Using health-related quality-of-life information: clinical encounters, clinical trials, and health policy.
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Clinical Trials as Topic↗
Biomedical subjects
J C Weeks
Publications and source records attributed to J C Weeks.
Oral care of people with disability: a qualitative exploration of the views of nursing staff.
This study aimed to identify influences, attitudes and actions of nursing staff in relation to oral care for people with disabilities. Individual in-depth interviews of twenty two nursing staff were conducted. Enabling and inhibiting factors in the reported attitudes, approaches and practices were identified. The main enabling factors were that nursing staff saw mouth care as part of their role and took an empathic and caring approach to its delivery. They aimed to make the residents socially acceptable, improve their self-esteem and make their mouths clean and breath fresher. Inhibiting factors were: a lack of training, time constraints associated with workload, and poor understanding of the processes causing dental disease. The study concludes that improvements in oral care by nursing staff can be encouraged by working with nurses' attitudes, values and beliefs. Once the desired behaviour change has occurred then the lack of knowledge can be addressed.
Attitude of Health Personnel↗
Controversies regarding laparoscopic colectomy for malignant diseases.
Surgical investigators have shown that a hemicolectomy can be done laparoscopically. This minimally invasive approach to treat colon cancer potentially reduces hospitalization time, hastens return to normal activity, and reduces health care costs. Hopefully, all of these favorable outcomes can be achieved without compromising cancer control. At present, however, the issues regarding laparoscopic colectomy are not clear, and prospective studies are necessary to validate that this new procedure is superior to open colectomy. Because cancer control might be compromised by this new procedure, laparoscopic colectomy should not be accepted by the surgical community because of the allure of new technology or the hope that it is equivalent to open colectomy in controlling a curable disease. Rather, a randomized trial of laparoscopic colectomy compared with open colectomy is needed to prove that cancer control is not different and that laparoscopic colectomy is cost-effective.
Colectomy↗
Effects of a protein synthesis inhibitor on the hormonally mediated regression and death of motoneurons in the tobacco hornworm, Manduca sexta.
The larval-pupal transformation of Manduca sexta is accompanied by the loss of the abdominal prolegs. The proleg muscles degenerate, the dendritic arbors of proleg motoneurons regress, and a subset of the proleg motoneurons dies. The regression and death of proleg motoneurons are triggered by the prepupal peak of ecdysteroids in the hemolymph. To investigate the possible involvement of protein synthesis in these events, we gave insects repeated injections of the protein synthesis inhibitor, cycloheximide (CHX), during the prepupal peak. Examination of insects 3-5 days following CHX treatment showed that CHX inhibited the death of proleg motoneurons and the production of pupal cuticle in a dose-dependent fashion. When insects were allowed to survive for 10 days after the final CHX injection, motoneuron death and pupal cuticle production sometimes occurred belatedly, apparently in response to the ecdysteroid rise that normally triggers adult development. CHX treatments that inhibited motoneuron death were less effective in inhibiting dendritic regression in the same neurons. In another set of experiments, abdomens were isolated from the ecdysteroid-secreting glands prior to the prepupal peak, and infused with 20-hydroxyecdysone (20-HE). Single injections of CHX delivered just prior to the start of the 20-HE infusion inhibited motoneuron death and pupal cuticle production, but in the range of doses tested, did not prevent dendritic regression. Our findings suggest that protein synthesis is a required step in the steroid-mediated death of proleg motoneurons, and that dendritic regression is less susceptible to inhibition by CHX than is motoneuron death.
Abdomen↗
Organization of the larval pre-ecdysis motor pattern in the tobacco hornworm, Manduca sexta.
