Biomedical subjects

C Wheeler

Publications and source records attributed to C Wheeler.

At least 19 recordsLinked to original sources

PubMed1996

Human papillomavirus genotype as a predictor of persistence and development of high-grade lesions in women with minor cervical abnormalities.

Women referred for colposcopy with mild and moderate dyskaryosis and found to have only minor cervical abnormalities were screened for oncogenic human papilloma virus (HPV) types. The natural development of these abnormalities in 42 HPV-positive women was assessed by cytology and colposcopy at 6-month intervals for up to 2 years. As is the case with cancers and high-grade cervical intra-epithelial neoplasia (CIN), minor cervical abnormalities were frequently found to be associated with HPV16, -18, -31 and -33. Viral persistence and the development of high-grade lesions were found to be closely associated with HPV16; 56% of HPV16 isolates were persistent compared to 7% of other HPV types, and all 4 subsequent CIN 3 lesions were in women with persistent infection. A striking association of persistence with a variant of HPV16 having a base change at nucleotide 350 was observed. Ten of 12 women with this variant had persistent infection compared to only 1 of 16 women infected with the HPV16 prototype.

Adult↗

PubMed1996

Donor immunization with Haemophilus influenzae type b (HIB)-conjugate vaccine in allogeneic bone marrow transplantation.

Bone marrow transplant patients are at increased risk for infections with polysaccharide encapsulated organisms and respond poorly to polysaccharide vaccines. We evaluated the effect of donor immunization with Haemophilus influenzae type b (HIB) polysaccharide-conjugate vaccine on recipient antibody responses following allogeneic bone marrow transplantation. Thirty-two allogeneic transplant patients and their donors were immunized before transplantation with HIB-conjugate, tetanus toxoid and 23-valent pneumococcal vaccines. Following transplantation, patients received HIB-conjugate and tetanus toxoid vaccines at 3, 6, 12, and 24 months and 23-valent pneumococcal vaccine at 12 and 24 months. Thirty-three patients with unimmunized donors were immunized following transplantation in an identical manner. Patients whose donors were immunized had significantly higher total anti-HIB antibody concentrations at 3 months (P = .0001), 6 months (P = .0001), 12 months (P = .0001), and 24 months (P = .002) after transplant compared with patients whose donors were unimmunized. Higher antitetanus toxoid antibody concentrations were also noted in patients with immunized donors, whereas donor immunization with pneumococcal vaccine had no effect on antibody concentrations following transplantation. Donor immunization with HIB-conjugate vaccine resulted in higher antibody concentrations in patients as early as 3 months after allogeneic transplantation and may be an effective strategy to prevent HIB infections.

Adolescent↗

PubMed1996

Relaxin secretion in in vitro fertilization pregnancies.

OBJECTIVE: This study was designed to determine whether the late luteal functional status of the corpora lutea in in vitro fertilization cycles alters the secretion of relaxin during pregnancy. STUDY DESIGN: Analysis of serum relaxin, human chorionic gonadotropin, and steroid concentrations in sera of women with pregnancies viable beyond the twelfth week as a result of in vitro fertilization treatment was performed. RESULTS: The serum estradiol and progesterone concentrations decreased 5.5- and 4-fold from days 5 to 6 after human chorionic gonadotropin to days 11 to 13 after human chorionic gonadotropin, respectively. The serum relaxin concentration increased 8-fold between the 11- to 15-day interval and the 16- to 50-day interval after human chorionic gonadotropin and another 6-fold to the 51- to 90-day interval after human chorionic gonadotropin (all p < 0.01). Multiple linear regression analysis showed that the serum estradiol level 11 to 13 days after human chorionic gonadotropin and the serum human chorionic gonadotropin level 11 to 15 days after human chorionic gonadotropin were the most powerful paired predictors of the concentration of serum relaxin measured in the 11- to 15-day interval after human chorionic gonadotropin interval (R2 = 0.39, n = 50), the 16- to 50-day interval (R2 = 0.61, n = 51), and the 51- to 90-day interval (R2 = 0.55, n = 39). CONCLUSION: Secretion of relaxin is determined by an interaction of the late luteal functional status of the corpora lutea and the human chorionic gonadotropin secreted by the implanting pregnancy. These data allow for the hypothesis that inducing functional luteolysis by substituting one or more injections of luteinizing hormone for the human chorionic gonadotropin injection may decrease secretion of steroids, relaxin, and other factors from the corpora lutea during pregnancy, decreasing the risk of premature delivery in multiple gestations and the ovarian hyperstimulation syndrome.

