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Biomedical subjects

J C Weeks

Publications and source records attributed to J C Weeks.

At least 73 records · Page 4Linked to original sources
PubMed1997

Age-related patterns of care: evidence against ageism in the treatment of early-stage breast cancer.

PURPOSE: To assess whether the use of adjuvant systemic therapy in postmenopausal women with early-stage breast cancer is influenced by patient age. METHODS: A retrospective cohort study based on data collected from medical records and from patients and their surgeons was performed among 746 postmenopausal patients diagnosed with early-stage breast cancer at 30 hospitals located throughout Minnesota. The adjusted odds of receiving hormonal therapy, chemotherapy, and both hormonal therapy and chemotherapy as a function of age was determined. RESULTS: Among women with negative lymph nodes, 62% received some form of adjuvant drug therapy. For these women, the likelihood of receiving hormonal therapy or both hormonal therapy and chemotherapy did not vary with patient age and the likelihood of receiving chemotherapy declined with age. Among women with positive lymph nodes, 92% received some form of adjuvant therapy. For these women, the likelihood of receiving hormonal therapy increased with age and the likelihood of receiving chemotherapy declined with age, as did the likelihood of receiving both hormonal therapy and chemotherapy. CONCLUSION: The observed associations between age and the use of adjuvant systemic therapy appear to reflect, in general, available information about treatment efficacy and do not suggest underuse among elderly women with early-stage breast cancer. The use of adjuvant therapy depends on clinical factors that predict the increased risk of metastases or the increased likelihood of response to treatment, rather than other sociodemographic factors. Our results also suggest that younger postmenopausal women with positive lymph nodes compared with older women may be undertreated with respect to tamoxifen because of the substitution of chemotherapy for hormonal therapy.

Age Factors↗
PubMed1997

Outcomes assessment in the NCCN.

Outcomes assessment has two primary goals: the evaluation of treatments and the evaluation of quality of care. Data on the outcomes associated with specific interventions may provide an empiric basis for guidelines in areas for which no randomized trial data are available. Also, monitoring of patterns of care and outcomes is an essential component of institutional efforts to implement guidelines and to benchmark themselves against regional and national norms. The National Comprehensive Cancer Network (NCCN) has adopted a three-phase approach to its outcomes assessment program. Phase 1, already completed, involved taking a systematic inventory of members' existing institutional data sources. Phase 2, which is currently in progress, entails pooling data from existing outcomes data bases. In particular, tumor registry data from the National Cancer Data Base are being used to examine patterns of care and outcomes in NCCN institutions and to benchmark them against national norms. Phase 3, begun within the past year, involves the creation of a uniform outcomes assessment system for the NCCN.

Breast Neoplasms↗
PubMed1996

Target muscles and sensory afferents do not influence steroid-regulated, segment-specific death of identified motoneurons in Manduca sexta.

Programmed cell death plays a critical role in sculpting the nervous system during embryonic development. In holometabolous insects, cell death also plays an important role in the reorganization of the nervous system during metamorphosis. In Manduca sexta, cell death and the factors that regulate it can be studied at the level of individually identified neurons. The accessory planta retractor (APR) motoneurons undergo segment-specific death during the larval-pupal transformation. APRs in abdominal segments 1, 5, and 6 die at pupation; those in abdominal segments 2, 3, and 4 survive until adulthood. Juvenile hormone and ecdysteroids regulate the metamorphic restructuring of the nervous system, but the factors that determine which APRs will live and which will die are not known. The present study assessed the possible importance of cell-cell interactions in determining APR survival at pupation by removing APR's target muscle or mechanosensory input early in the final larval instar, prior to the hormonal cues that trigger the larval-pupal transformation. The motoneurons showed their normal, segment-specific pattern of death in nearly all cases. These results suggest that target muscles and sensory input play little or no role in determining the segment-specific pattern of APR survival at pupation.

Afferent Pathways↗
PubMed1996

Cell culture approaches to understanding the actions of steroid hormones on the insect nervous system.

