Embodied cognitive restructuring: The impact of posture and movement on changing dysfunctional attitudes.

BACKGROUND AND OBJECTIVES: Previous theoretical and empirical work has pointed to the important role of the body in emotion generation and emotion regulation. In the present study, we wanted to investigate if the performance of certain body postures and movement could facilitate cognitive restructuring of dysfunctional cognitive attitudes more effectively than traditional, verbal-only methods. METHODS: In total, 130 participants were randomized to one of two groups. One group was subjected to cognitive restructuring (i.e., restructure only group; CR-only), verbally exploring a dysfunctional attitude from a curious, strong, and courageous perspective. The other group received the same verbal instructions but in addition to this, was asked to perform different bodily exercises (i.e., motor-enhanced restructuring group; M-CR) supposed to enhance experience of the different perspectives from which cognitive restructuring was employed. RESULTS: Results confirmed the primary hypothesis, showing that the M-CR-group showed a larger decline in belief in dysfunctional attitudes compared with the CR-only group (F = 4.2, p = 0.041, d = 0.25). No differences on secondary outcomes were observed between the two groups. LIMITATIONS: Future research should explore the effects of motor-enhanced CR both more long-term (e.g., durability over weeks) and in clinical samples (e.g., anxiety and depression). CONCLUSION: Should the findings be replicated in clinical samples, it is encouraging that simple bodily exercises can enhance the effect of one of the most central skills of cognitive therapy.

Phase III evaluation of four doses of megestrol acetate as therapy for patients with cancer anorexia and/or cachexia.

PURPOSE: Several placebo-controlled randomized clinical trials have demonstrated that megestrol acetate can result in appetite stimulation and nonfluid weight gain in patients with cancer anorexia/cachexia. The present trial was designed to compare megestrol acetate doses ranging from 160 to 1,280 mg/d. METHODS: This trial randomized 342 assessable patients with cancer anorexia/cachexia to receive oral megestrol acetate at doses of 160, 480, 800, or 1,280 mg/d. Patients were evaluated monthly by history, examination, patient-completed questionnaires, and serum albumin levels. RESULTS: The data demonstrate that there is a positive dose-response effect for megestrol acetate on appetite stimulation (P < or = .02). In concert, there was a trend for more nonfluid weight gain with higher drug doses. Megestrol acetate was well tolerated in this group of patients with advanced malignant disease. CONCLUSION: The positive dose-response effect that we observed for megestrol acetate on appetite stimulation supports both our prestudy hypothesis and other available literature. Nonetheless, based primarily on the cost and inconvenience associated with the use of higher doses of this drug, it is reasonable to use 160 mg/d for the initial treatment of cancer anorexia/cachexia in routine clinical practice.

Sucralfate in the prevention of treatment-induced diarrhea in patients receiving pelvic radiation therapy: A North Central Cancer Treatment Group phase III double-blind placebo-controlled trial.

PURPOSE: Randomized studies have suggested that sucralfate is effective in mitigating diarrhea during pelvic radiation therapy (RT). This North Central Cancer Treatment Group study was undertaken to confirm the antidiarrheal effect of sucralfate. Several other measures of bowel function were also assessed. PATIENTS AND METHODS: Patients receiving pelvic RT to a minimum of 45 Gy at 1.7 to 2.1 Gy/d were eligible for the study. Patients were assigned randomly, in double-blind fashion, to receive sucralfate (1.5 g orally every 6 hours) or an identical looking placebo during pelvic RT. RESULTS: One hundred twenty-three patients were randomly assigned and found assessable. Overall, there was no significant difference in patient characteristics between those receiving sucralfate and those receiving placebo. Moderate or worse diarrhea was observed in 53% of patients receiving sucralfate versus 41% of those receiving placebo. Compared with patients receiving placebo, more sucralfate-treated patients reported fecal incontinence (16% v 34%, respectively; P =. 04) and need for protective clothing (8% v 23%, respectively; P =. 04). The incidence and severity of nausea were worse among those taking sucralfate (P =.03). Analysis of patient-reported symptoms 10 to 12 months after RT showed a nonsignificant trend toward more problems in patients taking sucralfate than in those taking placebo (average, 2.3 v 1.9 problems, respectively; P =.34). CONCLUSION: Sucralfate did not decrease pelvic RT-related bowel toxicity by any of the end points measured and seems to have aggravated some gastrointestinal symptoms.