The tobacco hornworm, Manduca sexta, undergoes several larval molts before transforming into a pupa and then an adult moth. Each molt culminates in ecdysis, when the old cuticle is shed. Prior to each larval ecdysis, the old cuticle is loosened by pre-ecdysis behavior, which consists of rhythmic compressions that are synchronous along the abdomen and on both body sides, and rhythmic retractions of the abdominal prolegs. Both pre-ecdysis and ecdysis behaviors are triggered by a peptide, eclosion hormone. The aim of the present study was to investigate the neural circuitry underlying larval pre-ecdysis behavior. The pre-ecdysis motor pattern was recorded in isolated nerve cords from eclosion hormone-treated larvae, and the effects of connective transections and ionic manipulations were tested. Our results suggest that the larval pre-ecdysis compression motor pattern is coordinated and maintained by interneurons in the terminal abdominal ganglion that ascend the nerve cord without chemical synaptic relays; these interneurons make bilateral, probably monosynaptic, excitatory connections with identified pre-ecdysis motor neurons throughout the abdominal nerve cord. This model of the organization of the larval pre-ecdysis motor pattern should facilitate identification of the relevant interneurons, allowing future investigation of the neural basis of the developmental weakening of the pre-ecdysis motor pattern that accompanies the larval-pupal transformation.
Animals↗
Muscarinic acetylcholine receptors modulate the excitability of an identified insect motoneuron.
1. With the use of an isolated, perfused ganglion preparation from the tobacco hornworm, Manduca sexta, we have examined the responses of an identified proleg retractor motoneuron (designated PPR) to trains of stimuli delivered to sensory branches of the ventral nerve (VN). 2. Trains of stimuli (50 Hz, 100 ms to 5 s) delivered to the proleg sensory nerve, VNA, caused PPR to depolarize and initiate a bout of spiking activity that outlasted the stimulus. A fast component of this response was due to monosynaptic input from planta hair sensory neurons, acting on nicotinic acetylcholine receptors (nAChRs). The fast response to VNA stimulation was abolished when the ganglion was treated with the nicotinic antagonist, mecamylamine, leaving a slow, long-lasting depolarization of PPR, which we have called the slow excitatory postsynaptic potential (sEPSP). 3. A sEPSP could be evoked by stimulation of all the major subbranches of VNA ipsilateral to PPR's cell body. Small sEPSPs were also evoked by stimulation of all but one of the major contralateral subbranches of VNA. 4. During a sEPSP the spike threshold of PPR became more negative. This increase in excitability was not correlated with changes in membrane potential measured at the cell body, and there was no detectable change in input resistance. We conclude that the spike-threshold change reflects either a depolarization electrically remote from the cell body, or a change in PPR's spike initiation properties that are not reflected in the membrane potential. 5. Both the sEPSP and the associated change in PPR's spike threshold were blocked by several muscarinic antagonists. Scopolamine was effective at concentrations > 2 x 10(-7) M, atropine at concentrations > 1 x 10(-6) M, and pirenzepine at 5 x 10(-5) M. 4-Diphenylacetoxy-N-methylpiperidine (4-DAMP), methoctramine, hexahydrosiladifenidol, and AF-DX 116 were all poor antagonists. 6. Bath application of the muscarinic agonist oxotremorine-M (oxo-M) at concentrations > 3 x 10(-7) M increased the spontaneous spiking activity of PPR and other proleg motoneurons. In PPR, this increased activity was accompanied by a small depolarization and a more negative spike threshold, both of which were inhibited by 1 x 10(-7) M scopolamine. 7. At concentrations > 6 x 10(-8) M, bath-applied oxo-M depolarized PPR even when spike activity in the ganglion was blocked with tetrodotoxin. During such spike blockage, pressure ejection of brief puffs of oxo-M into the neuropil evoked a long-lasting depolarization of PPR that resembled the sEPSP.(ABSTRACT TRUNCATED AT 400 WORDS)
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
Hormonal regulation and segmental specificity of motoneuron phenotype during metamorphosis of the tobacco hornworm, Manduca sexta.
