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Biomedical subjects

B A Parker

Publications and source records attributed to B A Parker.

18 recordsLinked to original sources

Relation between food intake and visual analogue scale ratings of appetite and other sensations in healthy older and young subjects.

OBJECTIVE: Visual analogue scales are widely used in appetite research, yet the validity of these scales to evaluate appetite and mood has not been assessed in older subjects. The aim of this study was to determine the relations between food intake and visual analogue scale (VAS) ratings of appetite and nonappetite sensations in healthy older and young subjects. DESIGN: Retrospective combined analysis of four single-blind, randomised, controlled appetite studies. SETTING: All studies were conducted in the University of Adelaide, Department of Medicine, Adelaide, Australia. SUBJECTS: A total of 45 healthy young men (n=24) and women (n=21) aged 18-35 y and 45 healthy older men (n=24) and women (n=21) aged 65-85 y were recruited by advertisement. INTERVENTIONS: Oral, intraduodenal or intravenous administration of treatments which suppressed food intake were compared to control. Up to 90 min after treatment, a test meal was offered and subjects ate freely for between 30 and 60 min. Perceptions were assessed by 100-mm visual analogue scales administered at regular intervals. RESULTS: Food intake at the test meal was positively related to perceptions of hunger, drowsiness, and calmness at both baseline and premeal (r>0.16, P<0.05), and inversely related to premeal ratings of fullness (r> 0.2, P<0.05) in both older and young subjects. Food intake was related to VAS ratings at least as strongly, if not more so, in older as in young subjects. CONCLUSIONS: These observations (i) confirm that food intake is related to perceptions of hunger and fullness as assessed by VAS in healthy older and young subjects, and (ii) suggest that sensations, not obviously associated with appetite, including 'drowsiness' and 'calmness', are also associated with food intake.

Adolescent↗

Dose-escalated cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide (CHOPE) chemotherapy for patients with diffuse lymphoma: Cancer and Leukemia Group B studies 8852 and 8854.

BACKGROUND: To address the feasibility and outcome of moderate dose intensification with granulocyte-colony stimulating factor (G-CSF) for patients with aggressive non-Hodgkin lymphoma (NHL), the Cancer and Leukemia Group B (CALGB) conducted two studies evaluating dose-escalated cyclophosphamide and etoposide in the cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide (CHOPE) regimen. METHODS: Eligibility criteria included histologically documented, diffuse small cleaved, diffuse mixed, diffuse large cell, or immunoblastic lymphoma, Stage III--IV or bulky Stage II disease, and an ECOG performance status of 0--1. CALGB 8852, a group-wide study, accrued 227 patients: 120 patients in the pilot study to determine the maximum tolerated dose (MTD) without G-CSF and 107 in the pilot study of dose-escalated CHOPE with G-CSF. CALGB 8854, a limited-institution, Phase I study, enrolled 38 patients and determined the MTD of CHOPE with G-CSF to be used in CALGB 8852. The MTD in both studies was defined as the dose at which 50% of patients had 1) Grade 4 neutropenia or thrombocytopenia lasting 7 days or more, or 2) Grade 3--4 hemorrhage or nonhematologic toxicity (excluding alopecia, nausea, and emesis), or 3) were prevented from receiving 100% of drug on Day 22. RESULTS: The MTD of CHOPE without G-CSF was cyclophosphamide 1000 mg/m(2) on Day 1 and etoposide 100 mg/m(2) on Days 1--3 with doxorubicin 50 mg/m(2) on Day 1, vincristine 1.4 mg/m(2) (maximum, 2 mg) on Day 1, and prednisone 100 mg on Days 1--5. With the addition of G-CSF at 200 microg/m(2) on Days 5--19, the MTD was cyclophosphamide 1500 mg/m(2) and etoposide 160 mg/m(2) on Days 1-3 with standard doses of doxorubicin, vincristine, and prednisone. Increasing the dose of G-CSF from 200 microg/m(2) to 400 microg/m(2) did not allow for further dose escalation. The primary toxicity in all cohorts was neutropenia. Four toxic deaths occurred on CALGB 8852. The 5-year failure free survival (FFS) and overall survival (OS) rates for eligible patients on CALGB 8852 were 31% (95% confidence interval [95%CI], 23--39) and 48% (95%CI, 40--57), respectively. The 5-year FFS and OS rates for eligible patients on CALGB 8854 were 34% (95%CI, 17--52) and 51% (95%CI, 33--70), respectively. CONCLUSIONS: Moderate dose escalation with G-CSF is feasible. However, response and survival rates of patients who receive dose-escalated CHOPE, even with the addition of G-CSF, appear similar to the rates reported with standard-dose CHOP.