Transdermal clonidine for ameliorating tamoxifen-induced hot flashes.

PURPOSE: To determine the efficacy of transdermal clonidine for alleviating tamoxifen-induced hot flashes in women with a history of breast cancer. PATIENTS AND METHODS: A randomized, double-blind, crossover design was used in this prospective study. Women with a history of breast cancer who were receiving tamoxifen and suffering from hot flashes were potentially eligible for this protocol study. RESULTS: Clonidine did reduce hot-flash frequency to a degree that was statistically impressive (P < .0001), but clinically moderate (20% reduction from baseline). It also decreased hot-flash severity (P = .02, 10% reduction from baseline). Clonidine was related to increased mouth dryness (P < .001), constipation (P < .02), itchiness under the patch (P < .01), and drowsiness (P < .05). CONCLUSION: Better means are needed to alleviate hot flashes among patients in whom estrogen therapy is contraindicated.

Phase III controlled evaluation of sucralfate to alleviate stomatitis in patients receiving fluorouracil-based chemotherapy.

PURPOSE: Stomatitis is a major dose-limiting toxicity of bolus fluorouracil (5FU)-based chemotherapy regimens, despite the use of oral cryotherapy. Pursuant to preliminary data that suggested a sucralfate oral solution could alleviate chemotherapy-induced oral mucositis, we developed a prospective trial to test this contention. PATIENTS AND METHODS: A phase III, double-blind, placebo-controlled clinical trial was designed. Patients were entered onto the study at the time of the first cycle of 5FU-based chemotherapy. All patients received oral cryotherapy for 30 minutes with each dose of 5FU. In addition, each patient was randomized to receive either a sucralfate solution or a placebo solution to be used if they developed mouth tenderness or mouth sores. The study solution was to be used four times daily for 7 days starting on the first day of mouth tenderness or mouth sores. Stomatitis scores were determined by health care providers and by patients themselves. RESULTS: There was a total of 131 assessable patients entered onto this trial, 50 of whom developed mucositis and used the study medication (27 sucralfate and 23 placebo). There was no suggestion of any difference in stomatitis severity or duration on either protocol arm. CONCLUSION: The resultant data from this clinical trial did not support the prestudy hypothesis that sucralfate would be beneficial for the treatment of 5FU-induced stomatitis.

Phase III clinical trial of the combination of cisplatin, dacarbazine, and carmustine with or without tamoxifen in patients with advanced malignant melanoma.

PURPOSE: A prospective randomized phase III clinical trial was conducted to assess whether the addition of tamoxifen (TAM) to the three-agent regimen of cisplatin (CDDP), dacarbazine (DTIC), and carmustine (BCNU) significantly increased the progression-free survival and overall survival of patients with advanced malignant melanoma. PATIENTS AND METHODS: Patients with advanced malignant melanoma were treated with CDDP + DTIC + BCNU (CDB) with or without TAM. The dose schedule was CDDP 25 mg/m(2) given intravenously (IV) for 30 to 45 minutes in 500 mL of dextrose and (1/2) normal saline (NS) on days 1 to 3 of a 3-week cycle; DTIC 220 mg/m(2) IV for 1 hour in 500 mL of dextrose and (1/2) NaCl on days 1 to 3 of a 3-week cycle; BCNU 150 mg/m(2) IV for 2 to 3 hours in 750 to 1,000 mL of dextrose and 5% water on day 1 of every odd 3-week cycle; and TAM 20 mg taken orally every morning. RESULTS: There were 184 eligible patients enrolled. These patients were observed until death or for a minimum of 1.3 years. At last contact, 12 were still alive. The median time to progression was 3.4 months on the CDB arm and 3.1 months on the CDB + TAM arm. The median survival time was 6.8 months with CDB and 6.9 months with CDB + TAM. Progression-free survival (P =.429) and overall survival (P =.545) were not found to differ by treatment. CONCLUSION: The addition of TAM to this three-agent regimen of CDB was not found to provide a meaningful clinical advantage in the treatment of patients with advanced malignant melanoma.

