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Biomedical subjects

L H Baker

Publications and source records attributed to L H Baker.

At least 73 records · Page 4Linked to original sources

Cognitive-behavioral intervention for irritable bowel syndrome.

A 41-year-old white man with a 2-year history of irritable bowel syndrome (IBS) was referred for psychological treatment. At the time of assessment he was being treated with Metamucil and Darvocet N-100s with little success. A detailed psychosocial assessment indicated several areas for cognitive-behavioral intervention. Nine months after the patient began treatment, the frequency of IBS episodes had greatly reduced, he was off narcotic pain medication, and his general health was improved as measured by clinic and emergency room visits. We suggest that psychological interventions of the type described here can be an efficacious and cost-effective treatment for IBS.

Adult↗

Randomized comparison of cyclophosphamide, imidazole carboxamide, and adriamycin versus cyclophosphamide and adriamycin in patients with advanced stage malignant mesothelioma: a Sarcoma Intergroup Study.

In 1980, a consensus chemotherapy intergroup study for advanced malignant mesothelioma was initiated based on a collaborative agreement among the Eastern Cooperative Oncology Group (ECOG), the Southwest Oncology Group (SWOG), and the Southeastern Cancer Study Group (SECSG). The purpose of the study was to evaluate cyclophosphamide (500 mg/m2 day 1), imidazole carboxamide (250 mg/m2 days 1 through 5), and doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) (50 mg/m2 day 1) v cyclophosphamide (500 mg/m2) and doxorubicin (50 mg/m2) in a randomized prospective clinical trial involving 76 fully evaluable patients with advanced stages II to IV malignant mesothelioma. A total of nine responses (12%) were documented, including three complete and six partial responses. There was no significant difference in response duration or survival between treatment arms. Leukopenia (greater than 2,000/microL) was observed in 46% of patients treated with the three-drug combination and 38% of patients receiving the two-drug combination. The variables of performance status 0-1 and the absence of prior chemotherapy/radiotherapy were significant with respect to favorable impact on survival. We conclude, based on the minimal benefit observed, that the combination of cyclophosphamide and doxorubicin with or without imidazole carboxamide does not warrant further investigation in patients with advanced-stage malignant mesothelioma.

Adult↗

Phase II randomized trial of cisplatin chemotherapy regimens in the treatment of recurrent or metastatic squamous cell cancer of the cervix: a Southwest Oncology Group Study.

Cisplatin has proven to be the most active single agent in the treatment of metastatic and recurrent squamous cell cancer of the cervix. In a previous southwest Oncology Group (SWOG) pilot study, the addition of cisplatin to a mitomycin-C, vincristine, and bleomycin (MVB) regimen resulted in a relatively high percentage of durable complete responses. To gain more experience with cisplatin-based chemotherapy regimens, the SWOG initiated a phase II randomized trial of cisplatin, mitomycin-C plus cisplatin (MC), and MVB plus cisplatin (MVBC) in 119 patients with advanced squamous cell cancer of the cervix and no prior chemotherapy exposure. Because of slow patient accrual early in the trial, the cisplatin arm was discontinued. Five patients were declared ineligible according to protocol criteria. The three treatment groups were relatively well matched for age, prior radiation exposure, and sites of measurable disease. The overall objective response rates for cisplatin, MC, and MVBC treated patients were 33%, 25%, and 22%, respectively. Median response durations were greater than 6 months. Median survival durations associated with cisplatin, MC, and MVBC treatment were 17.0, 7.0, and 6.9 months, respectively. There were no drug-related deaths. Severe or life-threatening leukopenia and thrombocytopenia were observed in 18% to 24% of patients treated with MVBC and MC, but in none of those receiving cisplatin alone. We conclude that the low response rates and short durations of both response and survival observed in patients randomized to the two chemotherapy combinations suggest that only enhanced toxicity was gained through the addition of mitomycin-C or MVB to cisplatin in patients with advanced cervix cancer.

Adult↗

Combination chemotherapy using adriamycin, DTIC, cyclophosphamide, and actinomycin D for advanced soft tissue sarcomas: a randomized comparative trial. A phase III, Southwest Oncology Group Study (7613).