Adult↗

Kinetics of formation of Di-D-fructose dianhydrides during thermal treatment of inulin.

Thermal treatments of solid mixtures of inulin and citric acid result in the formation of di-D-fructose dianhydrides and oligomers derived therefrom. The kinetics of formation of these compounds have been investigated and simulated in computer studies. A mechanism is proposed. The conditions used in this study were analogous to the conditions pertaining to the roasting of chicory, during which similar compounds are formed.

Anhydrides↗

Initial clinical trial of a high-affinity retinoic acid receptor ligand (LGD1550).

Retinoids mediate their biological response by binding to specific nuclear receptors, including retinoic acid receptors and/or retinoid X receptors. LGD1550 is a high-affinity ligand for all three retinoic acid receptors (alpha, beta, and gamma isoforms) and a potent inhibitor of AP-1, a protein that is closely linked with trophic responses and malignant transformation. We conducted a dose ranging study to evaluate the pharmacokinetics, safety, clinical tolerance, and potential efficacy of this drug in patients with advanced cancer. Twenty-seven patients received oral doses of LGD1550 once per day at doses ranging from 20-400 microg/m2. Skin toxicity was the dose-limiting reaction at the 400 microg/m2 daily dose level. Less prominent reactions included nausea and headache. No major antitumor effects were observed. Pharmacokinetic studies in 15 patients at five dose levels showed that the peak plasma concentration (Cmax) and areas under the plasma concentration-time curve on day 1 were dose-proportional and were similar to values obtained on days 15, 29, and 84. Unlike other retinoids, LGD1550 did not induce its own metabolism, and there was little evidence of drug accumulation. The t1/2 was approximately 5 h after both the initial and repeated doses. We conclude that once-daily doses of LGD1550 of up to 300 microg/m2 are relatively well tolerated. Additional clinical explorations are warranted, especially in patients with cancers of the prostate, thyroid, head and neck, and cervix.

Adult↗

Clinical study of 9-cis retinoic acid (LGD1057) in acute promyelocytic leukemia.

The use of all-trans retinoic acid (RA) for remission induction markedly increases survival of patients with acute promyelocytic leukemia (APL) compared to patients treated solely with cytotoxic chemotherapy. However, clinical resistance to this agent develops rapidly, which has been associated with a progressive decline in plasma drug concentrations. Previous studies suggested that 9-cis RA, a retinoid receptor 'pan agonist' did not induce its own catabolism to the same extent as all-trans RA. Therefore, we conducted a dose-ranging study of this compound in patients with both relapsed and newly diagnosed APL. We treated 18 patients with morphologically diagnosed APL (13 relapsed, five newly diagnosed). The daily dose of 9-cis RA ranged from 30 to 230 mg/m2/day given as a single oral dose. Four of 12 (33%) relapsed patients (three of whom were previously treated with all-trans RA) and four of five (80%) newly diagnosed patients achieved complete remission. The sole failure in the newly diagnosed group died early from an intracranial hemorrhage. One other patient with t(9;12) translocation had substantial hematologic improvement. The drug was generally well tolerated; headache and dry skin were the most common adverse reactions. Three patients were treated with corticosteroids for signs of incipient 'RA syndrome.' These preliminary data suggest that 9-cis RA is an effective agent for remission induction and deserves further investigation in patients with retinoid-sensitive APL.