A phase II study of sequential combination chemotherapy with cyclophosphamide, prednisone, and 2-chlorodeoxyadenosine in previously untreated patients with chronic lymphocytic leukemia.

In an earlier study of previously untreated patients with chronic lymphocytic leukemia (CLL), we used a concomitant combination of chlorambucil and 2-chlorodeoxyadenosine and reported overall (OR) and complete (CR) remission rates of 80% and 20%, respectively. After a median follow-up of 5 years, more than 80% of the responders have had a relapse. In the current phase II study of 27 previously untreated patients with CLL, we used a sequential combination of six cycles of intravenous cyclophosphamide (1 g/m2) plus oral prednisone (100 mg/m2 per day for 5 days) followed by two to six cycles of 2-chlorodeoxyadenosine (5 mg/m2 per day for 5 days). The OR and CR rates were 96% and 33%, respectively. After a median follow-up of 29 months, 35% of the responders have had a relapse. Progression-free survival was significantly better in CR patients than in those with partial remission. However, minimal residual disease was phenotypically detected in four of the nine CR patients. Despite the fact that the current OR and CR rates are superior to those seen in a historical cohort treated with a concomitant schedule, a longer follow-up period is needed to assess the durability of these remissions, and a controlled trial is necessary to estimate the impact on overall survival and toxicity.

Phase III evaluation of octreotide versus chemotherapy with 5-fluorouracil or 5-fluorouracil plus leucovorin in advanced exocrine pancreatic cancer: a North Central Cancer Treatment Group study.

There continues to be a need for new systemic approaches for the treatment of advanced pancreatic cancer. The purpose of this study was to compare the antitumor activity of the somatostatin analogue octreotide to 5-fluorouracil chemotherapy in a Phase III setting. Eighty-four patients with an Eastern Cooperative Oncology Group performance status of 0 or 1 and limited tumor volume were randomized to receive octreotide 200 microg three times daily or 5-fluorouracil with or without leucovorin. After the first 12 patients had been randomized to octreotide, we increased the dose in the remaining patients to 500 microg three times daily. This change was based on early reports in other studies, suggesting that our original dose may not have been effective and that higher doses of octreotide were well tolerated. A planned interim analysis performed after 84 patients were enrolled demonstrated inferior time to progression and survival for the patients randomized to octreotide. Further accrual to the octreotide arm of this protocol was therefore terminated. Octreotide in doses of 200-500 microg three times daily does not delay progression or extend survival in patients with advanced pancreatic cancer compared with treatment with 5-fluorouracil with or without leucovorin.

Alleviation of cytotoxic therapy-induced normal tissue damage.

Cytotoxic chemotherapy and radiation therapy damage normal body tissues, resulting in stomatitis, conjunctivitis, esophagitis, proctitis, and dermatitis. Pursuant to this, the North Central Cancer Treatment Group has developed a series of clinical trials designed to study antidotes for these pathologic processes. These trials have demonstrated clinically helpful therapies (eg, oral cryotherapy for decreasing mucositis induced by 5-fluorouracil) and also have demonstrated lack of benefit for other proposed treatments. Results from several ongoing clinical trials should become available in the near future.

Alleviation of cancer anorexia and cachexia: studies of the Mayo Clinic and the North Central Cancer Treatment Group.

Anorexia and cachexia are common clinical problems of many patients with advanced cancer. Approximately 20 years ago, a controlled, clinical study demonstrated that dexamethasone could stimulate appetites of patients with advanced gastrointestinal cancer without causing any apparent effect on patient weight or survival. More recently, two double-blind, placebo-controlled trials investigated cyproheptadine and megestrol acetate in patients with cancer anorexia/cachexia. The first of these studies suggested that cyproheptadine could mildly stimulate appetite without causing any discernible effect on patient weight. Megestrol acetate, on the other hand, can clearly cause an increase in patient-perceived appetite and food intake and can also lead to substantial nonfluid weight gain in a proportion of patients with cancer anorexia/cachexia. Ongoing studies have been designed to better study the appetite-enhancing effects of megestrol acetate. In addition, current studies are evaluating the effect of the drug hydrazine sulfate on the appetite and weight status of patients with advanced lung or colon cancer.