During metamorphosis of the hawkmoth, Manduca sexta, ecdysteroids regulate the dendritic remodeling and programmed death of identified motoneurons. These changes contribute to the dramatic reorganization of behavior that accompanies metamorphosis. As a step toward elucidating cellular and molecular mechanisms by which ecdysteroids affect neuronal phenotype, we have investigated the responses of Manduca motoneurons to ecdysteroids in vitro. Following dendritic regression at the end of larval life, thoracic leg motoneurons placed in culture respond to ecdysteroids by an increase in branching complexity, similar to events in vivo. Growth cone structure is affected markedly by ecdysteroids. At pupation, a rise in ecdysteroids triggers the segment-specific death of proleg motoneurons: the same segmental pattern of death is observed when motoneurons from different segments are removed from the nervous system and exposed to ecdysteroids in vitro. These studies provide strong evidence that Manduca motoneurons are direct targets of steroid action and set the stage for further studies of the specific mechanisms involved.

Animals↗
PubMed1996

Use of hematopoietic colony-stimulating factors: the American Society of Clinical Oncology survey. The Health Services Research Committee of the American Society of Clinical Oncology.

PURPOSE: Dissemination of use of the hematopoietic colony-stimulating factors (CSFs) is unprecedented in oncology, with almost all physicians having experience with granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) shortly after the drugs received Food and Drug Administration (FDA) approval in 1991. The American Society of Clinical Oncology (ASCO) Health Services Research Committee sought to assess patterns of use of CSFs before dissemination of its first-ever publication of ASCO guidelines. METHODS: A questionnaire describing clinical scenarios was mailed to American oncologists and hematologists who practice medical oncology. In each scenario, the physician was asked whether he would prefer to use a CSF to prevent or treat neutropenia. RESULTS: The response rate to the mailed survey was 49% (N = 475). Most physicians preferred to use CSFs for secondary prophylaxis in patients receiving chemotherapy at rates of 44% to 85%, rather than reduce doses. Patterns of use did not differ for palliative, curative, or adjuvant chemotherapy. While the majority of CSF patterns of care were similar to those recommended in the ASCO guidelines, more than half of the physicians chose to use CSFs in the treatment of febrile neutropenia, an area not supported in the subsequent guidelines. In general, physicians at academic medical centers and in Health Maintenance Organization (HMO) practices were more likely to prefer dose-reduction strategies over addition of CSFs, while fee-for-service physicians preferred the opposite strategies. CONCLUSION: Variations in CSF preferences for use were related to differences in clinical characteristics (history of afebrile v febrile neutropenia), drug characteristics (G-CSF or GM-CSF), and physician practice characteristics (HMO or fee-for-service setting). However, before dissemination of the guidelines, the majority of American oncologists preferred strategies that were subsequently included in the ASCO CSF guidelines. CSF guidelines would be most likely to reduce CSF use for treatment of afebrile and uncomplicated febrile neutropenia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Novel dual innervation of a larval proleg muscle by two similar motoneurons in the tobacco hornworm Manduca sexta.

In Manduca sexta, the accessory planta retractor muscle (APRM), which retracts the larval proleg, is innervated by two excitatory motoneurons, the accessory planta retractor motoneurons (APRs). These muscles and motoneurons have been the focus of a number of developmental and behavioral studies. The present study investigated properties of the pair of APRs that innervate each APRM and determined their pattern of innervation of APRM fibers. Members of APR pairs could not be distinguished by their anatomical or electrical properties (resting membrane potential, input resistance and spike threshold). Spontaneous synaptic inputs to members of APR pairs were highly correlated, whereas spontaneous synaptic inputs to APRs and functionally dissimilar motoneurons were not well correlated. Synaptic inputs from identified mechanosensory neurons and interneurons to the two APRs were qualitatively similar, but the magnitude of the response to sensory stimulation sometimes differed within a pair. Both APRs produced large, rapidly rising excitatory junction potentials in APRM fibers. Within the APRM, some fibers were singly innervated by one or the other APR while the remaining fibers were dually innervated by both APRs. In dually innervated fibers, the motor terminals of the two APRs were spatially segregated. This innervation pattern appears to be unique among insects and shares some properties with the innervation of vertebrate muscle.