The term soft tissue sarcoma refers to a large variety of malignant tumors arising in extraskeletal connective tissues that connect, support, and surround discrete anatomic structures. All visceral organs also contain a connective stroma that can undergo malignant transformation. Because of the histological similarities of this group of tumors and their relative rarity, treatment prescriptions for patients that have disseminated disease are most often uniform. In this study, we asked the question whether adding a third drug (cyclophosphamide or actinomycin D) to Adriamycin (Adr [Adria Laboratories, Columbus, OH])-(3,3-dimethyl-1-triazeno)- imidazole-4-carboxamide (DTIC) would improve the response rate and/or survival. A unique feature of this cooperative group clinical trial was the mandatory pathology review of the histological material. All patients of the Southwest Oncology Group between June 1, 1976, and November 17, 1979, who had a biopsy-confirmed diagnosis of a soft tissue sarcoma with convincing clinical or biopsy-documented evidence of metastatic disease were eligible for the study. Patients were randomized to receive (1) Adr, 60 mg/m2 intravenously, day 1, and DTIC, 250 mg/m2 every 3 weeks (104 patients); (2) Adr and DTIC as in (1) and cyclophosphamide, 500 mg/m2, day 1 (112 patients); or (3) Adr and DTIC as in (1) and actinomycin D, 1.2 mg/m2, day 1, (119 patients). There was no statistically significant difference in response rates (33%, 34%, and 24%) (P = .25). Median durations of response were 31 weeks in the Adr-DTIC arm, 26 weeks in the cyclophosphamide-DTIC-Adr arm, and 23 weeks in the Adr-DTIC-Actinomycin D arm (P = .78). Median durations of survival were 37, 42, and 50 weeks, respectively. Again, no statistically significant differences were observed (P = .59). Toxicities from each of these treatment arms were formidable and were equivalent. Prognostic factor analysis showed a prognosis based on bone marrow reserve, sex, and pathology subtype favorable to patients.

Adolescent↗

CBDCA: phase II evaluation in advanced colorectal carcinoma.

Carboplatin (CBDCA) (NSC-241240) was administered to 25 consecutive patients with measurable colorectal carcinomas. Twenty-four patients were previously untreated, with a median performance status of 80. The dose schedule was 400 mg/m2 every 28 days and was escalated to 450 mg/m2 if no side effects or grade I toxicities occurred. All patients are assessable for toxicity and response. No complete response was observed; one partial response, lasting 23 weeks, was noted. Toxicity was primarily hematological. Neither auditory nor renal toxicities were observed. CBDCA administered in the above schedule has little therapeutic efficacy in previously untreated colorectal carcinoma patients.

Adenocarcinoma↗

Ambulatory blood pressure monitoring in patients with panic disorder.

To assess possible changes in blood pressure and heart rate associated with panic attacks, we performed automatic ambulatory blood pressure monitoring in 12 newly diagnosed, drug-free, and normotensive (casual blood pressure, less than 140/90 mm Hg) medical patients recently diagnosed with panic disorder. Detailed journals were designed for the study to assess the timing and symptoms of the panic attacks and the levels of activity. Systolic blood pressure increased by 27 +/- 9 mm Hg during the hour of the panic attack compared with the hour immediately prior to the episode of anxiety, while diastolic blood pressure increased by 5 +/- 2 mm Hg. The ambulatory heart rate increased by 14 +/- 6 beats per minute during the hour of panic attack vs the hour immediately prior to the attack. There was a strong relationship between the increase in heart rate and increase in systolic blood pressure. These data confirm that normotensive patients with panic disorder have episodically hypertensive blood pressure readings associated with an increase in heart rate; these hemodynamic alterations appear to be secondary to their panic attacks and not to increased physical activity. However, despite these episodic "hypertensive" periods, the mean ambulatory blood pressures remain within the normotensive range.

Adult↗

Phase I study of echinomycin.

Echinomycin was administered to patients with advanced carcinoma in escalating doses ranging from 60 to 1500 micrograms/m2 given weekly by 15-minute iv infusions for four doses, with a subsequent 2-week rest period. Dose-limiting nausea, vomiting, and anorexia associated with varying degrees of renal and hepatic dysfunction proved dose-limiting at the 1500-micrograms/m2 level. Thrombocytopenia was noted in 15% of patients receiving greater than or equal to 700 micrograms/m2 and was severe in 11% without an evident dose-response relationship. Leukopenia was rare and mild when encountered. Allergic reactions were observed. Phase II trials are feasible using a dose schedule of 1200 micrograms/m2/week X 4 weeks.

Carcinoma↗

A useful high-dose intermittent schedule of adriamycin and DTIC in the treatment of advanced sarcomas.

One-hundred-fourteen evaluable patients with metastatic soft tissue or bony sarcoma with measurable disease were treated with Adriamycin (doxorubicin) administered intravenously at a dose of 60 mg/M2 on day 1, followed by DTIC (dacarbazine) at a dose of 750 mg/M2; courses were administered at 3-week intervals. Ten complete remissions and 17 partial remissions were observed. The most responsive cell type was malignant fibrous histiocytoma with a response rate of 54%. This treatment schedule was very well tolerated, with only moderate myelosuppression and moderate nausea and vomiting. Cardiac toxicity was identified in three patients, with two patients demonstrating electrocardiogram (EKG) changes and arrhythmias and only one patient developing heart failure. The 24% overall response rate suggests no compromise in activity on this schedule, with a significant reduction in toxicity.