Chorionic Gonadotropin↗

PubMed1996

Clinical phenotypes of different MPZ (P0) mutations may include Charcot-Marie-Tooth type 1B, Dejerine-Sottas, and congenital hypomyelination.

Hereditary demyelinating peripheral neuropathies consist of a heterogeneous group of genetic disorders that includes hereditary neuropathy with liability to pressure palsies (HNPP), Charcot-Marie-Tooth disease (CMT), Dejerine-Sottas syndrome (DSS), and congenital hypomyelination (CH). The clinical classification of these neuropathies into discrete categories can sometimes be difficult because there can be both clinical and pathologic variation and overlap between these disorders. We have identified five novel mutations in the myelin protein zero (MPZ) gene, encoding the major structural protein (P0) of peripheral nerve myelin, in patients with either CMT1B, DSS, or CH. This finding suggests that these disorders may not be distinct pathophysiologic entities, but rather represent a spectrum of related "myelinopathies" due to an underlying defect in myelination. Furthermore, we hypothesize the differences in clinical severity seen with mutations in MPZ are related to the type of mutation and its subsequent effect on protein function (i.e., loss of function versus dominant negative).

Adult↗

PubMed1996

Double dose-intensive chemotherapy with autologous stem-cell support for metastatic breast cancer: no improvement in progression-free survival by the sequence of high-dose melphalan followed by cyclophosphamide, thiotepa, and carboplatin.

PURPOSE: Twenty-one percent of responding metastatic breast cancer patients remain progression-free a median 50 months following one intensification cycle of cyclophosphamide (6,000 mg/m2), thiotepa (500 mg/ m2), and carboplatin (800 mg/m2) (CTCb) with autologous bone marrow transplantation (ABMT). This trial studied whether the sequence of high-dose melphalan followed by CTCb resulted in improved disease response and duration. METHODS: Women with at least partial responses (PRS) to induction received melphalan (140 or 180 mg/ m2) with peripheral-blood progenitor cell (PBPC) and granulocyte colony-stimulating factor (G-CSF) support. They were monitored as outpatients. After recovery, patients were hospitalized for CTCb with marrow, PBPC, and G-CSF support. RESULTS: Data on 67 women, at a median of 25 months from CTCb, were examined. After melphalan, 49 (73%) required admission for fever (89%), mucositis (35%), or infection (15%) (median stay, 8 days). All received CTCb. For the first 33 patients, the median days from start of melphalan to CTCb was 24. After liver toxicity (one death from venoocclusive disease [VOD]) developed in 11 patients during CTCb, the interval between intensifications was increased to 35 days without incident. Twenty-three patients (34%) are progression-free a median of 16 months post-CTCb. The median progression-free survival (PFS) and survival times for the whole group are estimated at 11 and 20 months, respectively. CONCLUSION: Treatment with this sequence of high-dose melphalan followed by CTCb has not resulted in superior PFS to date, when compared with single-intensification CTCb. This report discusses factors related to patient selection, the role of induced drug resistance, and the schedule of administration of alkylating agenting that may adversely influence outcome.

Adolescent↗

PubMed1996

Haemophilus influenzae type b (HIB)-conjugate immunization before bone marrow harvest in autologous bone marrow transplantation.

Immune reconstitution following autologous bone marrow transplantation (ABMT) is characterized by defects in B cell and T cell function and loss of specific antibody. In the late post-transplant period, patients are at risk for infections with polysaccharide encapsulated organisms and respond poorly to polysaccharide vaccines. We examined whether immunizing ABMT patients before bone marrow (BM) harvest enhanced the early recovery of specific antibody. Twelve patients were immunized before BM harvest with Haemophilus influenzae type b (HIB)-conjugate, tetanus toxoid and polysaccharide pneumococcal vaccines. Forty-one comparable ABMT patients not immunized prior to BM harvest were also studied. Following ABMT, both groups of patients were immunized with HIB-conjugate and tetanus toxoid vaccines at 3, 6, 12 and 24 months and with pneumococcal vaccine at 12 and 24 months. Patients immunized before BM harvest had higher HIB antibody concentrations during the first 2 years post-transplant, the differences reaching significance at 3 months (P = 0.0001) and following the 24-month dose (P = 0.048). Tetanus toxoid antibody concentrations were also significantly higher at 3 months (P = 0.001) and 6 months (P = 0.032) in patients immunized before BM harvest. There were no differences in pneumococcal antibody concentrations between the two groups. Immunization of patients before bone marrow harvest resulted in higher anti-HIB antibody concentrations following ABMT and may be an effective strategy to prevent infectious complications.