Adolescent↗

Microsatellite instability correlates with reduced survival and poor disease prognosis in breast cancer.

Size changes in microsatellite sequences have been detected in many types of cancer, but the influence of this form of genetic instability on disease progression remains unclear. We determined the incidence of microsatellite instability in breast cancer by comparing PCR-amplified sequences from paraffin-embedded samples of normal and tumor tissue from affected individuals. This analysis showed that at least 30% of breast cancers exhibit microsatellite instability (MI). Of importance, MI correlated with indicators commonly associated with poor disease prognosis, including lymph node status, tumor size, and advanced tumor stage. Individuals with MI+ tumors also showed significantly reduced disease-free and overall survival. These data contrast with studies showing that MI correlates with improved prognosis in colon and gastric cancers. We propose that defects resulting in MI promote disease progression and result in a poor prognosis in breast cancer.

Breast Neoplasms↗

Radioimmunotherapy of relapsed B-cell lymphoma with yttrium 90 anti-idiotype monoclonal antibodies.

Tumor-specific anti-idiotype (anti-Id) monoclonal antibodies (MoAbs) to B-cell lymphomas have been administered to patients, resulting in significant clinical responses. However, clinical responses have been limited by the emergence of Id-negative lymphoma. To overcome the problem of tumor heterogeneity, we conducted a pilot evaluation of the safety and effectiveness of yttrium 90 (90Y)-labeled anti-Id and shared Id (sId) MoAbs in non-Hodgkin's B-cell lymphoma. Nine patients with relapsed B-cell lymphoma in whom tumor was successfully targeted with 111In-labeled anti-Id MoAb were treated with 90Y-labeled anti-Id MoAb. A total of 19 courses (one to four per patient) were administered using 1,000 to 2,320 mg unlabeled clearing MoAb and 10 to 54 mCi 90Y MoAb per patient. Two of nine patients had a complete response, one a partial response, three stable disease, and three disease progression. Time to progression varied from 1 to 12 months. Toxicities were predominately hematologic, and only one patient developed infection and required transfusion. At progression, three of five assessable patients had Id-positive lymphoma and two had Id-negative lymphoma. Human antimouse antibodies (HAMA) did not develop in the patients after treatment. 90Y anti-Id MoAbs demonstrated excellent in vivo stability, produced significantly tumor regression in three of nine patients, exhibited acceptable toxicities, and elicited no HAMA formation. Further investigation of repetitive, low-dose 90Y anti-Id and MoAb therapy is warranted; however, the advantages of a pan B MoAb may prove the latter to be the agent of choice for the radio immunotherapy of B-cell lymphoma.

Adult↗

Regional differences in the incidence and treatment of carcinoma in situ of the breast.

Greater use of mammography in the United States in recent years has increased the detection of early neoplasms of the breast, including carcinoma in situ. However, the occurrence and treatment of diagnosed carcinoma in situ of the breast has not been fully described. Our goal was to examine temporal, geographic, and demographic patterns in the incidence and treatment of in situ breast cancer. The study included data from all women with in situ breast cancer that had been detected in the nine Surveillance, Epidemiology, and End Results areas of the United States from 1975 through 1990 (Surveillance Program, Cancer Statistics Branch, Bethesda, MD: National Cancer Institute, November, 1993). We calculated age-adjusted incidence rates (1970 United States standard) using data on histology and treatment from the Surveillance, Epidemiology, and End Results data tape. We assessed predictors of treatment by mastectomy using multiple logistic regression. From 1975-1979 to 1986-1990, the age-adjusted incidence rate of in situ breast cancer increased from 4.7 to 16.9/100,000 women. The increase occurred in all age groups and among both white and black women. However, there was nearly a 2-fold difference in incidence rates across geographic areas in 1986-1990, ranging from < 12/100,000 in Iowa and New Mexico to > 20/100,000 in San Francisco and Seattle. Geographic variability in treatment was also evident, with mastectomy, rather than breast-conserving therapy, performed on 46% of the women with in situ breast cancer in San Francisco and on 66% of those in Iowa. The incidence of diagnosed in situ breast cancer increased markedly during the 1980s, and there was substantial geographic variability in the rates of detection of these tumors and in the type of therapy received. Although mastectomy became a less common treatment over time, it was still performed on a high proportion of women with in situ breast cancer during the latter part of the decade.

