amgen and Sanofi-Synthelabo for the potential treatment of prostate cancer, breast cancer and hormone-related disorders [285672,328910]. Abarelix has entered phase III clinical trials for hormonally responsive prostate cancer [311887], and a sustained-release formulation is in a phase I/II clinical trial for endometriosis [317822]. In June 1997, Praecis entered into a collaboration with Sanofi-Synthelabo for the continued development and future marketing of Abarelix for the treatment of prostate cancer and other hormone-related disorders in Europe [248307]. In June 1998, Roche gained marketing rights in the US and elsewhere, under a joint development agreement [289677], which was later terminated. In March 1999, Amgen gained rights to develop Abarelix in the US, Canada, Australia, Asia and other secondary markets [317822]. Sanofi-Synthelabo expects to launch the compound in Europe in 2001 [345341,346302]. In March 1999, Merrill Lynch predicted sales in 2001 of US$75 million, with peak sales of up to US$400 million [336561]. In October 1999, Merrill Lynch predicted sales in 2003 of EUR 100 million [346209] and Lehman Brothers predicted sales of US$50 million in 2002 rising to a peak of US$150 million in 2010 [346267].

Animals↗
PubMed1999

Optimizing syngeneic orthotopic murine bladder cancer (MB49).

The syngeneic orthotopic murine bladder cancer model MB49 is hampered by unreliable tumor implantation. We optimized this model by a simple modification of the standard implantation technique in three groups of mice. Fifty thousand (group I), 20,000 (group II), or 10,000 (group III) tumor cells were implanted into cauterized bladders by transurethral instillation, and dwell time was prolonged to 3 h. Tumor take, survival, and bladder weights were determined as outcome variables. To verify whether this modification maintained its sensitivity to topical immunotherapy, an initial tumor load of 100,000 MB49 cells was given, and mice were treated intravesically with Bacillus Calmette-Guérin or phosphate-buffered saline. The prolonged dwell time of tumor cells resulted in take rates of 100% in all three groups. Survival and bladder weights were significantly correlated with the number of instilled cells. Even with the highest tumor load, Bacillus Calmette-Guérin therapy improved survival and reduced bladder weights significantly, as compared to PBS. Thus, the modified model is highly reliable and maintains its susceptibility to topical immunotherapy.

Animals↗
PubMed1999

[Effectiveness and tolerance of 1 dosage forms (subcutaneous and intramuscular) of decapeptyl depot in patients with advanced prostate carcinoma].

The intramuscular (i.m.) administration of Decapeptyl Depot has been approved in Germany for the treatment of advanced hormone dependent prostate cancer since July 1990. In this study a reformulated Decapeptyl Depot, administered as a first-line endocrine therapy, was injected intramuscularly (i.m.) or subcutaneously (s.c.) every 28 days for 6 months. At 12 different hospitals, 52 prostate cancer patients were treated, whereby 25 patients received a s.c. injection and 27 patients a i.m. injection. Testosterone was measured as the main parameter: after 28 days, both the s.c. and the i.m. application form of Decapeptyl Depot successfully reduced initial testosterone levels of at least 2.3 ng/ml to steady-state castration levels below 1.2 ng/ml, maintaining this complete suppression for the entire length of the trial (168 days). Decapeptyl Depot was well tolerated and very acceptable to the patients in both groups. Side effects were few and predictable, being largely associated with decreased testosterone concentrations. No cumulation in triptorelin serum levels was observed within the 6 months of treatment. Decapeptyl Depot, administered subcutaneously or intramuscularly was effective and safe in the treatment of patients with advanced prostate cancer.

Antineoplastic Agents, Hormonal↗
PubMed1999

Interference of modern antibacterials with bacillus Calmette-Guerin viability.

