Methylglyoxal-bis(guanylhydrazone) in hormone-resistant adenocarcinoma of the prostate.

Methylglyoxal-bis(guanylhydrazone) (MGBG), an inhibitor of polyamine synthesis, was administered to 35 patients with hormone-resistant advanced adenocarcinoma of the prostate in doses of 500 or 600 mg/m2 per week intravenously. Of 31 patients with bidimensional measurable soft-tissue lesions, 25 had an adequate trial, defined as four or more doses. Six (24%; 95% confidence limits, 8% to 32%) patients achieved a partial remission (greater than or equal to 50% reduction in tumor size) in soft-tissue disease. Response was noted to start after one to two doses and persisted for a median of three months (range, 1 to 4 months). Toxicity was tolerable, and significant myelosuppression was not observed. The lack of response in osseous metastases may be secondary to the short duration of remission or to the presence or inducibility of the enzyme ornithine decarboxylase in bone. Since some animal prostatic cancer tumor models are sensitive to cytotoxic drugs that produce polyamine inhibition, clinical trials of MGBG combined with other inhibitors of the polyamine pathway should be explored.

Orchiectomy alone in the treatment of clinical stage I nonseminomatous germ cell tumor of the testis.

Forty-five patients with clinical stage I nonseminomatous germ cell tumor of the testis (NSGCTT) were entered in a prospective clinical trial to receive no treatment other than orchiectomy until clinical evidence of relapse. Of this group, 36 patients (80%) have been continuously free of disease for a median duration of 19.5 months after orchiectomy. Nine patients (20%) have relapsed, eight within seven months of orchiectomy. Seven of nine relapsing patients have been rendered free of disease with chemotherapy and/or surgery for a median duration of seven months (range, one to 33 months) after completion of treatment; the other two patients are presently under treatment although one has progressive disease. The relapse rate was higher in patients with embryonal carcinoma than in those with teratocarcinoma, 57% versus 17%. These preliminary results imply that the omission of routine lymphadenectomy or lymph-node irradiation in clinical stage I NSGCTT deserves further trial.

Lymphocele after pelvic lymphadenectomy for urologic cancer.

Pelvic lymphadenectomy is used widely for staging prostatic or bladder carcinoma. In 9 of 187 patients (4.7 per cent) who underwent bilateral pelvic lymphadenectomy for urologic cancer pelvic lymphocele diveloped. The management of these patients is presented along with review of causes, clinical features, diagnosis, and treatment. Pelvic CT scan is a noninvasive modality which aids in the diagnosis of this complication. Minidose heparin used for prophylaxis of thromboembolic complications may increase lymphocele formation.

Phase-II trial of 4-demethoxydaunorubicin (DMDR) for advanced hypernephroma.

A phase-II trial of 4-demethoxydaunorubicin (4-DMDR) was performed in 21 patients with advanced renal cell carcinoma. The drug had demonstrated a broader spectrum of activity with less cardiotoxicity in preclinical evaluation than the parent compound daunorubicin. The starting dose was 12.5 mg/m2, with escalations to 15 and 17.5 mg/m2 in the absence of toxicity. Myelosuppression was the primary toxicity and cardiac toxicity was not seen in four patients who received four or more doses of DMDR. No responses were seen in 19 adequately treated patients, including 14 who had received no prior therapy.

Etoposide in prostatic cancer: experimental studies and phase II trial in patients with bidimensionally measurable disease.

Etoposide, a semisynthetic derivative of podophyllotoxin, was evaluated concurrently in vitro against a human derived hormone-resistant cell line, PC-3, and in vivo in bidimensionally measurable hormone-resistant human prostatic cancer. In vitro, a dose-response relationship was observed, with 74% inhibition at 10 micrograms/ml (1 h incubation) and greater than 99% inhibition at 90 micrograms/ml, both in the range of clinically achievable concentrations. In vivo, 1 PR (5%, 95% confidence limits 0-12%) of 18+ months was observed in 20 adequately treated patients. The results confirm the limited role of etoposide in hormone-refractory disease and the need for new model systems for evaluation of potential chemotherapeutic compounds in this disease.

Effects of acid treatment on the trace metal content of chromatographic silica: bulk analysis, surface analysis and chromatographic performance of bonded phases.

A series of studies has been carried out on the effect of refluxing silica chromatography particles for 0.5 h and 18 h in water, dilute hydrochloric acid and dilute hydrofluoric acid. The bulk and surface trace metal concentrations were measured by inductively-coupled plasma atomic emission spectroscopy, static secondary ion mass spectrometry (SSIMS) and X-ray photoelectron spectroscopy. Diffuse reflectance Fourier transform infrared spectroscopy was used to determine changes in 'isolated" and "bonded" silanol groups. The chromatographic behaviour of a series of weakly basic analytes was investigated on C8 and C18 bonded phases manufactured from the acid-treated silicas. The different reflux treatments all resulted in a reduction in the numbers of isolated silanols compared with the untreated silica and SSIMS analysis suggested that the HF-treated silicas had undergone a more efficient surface rehydroxylation. Bulk trace metals were removed most effectively by the HF treatment, with the multivalent elements (Ti and Al) being the most difficult to remove. Surface specific analysis suggested that trace metals were removed more rapidly from the surface of the silica compared to the bulk matrix and that the acid treatments resulted in halide contamination of the silica surface. Evidence is presented to suggest that the bulk metal content of the silica is not representative of the concentration of metals at the chromatographic surface. The chromatographic investigations showed that the HF-treated silica gave substantially better performance towards weak bases than the HCl-treated silicas.