Adolescent↗

PubMed1995

Sequence analysis of wheat grain allergens separated by two-dimensional electrophoresis with immobilized pH gradients.

Micropreparative two-dimensional (2-D) gel electrophoresis with immobilized pH gradients (4-8) in the first dimension (IPG-DALT) was optimized for the separation of salt-soluble wheat grain proteins, associated with bakers' asthma disease. The resolved polypeptides were electroblotted onto a polyvinylidene difluoride (PVDF) membrane and incubated with the pooled sera from four asthmatic bakers. Bound IgE was demonstrated by alkaline phosphatase conjugated anti-human IgE. Major IgE binding was detected in the 27 kDa, 37 kDa and, to a lesser extent, in the 14-18 kDa area of the 2-D immunoblots, respectively. Since the main purpose of our study was to determine the N-terminal amino acid sequences of the major wheat grain allergens, N-terminal sequencing was performed for six out of a total of eleven major allergens located in the 27 kDa area, for one out of two 37 kDa allergens, and for two out of four 14-18 kDa allergens. Our results revealed that two of the 27 kDa polypeptides are clearly related to several Acyl-CoA oxidase variants of barley and rice, whereas no significant homologies were found for the remaining four 27 kDa allergens analyzed. The N-terminus of the 37 kDa allergen appeared to be blocked so that no sequence information was obtained, while the two 14-18 kDa allergens analyzed were identified as members of the wheat alpha-amylase-inhibitor family.

Allergens↗

PubMed1995

High-dose ifosfamide, carboplatin, and etoposide pharmacokinetics: correlation of plasma drug levels with renal toxicity.

An autologous bone marrow transplant regimen of ifosfamide, carboplatin, and etoposide (ICE) has been developed as treatment for certain malignancies. At maximum tolerated doses renal insufficiency precludes dose escalation. The objective was to examine whether measurement of plasma drug levels early during treatment would provide warning of renal failure. Nine patients received a 96-h continuous infusion of ifosfamide 16,000 mg/m2, carboplatin 1600 mg/m2, and etoposide 1200 mg/m2. Pharmacokinetics, including drug levels and plasma concentration-time curves, of ifosfamide, ultrafiltrable platinum (uPt) and etoposide were analyzed and correlated with renal function. One of the nine patients developed anuric renal failure requiring hemodialysis. By 17 h from the start of infusion, this patient showed substantially higher drug levels of ifosfamide (200 vs mean 217 microM) and uPt (19 vs mean 10 microM) than those patients with preserved renal function. The 95% confidence intervals suggested that a 16-22 h ifosfamide level > 153 microM and an uPt level > microM predict the development of significant renal dysfunction. Although drug levels were substantially higher at 56 h, the serum creatinine did not yet reflect kidney injury. This study suggests that high plasma ifosfamide and uPt levels, analyzed early in the course of a 96-h infusion of high-dose ICE, provide warning of severe and potentially fatal renal injury. Since ICE has substantial activity in a number of malignancies, but significant renal morbidity, real-time pharmacokinetic-guided dosing may reduce treatment-related toxicity.

Acute Kidney Injury↗

PubMed1995

Improved survival for patients with acute myelogenous leukemia.