PURPOSE: We determine the effects of modern antibacterial chemotherapeutics on bacillus Calmette-Guerin (BCG) viability, particularly those of cycloserine, which has been recommended for treating BCG induced sepsis. MATERIALS AND METHODS: The minimal inhibitory concentrations of 31 antibacterial drugs against Connaught BCG strain were determined in vitro by the radiometric BACTEC 460TB method. Minimal inhibitory concentrations were compared with the drug concentrations achievable in blood and urine to estimate systemic or intravesical susceptibility. Susceptibility testing of cycloserine was performed with Connaught, Tice and RIVM BCG strains, using the modified proportion method on Lowenstein-Jensen agar. RESULTS: Connaught BCG was susceptible to quinolones in systemic infections but resistant to beta-lactams, macrolides and some aminoglycosides. It was resistant to pyrazinamide but showed good susceptibility toward the other antituberculosis drugs tested. All 3 BCG strains analyzed were resistant to cycloserine. Most antibacterials may interfere with BCG in the bladder because of high urinary recovery. CONCLUSIONS: Antibacterial drug interference with BCG viability should be avoided during intravesical instillation therapy. In cases of severe complications quinolones rather than cycloserine may be given in addition to standard triple antituberculosis drug therapy or if one of these drugs is not tolerated. Our data may contribute toward enhancing the therapeutic safety and efficacy of intravesical BCG immunotherapy by the appropriate use of antibacterial drugs.

Antibiotics, Antitubercular↗
PubMed1999

Bacillus-Calmette-Guérin (BCG) and 3D tumors: an in vitro model for the study of adhesion and invasion.

PURPOSE: To study adhesion, penetration and internalization of BCG and effector-cells to and into three-dimensional in vitro cell aggregates from benign and malignant urothelial origin mimicking small in vitro tumors. MATERIALS AND METHODS: Multicellular spheroids (MCS) were generated by "liquid-overlay" technique. Adhesion and penetration of viable FITC-labelled BCG into MCS from urothelial cancer cell lines and normal urothelial cells was studied by electron microscopy (TEM) and fluorescence microscopy. Spheroid growth during BCG-co-incubation was determined by light microscopy. Peripheral blood mononuclear cells (PBMC) were stimulated with BCG to generate BCG-activated-killer (BAK) cells. The infiltration of these effectors and of lymphokine-activated killer (LAK) cells into MCS was examined at different intervals by means of immunohistochemistry. The resulting cytotoxicity was judged in a 3H-l-methionine release assay. RESULTS: BCG adhered to MCS from tumor cells but not to benign cell MCS. Intracellular internalization of the bacteria was detectable in superficial tumor cell-layers (1-5) whereas BCG was not found in deeper layers. Proliferation of malignant MCS was reduced in the presence of BCG. Benign MCS showed contact inhibition growth arrest, which was not altered by BCG. BAK and LAK effector cells both infiltrated tumor cell MCS as opposed to unstimulated PBMC. In contrast to LAK cells, BAK cells did not infiltrate into benign cell MCS and were not cytotoxic towards them. CONCLUSION: With regard to the clinical situation the selective adhesion and internalization of BCG to malignant cells might explain why BCG has been rarely found in follow-up biopsies in tumor free patients. More interestingly, the selective adhesion of BCG to and infiltration of BAK effector cells into malignant cell spheroids suggests a selective mode of action of BCG.

Adjuvants, Immunologic↗
PubMed1999

Intra-abdominal abscess due to patient non-compliance after construction of an ileal neobladder: case report and review of the literature.

PURPOSE: A case report of patient with an intra-abdominal abscess 8 weeks after radical cystectomy and construction of an ileal neobladder is presented. METHODS/RESULTS: The patient was admitted with nausea, vomiting and singultus. A perforation of the neobladder due to overdistension was assumed to be the underlying cause of the intra-abdominal abscess formation as the patient admitted infrequent voiding during the day and no emptying of the neobladder at night. The patient underwent explorative laparotomy and 4200 mL of pus was removed from the abdominal cavity. The patient made an uneventful recovery and was discharged from hospital after 5 weeks. Neobladder function remained stable and the patient was leading a normal life at 24 months follow-up. CONCLUSIONS: The present case demonstrates the need for careful patient selection prior to radical cystectomy with continent urinary diversion. Reduced compliance and mental disabilities of a patient can increase the complication rate.