The abdominal prolegs of Manduca sexta larvae are eliminated at the onset of metamorphosis. Previous work showed that the prepupal peak of ecdysteroids in the hemolymph causes the dendritic arbors of proleg motoneurons to regress and a stereotyped subset of the motoneurons to die. In the present study we investigated the parameters of ecdysteroid exposure that are important for eliciting these responses by directly infusing 20-hydroxyecdysone (20-HE) into the hemolymph of insects deprived of their own endocrine glands. Doses of 20-HE that were near threshold for evoking regression or death were consistently more effective when infused over a longer duration. Theoretical calculations of hemolymph hormone profiles produced by the infusions support a model of ecdysteroid action in which the hormone concentration must remain above a threshold level for a critical duration of time to be physiologically effective. We further found that segmental location can influence both the metamorphic fate and the hormonal sensitivity of Manduca motoneurons.
Animals↗
Cost effectiveness of prophylactic intravenous immune globulin in chronic lymphocytic leukemia.
BACKGROUND: A recent randomized controlled trial of intravenous immune globulin in patients with chronic lymphocytic leukemia and hypogammaglobulinemia demonstrated a statistically significant reduction in the rate of bacterial infections among patients who received intravenous immune globulin. We used decision-analysis techniques to determine whether prophylactic intravenous immune globulin is likely to result in an overall clinical benefit to patients who receive this treatment and to examine its cost effectiveness. METHODS: We constructed a model to compare two strategies: treatment with intravenous immune globulin at a dose of 400 mg per kilogram of body weight every three weeks and no immune globulin therapy. Baseline estimates of the efficacy of intravenous immune globulin were derived from the published results of the randomized trial. The costs of treatment, complications, and infections were estimated on the basis of component costs. Health outcomes were measured in terms of gains in quality-adjusted life expectancy. RESULTS: Intravenous immune globulin therapy can result in a loss of quality-adjusted life expectancy when the inconvenience of treatment is taken into account. If the inconvenience of treatment is not considered, therapy results in a gain of 0.8 quality-adjusted days per patient per year of therapy at a cost of $6 million per quality-adjusted life-year gained. CONCLUSIONS: Decision-analysis modeling may be applied to the results of randomized controlled trials to assess the potential clinical and financial effects of adopting the intervention in medical practice. In the case of intravenous immune globulin therapy in patients with chronic lymphocytic leukemia and hypogammaglobulinemia, this type of analysis suggests that treatment might not result in improved quality or length of life and that it is extraordinarily expensive in comparison with other treatments generally accepted as cost effective.
Agammaglobulinemia↗
Reidentification of larval interneurons in the pupal stage of the tobacco hornworm, Manduca sexta.
The abdominal prolegs are the primary locomotory appendages of Manduca sexta larvae. After the prolegs are lost at pupation, some of the proleg motoneurons die while the survivors are respecified to carry out different functions in the adult moth. As a first step toward investigating the process of functional respecification at the synaptic level, we searched for larval interneurons that affected the activity of proleg motoneurons, and followed these interneurons into the pupal stage. Interneurons were judged to be individually identifiable based on their effects on proleg motoneuron activity and their anatomical features. Seven larval interneurons were identified and placed in five physiological classes based on their effects on proleg motoneurons: ipsilateral excitors, contralateral excitors, ipsilateral inhibitors, contralateral inhibitors, and bilateral inhibitor-excitors. Four of the larval interneurons produced apparently monosynaptic postsynaptic potentials in proleg motoneuron. Of the five larval interneurons that were reidentified in the early pupal stage, two showed minor but consistent structural modifications from the larval stage. Interneurons that produced unitary postsynaptic potentials in larval motoneurons continued to do so in pupal motoneurons. These studies demonstrate that individually identified interneurons can be followed through the larval-pupal transformation, during the initial stages of motoneuron respecification.
Action Potentials↗
Activity-dependent induction of facilitation, depression, and post-tetanic potentiation at an insect central synapse.