PURPOSE: Despite improvement in chemotherapy and supportive care over the past two decades, overall survival for patients with acute myelogenous leukemia (AML) remains poor; only 25% to 30% of individuals with this disorder will be cured. In 1987, we initiated a prospective multiinstitution study designed to improve long-term survival in adults with AML. METHODS: We modified the usual 7-day treatment scheme of daunorubicin and cytarabine with high-dose cytarabine (HiDAC) on days 8 through 10 (3 + 7 + 3). Allogeneic or autologous bone marrow transplantation (BMT) was offered to all patients who entered complete remission (CR) to decrease the rate of leukemic relapse. Data were analyzed by intention to treat. RESULTS: CRs were achieved in 84 of 94 patients (89%; 95% confidence interval [CI], 83 to 95). Because of the high remission rate, factors previously thought to predict outcome, such as cytogenetics, WBC count, French-American-British (FAB) classification, sex, and age, were not useful prognostic variables. The overall survival rate for the entire cohort of patients from data of diagnosis is 55% at 5 years. Sixty percent of all patients who achieved a CR underwent marrow grafting. There was no significant difference in event-free survival (EFS) at 5 years comparing patients assigned to receive allogeneic BMT with patients assigned to receive autologous BMT (56% v 45%, P = .54). CONCLUSION: The long-term disease-free survival observed in this study is excellent compared with historical data. This improvement in survival is probably due to the high rate of remission induction, as well as to the effective nature of the consolidation therapy.

Adolescent↗

PubMed1995

Prognostic factors for prolonged progression-free survival with high-dose chemotherapy with autologous stem-cell support for advanced breast cancer.

PURPOSE: With a median observation time of 50 months from transplant, 13 (22%) of 62 women with metastatic breast cancer treated with high-dose chemotherapy at the Dana-Farber Cancer Institute (DFCI)/Beth Israel Hospital (BIH) remain progression-free. This study determined factors prognostic for prolonged progression-free survival (PFS). METHODS: From June 1988 to January 1992, women who responded to standard chemotherapy received high-dose cyclophosphamide, thiotepa, and carboplatin with autotransplantation. Data encompassing initial breast cancer diagnosis, metastatic presentation, and response to induction treatment were examined for correlations with improved PFS. RESULTS: The 5-year PFS rate for the entire group is estimated to be 21% (95% confidence interval [CI], 10% to 32%). For those patients who attained a complete response (CR) to induction therapy, the 5-year PFS rate is estimated to be 31% (95% CI, 0% to 63%). In univariate analyses, a single metastatic site, CR to induction therapy, prolonged interval from primary diagnosis to first metastases, estrogen receptor (ER)-negative tumors, and older age (> or = 40 years) were associated with prolonged PFS. In multivariate analyses, single metastatic site (P = .002) and attainment of a CR to induction chemotherapy (P = .04) were the most significant predictors for PFS, with a strong trend observed for an interval from primary diagnosis to onset of metastatic disease of 24+ months (P = .066). CONCLUSION: We and others have shown that 10% to 25% of women with metastatic breast cancer are progression-free after high-dose chemotherapy with autotransplantation. Those with chemosensitive disease, minimal tumor bulk, and a prolonged disease-free interval appear to benefit most. Emphasis should continue to focus on the development of more effective cytotoxic regimens and biologic approaches to increase the percentage of patients who may benefit from this approach.

Adolescent↗

PubMed1995

Phase I study of high-dose ifosfamide, carboplatin and etoposide with autologous hematopoietic stem cell support.

More effective high-dose combination regimens are needed which have broad cytotoxic activity, steep dose-response relations and non-overlapping non-hematologic toxicities (to allow administration of full doses of each agent). This study was designed to define the dose-limiting toxicities and maximum tolerated doses of ifosfamide, carboplatin and etoposide (ICE) with hematopoietic stem cell support. Ifosfamide and carboplatin were initially fixed at 75% and 80% of the single agent maximum tolerated doses, respectively, and etoposide added to the combination. After the dose-limiting toxicity of etoposide was reached, its dose was fixed and ifosfamide and carboplatin were individually dose escalated as tolerated. All agents were given by 96h continuous infusion (days -7 to -3). Autologous marrow, with or without peripheral blood progenitor cells, was reinfused on day 0. Forty eight adults with advanced malignancies were enrolled in cohorts of three to five patients. At the maximum tolerated doses of ifosfamide 16 g/m2, carboplatin 1.8 g/m2 and etoposide 1.2 g/m2, renal toxicity precluded further dose escalation. Two patients died of organ (renal, CNS) toxicity (4%). Renal toxicity was particularly prominent in patients with prior cisplatin exposure. An early chemotherapy-stopping rule was developed, supported by pharmacologic analysis, which resulted in immediate discontinuation of ifosfamide and carboplatin if the serum creatinine, monitored twice daily during chemotherapy, exceeded 1.5 mg/dl and was > 0.5 mg/dl above baseline. High-dose ICE is well tolerated if serum creatinines are carefully monitored during chemotherapy administration. The early chemotherapy-stopping rule may enhance safety of the regimen but requires validation by addition correlation with pharmacokinetic data for each of the chemotherapeutic agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Polysaccharide conjugate vaccine responses in bone marrow transplant patients.