Abdominal Abscess↗
PubMed1999

Effects of acetylic salicylic acid and pentoxifylline on the efficacy of intravesical BCG therapy in orthotopic murine bladder cancer (MB49).

PURPOSE: Intravesical immunotherapy with bacillus Calmette-Guerin (BCG), which has become the gold standard in the adjuvant treatment of superficial bladder cancer, is hampered by local side effects. Anti-inflammatory drugs may be helpful, but as an undesired side effect, therapeutic efficacy of BCG might be impaired. Therefore, we investigated the effects of anti-inflammatory drugs on the efficacy of intravesical BCG in an animal model. MATERIALS AND METHODS: Syngenic tumor cells were implanted into the bladders of 75 mice according to our modification of the method. Mice were randomized to 5 groups with 15 animals each and treated with phosphate buffered saline (PBS), group 1; BCG, group 2; BCG + acetylic salicylic acid (ASA), group 3; BCG + pentoxifylline (POF), group 4; autoclaved BCG (aBCG), group 5. Intravesical instillation of 1.35 mg. BCG was initiated one day after tumor inoculation and repeated in weekly intervals for 4 instillations altogether. ASA and POF in doses of 200 mg./kg. and 150 mg./kg., respectively, were given continuously with the drinking water starting at the first instillation. Autoclaved BCG served as control for the importance of viability and was given at the same dose as viable BCG. Mice were monitored for survival, gross hematuria and body weight and after 28 days evaluated for bladder weight and tumor occurrence. RESULTS: Autoclaved BCG and PBS had no effect on tumor growth, whereas animals treated with viable BCG alone and in combination with POF and ASA, respectively, showed a significant reduction in bladder weight: PBS, 248 mg.; BCG, 140 mg. (p = 0.0009); BCG + ASA, 123 mg. (p = 0.0001); BCG + POF, 145 mg. (p = 0.0004); autoclaved BCG, 283 mg. (p = 0.21). Mice treated with BCG, BCG + ASA and BCG + POF showed a significantly higher proportion of survival until day 28 as compared to PBS alone. Autoclaved BCG had no therapeutic efficacy (Kaplan-Meier method/log rank test: BCG, p = 0.0053; BCG + ASA, p = 0.0044; BCG + POF, p = 0.0027; aBCG, p = 0.33). No significant differences among the 3 groups treated with viable BCG, with or without anti-inflammatory drugs, regarding bladder weight and survival were detectable. CONCLUSIONS: The efficacy of BCG therapy in murine orthotopic bladder cancer is dependent on BCG viability and is not compromised by ASA or POF. Clinical trials to evaluate the efficacy of routine ASA or POF to reduce BCG side effects in patients, using self-assessment criteria, should be initiated.

Adjuvants, Immunologic↗
PubMed1998

Treatment of posttransplant hypertension by laparoscopic bilateral nephrectomy?

BACKGROUND: Hypertension is an important risk factor for the development of chronic graft failure and decreased graft and patient survival after renal transplantation. METHODS: Between September 1994 and August 1996, 14 patients underwent laparoscopic bilateral nephrectomy for treatment of drug-resistant hypertension after successful renal transplantation. Common causes of hypertension were largely excluded before bilateral nephrectomy. A scoring system was developed for comparison of different antihypertensive regimes. In this system, points were given according to type and dosage of each antihypertensive drug. RESULTS: At 6-month follow-up, all patients showed well-controlled blood pressure (median of mean arterial pressure: 104 vs. 130 mmHg preoperatively, P<0.001, n=14), and significantly fewer antihypertensive drugs were needed according to the scoring system (48.9+/-20.9 points vs. 105.9+/-23.5 points preoperatively, P<0.001, n=14). During laparoscopy, three conversions to open surgery were necessary. Postoperatively, four complications occurred. After laparoscopy, immunosuppression and other oral medication were given continuously. The hospital stay ranged between 3 and 6 days (median: 5 days). CONCLUSIONS: The results indicate that bilateral nephrectomy using the laparoscopic technique can be an effective alternative method for a selected group of patients with severe hypertension, which is unresponsive to conservative management after successful renal transplantation with regard to improving the long-term graft survival.