Animals↗
PubMed1996

The initiation of pre-ecdysis and ecdysis behaviors in larval Manduca sexta: the roles of the brain, terminal ganglion and eclosion hormone.

Each larval molt of Manduca sexta culminates in the sequential performance of pre-ecdysis (cuticle loosening) and ecdysis (cuticle shedding) behaviors. Both behaviors are thought to be triggered by the release of a peptide, eclosion hormone (EH), from brain neurons whose axons extend the length of the nervous system. EH bioactivity appears in the hemolymph at the onset of pre-ecdysis behavior, and EH injection can trigger pre-ecdysis and ecdysis behaviors prematurely. The present study examined the effects of removing or disconnecting portions of the central nervous system prior to the time of EH release on the initiation of pre-ecdysis and ecdysis behaviors at the final larval molt. We found that the initiation of pre-ecdysis abdominal compressions at the appropriate time required the terminal abdominal ganglion (AT) but not the brain; the initiation of pre-ecdysis proleg retractions at the appropriate time required neither the AT nor the brain; the initiation of ecdysis at the appropriate time usually required the brain but did not require the AT; and premature pre-ecdysis (but not ecdysis) could be elicited in isolated abdomens by injection of EH. Finally, pre-ecdysis behavior performed by brainless larvae was not associated with the normal elevation of EH bioactivity in the hemolymph or the normal loss of EH immunoreactivity from peripheral neurohemal release sites.

Animals↗
PubMed1996

Habituation and dishabituation of the proleg withdrawal reflex in larvae of the sphinx hawk, Manduca sexta.

The neural circuit for the proleg withdrawal reflex (PWR) of Manduca sexta larvae exhibits activity-dependent plasticity. This study demonstrates habituation and dishabituation of PWR behavior. Repeated deflection of 1 or 5 mechanosensory hairs on a proleg at a 60-s interstimulus interval (ISI) for 20 trials produced a significant decrease in evoked force of proleg withdrawal. Habituation was similar with 30-s and 60-s ISIs and nonsignificant with a 5-min ISI or without repeated stimulation. Habituated responses recovered after cessation of stimulation or pinch of the body wall (dishabituation). The role of intersegmental influences was tested by severing connectives to leave different numbers of ganglia connected to the test segment. Habituation was robust even in test segments that were disconnected from the rest of the central nervous system. The PWR of Manduca is appropriate for further analysis of cellular mechanisms underlying learning.

Animals↗
PubMed1995

A single pair of interneurons controls motor neuron activity during pre-ecdysis compression behavior in larval Manduca sexta.

Manduca sexta molts several times as a larva (caterpillar) before becoming a pupa and then an adult moth. Each molt culminates in ecdysis behavior, during which the old cuticle is shed. Prior to each larval ecdysis, the old cuticle is loosened by pre-ecdysis behavior, which includes rhythmic, synchronous compressions of the abdomen. A previous study indicated that motor neuron activity during pre-ecdysis compression behavior is driven by an ascending neural pathway from the terminal abdominal ganglion. The present study describes a pair of interneurons, designated IN-402, that are located in the terminal ganglion and belong to the ascending pathway. Each IN-402 is synchronously active with pre-ecdysis compression motor bursts, and bilaterally excites compression motor neurons throughout the abdominal nerve cord via apparently monosynaptic connections. The pair of IN-402s appears to be the sole source of rhythmic synaptic drive to the motor neurons during the pre-ecdysis compression motor pattern. These interneurons play a key role in the production of larval pre-ecdysis behavior, and are candidates for contributing to the developmental weakening of pre-ecdysis behavior at pupation.

Animals↗
PubMed1995

Steroid hormone effects on neurons subserving behavior.

