Factors affecting pretreatment immune competence in cancer patients

Summary The assessment of changes in immune competence due to cancer demands carefully controlled studies with simultaneous consideration of other factors such as age, sex, and general ill health. To determine the effect of each factor, immune competence was measured in 112 healthy individuals, 134 patients with benign disease, and 350 patients with cancer (breast, colorectal, and stomach) with a wide spectrum of parameters.In normal subjects, advancing age was associated with a significant reduction in percentage lymphocyte count (LC), absolute and percentage T cell counts, and responses to phytohaemagglutinin (PHA) and pokeweed mitogen (PWM). In patients with benign disease, advancing age was associated with depression of serum IgM levels, absolute and percentage LC, responses to PHA, and delayed cutaneous hypersensitivity (DCH) responses to tuberculin PPD (Mantoux), and dinitrochlorobenzene (DNCB), but elevation of serum IgA levels.No significant sex effects were demonstrated in either group of subjects.The effects of general ill health were determined by comparing individuals in good health (normal subjects and patients with minor benign breast disease) with those who had poor health (patients with significant benign gastrointestinal disease). The latter showed significant depression of DNCB sensitivity and lymphocyte reactivity to PHA, whereas total WBC and LC were significantly elevated.To determine the effects due to cancer, controls were matched for their general state of health and site of disease, in addition to completing all studies prior to any form of therapy. Age differences were corrected for by application of the findings of the above study. This age correction resulted in marked alterations in the significance of observed differences between cancer patients and controls. The previous significance of many differences either disappeared or was reduced, although in two instances significance was attained only after age correction. The only consistent immunodepression observed in the three types of cancer patient tested was impaired reactivity to DNCB. Responses were impaired even in early disease at all three sites.We have shown that the immunodepression exhibited by cancer patients is a summation of the effects due to age, general ill health, and malignancy. Some of the changes previously ascribed to cancer are due to these other factors.     

EFFECT OF REMOVAL OF CO-OCCURRING SPECIES ON DISTRIBUTION AND ABUNDANCE OF ERYTHRONIUM AMERICANUM (LILIACEAE), A SPRING EPHEMERAL

Growth of spring ephemerals in northern forests is limited to early spring when competition for resources from other species is at a minimum. The abundance of resources during this vernal period suggests that spring ephemerals might grow continuously over a wide range of sites, but distributions tend to be patchy. I hypothesized that co-occurring plants that grow later in the season compete for resources to a limited extent, but that competition from these other species is sufficient to restrict the spread of spring ephemerals into unoccupied sites. Population dynamics of Erythronium americanum were compared on sites at the Hubbard Brook Experimental Forest in New Hampshire subjected to varying removals of cooccurring plants. During the 3-year period after removal of only overstory trees the density and frequency of occurrence of Erythronium increased by 225% and 180%, respectively, and removal of all co-occurring vegetation after 1 year's regrowth had an even more pronounced effect (400% and 195% increases, respectively). The abundance of Erythronium in the undisturbed forest did not change over the 3-year period. Elevational distribution of Erythronium also was directly related to the extent of removal of summer plants. Recruitment was mostly vegetative, but flower production on the tree removal site increased by a factor of six, and some distant sites apparently were colonized by seedlings. For several years following large-scale disturbances that eliminate co-occurring vegetation, the vernal growing season is lengthened and resources are more available, and spring ephemerals such as Erythronium americanum exploit these resource-rich opportunities to expand populations and colonize new sites. It appears that, as forest succession proceeds, the size and survival of newly established colonies are gradually constrained by competition from co-occurring species that grow later in the season.     

The effects of pentobarbital, fentanyl-droperidol, ketamine-xylazine and ketamine-diazepam on core and surface body temperature regulation in adult male rats

Many commonly used anesthetics cause hypothermia by inhibiting central and peripheral thermoregulatory mechanisms. Although it is probable that a loss of thermal homeostasis contributes directly to the high mortality frequently reported following anesthesia of laboratory rodents, this adverse effect has been investigated rarely in the past. This study compared the effects of three parenteral anesthetics (pentobarbital, ketamine-xylazine and ketamine-diazepam) and a neuroleptanalgesic (fentanyl-droperidol) on core and surface body temperature regulation in rats. Results showed a profound hypothermia with all dosages of pentobarbital, while ketamine-xylazine and ketamine-diazepam caused a dose-dependent depression in core and surface body temperature. All dosages of fentanyl-droperidol (Innovar-Vet) caused minimal depression in thermoregulation, suggesting that it is the drug which requires the least external thermal support. Results of this study also suggested that inability to compensate for heat loss, particularly from the body core, may profoundly influence anesthetic toxicity and the safety of anesthetic procedures.     

The effects of pentobarbital, fentanyl-droperidol, ketamine-xylazine and ketamine-diazepam on arterial blood pH, blood gases, mean arterial blood pressure and heart rate in adult male rats

Although anesthetics are known to cause respiratory and cardiovascular depression in humans, these adverse effects rarely have been investigated in laboratory rodents. This study evaluated the effects of four different injectable drugs, pentobarbital, fentanyl-droperidol (Innovar-Vet), ketamine-xylazine and ketamine-diazepam on the respiratory and cardiovascular systems of rats. Results showed marked acidosis, hypercarbia and hypoxia with high doses of Innovar-Vet, moderate respiratory depression with all dosages of pentobarbital and minimal respiratory depression with ketamine-xylazine and ketamine-diazepam. Innovar-Vet, ketamine-xylazine and pentobarbital caused profound hypotension, particularly at high dosages, while ketamine-diazepam caused the least depression in mean arterial blood pressure of all drugs evaluated. None of the drugs studied produced significant alterations in heart rate. Throughout all dosages investigated, the ketamine-diazepam combination showed the least overall effects on ventilation and perfusion of the four parenteral drug combinations studied.     

Cell killing by various monofunctional alkylating agents in Chinese hamster ovary cells

Cell killing by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), N-methyl-N-nitrosourea (MNU), N-ethyl-N-nitrosourea (ENU), and methyl methanesulfonate (MMS) was measured in Chinese hamster ovary (CHO) cells using the colony-formation assay. Cell killing by these agents was determined in exponentially growing asynchronous cells, in synchronous cells as a function of cell-cycle position and in nondividing cells. Distinct differences in the cytotoxic effect of the 4 alkylating agents were found in respect to dose-response, cell cycle phase-sensitivity and growth state. MNNG and MNU showed the same biphasic dose-survival relationship in exponentially growing cells, with an initial steep decline followed by a shallow component. The shallow component disappeared in growth-arrested cells. MNNG and MNU differed, however, in the cell-cycle age response. No cell-cycle phase difference was seen with MNNG, whereas cells in G1 seemed more sensitive to MNU than cells in S phase. MMS and ENU both showed shouldered dose-response curves for exponentially growing asynchronous cells, and the same cell-cycle pattern for synchronous cultures with cells in early S phase being the most sensitive. However, survival of nondividing cells versus dividing cells was reduced much more by MMS than by ENU. Caffeine, which interferes with the regulation of DNA synthesis and is known to modify cell killing by DNA-damaging agents, enhanced cell killing by all agents. It is concluded that there must be a number of factors which contribute to cell killing by monofunctional alkylating agents, and that besides alkylation of DNA reaction with other cellular macromolecules should be considered.