Adult↗
PubMed1998

Clinical multi-colour fluorescence imaging of malignant tumours--initial experience.

PURPOSE: The detection of malignant tumours relies on a variety of diagnostic procedures including X-ray images and, for hollow organs, endoscopy. The purpose of this study was to present a new technique for non-invasive tumour detection based on tissue fluorescence imaging. MATERIAL AND METHODS: A clinically adapted multi-colour fluorescence system was employed in the real-time imaging of malignant tumours of the skin, breast, head and neck region, and urinary bladder. Tumour detection was based on the contrast displayed in fluorescence between normal and malignant tissue, related to the selective uptake of tumour-marking agents, such as haematoporphyrin derivative (HPD) and delta-amino levulinic acid (ALA), and natural chromophore differences between various tissues. In order to demarcate basal cell carcinomas of the skin, ALA was applied topically 4-6 h before the fluorescence investigation. For urinary bladder tumour visualisation (transitional cell carcinoma of different stages including carcinoma in situ), ALA was instilled into the bladder 1-2 h prior to the study. Malignant and premalignant lesions in the head and neck region were imaged after i.v. injection of HPD (Photofrin). Finally, the extent of in situ and invasive carcinomas of the breast was investigated in surgically excised specimens from patients that received a low-dose injection of HPD 24 h prior to the study. The tumour imaging system was coupled to an endoscope. Fluorescence light emission from the tissue surface was induced with 100-ns-long optical pulses at 390 nm, generated from a frequency-doubled alexandrite laser. With the use of special image-splitting optics, the tumour fluorescence, intensified in a micro-channel plate, was imaged in 3 selected wavelength bands. These 3 images were processed together to form a new optimised-contrast image of the tumour. This image, updated at a rate of about 3 frames/s, was mixed with a normal colour video image of the tissue. RESULTS: A clear demarcation from normal surrounding tissue was found during in vivo measurements of superficial bladder carcinoma, basal cell carcinoma of the skin, and leukoplakia with dysplasia of the lip, and in in vitro investigations of resected breast cancer. CONCLUSIONS: The initial clinical experience of using multi-colour fluorescence imaging has shown that the technique has the potential to reveal malignant tumour tissue, including non-invasive early carcinoma and also precancerous tissue. Further investigations are needed to fully develop the method.

Adult↗
PubMed1998

Laparoscopic nephrectomy: comparison of dialysis and non-dialysis patients.

BACKGROUND: Laparoscopy is believed to result in possible clinical benefits for the patient. We report our experience with renal laparoscopy in dialysis patients and compare the results with those from non-dialysis patients. METHODS: Between December 1994 and April 1997, 19 dialysis patients underwent laparoscopic nephrectomy or nephroureterectomy at our hospital. The group consisted of 11 female and eight male patients (mean age 45 years). In nine patients the indication for nephrectomy was chronic pyelonephritis. Nephroureterectomy for vesicoureteral reflux with recurrent episodes of pyelonephritis or analgesic nephropathy for exclusion of transitional cell carcinoma of the upper urinary tract was considered in nine other patients. Laparoscopic bilateral nephrectomy for drug-resistant hypertension was performed in one patient. In comparison, a consecutive group of non-dialysis patients who had undergone renal laparoscopy was reviewed. RESULTS: In the dialysis group, one patient had to be converted to open nephrectomy due to bleeding. Six dialysis patients required blood transfusions compared with none in the non-dialysis group. There were four complications in the dialysis group and two in the non-dialysis group. Both groups had comparable results for operative times, analgesic consumption, postoperative start of oral intake and mobilization, and duration of hospitalization and convalescence. CONCLUSIONS: Laparoscopic nephrectomy in dialysis patients has acceptable results. The higher transfusion rate is probably due to a lower preoperative haemoglobin and is not aggravated by possible affects of the clotting system in patients with chronic uraemia.

