Concentrations In Cancer Patients Research Articles

Hemorheological parameters in patients with gynecologic malignancies

Thromboembolic events account for a significant number of complications during surgical and chemotherapeutic treatment for gynecologic malignancies. Besides changes in the hemostatic system, changes in hemorheological parameters facilitate initiation and promotion of thrombotic disease. We used a rheoaggregometer to determine erythrocyte aggregation and a capillary viscosimeter to evaluate plasma viscosity in patients with gynecologic malignancies at the time of primary diagnosis and during follow-up and compared the results to those for a normal control group. We found a significant elevation in plasma viscosity and erythrocyte aggregation as well as in fibrinogen and globulin concentrations in cancer patients. The extent of this rise was related to the tumor volume. Treatment with cisplatin, doxorubicin, and cyclophosphamide resulted in a further rise in erythrocyte aggregation which is attributed to a direct effect on the erythrocyte membrane. Thus, additional factors contributing to the risk of thrombosis in these patients were defined. Additional administration of rheologically active agents might improve the results of thrombosis prophylaxis.

Pharmacokinetics of n‐4‐hydroxyphenyl‐retinamide and the effect of its oral administration on plasma retinol concentrations in cancer patients

Concurrent with a phase-II trial of 4HPR in patients with various cancers, we studied the plasma pharmacokinetics of both 4HPR and its major metabolite 4MPR as well as the effect of 4HPR administration on plasma retinol concentrations using a simple, specific and sensitive HPLC procedure. Initial estimates of plasma pharmacokinetic parameters after oral administration of 4HPR (300 mg/day) [corrected] in 3 cancer patients were the following: 4HPR, t beta 1/2 = 13.7 hr, AUC = 3.49 micrograms.hr/ml, CL = 56.57 L/hr/m2; 4MPR, t beta 1/2 = 23.0 hr, AUC = 1.15 micrograms.hr/ml, CL = 239.29 L/hr/m2. We also found that oral administration of 4HPR resulted in a rapid, profound and significant reduction in plasma retinol concentrations. The mean plasma retinol concentrations for 9 patients decreased 60% from baseline to below 200 ng/ml within 1-2 weeks of 4HPR dosing initiation. In addition, there was a concurrent, significant reduction in plasma retinol-binding protein levels in these patients. The mechanism whereby 4HPR reduces plasma retinol levels in vivo has not been determined. The addition of 4HPR to pooled human plasma at 37 degrees C in vitro did not reduce endogenous retinol levels, suggesting no direct chemical interaction between these 2 retinoids.

Plasma melatonin levels in patients suffering from colorectal carcinoma.

Plasma melatonin was determined in samples of patients with colorectal carcinoma and in controls using an iodinated radioimmunoassay. Both groups showed large individual variability in absolute melatonin levels. However, during the night, melatonin concentration in cancer patients was significantly lower than in controls.

Effect of thyrotropin releasing hormone injection on blood growth hormone (GH), TSH and growth hormone releasing hormone (GHRH) concentrations in cancer patients.

In order to investigate whether endogenous GHRH and somatostatin were involved in the mechanism of the paradoxical GH rise after TRH injection, changes in serum GH and plasma GHRH were examined before and after TRH injection in 12 cancer patients and changes in serum TSH and GH were similarly studied in 76 cancer patients including 31 GH-responders and 45 GH-nonresponders to TRH. TRH stimulated GH secretions without altering the circulating GHRH concentration in 4 of the 12 cancer patients. There was neither a significant correlation between the increase from the basal to maximum GH and GHRH after TRH injection in the 12 cancer patients nor a reciprocal relationship between the increase in GH and TSH after TRH injection in the 76 cancer patients. These findings suggested that the paradoxical GH rise after TRH injection in cancer patients was exerted by its direct action at the pituitary level, and not mediated through the hypothalamus.