Bone marrow transplant patients have impaired responses to pure polysaccharide (PS) vaccines and are at an increased risk for disease caused by PS encapsulated pathogens such as Haemophilus influenzae type B (HIB) and Streptococcus pneumoniae. We immunized 35 BMT patients (21 allogeneic and 14 autologous) ages 2-45 years with pure PS pneumococcal (Pnu-imune 23) HIB-conjugate (HibTITER), and tetanus toxoid vaccines. Patients were assigned to receive vaccines at either 12 and 24 months after transplantation or at 24 months only. Only 19% of all enrolled patients developed protective antibody concentrations (> or = 0.300 microgram antibody nitrogen/ml) to the 6 pneumococcal serotypes measured after the 24-month immunization. Poor response to pneumococcal vaccine was not different for the 2 study groups and was similar to previous studies. In contrast, HIB-conjugate vaccine elicited protective concentrations of antibody (> or = 1.0 microgram/ml) in 56% of patients after 1 dose and in 80% after 2 doses. The group that received 2 doses of HIB-conjugate vaccine had a significantly higher geometric mean antibody concentration of 14.5 micrograms/ml as compared with 1.43 micrograms/ml for those receiving only 1 dose (P = 0.012). Responses to tetanus toxoid vaccine were similar to HIB-conjugate vaccine, with a booster response documented after the second dose. In summary, 2 doses of HIB-conjugate vaccine given at 12 and 24 months after transplantation produced protective antibody concentrations in 80% of patients. While the response to pure PS pneumococcal vaccine was poor, the results with HIB-conjugate vaccine suggest that future pneumococcal conjugate vaccines may also benefit BMT patients.

Adolescent↗

PubMed1994

Recombinant human erythropoietin for the treatment of the anaemia associated with autologous bone marrow transplantation.

Patients with solid tumours undergoing high-dose chemotherapy with autologous bone marrow transplantation use an average of 10 units of packed red blood cells (PRBC) while awaiting haemopoietic reconstitution. They are also known to have inappropriately low endogenous erythropoietin levels for their degree of anaemia. This pilot study was designed to determine the effects of recombinant human erythropoietin (rHuEPO) on erythroid recovery and PRBC transfusion requirements. Ten patients received high-dose chemotherapy (days -7 to -3), bone marrow reinfusion (day 0), and then rHuEPO (day 1 onward). RHuEPO (200 units/kg intravenous bolus daily), along with iron supplementation, was administered for 28 d or until a haematocrit (Hct) of 35% (independent of transfusions) was reached, whichever occurred first. PRBCs were routinely given for Hct < or = 25% and platelets for counts < 20,000/microliters. Eight (80%) patients developed a brisk reticulocytosis (median peak reticulocyte count 0.32 x 10(9)/l) and a haematocrit > or = 30% independent of red blood cell transfusions within 32 d of receiving marrow, as compared to 20/37 (54%) similarly treated controls. An unexpected finding was the more rapid engraftment in myeloid and platelet lineages in a subset of rHuEPO-treated patients. Quick return of red blood cells (17 v 33 d) (P = 0.0001), platelets (14 v 19 d) (P = 0.04), and neutrophils (13 v 25 d) (P = 0.01) (with circulating myeloblasts and early myeloid forms) characterized recovery from an ifosfamide-based intensification with rHuEPO support. Similar trilineage enhancement of haemopoiesis did not occur with the possibly more myeloablative cyclophosphamide-based regimens. Despite the enhancement by rHuEPO on reticulocytosis, there was no significant decrease in PRBC transfusion requirements. RHuEPO proved to be a well-tolerated agent in enhancing reticulocytosis following high-dose chemotherapy. Further study to elucidate the activity of erythropoietin on both erythroid and non-erythroid growth and maturation appears warranted.