Adult↗
PubMed1998

Leuprorelin three-month depot in the treatment of advanced and metastatic prostate cancer: long-term follow-up results.

OBJECTIVES: To determine median survival time, median time to tumor progression and maintenance of testosterone suppression (i.e. < or = 50 ng/dl) during long-term treatment with subcutaneous injections of leuprorelin acetate 3-month depot (LAD-3M). In Germany 62 patients with advanced prostate cancer participated in a prospective, randomized, multicenter phase II trial as part of a European study. Of these, 37 patients entered the follow-up study. METHODS: Standard clinical investigations and methods were employed in the study. RESULTS: Twenty-five of the 62 (40.3%) patients died during the course of the study. No death had a causal relationship with the study drug. Median survival time, median time to tumor progression and median period of progression-free survival were 1,149 (3.1 years), 1,015 (2.8 years) and 680 days (1.9 years), respectively. Adequate suppression of testosterone serum levels to the castration range was confirmed. Objective and subjective response as well as the safety profile were comparable to previously published results with LAD-3M, LAD-1 M and other LHRH analogues. CONCLUSIONS: The results of this follow-up study confirm long-term efficacy and safety of LAD-3M for treatment in advanced prostate cancer. LAD-3M is a suitable alternative to the established shorter-acting LHRH-a depot formulations.

Aged↗
PubMed1998

Comparison of laparoscopic and open nephroureterectomy for benign disease.

PURPOSE: We report our experience with laparoscopic nephroureterectomy for benign disease and compare the results to a contemporary group of patients undergoing open nephroureterectomy. MATERIALS AND METHODS: Between October 1994 and March 1997, 12 women and 4 men with a mean age of 50 years (range 22 to 70) underwent laparoscopic nephroureterectomy at our hospital. Indications for operation were nonfunctioning kidneys due to vesicoureteral reflux with recurrent episodes of pyelonephritis or analgesic nephropathy before a planned renal transplantation. In comparison 11 women and 4 men with a mean age of 40 years (range 18 to 64) underwent open nephroureterectomy for various benign diseases. RESULTS: Laparoscopic and open nephroureterectomy had no significant differences regarding operative times (100 versus 124 minutes) and complication rates (25 versus 20%). In the laparoscopy group conversion to open surgery was not necessary. Patients who underwent laparoscopic nephroureterectomy had significantly less consumption of morphine equivalent for postoperative pain control (12 versus 40 mg.), shorter time to achieve mobilization and oral intake (11 versus 39 hours), shorter hospital stay (6 versus 12.7 days) and faster return to normal activities (21 versus 39 days). CONCLUSIONS: Laparoscopic nephroureterectomy in patients with benign disease has similar operative results but obvious postoperative advantages compared to the open approach.

Adolescent↗
PubMed1998

Treatment of recurrent penile condylomata acuminata with external application and intraurethral instillation of bacillus Calmette-Guerin.

PURPOSE: Condylomata acuminata are caused by human papillomavirus infection. Despite numerous treatment modalities these patients often demonstrate recurrent disease. We report initial experience with bacillus Calmette-Guerin (BCG) therapy in patients not responding to standard treatment. MATERIALS AND METHODS: Between October 1994 and March 1997, 6 men with rapidly recurrent external and intraurethral condylomata acuminata underwent BCG therapy after initial laser treatment. External application and intraurethral instillation of BCG were performed 6 times in weekly intervals. Followup studies included examination and endoscopic inspection of the urethra and bladder. RESULTS: Of the patients 3 completed 1 course of BCG and had no relapse of condylomata acuminata, 2 underwent a second course of BCG and 1 had relapse, and 1 had relapse after discontinuing therapy due to penile edema. The annual recurrence rate decreased from 3.2 before to 0.75 after BCG therapy (p < 0.05, test of equality of 2 percentages). CONCLUSIONS: Immunotherapy with BCG is accepted treatment for superficial transitional cell carcinoma. The BCG induced immune response appears to reduce the recurrence rate in patients with condylomata acuminata.

Adjuvants, Immunologic↗