Electrocardiographic patterns in African University strength and endurance athletes of Zulu descent.

AIM: There is concern over the effect of training on heart function of athletes as recorded by 12-lead electrocardiography (ECG). Although ECG abnormalities with respect to ethnic origin of black athletes from the Caribbean, West Africa and East Africa have been reported, black athletes from southern Africa, specifically participating in different sports, have never been investigated before. The purpose of this study was to analyze the ECG patterns in South African students of Zulu descent, who represented our university in boxing (endurance modality) and body building (resistance modality) at a regional level. METHODS: Fifteen subjects each were assigned to an endurance (E), resistance (R) or control (C) group, respectively. ECG patterns were recorded with a 12-lead ECG. RESULTS: Our subjects indicated no significant differences in ECG patterns in relation to whether they participate in strength or endurance related sport. However, 80% of the endurance group and 67% of the resistance displayed ECG criteria indicative of left ventricular hypertrophy (LVH), group E displays higher R5/S1-wave voltages (E=43.3 mm; R=36.8 mm; C=37.1 mm) as well distinctly abnormal ECG patterns (E=87%; R=73%; C=53%), raising clinical suspicion of structural heart disease. Our cohort presented with non-significant, marked ST-segment elevation (53% of both the E and R groups) and inverted T-waves in 27% of the E group. CONCLUSION: Similar to findings in other ethnic Africans, a large proportion of our Zulu study population displayed ECG criteria indicative of LVH on the evidence of a marked increase of R5/S1-wave voltage and ST/T-segment changes with no differences in relation to whether they participate in strength or endurance related sport.

A randomized, placebo-controlled, double-blind phase 2 study of docetaxel compared to docetaxel plus zosuquidar (LY335979) in women with metastatic or locally recurrent breast cancer who have received one prior chemotherapy regimen.

PURPOSE: To determine if concomitant administration of docetaxel plus zosuquidar.3HC1 can prolong progression-free survival in patients with metastatic breast cancer. METHODS: A randomized, double-blind, multicenter, placebo-controlled clinical trial comparing docetaxel plus 500 mg zosuquidar.3HCl (DZ) with docetaxel plus placebo (DP). RESULTS: A total of 170 patients were enrolled and randomly assigned to treatment. The median age was 53 years (range, 31-74 years). 81.7% of patients had prior chemotherapy in the adjuvant setting and 18.3% in the neoadjuvant setting. The median progression-free survival time was statistically different between groups [7.2 months (DZ) vs. 8.3 months (DP)]. Once the stratification factor relative to progression following prior chemotherapy was considered, no significant treatment difference existed. CONCLUSION: The combination of zosuquidar.3HCl plus docetaxel is safe. The analysis of efficacy data is complex, but it can be concluded that there is no difference in progression-free survival, overall survival, or response rate in the study as a whole.

Comparison of an LH-RH analogue (Goeserelin acetate, 'Zoladex') with combined androgen blockade in advanced prostate cancer: final survival results of an international multicentre randomized-trial. International Prostate Cancer Study Group.

OBJECTIVE: The aim of this study was to compare the effects of the nonsteroidal antiandrogen flutamide plus the LH-RH analogue goserelin acetate (combined androgen blockade [CAB]) with goserelin acetate alone in patients with advanced prostate cancer. The original analyses at 25 and 56 months of follow-up have been reported previously, and here we report the final survival analysis after 10 years of follow-up. METHODS: 589 patients with advanced prostate cancer (55% with metastatic [M1] and 45% with locally advanced [M0] disease) were randomized to receive goserelin acetate 3.6 mg either alone or in combination with flutamide (250 mg three times daily). RESULTS: A total of 583 patients were included in the analysis. There was a small, but nonsignificant, benefit for CAB compared with goserelin acetate alone in all patients with respect to survival (hazard ratio 0.88, 95% CI 0.73, 1.06). Subgroup analysis of M0 and M1 patients showed similar results (M0: hazard ratio 0.92, 95% CI 0.68, 1.25; M1: hazard ratio 0.85, 95% CI 0.66, 1. 08). The treatment effect was not significantly different for M0 and M1 patients (p = 0.685). CONCLUSIONS: In this large randomized trial containing significant numbers of M0 patients, after 10 years there was a small but nonsignificant benefit for CAB over castration alone.