Adult↗

PubMed1994

Double dose-intensive chemotherapy with autologous marrow and peripheral-blood progenitor-cell support for metastatic breast cancer: a feasibility study.

PURPOSE: Twenty-seven percent of responding metastatic breast cancer patients remain progression-free a median 29 months following one intensification course of cyclophosphamide (6,000 mg/m2), thiotepa (500 mg/m2), and carboplatin (800 mg/m2) (CTCb) with autologous bone marrow transplantation (ABMT). European investigators report high complete response (CR) rates with melphalan for breast cancer. This trial studied the feasibility of two tandem high-dose intensification therapies in an attempt to optimize disease response and duration. PATIENTS AND METHODS: Women with at least partial responses (PRs) to induction therapy received melphalan (140 to 180 mg/m2), followed 24 hours later by chemotherapy and granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral-blood progenitor cells (PBPCs) and subsequent G-CSF until WBC recovery. The women were monitored as outpatients. After recovery, patients were hospitalized for CTCb with marrow, PBPC, and G-CSF support. RESULTS: Twenty women were assessable. Fourteen (70%) required admission for fever (10% infection) or mucositis (35%) after melphalan (median stay, 5 days). Median days of absolute neutrophil count (ANC) less than 500/microL and platelet count less than 20,000/microL were 6 and 5.5, respectively. Patients received CTCb 25 days after starting melphalan and had a hospital stay of 25 days. After CTCb, median days of ANC less than 500/microL and platelet count less than 20,000/microL were 11.5 and 24, respectively. Grade 3 toxicities included venoocclusive disease (VOD) (10%), mucositis (45%), and infection (20%). Toxicities were reversible without mortality. CONCLUSION: With mobilized PBPCs and growth factors, double dose-intensive chemotherapy is feasible with acceptable toxicity. When compared with trials using marrow alone, these supportive adjuncts decrease sepsis and organ toxicity. The concepts of dose and dose-intensity may now be more effectively and safely studied in chemosensitive tumors, including breast cancer.

Adult↗

PubMed1994

High-dose cyclophosphamide, thiotepa, and carboplatin with autologous marrow support in women with measurable advanced breast cancer responding to standard-dose therapy: analysis by age.

The analysis was undertaken to determine if the time to progression and survival for women with breast cancer treated with high-dose chemotherapy after a conventional-dose induction therapy differs significantly for women younger and older than 40 years of age. All patients treated in phase II or III protocols of high-dose chemotherapy for breast cancer are included in this analysis. Women were treated on one of six protocols: four sequential phase II protocols for metastatic breast cancer involving cyclophosphamide at a dose of 6000 mg/m2, thiotepa at 500 mg/m2, and carboplatin at 800 mg/m2 (CTCb) chemotherapy; one phase II study of CTCb chemotherapy for stage III or inflammatory breast cancer; and a Cancer and Leukemia Group B phase III study of cyclophosphamide, carmustine, and cisplatin for women with more than 10 involved lymph nodes after primary therapy. Eligibility criteria for the patients with metastatic disease included histologically documented breast cancer, at least a partial response to conventional dose therapy, no prior pelvic radiotherapy, cumulative doxorubicin of less than 500 mg/m2, and physiologic age of 18-55 years. Patients with inadequate renal, hepatic, pulmonary, and cardiac function or tumor involvement of marrow or central nervous system were excluded. Of 99 registered patients, three (3%) died of toxicity. There were no toxic deaths in protocols for stage II and III disease, and to date none of these patients have relapsed. Thus, there are no differences by age for these studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

The diagnosis of schizophrenia and its impact on the primary caregiver.

This qualitative study investigates how the diagnosis of schizophrenia in a young adult impacts on the primary caregiver in the family. In this study all participants were mothers who had sons recently diagnosed with schizophrenia. An extensive literature review revealed a lack of research in this area. The research methodology is described. Data analysis determined themes or patterns of experience amongst participants in this study. From this small study it was seen that the impact on the participants was intensely traumatic and far reaching. Six themes emerged: trauma/distress, fear, uncertainty, relief, disruption and powerlessness. The results have major implications for nurses and other health professionals working in the Mental Health field.