Antineoplastic Combined Chemotherapy Protocols↗

High-dose mitomycin-C with autologous bone marrow transplantation in patients with refractory malignancies. Influence of dose schedule on pharmacokinetics and nonhematopoietic toxicities.

Thirteen courses of high-dose mitomycin-C with autologous bone marrow transplantation (ABMT) were administered to 12 patients. Four dose schedules were evaluated: A) 60 mg/M2 X 1, 60-min infusion; B) 30 mg/M2/day X 2, 15-min infusion; C) 30 mg/M2/day X 2, 60-min infusion; D) 15 mg/M2/day X 4, 60-min infusion. Pharmacokinetic studies using HPLC technique were done in nine patients. All patients have since died and autopsies were performed in nine patients. Two major nonhematopoietic toxicities were encountered and were dose-schedule dependent: hemorrhagic colitis (six of six courses in Schedules A and B; two of seven in Schedules C and D), and hepatic dysfunction (five of six in Schedules A and B; two of seven in Schedules C and D). Histopathologic evidence of venocclusive disease of the liver was present in four of five autopsies in Schedules A and B, and two of four in Schedules C and D. One patient died as a result of liver failure associated with submassive hepatic necrosis. Saturation kinetics described by other investigators cannot be confirmed by our pharmacokinetic analyses in nine patients. Severe nonhematopoietic toxicities of mitomycin-C were found at three times the conventional dose; thus, this drug is assessed as not being clinically useful as a single agent in ABMT.

Adult↗

Phase I evaluation and clinical pharmacology of tricyclic nucleoside 5'-phosphate using a weekly intravenous regimen.

Tricyclic nucleoside phosphate (TCN-P) was selected for clinical trials because of its unusual chemical structure and activity against L1210 murine leukemia and MX-1 mammary xenograft. Inhibiting DNA synthesis, TCN-P was more toxic during S-phase of cell cycle. A phase I study was conducted in 24 patients with advanced solid cancers. The drug was given as a slow i.v. injection over 5 min on Days 1, 8, 15, and 22 of a 42-day cycle with a 2-week rest. Five dose levels ranging from 12 to 96 mg/m2 were studied with 3 to 12 patients treated at each level; a total of 106 doses was administered. The major hematological toxicity was thrombocytopenia, with a median nadir occurring at Day 34 of the cycle and first appearing at doses greater than 24 mg/m2. Anemia was seen at each dose level occurring between Days 8 and 34. Non-myelosuppressive toxic effects included stomatitis, anorexia, transient fever, nausea and vomiting, and dose-limiting hyperglycemia and diarrhea. The highest tolerated dose was 48 mg/m2. Plasma, pleural fluid, urine, and tissue samples were analyzed for TCN-P and tricyclic nucleoside (TCN) in selected patients by high-performance liquid chromatography. Plasma decay curves revealed extended retention of both TCN and TCN-P. Autopsy specimens obtained 61 days after therapy showed the highest residues of TCN-P in liver metastases and of TCN in gall bladder, bile, and pancreas. No drug was detected in urine samples of two patients. Prolonged retention and erratic plasma levels of the drug are probably due to extensive enterohepatic circulation, as well as repeated interconversion between TCN-P and TCN within cells. This weekly schedule produced unexpected clinical toxicity and should not be pursued.

Acenaphthenes↗

Episodic hypertension secondary to panic disorder.

Episodic elevation of blood pressure was evaluated in two middle-aged men by assessing home, clinic, and 24-hour ambulatory values following exclusion of secondary forms of hypertension. Both individuals had normotensive home and clinic readings. The 24-hour blood pressure was 125/85 +/- 12/9 mm Hg in patient 1 and 119/84 +/- 13/13 mm Hg in patient 2; however, both patients experienced large, sustained rises in blood pressure associated with panic attacks that were not abolished with prophylactic benzodiazepine therapy. Episodic blood pressure elevations were not associated with concomitant increases in heart rate. Patient 1 underwent extensive psychological investigation that diagnosed a panic disorder, and he underwent therapy that reduced the frequency and intensity of his panic-related hypertensive episodes. Because patient 2 demonstrated hypertensive readings at work, he was given a beta-blocking agent that ultimately controlled his blood pressure during episodes of anxiety and panic. These findings suggest that patients with panic attacks may present with episodic hypertension and that ambulatory blood pressure monitoring is useful in the diagnosis of this disorder and in assessment of treatment outcome.

Adult↗

Reversed-phase high-performance liquid chromatographic determination of tricyclic nucleoside and tricyclic nucleoside 5'-phosphate in biological specimens.