Phase II trial of 10-deazaaminopterin for advanced hypernephroma.

10-Deazaaminopterin, a derivative of aminopterin with enhanced cellular uptake relative to methotrexate, was given to fourteen patients with advanced measurable hypernephroma. The dose-limiting toxicity was mucositis. Abnormalities in liver function were seen in 8 patients. No responses were seen in 13 adequately treated patients including 10 who had received no prior chemotherapy. The unique transport of this new group of compounds is discussed.

Phase II trial of 4'epi-adriamycin for advanced hypernephroma.

4'Epi-adriamycin in doses of 85-110 mg/m2 I.V. Q3W was given to 20 patients with advanced bidimensionally measurable hypernephroma. Forty-five doses were administered, with 10 patients receiving 3-7 doses. Myelosuppression (WBC nadir 2600 cells/mm3, range 1000-3400) occurred in 63% and thrombocytopenia in 16% of cases. There was no objective response in 19 adequately treated cases.

Transthoracic aspiration cytology of pulmonary lesions.

In a seven-year period (1974 to 1981), 1,390 patients had transthoracic aspiration biopsy for radiologically suspected pulmonary neoplasms. Of the 1,209 proven malignant neoplasms, 1,059 (88%) were cytologically diagnosed as malignant. There were only two (0.2%) false-positive diagnoses both due to florid bronchoalveolar hyperplasia associated with granulomatous disease. Cytologic and histologic correlations for primary lung cancers were 92% for adenocarcinoma, 87% for oat cell (small cell) carcinoma, and 83% for epidermoid carcinoma. Characteristic cytomorphology of pulmonary carcinomas, some metastatic neoplasms, and inflammatory lesions are described.

Compartment syndrome. A complication of intravenous regional anesthesia in the reduction of lower leg shaft fractures.

Forty-one consecutive patients who had closed reduction of closed lower leg shaft fractures under an intravenous regional anesthetic are reviewed for the complication of compartment syndrome. Four patients were graded as having mild compartment syndrome, two as moderate, and five as severe, giving an overall rate of 27%. This was compared with a control group of 39 consecutive patients who also underwent closed reduction of closed lower leg shaft fractures, but under general anesthesia or intravenous analgesia alone rather than an intravenous regional anesthetic. In the control group, three patients were graded as having mild compartment syndrome, and two as severe, giving an overall complication rate of 13%. The authors feel that the use of the thigh tourniquet with the intravenous regional anesthetic technique increases the frequency of compartment syndrome as a complication in lower leg fractures.

Laboratory and on-ice test comparisons of anaerobic power of ice hockey players.

The suitability of the Wingate Anaerobic Test (WAT40) as a laboratory measure of anaerobic capacity (AnCap) and power (AnPow) of ice hockey players was tested against the Reed Repeat Sprint Skate-RSS (1979) and the Sargeant Anaerobic Skate (SAS40). Twenty-four university and Junior A players (20.2 +/- 1.6 years), assigned by random draw, performed the three tests over a seven day period. Blood lactate taken from an unwarmed finger tip was used to assess work intensity. The AnCap (7.7 +/- 0.2 Watts X kg-1) and AnPow (10.1 +/- 0.2 Watts X kg-1) for WAT40 were significantly lower (p less than 0.05) than for RSS (AnCap 9.3 +/- 0.8 Watts X kg-1; AnPow 11.5 +/- 1.1 Watts X kg-1) and SAS40 (AnCap 9.7 +/- 0.8 Watts X kg-1; AnPow 11.9 +/- 1.8 Watts X kg-1). SAS40 was significantly higher (p less than 0.05) than RSS for both AnCap and AnPow. The RSS (r = 0.96; ME 4.5%) and SAS40 (r = 0.97; ME = 3.6%) showed excellent test-retest reliability and reproducibility for AnCap but were only fair on AnPow (RSS: r = 0.73; ME = 10.7%; SAS40: r = 0.65; ME = 18.4%). While the correlations among the tests (AnCap: SAS40 vs WAT40, r = 0.73; RSS vs WAT40, r = 0.69) were significant (p less than 0.05), the highest predictive capability estimate (r2) was only 53.3%. The correlations for blood lactates (WAT40: 10.8 +/- 1.5 mmol X l-1; SAS40: 10.7 +/- 1.9 mmol X l-1; RSS: 11.5 +/- 1.6 mmol X l-1) were not significant. Based upon the particular protocol used, the laboratory test WAT40 does not demonstrate a high relationship with on-ice measures of AnCap and AnPow in this group of ice hockey players.

Application of active recovery techniques for a simulated ice hockey task.

Three, 15 minute recovery modes between two maximal effort, intermittent work bouts were tested using eight male hockey players (21.9 +/- 1.4 yrs.). The work bouts were comprised of six, 45 second skating trials, each interspersed with 90 seconds of rest. Performance scores were based on average distance skated/trial. Changes in lactate concentrations were determined from venous samples obtained at rest, prior to and following the recovery mode. Bench-stepping during recovery resulted in significantly lower lactates (6.1 +/- 2.2 mmol . 1-1) than for rest recovery (8.1 +/- 1.6 mmol . 1-1), while skating recovery was not significantly different from either bench-stepping or rest. Subsequent performance (WB2) was significantly lower than initial performance (WB1) for all treatments and it was unrelated to differing post-recovery lactate concentrations. It was concluded that bench-stepping enhanced lactate removal but subsequent performance was unaffected by any treatment.