Phase II trial of i.v. vinorelbine and cisplatin in inoperable locally advanced or disseminated non-small-cell lung cancer: the South African experience.

PURPOSE: This multicentre phase II trial was conducted in South Africa to evaluate the activity of a combination of vinorelbine, administered in a new schedule, and cisplatin, in chemonaive patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between September 1995 and December 1996, 35 patients were enrolled. All patients had at least one bidimensionally measurable lesion. Vinorelbine was administered intravenously on day 1 and day 8 at a dose of 30 mg/m2 and cisplatin was administered intravenously on day 1 at a dose of 100 mg/m2. The chemotherapy cycle was repeated every three weeks. RESULTS: Of 35 evaluable patients, 14 (40%) achieved a response (one complete response and 13 partial responses). The median time to progression was 6.4 months (range 12-572 days) and the median survival was 15.7 months (range 12-882+ days). One-year survival was 56%. Toxicity was manageable and consisted of nausea and vomiting (grade 3 in 45% of patients) and grade 3-4 neutropenia seen in 13 patients with three patients experiencing grade 3 infection. Other side-effects were mild, including constipation grade 3 in 9.1%. A total of 153 courses were administered with patients receiving a median dose intensity of 81.7% for vinorelbine, while that of cisplatin was 74.1%. CONCLUSION: The combination of vinorelbine and cisplatin demonstrated substantial activity in terms of objective response and survival with manageable side-effects in patients with advanced NSCLC. These findings confirm the data from previous randomised studies. Further studies are ongoing in order to evaluate the efficacy of this combination in the neoadjuvant and adjuvant setting.

Fadrozole versus megestrol acetate: a double-blind randomised trial in advanced breast cancer.

Ninety-six patients were entered into a randomised, double-blind, double-dummy, clinical trial to assess the efficacy and safety of fadrozole as compared to megestrol acetate as second-line hormonal treatment for patients with advanced breast cancer. Analysis of results was on an intention-to-treat basis and included response rate, time to progression (TTP), time to treatment failure (TTF) and survival. Forty-six patients received fadrozole and 50 were randomised to megestrol acetate. Patients and pretreatment prognostic variables were balanced in the two arms of the trial. The objective response rates [3/46 (7%) for fadrozole and 3/50 (6%) for megestrol acetate], TTP, TTF and survival were similar in the two arms of the trial. Toxicity was also similar in the two arms of the trial and consisted mainly of oedema, hypertension and minor gastrointestinal symptoms. Fadrozole appears to be as active as megestrol acetate in second-line hormonal treatment of advanced breast cancer.

Oral granisetron alone and in combination with dexamethasone: a double-blind randomized comparison against high-dose metoclopramide plus dexamethasone in prevention of cisplatin-induced emesis. The Granisetron Study Group.

PATIENTS AND METHODS: Three anti-emetic treatment regimens were compared in 357 patients receiving cisplatin therapy (mean dose 81 mg/m2) in this double-blind randomized study. Regimens studied were i) granisetron 1 mg bd orally for 7 days (granisetron alone); ii) gran 1 mg bd orally for 7 days plus prophylactic dexamethasone (12 mg i.v.) on the first day only (gran/dex); iii) metoclopramide (3 mg/kg i.v. loading dose; 4 mg/kg i.v. infusion) plus dex (12 mg i.v.) on the first day followed by met 10 mg orally tds for a further 6 days (met/dex). RESULTS: At 24 hours, gran/dex was significantly superior to met/dex in terms of total anti-emetic control, defined as no nausea, no vomiting, no rescue anti-emetic therapy, not withdrawn (54.7% gran/dex vs. 37.2% met/dex; P < 0.01). There was also a significant delay in time to onset of nausea (P < 0.01) and vomiting (P < 0.01) following gran/dex compared with met/dex. Oral granisetron alone was as effective as met/dex in control of acute emesis in all parameters examined. There were no significant differences between the three groups in the control of delayed nausea and vomiting. The most common adverse experiences in both granisetron groups were headache and constipation, both characteristic of 5-HT3 antagonists. Agitation, somnolence, diarrhoea and decreased appetite were reported more frequently by the met/dex group. CONCLUSIONS: Oral granisetron as a single agent is as effective as high doses of i.v. met/dex in preventing cisplatin-induced emesis. Oral granisetron in combination with a corticosteroid provides superior anti-emetic control to the met/dex regimen in patients undergoing highly emetogenic chemotherapy.

