Adverse relationship between blood transfusions and survival after colectomy for colon cancer

Random-donor blood transfusions are deliberately given before cadaver renal allografting to improve allograft survival. Since host modifications that improve the outcome of an allograft might be associated with a decreased ability of the host to control cancer growth, the relationship between blood transfusions and the outcome of 146 Dukes' stages A, B, and C colon cancers treated by resection during the years 1974 to 1979 was studied. It was found that 65 patients (45%) had been transfused and that at 5 years, overall survival was significantly better in the nontransfused patients compared to the transfused patients (0.68 and 0.51 5-year product limit survival fractions respectively; P = 0.03 for unadjusted log-rank comparison of entire survival curves). Relative risk of death due to cancer in transfused patients versus nontransfused patients was 2.3 (P = 0.05) when controlled for sex, age, stage, histologic differentiation, cancer location, and pre-resection hemoglobin level using Cox regression analysis. Thus, blood transfusion appears to be an additional important prognostic variable. The hypothesis suggested but not proven by these data that the outcome for some malignancies may be related to the immunomodulating effects of blood transfusions needs further study.     

Hypersensitivity reactions to trimetrexate

Summary Trimetrexate is a nonclassical antifol currently being tested for efficacy in cancer patients and as an antiparasitic agent against Pneumocystis carinii pneumonia in AIDS patients. We have now received the first reports of hypersensitivity reactions in Phase II cancer trials. Two types of reactions were noted. The most severe reaction, immediate hypotension with loss of consciousness, occurred in only one patient. Four other patients exhibited an immediate systemic effect with one or more of the following symptoms: facial flushing, fever, shaking, pruritus, bronchospasm, periorbital edema, and difficulty in swallowing. Immediate hypersensitivity should now be considered a known side effect of trimetrexate therapy, occurring in < 2% of patients.     

5-Fluorouracil-associated cardiotoxicity

Cardiotoxicity manifested as myocardial ischemia is not generally recognized as a side effect of 5-fluorouracil. However, there have been at least 35 cases reported since 1975. In only one of these cases was a somewhat detailed evaluation done to rule out underlying coronary disease. The case reported here of 5-FU cardiotoxicity included an extensive cardiac evaluation to rule out underlying coronary disease and to assess spasm. The literature on 5-FU cardiotoxicity is also reviewed, and its possible mechanisms are analyzed.     

Epidemiologic studies of low-back pain

The records of 3920 patients (2068 females, 1852 males) entering a model family practice unit between 1975 and 1978 have been analyzed. Eleven percent of males and 9.5% of females reported an episode of low-back pain during that 3-year interval. The complaint of medically reported low-back pain was significantly related to occupational factors such as truck driving (p < 0.001), lifting, carrying, pulling, pushing, and twisting (P < 0.001 for all variables) as well as nondriving vibrational exposure (P < 0.001). Patients reporting low-back pain also reported more episodes of anxiety (P < 0.001) and depression (P < 0.001) and had more emotionally stressful occupations (P < 0.001). The mean number of pregnancies was greater in women with low-back pain (2.6) than in those without (1.6) (P < 0.001). The low-back pain sufferers were more likely to be cigarette smokers (P < 0.001), particularly when smoking was accompanied by a chronic cough (P < 0.001). This population is currently under prospective study to define the relevance of each of these risk factors to the complaint of low-back pain.     

Therapeutic angiogenesis: translating experimental concepts to medically relevant goals

Angiogenesis is central to many physiological and pathological phenomena. In physiological angiogenesis, new vessels are well shaped and their growth is finely tuned to match the metabolic needs of tributary tissues. Accordingly, neovascularization is activated by physical exercise and destabilized by non-use. In contrast, pathological blood vessels that are observed in retinal neovascularization, cancer or in ischemic tissues are leaky, irregularly shaped, and tend to form arterial-venous fistulae. A great deal of attention is focused on new approaches for medical manipulation of vascular growth. These methods are aimed at facilitating the reperfusion of ischemic tissues or eradicating pathological vasculature. In this position paper, we challenge the rationale of therapeutic angiogenesis for the cure of myocardial and peripheral ischemia. Therapeutic angiogenesis aims at combating the insufficiency of, or insensitivity to angiogenic factors in the setting of atherosclerotic-induced arterial occlusion. However, clinical evidence indicates that such a defect is not common among patients with ischemic disease, as a whole. Genetic and environmental factors could account for the great heterogeneity in the expression of the master angiogenic factors. Future improvements in the strategy would require the introduction of in vitro assays and in vivo imaging systems for assessing human angiogenesis. Finally, the promise is to find individualized angiogenesis-based therapies for a genuine cure of ischemia and prevention of organ failure.