Gastrointestinal ostomies and sexual outcomes: a comparison of colorectal cancer patients by ostomy status.

PURPOSE: Research examining effects of ostomy use on sexual outcomes is limited. Patients with colorectal cancer were compared on sexual outcomes and body image based on ostomy status (never, past, and current ostomy). Differences in depression were also examined. METHODS: Patients were prospectively recruited during clinic visits and by tumor registry mailings. Patients with colorectal cancer (N = 141; 18 past ostomy; 25 current ostomy; and 98 no ostomy history) completed surveys assessing sexual outcomes (medical impact on sexual function, Female Sexual Function Index, International Index of Erectile Function), body image distress (Body Image Scale), and depressive symptoms (Center for Epidemiologic Studies Depression Scale-Short Form). Clinical information was obtained through patient validated self-report measures and medical records. RESULTS: Most participants reported sexual function in the dysfunctional range using established cut-off scores. In analyses adjusting for demographic and medical covariates and depression, significant group differences were found for ostomy status on impact on sexual function (p < .001), female sexual function (p = .01), and body image (p < .001). The current and past ostomy groups reported worse impact on sexual function than those who never had an ostomy (p < .001); similar differences were found for female sexual function. The current ostomy group reported worse body image distress than those who never had an ostomy (p < .001). No differences were found across the groups for depressive symptoms (p = .33) or male sexual or erectile function (p values ≥ .59). CONCLUSIONS: Colorectal cancer treatment puts patients at risk for sexual difficulties and some difficulties may be more pronounced for patients with ostomies as part of their treatment. Clinical information and support should be offered.

Role of calcium in phorbol-ester-induced contractions of the canine saphenous vein.

The role of calcium in phorbol-12,13-dibutyrate (PDB)-induced contractions of the canine saphenous vein (CSV) was examined. Phorbol-12,13-dibutyrate elicited concentration-dependent contractions in CSV (EC50 = 1.6 +/- 0.2 X 10(-7) M) which were not affected by atropine (10(-6) M), pyrilamine (10(-6) M), and phentolamine (10(-5) M). The maximum contraction induced by PDB (10(-6) M) was slightly greater than that elicited by phenylephrine (PE; 10(-4) M). Phorbol-12,13-dibutyrate produced maximal 45Ca2+ uptake (0.80 +/- 0.07 mmol/kg wet wt) comparable with that induced by PE (0.90 +/- 0.04 mmol/kg wet wt) which was approximately fourfold above basal 45Ca2+ uptake (0.21 +/- 0.02 mmol/kg wet wt). The increase in 45Ca2+ uptake stimulated by PDB and PE was completely abolished by La3+ (5 mM). In the absence of Ca2+ entry, the contractions to PDB were reduced by only 29 +/- 3.4%. Substantial responses to PDB (51.3 +/- 4.8% of control) remained after reduction of intracellular Ca2+ store by repeated challenges with PE (10(-4) M) in the presence of La3+. Similar results were obtained when the contractions of CSV to PDB were determined in zero external Ca2+ medium. The data suggest that PDB utilizes both extracellular and intracellular Ca2+ for contractions of CSV.

Daunomycin inhibits the uptake of adenine, amino acids, and glucose into cardiac myocytes.

Daunomycin and adriamycin are widely used antitumor agents which induce dose-dependent cardiotoxicity. The mechanisms by which daunomycin causes cardiotoxicity have been investigated in neonatal rat cardiac myocytes maintained in tissue culture. Daunomycin inhibited the uptake of adenine, amino acids, and deoxyglucose in a dose-dependent fashion. The uptake of both adenine and methionine was inhibited without any delay while the glucose uptake (deoxyglucose) was inhibited after a delay of 2 hr. Since daunomycin affected the uptake of both adenine and amino acids without any delay and since daunomycin did not affect the incorporation of adenine into nucleotide and amino acids into proteins once these were transported into the cell, it is possible the daunomycin exerted these effects by acting directly on the cell membrane. Thus, one of the early toxic manifestations of anthracycline antibiotics may be on the transport of nutrients such as amino acids, glucose, and adenine.

Effects of adrenalectomy on activation of glycogen phosphorylase in rat myocardium.

Adrenalectomy causes a depressed glycogenolytic response to catecholamines in myocardium. Total phosphorylase activity (a + b) is 20% lower in isolated, perfused hearts from adrenalectomized (ADX) rats compared with hearts from sham-operated (sham) rats even though the basal activity ratios (-AMP/+AMP) do not differ. In response to epinephrine (50 nM), the sham group has a higher activity ratio than the ADX group (0.23 vs. 0.16); the difference in specific activities of phosphorylase a in the two groups is even greater, 87 versus 49 U/mg protein. The glycogen content of the heart is 30% lower in the ADX group. Adrenalectomy does not alter the accumulation of cAMP and activation of cAMP-dependent protein kinase caused by epinephrine. Although rat heart contains a heat-stable phosphatase inhibitor, the activity of this inhibitor, as judged by phosphorylase phosphatase activity, is not altered by epinephrine stimulation or by adrenalectomy. Epinephrine perfusion increases the activity ratios (pH 6.8:8.2) of phosphorylase kinase equally in sham and ADX hearts; however, the specific activities of phosphorylase kinase (basal and hormone-stimulated) at either pH are lower after adrenalectomy. The sensitivity of phosphorylase kinase activity to stimulation by calcium is the same in the sham and ADX groups. A radioimmunoassay for phosphorylase kinase detects 10% less of this enzyme in hearts from adrenalectomized animals. Specific activities at pH 6.8 and 8.2 based on the quantity of phosphorylase kinase detected by radioimmunoassay suggest a lower phosphorylation state in the ADX group. Decreases in quantities of phosphorylase and phosphorylase kinase and enzyme dissociation due to glycogen depletion could all contribute to a depressed glycogenolytic response in the ADX group.

Hormonally specific expression of cardiac protein kinase activity.

The relationship between the effects of isoproterenol and prostaglandin E(1) (PGE(1)) on contractile state, cyclic AMP accumulation, and the activation states of protein kinase (ATP: protein phosphotransferase, EC 2.7.1.37), phosphorylase kinase, glycogen synthase, and glycogen phosphorylase have been studied in the isolated perfused rat heart. Perfusion of hearts with isoproterenol (10 or 80 nM) caused enhancement of left ventricular dP/dt (P, pressure), increased intracellular cyclic AMP, increased the activation states of protein kinase, phosphorylase kinase, glycogen phosphorylase, and conversion of glycogen synthase to a less active form. PGE(1) (2 or 30 muM) increased cyclic AMP accumulation and activated protein kinase, but caused no detectable changes in dP/dt or the activation states of the protein kinase substrates involved in glycogen metabolism. Perfusion of hearts with either 10 nM isoproterenol or 30 muM PGE(1) produced comparable increases in cyclic AMP accumulation and protein kinase activity. Exposure of hearts to a combination of these agents caused additive effects on cyclic AMP content and protein kinase activity. However, values for phosphorylase kinase, glycogen phosphorylase, glycogen synthase, and dP/dt did not differ from those observed in the presence of 10 nM isoproterenol alone. The failure of PGE(1) to stimulate phosphorylation of protein kinase substrates was not due to an increase in phosphorylase phosphatase activity. We conclude that an increase in intracellular cyclic AMP and the subsequent activation of protein kinase are insufficient to change either the activities of phosphorylase kinase, glycogen phosphorylase, and glycogen synthase or the inotropic state of heart muscle.