Recent advances in understanding effects of steroid hormones at the level of individual neurons have been achieved using model systems. Steroid hormone effects on dendritic morphology, synaptic function and ionic conductances have been implicated in the regulation of behavior in both vertebrates and invertebrates. Particularly exciting are studies demonstrating steroid hormone effects on specific synaptic connections and ionic currents. There also has been important progress in understanding the diversity of sites and mechanisms of hormone action, encompassing both genomic and non-genomic effects of steroids on neuronal properties.

Animals↗
PubMed1995

Special issues that arise in applying techniques of economic analysis to evaluation of cancer therapies.

The papers presented at this conference and reprinted in this monograph provide an opportunity to begin the process of establishing a shared language, set of goals, and "methods tool chest" for clinical researchers and economists to use in approaching the integration of economic analysis into cancer clinical trials. The first step in this process should be to recognize that there are several special issues that arise in applying the techniques of economic analysis to the evaluation of cancer therapies. These issues include the following: 1) The clinical course of cancer is complex, 2) clinical research and clinical trials are in the mainstream of cancer care, 3) cancer therapy is multidisciplinary, and 4) "best supportive care" is a rarely studied alternative.

Clinical Trials as Topic↗
PubMed1995

Economic considerations in comparing whole abdominal radiotherapy with combination doxorubicin-cisplatin chemotherapy in advanced endometrial carcinoma: how much economic data should be collected?

The key features of this study from the perspective of designing an economic analysis are that the resources consumed and the expected toxic effects are likely to be quite different in the two study arms, median survival will be measured in years, and the initial treatment assignment may affect the clinical course and resource consumption of the terminal phases of illness. Collecting complete data on all the costs associated with treatment, short-term toxic effects, long-term toxic effects, and treatment of recurrent disease as well as tracking the complex clinical course of patients over many years of follow-up would be an enormous undertaking. However, "phase II" or historical data on the costs and outcomes of care associated with each of these two treatment regimens would allow for a more tailored approach. But perhaps the first question that should be answered in designing an economic analysis to accompany a clinical trial is whether the resulting data are likely to be important. This study does not fulfill one of the main criteria for judging the appropriateness of including an economic analysis--large resource consequences. Fewer than 6000 cases of stage III or IV endometrial cancer occur annually in the United States, of which only a portion would be appropriate for the alternative treatment strategies evaluated in this protocol. Therefore, although the clinical question posed by this protocol is appropriate and important, the aggregate economic consequences of choosing one treatment approach over the other may not be of sufficient magnitude to justify the investment in a prospective economic analysis conducted alongside the clinical trial.

Abdomen↗
PubMed1995

Proposed phase III trial comparing laparoscopic-assisted colectomy versus open colectomy for colon cancer.

Despite many important medical advances, surgery remains the primary treatment modality for most of the 109,000 individuals who are newly diagnosed with colon cancer each year. Surgery not only provides extirpation of the primary tumor that relieves symptoms and prevents complications but also provides important staging information. Although oncologic results from open colectomy are well established, these traditional resective and staging techniques are challenged by the introduction of minimal-access surgery. Laparoscopic cholecystectomy, which shortens postoperative recovery and decreases disabilities and cost, has become the preferred surgical approach to cholelithiasis. Many propose that minimal-access surgery of the colon may offer similar advantages. Laparoscopic-assisted segmental resections of the colon can be performed using laparoscopic techniques to ligate vasculature and mobilize and exteriorize bowel and extracorporal techniques to resect and anastomose bowel. Collective preliminary data from a consortium of experienced laparoscopic surgeons support that laparoscopic-assisted colectomy is safe, feasible, and reduces recovery times and disabilities. Since differences between laparoscopic-assisted and open colectomy have not been rigorously tested, and concern has been raised regarding the adequacy of this technique for staging and treating colon cancer, a prospective randomized multi-institutional trial is proposed. The primary aim of such a trial will be to test the hypothesis that disease-free survival and overall survival are equivalent, regardless of whether patients receive laparoscopic-assisted or open colectomy. The secondary aim of the trial will be to determine the safety of of laparoscopic-assisted colectomy compared with open colectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials, Phase III as Topic↗
PubMed1995

Decreased monosynaptic sensory input to an identified motoneuron is associated with steroid-mediated dendritic regression during metamorphosis in Manduca sexta.