Adaptation, Psychological↗

PubMed1994

Reproducibility of a meal-based food frequency questionnaire. The influence of format and time interval between questionnaires.

OBJECTIVE: To compare the reproducibility and reported level of energy intake obtained using three versions of a meal-based food frequency questionnaire (FFQ) considering, firstly, the influence of FFQ format and, secondly, the influence of time interval between questionnaires. DESIGN: The study was conducted in two parts. In the first, subjects were randomly allocated to three groups (one for each FFQ) and sent, by mail, the same FFQ to complete on two separate occasions with a time interval of 4-6 weeks. In the second study, the reproducibility of one of the FFQs used in the initial study was compared, after an interval of 3 months, in a further group of people, matched as far as possible for gender, age and socio-economic status of area of residence. SUBJECTS: The study population was 651 supermarket shoppers from Geelong, a regional centre with a population of 150,000 situated in Victoria, Australia, who had previously responded to an in-store survey about meat purchasing patterns. Of the 651 shoppers, 144 women and nine men (38% of those eligible) in part I and 98 women and two men (45% of those eligible) in part II of the study satisfactorily completed a FFQ on both occasions. RESULTS: While there were few statistically significant differences in terms of mean nutrient intake and nutrient density between the three FFQ formats, all under-estimated energy intake relative to the minimum estimated energy requirements for a sedentary population. A significant decrease in reported intake of approximately 10% was also observed, regardless of FFQ format used, when the same questionnaire was completed a second time after an interval of 4-6 weeks. In contrast, when the time interval between questionnaires was increased to 3 months, there were few significant differences in intake between the first and second administrations. Moreover those changes in food intake which were significantly different after the longer interval were, in general, consistent with expected seasonal changes in food intake patterns. CONCLUSION: Under the conditions of our study differences in FFQ format appeared to have less effect on estimates of mean intake than the length of the time interval between questionnaires. Our results suggest that motivation to complete a FFQ is significantly diminished on the second occasion, when the interval between FFQs is only 4-6 weeks and to a lesser extent when it is 3 months. Researchers planning studies which aim to assess short-term changes in food intake by means of a FFQ, for example after an intervention programme, need to be aware of this effect and to determine its magnitude, by assessing the reproducibility of their FFQ over the relevant time-interval prior to the proposed intervention and by including an appropriate non-intervention comparison group in the design of their study if seasonal effects are likely to occur in the course of the study.

Energy Intake↗

PubMed1994

High-dose ifosfamide/carboplatin/etoposide with autologous hematopoietic stem cell support: safety and future directions.

Agents with broad cytotoxic activity, steep linear log dose-response relationships, relative non-cross-resistance, and nonoverlapping nonhematologic toxicities can be combined to create new high-dose combination regimens. We have previously reported phase I dose-escalation studies of ifosfamide, carboplatin, and the combination of the two. Etoposide has reported synergism with these alkylators and produces mucositis as its dose-limiting toxicity. The current study was designed to define the maximum tolerated doses of high-dose combination ifosfamide/carboplatin/etoposide (ICE), with stem cell support for amelioration of hematologic toxicity. Forty-eight adults with advanced malignancy received ICE chemotherapy by 96-hour continuous infusion. Initially, etoposide was added to fixed-dose ifosfamide and carboplatin, then the maximum tolerated dose of etoposide was fixed while doses of the alkylators were individually escalated. Autologous marrow, with or without peripheral blood progenitor cells, was reinfused 3 days after completing chemotherapy. The maximum tolerated doses of ifosfamide, carboplatin, and etoposide were identified as 16 g/m2, 1.8 g/m2, and 1.2 g/m2, respectively. Mortality was 4%. Patients who had prior cisplatin exposure were at increased risk for renal toxicity. If serum creatinine levels (monitored twice daily) rose sharply during chemotherapy, ifosfamide and carboplatin were immediately stopped. Severe multiorgan toxicity developed in the few patients who experienced early renal toxicity. Early stopping enhanced the safety of this regimen. Interpatient differences in chemotherapy drug metabolism or reduced renal clearance may predispose individuals to severe toxicity by increasing overall drug exposure. It was concluded that the ICE regimen is well tolerated and warrants further exploration as treatment of patients with small cell lung cancer, ovarian and germ cell carcinomas, and lymphomas in phase II trials.

Adult↗