Low molecular weight heparin versus acenocoumarol in the secondary prophylaxis of deep vein thrombosis.

The aim of this study was to determine the efficacy and safety of subcutaneous weight-adjusted dose low molecular weight heparin (LMWH) compared with oral anticoagulant (OA) in the prevention of recurrent venous thromboembolism. In a prospective multicenter trial, 202 patients with symptomatic proximal deep vein thrombosis (DVT) were included. As soon as the diagnosis of DVT was confirmed by phlebography, 101 were randomly assigned to receive LMWH (nadroparin) for secondary prophylaxis and 101 to receive OA (acenocoumarol). Patients in both groups were initially treated with nadroparin in a dose of 85 anti-Xa IU/kg s.c. every 12 h. Secondary prophylaxis with either nadroparin, 85 anti-Xa IU/kg s. c. once daily, or acenocoumarol was continued for at least 3 months. Three patients in the LMWH group and 6 in the OA group were excluded from analysis for various reasons. During the one-year combined secondary prophylaxis and surveillance period, 7 of of the 98 evaluable patients (7.1%) in the LMWH group and 9 of the 95 evaluable patients (9.5%) in the OA group had a documented recurrence of venous thromboembolism (Fisher's exact test, p = 0.61). Of these, 2 patients who received LMWH and 7 patients on acenocoumarol had recurrences in the 3-month period of secondary prophylaxis. Four patients (4.1%) in the LMWH group developed bleeding complications during this study period, as compared with 7 (7.4%) in the OA group (Fisher's exact test, p = 0.37). There were two major bleedings, one in the LMWH group and one in the OA group. Eleven patients died, 5 (5.1%) in the LMWH group and 6 (6.3%) in the OA group. It is concluded that nadroparin in a dose of 85 anti-Xa IU/kg s.c. once daily provides an effective and safe alternative to oral anticoagulants in the secondary prophylaxis of DVT.

The relationship between plasma triglycerides, cholesterol, total lipids and lipid peroxidation products during human atherosclerosis.

Concentrations of plasma triglycerides, cholesterol, total lipids and lipid peroxides in patients with atherosclerotic lesions of peripheral arteries, who were divided into groups according to the extent and intensity of the lesions, were estimated, as well as lipid peroxide levels in the arterial wall. Statistically highly significant increases of the estimated compounds were found in all groups in comparison with the controls. The existence of a positive correlation between the lipid peroxide concentration and other investigated components in plasma and between the lipid peroxide level in plasma and in the arterial wall was found. Possible mechanisms for lipid peroxide involvement in the process of originating atherosclerotic lesions are discussed.

Transdermal fentanyl in the management of cancer pain in ambulatory patients: an open-label pilot study.

We performed an open-label pilot study to define analgesic efficacy, acceptability, and toxicity of transdermal fentanyl in an ambulatory population of patients with cancer pain. Our 7-day study included 35 patients, all of whom had failed a trial of an opioid analgesic conventionally used for moderate pain. Patients received either a 25 micrograms/hr or 50 micrograms/hr fentanyl transdermal patch depending on prior opioid dose. Pain was measured daily utilizing visual analogue (VAS) and categorical (CAT) scales. Hours of nighttime sleep, quality of life, toxicities, and use of rescue medication were also assessed. There was a 24%-29% reduction in mean VAS and CAT pain scores as compared with the baseline and a 25% increase in mean hours of nighttime sleep. Fifty-nine percent of those patients responding (46% of all study patients) were satisfied to very satisfied with the analgesia provided by transdermal fentanyl. Six percent of all study patients were not at all satisfied with the pain relief obtained. Toxicities were similar to those seen with other opioids. No patient developed severe sedation or respiratory depression. The 25-50 micrograms/hr patch appears to be a safe starting dosage in ambulatory patients previously receiving opioids conventionally used for moderate pain.