Adult↗

Breast cancer.

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Adult↗

Role of the corpus callosum in expression of behavioral asymmetries induced by a unilateral dopamine lesion of the substantia nigra in the rat.

The present study examines the effects of sectioning the corpus callosum on the expression of asymmetric behaviors induced by a unilateral 6-hydroxydopamine (6-OHDA) lesion of the substantial nigra. Severing the corpus callosum eliminated the asymmetry in spontaneous investigation of edges in an open-field, without affecting total time of investigation. In contrast, callosotomy reduced the magnitude of externally cued turning, but failed to affect the directional distribution of responding. Moreover, it reduced the magnitude of apomorphine- but not amphetamine-induced turning. It is suggested that transcallosal communication is required for those behavioral asymmetries induced by a unilateral dopamine lesion which depend on head, rather than whole body movements.

Amphetamine↗

AMOPLACE treatment of intermediate-grade and high-grade malignant lymphoma: a Cancer and Leukemia Group B study.

PURPOSE: In an attempt to improve the efficacy of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy for intermediate-grade and high-grade non-Hodgkin's lymphomas, a phase II evaluation of a regimen consisting of Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), methotrexate, Oncovin (vincristine; Eli Lilly Co, Indianapolis, IN), prednisone, leucovorin, cytarabine (ara-c), cyclophosphamide, and etoposide (AMOPLACE) was conducted. This regimen includes three additional agents not found in CHOP, uses weekly doses of alternating myelosuppressive and nonmyelosuppressive drugs, and incorporates most single agents active against diffuse lymphomas. PATIENTS AND METHODS: Ninety-one previously untreated patients were enrolled and 60 patients were confirmed eligible after central pathology review. Fifty-eight percent of patients had diffuse large-cell lymphoma (DLCL), 83% had stage III or IV disease, and 45% had B symptoms. RESULTS: Patients were treated with six to eight cycles of AMOPLACE and analyzed for response and survival. With a median follow-up of 48 months, complete responses (CRs) were seen in 68% of all patients with failure-free survival (FFS) and overall survival (OS) estimates at 4 years of 45% and 54%. In the DLCL subset, the CR rate was 69% and FFS and OS estimates at 4 years were 49% and 60%, respectively. The major toxicity was myelosuppression, with 73% of patients having WBC nadirs less than 1,000/microL; two treatment-related deaths occurred. CONCLUSION: We conclude that AMOPLACE is associated with CR and OS rates comparable with those of other third-generation regimens.

Adult↗

Living with mental illness: the family as caregiver.

1. Families of persons with severe mental illness are often anguished because of stressors and are unprepared to be caregivers. Their needs must be addressed by mental health professionals. 2. Family members may experience grief, guilt, anger, powerlessness, and fear. 3. Education and peer groups may be most helpful to family members in dealing with their distress and becoming better prepared caregivers.

Adaptation, Psychological↗

Radioimmunotherapy of human B-cell lymphoma with 90Y-conjugated antiidiotype monoclonal antibody.

