Development and training of skeletal muscle ventricles with low preload.

One-layered skeletal muscle ventricles (SMV) were constructed from latissimus dorsi (LD) muscles extrathoracally in six calves and trained under electrical stimulation on totally implanted mock circulation systems. These ventricles had low preloads of about 5 mmHg. The results showed that training against a resistance similar to the human aorta does not create an effective blood pump. But conditioning against a highly complaint workload makes them six times more effective. Therefore, further research on this observation is mandatory. After a conditioning of 16 to 63 days, all implanted mock circulations became infected due to perforated skin, so these experiments had to be terminated. To avoid these infections, we developed and tested an intrathoracic implantable mock circulation system with a highly compliant workload. With a double-layered muscle pump, systolic pressure 120-140 mmHg was generated and an output of more than 31/min was obtained. SMVs with a low end-diastolic pressure seem to be suitable for construction of an effective blood pump between the left atrium and the aorta as a left heart assist device.

Zoladex: a sustained-release, monthly luteinizing hormone-releasing hormone analogue for the treatment of advanced prostate cancer.

Zoladex, a sustained-release luteinizing hormone--releasing hormone (LHRH) analogue administered by subcutaneous injection every 28 days, was evaluated at three dose levels in 46 men with untreated advanced prostate cancer. All three Zoladex doses yielded similar endocrinologic effects. After initial transient increases in serum luteinizing hormone, follicle-stimulating hormone, and testosterone concentrations, serum testosterone was suppressed uniformly to castration levels within 22 days. At a median follow-up of 41 weeks, Zoladex had maintained persistent suppression of serum testosterone. Measurements of serum Zoladex levels indicated that release of the drug from the injected depot was sustained over a period of 1 month and that there was no drug accumulation as evaluated over an initial 3-month period. No antibodies to Zoladex were detected. Tumor regression rates and side effects with Zoladex therapy were similar to those reported with daily injections of subcutaneous LHRH therapy. Signs and symptoms consistent with a brief tumor flare after the first injection of the LHRH analogue were noted in eight (17%) of the study entrants. Spinal cord compression was observed in two patients within 1 week from the onset of therapy. Zoladex is considered to be an effective, sustained-release LHRH analogue for the treatment of patients with prostate cancer.

Zoladex (ICI 118,630): clinical trial of new luteinizing hormone-releasing hormone analog in metastatic prostatic carcinoma.

Twenty-seven patients with metastatic adenocarcinoma of the prostate were treated with the new luteinizing hormone-releasing hormone analog, Zoladex (ICI 118,630) for up to ninety-eight weeks. Initially, treatment was randomized between Zoladex 250 micrograms and 500 micrograms self-injected subcutaneously every day for a minimum period of twelve weeks following which a sustained-release, once-monthly depot formulation of Zoladex 3.6 mg s.c. was used. Acute rises in serum gonadotropins and testosterone during the first two days were followed by declines in hormone levels over the following three weeks. Median time to castration with 500 micrograms/day was twenty-two days compared with forty-three days with 250 micrograms/day (p = 0.06). No significant endocrinologic changes occurred during the transfer to the depot, and serum testosterone remained 95 per cent suppressed throughout the duration of the study. After three months the median daily serum Zoladex concentrations ranged between 0.47 and 0.53 ng/ml and were not significantly different among the three dosage forms. No specific correlation among serum Zoladex concentrations, endocrinologic parameters, and tumor response rates were found. Hot flashes initially, and decreased libido were the only common complaints. Zoladex was well tolerated, and no side effects required dose-modification or removal from the study. Tumor response rates up to one year appeared to be comparable to the conventional endocrine therapies. This analog in monthly depot formulation is recommended for further clinical evaluation.