The proleg withdrawal reflex of Manduca sexta larvae is mediated by mono- and polysynaptic connections from afferents innervating mechanosensory planta hairs (PHs) to ipsilateral proleg retractor motoneurons. During the larval-pupal transformation, a rise in ecdysteroids causes the dendrites of proleg motoneurons to regress and, concurrently, the proleg withdrawal reflex is lost. The objective of this study was to identify synaptic correlates of dendritic regression that contributed to this behavioral change. The accessory planta retractor (APR) motoneuron regresses during the larval-pupal transformation and dies in a segment-specific pattern after pupation. The compound excitatory postsynaptic potential (cEPSP) evoked in APR by electrically stimulating the proleg sensory nerve decreased in amplitude during the larval-pupal transformation. The developmental decrease in cEPSP amplitude, the extent of APR's regression, and several of APR's intrinsic electrical properties were similar in segments in which the motoneuron was fated to live or die. In heterochronic mosaic pupae bearing retained larval PH afferents, APR's dendritic regression was associated with decreases in both the mean amplitude of monosynaptic EPSPs produced by PH afferents and the proportion of PH afferents that produced detectable EPSPs. These changes appeared due to a developmental decrease in the size of the synaptic currents produced by PH afferents. Evidence was also obtained suggesting that PH afferents do not regress at pupation. These findings support the hypothesis that the ecdysteroid-mediated regression of proleg motoneuron dendrites disconnects them from sensory inputs and, thereby, contributes to the elimination of the proleg withdrawal reflex.

Animals↗
PubMed1995

Using a pen-based computer to collect health-related quality of life and utilities information.

We have developed a system that uses the Newton MessagePad technology as part of a client-client-server paradigm to collect health-related quality of life information from breast cancer patients attending an outpatient clinic at the Dana-Farber Cancer Institute. Patients are asked to fill out an electronic questionnaire on the Newton, which then uploads the information into the institution's Oracle database. The program consists of a separate questionnaire engine and question base, facilitating questionnaire design and allowing us to give different questionnaires to different patients dynamically. The results of a preliminary trial show excellent user-acceptance of the device. Finally, we present a general framework for such systems and discuss issues that developers must consider when implementing a pen-based computer project.

Adult↗
PubMed1994

Influence of interganglionic interactions on steroid-mediated dendritic reorganization and death of proleg motor neurons during metamorphosis in Manduca sexta.

In Manduca sexta, the larval abdominal prolegs and their muscles degenerate at pupation. The proleg motor neurons undergo a period of dendritic regression, after which a specific subset of them dies. The surviving motor neurons undergo dendritic outgrowth during pupal-adult development, and most die after adult emergence. All of these events are regulated hormonally by ecdysteroids and juvenile hormone, but interactions of the motor neurons with other cells may potentially contribute as well. To investigate the possible influence of interganglionic neural interactions, we chronically isolated individual abdominal ganglia by severing the adjacent rostral and caudal connectives in the larval stage. Subsequent metamorphic changes in proleg motor neurons were examined in the isolated ganglia and ganglia adjacent to the isolated ganglia. Two abnormalities were observed: (1) some imprecision in the timing of motor neuron death, both at pupation and after adult emergence, and (2) the growth of ectopic neurites outside the neuropil boundaries during pupal-adult development (in ganglia with or without neuromas caused by connective transections). Other aspects of proleg motor neuron metamorphosis, including the segment-specific death of motor neurons at pupation, were the same as that in intact and sham-operated insects. Thus, interganglionic interactions appear to play a relatively minor role in the steroid-mediated metamorphic transformation of proleg motor neurons.

Animals↗