Exploratory photochemistry of 5-azido-8-alkoxy-substituted psoralens free and bound to DNA.

5-Azido-8-alkoxy psoralens were synthesized. Laser flash photolysis (LFP: XeF, 351 nm, 55 mJ, 17 ns) of the azides in acetonitrile or benzene solution produces the triplet nitrene and a small amount of ketenimine. Laser flash photolysis of the azides in methanol or aqueous solution cleanly produces the triplet nitrene. In aqueous solution containing highly polymerized calf thymus DNA, LFP produces a mixture of triplet nitrene and ketenimine corresponding to photolysis of free and bound psoralen, respectively. The two transients decay slowly but at different rates. Assignment of the transient spectra were secured by matrix EPR and UV-visible spectroscopy. The triplet nitrene lifetime is the same in buffer and in the presence and absence of calf thymus DNA. The results explain why psoralen azides are unable to efficiently nick plasmid DNA pBR322 upon UV activation.

Phase II study of 2-chlorodeoxyadenosine in combination with chlorambucil in previously untreated B-cell chronic lymphocytic leukemia.

The objective was to determine the safety and efficacy of adding a maximally tolerated dose of 2-chlorodeoxyadenosine (2-CdA) to standard chlorambucil (CLB) therapy in previously untreated B-cell chronic lymphocytic leukemia (CLL). Thirty patients with CLL (median age, 64 years) received two courses of 2-CdA given intravenously (2 mg/m2 daily for 7 days) added to biweekly administration of CLB at 30 mg/m2 given orally. The diagnosis of CLL, treatment indications, and response criteria were according to the National Cancer Institute established guidelines. Sixteen patients (53%) had advanced-stage disease, and four (13%) had trisomy 12 abnormality. The overall remission rate was 80%, including 20% complete remission (CR), 30% nodular partial remission (nPR), and 30% partial remission (PR). Minimal residual disease was detected phenotypically in two of five patients with CR and in eight of nine with nPR. Overall, CR, nPR, and PR rates were not influenced significantly by the presence of cytogenetic abnormalities or advanced clinical stage. With a median follow-up of 33 months, 58% of patients who had a response had relapse. Median time to progression in all 30 patients was 30 months, and time to progression and progression-free survival were not significantly different for the different response groups, clinical stages, or cytogenetic groups. Severe neutropenia and thrombocytopenia occurred in 33% and 7% of patients, respectively. Only two patients had documented bacterial infections, and four had herpetic infections. Concurrent combination chemotherapy with abbreviated doses of 2-CdA and standard-dose CLB is feasible and safe in previously untreated CLL. Antitumor activity may be superior to that of CLB alone given in conventional doses. Whether a different schedule of combining these two agents would result in improved outcome is being investigated.

Paclitaxel and G-CSF in previously untreated patients with extensive stage small-cell lung cancer: a phase II study of the North Central Cancer Treatment Group.

Paclitaxel is an antimicrotubule agent that interferes with cell division. It has demonstrated promising single-agent activity against non-small-cell lung cancer. The purpose of this study was to evaluate the therapeutic effectiveness of paclitaxel in previously untreated patients with extensive stage small-cell lung cancer (SCLC). The study was designed as a two-stage phase II trial. All patients who entered received paclitaxel by intravenous infusion at a dose of 250 mg/m2 during 24 hours. Granulocyte colony stimulating factor was also provided to ameliorate neutropenia. Cycles were repeated at 21-day intervals. Patients who achieved a complete response received a maximum of 10 cycles of treatment, whereas those who achieved a partial response/regression continued treatment until progression or undue toxicity developed. Patients who progressed or maintained stable disease for six cycles were crossed over to cisplatin and etoposide. Forty-three patients entered the study and all were evaluable for analysis. Responses were observed in 23 (53%) of the patients. There was no significant difference in the response rates in patients with measurable or evaluable disease (13/23 versus 10/20, p = 0.76). At the time of analysis, 39 patients had progressed with a median time to progression of 95 days, and 39 patients had died with a median survival of 278 days. The 1-year achieved survival rate was 24%. Significant neutropenia (absolute neutrophil count <1,000/microl) occurred in 24 (56%) of the patients, but only 2 patients experienced severe infection (grade > or = 3), and there were no septic deaths. The results indicate that paclitaxel is active against SCLC. Myelosuppression was the main side effect in this patient population. Response duration was short (median = 3.4 months), which suggests that paclitaxel is not sufficient as a single agent. Further studies of paclitaxel in combination with other agents against SCLC are currently in progress within the North Central Cancer Treatment Group and other cancer treatment groups. Key Words: Paclitaxel-G-CSF-Small-cell lung cancer-North Central Cancer Treatment Group.