CSF and plasma morphine concentrations in cancer patients during chronic epidural morphine therapy and its relation to pain relief

Seventeen patients with advanced cancer pain, treated with chronic epidural morphine, were studied. Minimum plasma and CSF morphine concentrations (Css min) were determined at pharmacokinetic steady state. A linear relationship was found between epidural morphine dose and concentrations obtained in plasma ( r = 0.92) as well as CSF ( r = 0.90). The line for best fit was much steeper for CSF than for plasma. The CSF/plasma concentration gradient of morphine at Css min was 132 ± 31 (mean ± S.E.M.). Large interindividual variations of morphine concentrations in CSF were found. It is suggested that the variations are due to substantial differences in transdural morphine diffusion between individuals. No correlation was found between pain relief, evaluated with a visual analog scale, and CSF morphine concentrations at pharmacokinetic steady state, when calculated in 9 patients. Mean duration of treatment was 104 days (range 14–366) and the daily dose was increased from 18 ± 2 to 87 ± 31 mg/day (mean ± S.E.M.). A total of 39 epidural catheters were inserted in 14 patients. The catheters were patent for 2–223 days with a mean of 38 days. When re-examined later during treatment, 2 out of 8 patients demonstrated decreased CSF morphine concentrations in spite of increased doses given. One patient with extremely high dose demand is reported on separately and data supporting the concept of a combined spinal and systemic brain morphine effect in such cases are presented. Side effects were not a major problem but the possibility of infectious complications should be considered during chronic epidural morphine therapy.

Radioimmunoassay of aldolase A. Determination of normal serum levels and increased serum concentration in cancer patients

A radioimmunoassay specific for human aldolase A subunits was used to measure human aldolase A (ALD-A) in human serum. The double antibody competitive inhibition radioimmunoassay technique used radioiodinated purified ALD-A as ligand, chicken antisera specific for human ALD-A and rabbit antichicken IgG. The serum levels of ALD-A in 42 normal healthy subjects ranged from 130 to 210 ng/ml (mean average, 171 +/- 39 ng/ml). In 177 hospitalized patients without cancer, muscle diseases, or hemolytic anemia, the ALD-A serum levels ranged from 125 to 220 ng/ml. In contrast, 82% of 260 patients with various types of malignancy had ALD-A serum concentrations above the normal range. The CEA levels increased only 44% of the sera of 80 patients with cancer of the digestive tract, whereas the ALD-A levels were increased in 86% of the patients. The AFP levels were greater than 100 ng/ml in only 70% of the sera of 33 liver cell carcinoma patients, whereas the ALD-A levels were increased in 94% of these sera. The measurement of serum ALD-A by radioimmunoassay may be a valuable adjunct in the clinical diagnosis of certain cancer patients.

Radioimmunoassays of abrin and ricin in blood.

Radioimmunoassays for abrin and ricin are described. There is little cross-reactivity between the two toxins. The procedures described are capable of determining blood concentrations down to 50-100 pg/ml, permitting identification of abrin and ricin poisoning and monitoring of the blood concentrations in cancer patients treated with these agents.

Probabilistic application of plasma carcinoembryonic antigen assay in cancer patients.

Plasma carcinoembryonic antigen (C.E.A.) levels in inpatients proved at necropsy to be cancer free were used to assess the ability of the C.E.A. assay to distinguish benign and malignant disease. The patients had a mean C.E.A. level significantly greater than that for young healthy people. In view of the considerable overlap of the ranges of plasma C.E.A. concentration in cancer patients and patients with non-malignant disease a probabilistic interpretation is advocated rather than the use of a simple cut-off between positive and negative. On the basis of the cancer-free control group, 19 out of 64 untreated patients with various solid tumours had plasma C.E.A. levels considered to correspond to a greater than 95% probability of cancer.

Beta-glucuronidase activity in adrenals of patients with or without cancer.

The mean β-glucuronidase concentration in the adrenal homogenate of male patients with cancer was found to be significantly lower than that of male patients without cancer. The patient's age appeared to be without effect on the adrenal β-glucuronidase concentration; an influence of the nutritional status independently of the disease could not be evaluated. Several cancer patients were treated with corticoids; this treatment was without effect on the adrenal β-glucuronidase concentration. Histochemically, the highest β-glucuronidase activity was localized in the zona glomerulosa in over 50% of cases; the other cortical layers or the medulla showed the highest activity in the remaining cases. The distribution of cell groups with β-glucuronidase activity was patchy. The localization of β-glucuronidase activity in the adrenals of patients with or without cancer was similar, but the number and intensity of areas with β-glucuronidase activity was decreased in the adrenals from cancer patients. Although the actual function of β-glucuronidase in the adrenal is not known, the preeminent localization in the glomerulosa and the lack of influence by stress and by steroid treatment on its concentration suggest a specific function in aldosterone metabolism. The changes in the adrenal β-glucuronidase concentration in cancer patients may be an indication of disturbance in aldosterone metabolism.