We report the first case of 90Y-conjugated monoclonal antibody (MoAb) administration for human radioimmunotherapy. Ten mCi 90Y-labeled antiidiotype (anti-Id) MoAb were administered to a patient with B-cell lymphoma whose tumor successfully imaged with 111In-labeled anti-Id MoAb. No significant toxicities were observed. More than 2 g of unlabeled anti-Id MoAb were administered while clearing the circulating IgM idiotype prior to administration of the 90Y-MoAb. Transient partial regression of disease was observed. Serial fine needle aspirations of a malignant lymph node documented in vivo anti-Id penetration into a site that did not image by radioimmunoscintigraphy. The radiosensitivity of B-cell lymphoma, the tumor specificity of anti-Id, the antitumor activity of anti-Id alone, and the safe administration of 10 mCi 90Y-labeled anti-Id MoAb in this report suggest further investigation of this radioimmunoconjugate for therapy of B-cell lymphoma is warranted.

Adult↗

Enema-induced hyperphosphatemia.

Severe hyperphosphatemia and hypocalcemia developed following the administration of a single hypertonic sodium phosphate enema in an adult with mild chronic renal insufficiency.

Aged↗

Hypervitaminosis A unmasked by acute viral hepatitis.

A case of acute hypervitaminosis A complicating viral hepatitis is reported. Twenty days after presenting with hepatitis B, a 42-yr-old vegetarian developed acute hypervitaminosis A in the absence of recent, massive exposure to the vitamin. Findings included headache, confusion, skin desquamation, and hypercalcemia. Prior to developing hepatitis, he had ingested supplemental vitamin A without recognized ill effect. Liver and serum vitamin A without recognized ill effect. Liver and serum vitamin A levels were both elevated; the liver biopsy showed abundant, lipid-filled Ito cells and perisinusoidal fibrosis. This case demonstrates that patients with excessive hepatic stores of vitamin A may develop hypervitaminosis A during acute, intercurrent liver disease. Levels of retinol binding protein are reduced in hepatitis. This phenomenon may account for the findings in this case, since vitamin A is more toxic when not specifically bound to retinol binding protein. The size of the population at risk for this complication of hepatitis in unknown, but presumably it is growing with the widespread use of supplemental vitamin A.

Adult↗

Regulation of simian virus 40 transcription: sensitive analysis of the RNA species present early in infections by virus or viral DNA.

We have examined the discrete species of simian virus 40 (SV40) RNA present very early in infection of monkey cells with wild-type virus, with mutant tsA58 virus, and with the corresponding DNAs to distinguish between two classes of models for control of late transcription: (i) positive control mediated by large-T antigen and (ii) negative control mediated by a repressor protein associated with viral DNA in the virion. Total cytoplasmic or nuclear polyadenylated RNAs from infected cells were denatured with glyoxal, separated by electrophoresis on agarose gels, and transferred to diazobenzyloxymethyl paper. The positions of specific early and late RNA species were determined with region-specific SV40 DNA probes. The technique can detect individual RNAs present at the level of less than one copy per cell. After 9.5 h at 37 degrees C, appreciable amounts of two early RNAs (2.6 kilobases [kb] and 2.9 kb) were present in the cytoplasm of cells infected with wild-type virus or DNA, along with much smaller amounts of two late RNAs, 1.6 kb (16S) and 2.5 kb (19S). The amounts of the late RNAs were reduced, but they were still synthesized in the presence of cytosine arabinoside, an inhibitor of DNA synthesis. In comparable infections with tsA58 virus or DNA at nonpermissive temperature (41 degrees C), substantial amounts of the two early RNAs were again present, but the two late RNAs could not be detected. However, small amounts of the late RNAs were found when infections with tsA58 virus or DNA were prolonged to 30 h at 41 degrees C. These results are not consistent with negative control of late transcription through the action of a repressor and, taken together with other data, suggest that T antigen has an active role in late RNA synthesis. Specific early and late viral RNAs were also detected in the nuclear poly(A)(+) fractions and were similar in size to the RNA species found in the cytoplasmic polyadenylated fractions. The late nuclear RNAs (1.8 and 2.9 kb) were significantly larger than the late cytoplasmic species, possibly because they are precursors. The 2.6- and 2.9-kb early RNAs found in the cytoplasm are probably the messengers for large-T and small-t antigens, respectively.

Animals↗