Combined levamisole with recombinant interleukin-2 (IL-2) in patients with advanced renal cell carcinoma: a phase II study.

Adoptive immunotherapy (AI) with interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells is an antineoplastic modality in which immune-activated cells are administered to a host having cancer in an attempt to mediate tumor regression. Levamisole (LEV), an immune stimulant, has been suggested as having therapeutic effectiveness in a variety of cancers. After a phase I trial of recombinant IL-2 plus LEV, a phase II trial of this combination was conducted in patients who had advanced renal cell carcinoma. The regimen was IL-2 at 3 x 10(6) U/m2 daily x 5 plus LEV at 50 mg/m2 perorally three times a day x 5. Only one of the 22 eligible patients had a regression. It was a partial regression, 85 days in duration. The median time to treatment failure (refusal, progression, or off study because of toxicity) was 36 days. The only grade 4 toxicity reported was lethargy. This regimen is not recommended for further testing in patients who have advanced renal cell carcinoma.

Phase III controlled evaluation of glutamine for decreasing stomatitis in patients receiving fluorouracil (5-FU)-based chemotherapy.

Mucositis is a prominent dose-limiting toxicity associated with 5-FU-based chemotherapy. On the basis of preliminary data suggesting that the amino acid glutamine could alleviate this problem, the authors developed this trial. Patients scheduled to receive their first 5-FU-based chemotherapy regimen were selected for study. Following stratification, patients were randomized, in a double-blind manner, to receive oral glutamine or a placebo preparation in a prophylactic manner. Patients in both groups were given oral cryotherapy before chemotherapy and were evaluated for mucositis by standard physicians' evaluation and by a self-report instrument. Sixty-six patients were randomized to receive glutamine and 68 to receive the placebo preparation. There were no significant differences or substantial trends in the mucositis scores between the two study arms as measured by either the physicians or the patients. It was concluded that the dose and schedule of glutamine used in this clinical trial does not alleviate 5-FU-induced mucositis.

RNA synthesis in guinea pig peripheral blood lymphocytes and heterophils during sensitization.

The synthesis of RNA in guinea pig leukocytes was investigated during sensitization by the use of tritiated uridine. The increase of the number of RNA-synthetizing heterophils was found in 21st day of sensitization. That was connected with morphological features of heterophils nuclei. Among lymphocytes in 11th day of sensitization the subpopulation of cells intensively synthetizing RNA was observed. The possible role of cells, which synthetize RNA in the process of sensitization is discussed.

Compensatory mechanisms in erythrocyte lipids in patients with atherosclerosis.

The quantitative composition of phospholipids and fatty acids of erythrocytes was investigated in patients with atherosclerosis. It was stated that the erythrocyte lipids of atherosclerotic patients contained smaller quantities of phosphatidylcholine and phosphatidylinositol, a significantly larger quantity of sphingomyelin, and higher sphingomyelin/phosphatidylcholine and cholesterol/phospholipid ratios. The existence of compensatory changes was stated, which was evident in the reduction of palmitic and stearic acids and the increase of linoleic and eicosatrienoic acids in erythrocyte phospholipids. These changes in fatty acid composition probably cause minimal changes in the membrane fluidity induced by an increased cholesterol/phospholipid and sphingomyelin/phosphatidylcholine ratios. This paper was the first evidence of occurrence of those changes in erythrocytes during spontaneous atherosclerosis in human.