A multicenter randomized trial comparing the luteinizing hormone-releasing hormone analogue goserelin acetate alone and with flutamide in the treatment of advanced prostate cancer. The International Prostate Cancer Study Group.

A prospective randomized trial was conducted to compare the effects of the nonsteroidal antiandrogen flutamide (250 mg. 3 times daily) plus the luteinizing hormone-releasing hormone analogue goserelin acetate (Zoladex) (3.6 mg. subcutaneous depot injection every 28 days) with goserelin acetate alone in advanced prostatic carcinoma. A total of 571 eligible patients, of whom 57% had distant metastases, showed no difference in subjective or objective response rates, interval to progression, treatment failure or survival after a median followup of 2 years. In the combination group more patients had an early decrease in elevated levels of tumor markers and the small number of patients with an increase in signs and symptoms within the first 4 weeks showed a significant decrease. However, increased gastrointestinal and hepatic toxicity in the combination group resulted in 44 patients being withdrawn from the trial. These results indicate that the combination of goserelin acetate with flutamide provides no long-term clinical benefit in patients with advanced prostatic carcinoma compared to goserelin acetate alone.

Assessing operability in squamous carcinoma of the oesophagus. Are pre-operative investigations unreliable?

Pre-operative investigations, although providing useful information, were unreliable in predicting resectability in patients with malignant oesophageal lesions. Chest radiographs excluded metastasis and active tuberculosis. The barium swallow examination determined the length of the lesion and displayed various displacements, none of which excluded resectability. Tumour infiltration of the airways was the only change visible at bronchoscopy that contraindicated resection. Computed axial tomography was unreliable in excluding extra-oesophageal tumour extension and operability. As all these pre-operative investigations have their limitations in assessing operability, exploration of the lesion is essential to determine resectability for squamous carcinoma of the oesophagus, provided there is prior histological confirmation of a malignant oesophageal lesion.

Anti-LPS antibodies reduce endotoxemia in whole body 60Co irradiated primates: a preliminary report.

Long periods in space may expose astronauts to the potentially harmful effects of ionizing radiation. We have used a primate model to evaluate any role of lipopolysaccharide (LPS, endotoxin) in radiation sickness. Vervet monkeys, which had been whole-body 60Co irradiated with an LD100 exposure, had periodic blood samples taken for the determination of LPS, anti-LPS IgG antibodies and bacteriological studies. On day 2 post-irradiation, primates were treated i.m. with either sterile 0.9% saline, or equine anti-LPS hyperimmune plasma (Anti-LPS), or orally with tripotassium-dicitrato-bismuthate ("Denol"). Gram positive bacteria were evident in blood samples of all animals as early as 2 d post-irradiation. Gram negative bacteria were found in the blood of saline- and Denol-treated primates by days 5 and 8, respectively, but first appeared on day 13 in the anti-LPS-treated animals. The saline controls and Denol-treated animals showed insignificant rises in plasma LPS on day 3, which increased further thereafter achieving significance on day 8 (p less than 0.01). These elevated levels persisted until death. However, in anti-LPS-treated monkeys, LPS concentrations remained below baseline until day 9, after which they rose significantly until death, but, were significantly less than the concentrations in both other groups (p less than 0.001). The anti-LPS-treated animals survived significantly longer than both the other groups (p less than 0.005). Since LPS may cause nausea, vomiting, diarrhea, anorexia and headaches, Anti-LPS administration may be of value in reducing plasma LPS concentration in humans and improving their performance and survivability.