An isocratic, sensitive, high-performance liquid chromatographic assay was developed for the determination of the tricyclic nucleoside 1,4,5,6,8-pentaazaacenaphthylene -3-amino-1,5-dihydro-5-methyl-1-beta-D-ribofuranosyl 5'-monophosphate (TCN-P; NSC 280594) and its dephosphorylated metabolite TCN (NSC 154020). Separation was obtained using a C18 Sep-Pak precolumn, a reversed-phase column, and a mobile phase of phosphate buffer--methanol (87.5:12.5, v/v) containing 0.0025 M tetrabutylammonium hydroxide. The absorbance of both TCN and TCN-P was monitored at 280 nm with a sensitivity limit of 10 ng/ml. The recovery was 54 +/- 6% and 51 +/- 8% (mean +/- S.D.) from plasma for TCN and TCN-P, respectively. Rapid enzymatic dephosphorylation of TCN-P in plasma and tissue samples was prevented by adding a large excess of adenosine 5'-monophosphate. The assay was used to determine plasma and tissue concentrations of TCN-P and TCN after administration of TCN-P to cancer patients in a Phase I clinical study.

Acenaphthenes↗

Progress in screening for early breast cancer.

Ten years have now passed since the American Cancer Society/National Cancer Institute sponsored Breast Cancer Detection Demonstration Projects (BCDDP) started to evaluate the use of mammography, physical examination, thermography, and breast self-examination in screening women for the presence of unsuspected breast cancer. Criteria have been developed to evaluate population screening as an approach to cancer control and breast cancer screening techniques. Combined physical examination and mammography have been particularly successful in detecting early breast cancer. Although the number of screening programs for breast cancer has increased in the past decade, real progress has been surprisingly slow and the issues in breast cancer screening have proved to be subtle and complex.

Adult↗

Dibromodulcitol (DBD), DTIC, and actinomycin-D in disseminated malignant melanoma. A phase I-II clinical trial.

Thirty-seven fully assessable patients with metastatic malignant melanoma were administered DTIC, actinomycin-D, and dibromodulcitol (DBD) on a q 3- to 4-week schedule. Doses of actinomycin-D and DTIC were 1.25 mg/m2 and 750 mg/m2, respectively, on day 1. DBD was progressively escalated in five dose levels in succeeding patients from an initial 90 mg/m2 daily, days 3-7, to a dose-limiting 230 mg/m2. Two complete and nine partial responses were observed for an overall response rate of 30%. Median duration of response was 18 weeks. Major toxicities observed were hematologic and gastrointestinal. Median survival of all patients was 30 weeks and did not differ significantly from our earlier trials of DTIC and actinomycin-D +/- chlorozotocin. Although the observed objective response rate was higher than our previous efforts in this disease, the addition of DBD failed to significantly impact on the survival of the entire treatment group. Further investigation of this chemotherapy combination does not appear warranted.

Adult↗

Phase II evaluation of aclacinomycin-A in patients with adenocarcinoma and large cell carcinoma of the lung.

Aclacinomycin-A (ACLA-A), the new anthracycline antibiotic that produces substantially less cardiotoxicity relative to doxorubicin, was evaluated in a phase II trial for advanced large cell and adenocarcinoma of the lung patients. Twenty-three patients with measurable disease were entered into the trial and received ACLA-A in doses of a weekly infusion of 65 mg/m2 and 85 mg/m2. Eighteen patients were evaluable for response and toxicity. Two patients were evaluable for toxicity only, one died before completion of a full course of therapy, and two did not receive the drug. There were no complete or partial remissions in this study. Three patients had disease stabilization for a median of 10 weeks (range 6-17). Toxicity was mainly hematologic. Nausea and vomiting were moderate. ACLA-A, in the dose schedules used, appears to have no activity in large cell and adenocarcinoma of the lung.

Aclarubicin↗

Reactivity to alcohol-related cues: physiological and subjective responses in alcoholics and nonproblem drinkers.

Physiological reactivity and self-reported desire to drink in nonproblem drinkers (N = 11 women and 15 men) and hospitalized alcoholics (N = 25 women and 34 men) were examined while subjects held and sniffed their preferred alcoholic beverage. Skin conductance level (SCL) and heart rate during alcohol exposure were significantly higher in the alcoholics than in the non-alcoholics. Self-reported desire to drink and SCL during alcohol exposure were correlated for alcoholics but not for nonalcoholics. Among alcoholics, SCL change was positively correlated with the number of heavy-drinking days in the month preceding admission to treatment. Consistent with conditioning models of relapse, alcoholics showed a distinctive response to alcohol cues, characterized by autonomic reactivity and concordance between this reactivity and self-reported desire for alcohol.

Adult↗