Radiation induced gram negative bacteremia and endotoxemia in rabbits: modification by anti-lipopolysaccharide hyperimmune equine plasma.

Lethal whole body irradiation damages the gut mucosa and leads to leakage of endotoxin or lipopolysaccharides (LPS) into the systemic circulation. Sixteen rabbits, irradiated with 900 rads 60Co, were randomly divided on day 4 into 2 groups, one of which received an intraperitoneal injection of normal saline (control) and the other (experimental) an equal volume of anti-LPS hyperimmune plasma. The time course of endotoxemia and bacteremia were determined for the duration of the experiment. While rabbits in both groups died within 13 days after irradiation, rabbits given saline died on average 2 days earlier, than rabbits given anti-LPS plasma. Plasma LPS concentrations rose to a small peak on day 2 prior to treatment. Thereafter plasma LPS in rabbits given saline increased forty fold by day 9. In contrast, in rabbits given anti-LPS plasma, LPS concentrations in the plasma remained within pretreatment limits (p 0.01). By day 12 after irradiation, plasma anti-LPS IgG had declined to 5.8% of pretreatment levels in rabbits given saline as compared to 46% in rabbits given anti-LPS plasma (p 0.005). Whilst both groups developed gram-positive bacteremia, rabbits given saline in addition also developed gram-negative bacteremia. No rabbits treated with Anti-LPS showed gram-negative bacteremia. Treatment with Anti-LPS plasma thus significantly protects radiated rabbits from the incidence of gram-negative bacteremia, development of high plasma LPS levels and hence endotoxemia, and prolongs survival to a certain extent.

Treatment for recurrent ovarian cancer. A report of 2 cases.

Two cases of recurrent ovarian adenocarcinoma were resistant to standard combination chemotherapy regimens. Complete response was achieved with salvage therapy comprising cis-platinum 120 mg/m2 intravenously every 3 weeks and VP-16 (etoposide; Bristol-Myers) 200 mg per os weekly.

Breast cancer prognosis in three different racial groups in relation to steroid hormone receptor status.

Follow-up studies on 466 patients over a 5-year period showed Whites to have an overall significantly longer disease-free interval and survival than Blacks and Asians. No racial differences in prognosis were seen in patients with Stage II disease (p greater than 0.2) but in Stage III, White patients had significantly longer disease-free periods than Blacks or Asians; the same was not true of survival. Whites had a 67% incidence of cytoplasmic estrogen receptor (CER) positive tumors compared with only 49% in Blacks and 41% in Asians. When tumors were assayed for CER, nuclear estrogen receptor (NER), and cytoplasmic progesterone receptor (CPR), there were no racial differences in the proportions of tumors containing all 3 receptors, but significant variations were found in neoplasms with no receptors and in those with apparently defective receptors. In White patients receptor status had no influence on prognosis (p greater than 0.3). Black patients whose tumors contained both CER and NER had a significantly better time to recurrence than those whose tumors lacked these receptors, while in Asian women the presence of CER alone, or CER together with NER, or CER, NER, and CPR, was indicative of a significantly longer disease-free period.

Clinical patterns of presentation of breast cancer in women of different racial groups in South Africa.

The ages at presentation of white patients with breast cancer were found to be significantly higher than those of blacks, Indians and coloureds; 73% of white women fell into the postmenopausal group, in marked contrast to only 35% of Indians, while blacks and coloureds had similar proportions of pre- and post-menopausal patients. A significantly higher incidence of poorly differentiated tumours was seen in Indian and black patients. Blacks showed a significant tendency to present with more advanced disease, while whites were generally diagnosed at a much earlier stage.