In Manduca sexta larvae, sensory neurons innervating planta hairs on the tips of the prolegs make monosynaptic excitatory connections with motoneurons innervating proleg retractor muscles. Tactile stimulation of the hairs evokes reflex retraction of the proleg. In this study we examined activity-dependent changes in the amplitude of the excitatory postsynaptic potentials (EPSPs) evoked in a proleg motoneuron by stimulation of individual planta hair sensory neurons. Deflection of a planta hair caused a phasic-tonic response in the sensory neuron, with a mean peak instantaneous firing frequency of greater than 300 Hz, and a tonic firing rate of 10-20 Hz. Direct electrical stimulation was used to activate individual sensory neurons to fire at a range of frequencies including those observed during natural stimulation of the hair. At relatively low firing rates (e.g., 1 Hz), EPSP amplitude was stable indefinitely. At higher instantaneous firing frequencies (greater than 10 Hz), EPSPs were initially facilitated, but continuous stimulation led rapidly to synaptic depression. High-frequency activation of a sensory neuron could also produce post-tetanic potentiation, in which EPSP amplitude remained elevated for several min following a stimulus train. Facilitation, depression, and post-tetanic potentiation all appeared to be presynaptic phenomena. These activity-dependent changes in sensory transmission may contribute to the behavioral plasticity of the proleg withdrawal reflex observed in intact insects.
Animals↗
Developmental attenuation of the pre-ecdysis motor pattern in the tobacco hornworm, Manduca sexta.
At the culmination of each molt, the larval tobacco hornworm exhibits a pre-ecdysis behavior prior to shedding its old cuticle at ecdysis. Both pre-ecdysis and ecdysis behaviors are triggered by the peptide, eclosion hormone (EH). Pre-ecdysis behavior consists of rhythmic abdominal compressions that loosen the old larval cuticle. This behavior is robust at larval molts, but at the larval-pupal molt the only comparable behavior consists of rhythmic dorso-ventral flexions of the anterior body. These flexions appear to be an attenuated version of the larval pre-ecdysis behavior because (1) they show the same EH dependence, and (2) the motor patterns recorded from EH treated, deafferented larval and pupal preparations are similar except that the pupal pattern is much weaker. Both patterns are characterized by rhythmic, synaptically-driven bursts of action potentials in motoneurons MN-2 and MN-3, which occur synchronously in all segments. However, the synaptic drive to the motoneurons and their resultant levels of activity are reduced during the pupal pre-ecdysis motor pattern, especially in posterior abdominal segments. Although the dendritic arbors of both motoneurons regress somewhat during the larval-pupal transformation, this does not appear to be the primary source of diminished synaptic drive because regression is greatest in the segments in which synaptic inputs remain the strongest. The developmental weakening of the pre-ecdysis motor pattern thus may be due to changes at the interneuronal level.
Aging↗
Value of follow-up procedures in patients with large-cell lymphoma who achieve a complete remission.
Salvage therapy for relapsed large-cell lymphoma (LCL) is more effective in patients with minimal disease, suggesting that early detection of relapse might increase the chance of long-term survival. To determine whether current follow-up procedures are effective in identifying preclinical disease, we analyzed patterns of relapse in 139 LCL patients who achieved a complete remission (CR) with high/moderate-dose methotrexate with leucovorin, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (M/m-BACOD). The timing and results of all posttreatment follow-up tests were examined in the 36 patients who relapsed from complete remission (CR) and 46 controls who remain in CR. Despite conscientious posttreatment follow-up, only two of the 36 relapses (6%) were detected before the development of symptoms. Sixty-seven percent of patients relapsed in new disease sites (42% in new and old sites, and 25% in new sites only). Consistent with this observation, the tests most sensitive to clinical relapse were those not targeted to specific sites of disease: gallium scan (sensitivity, 90%), physical examination (80%), and lactate dehydrogenase (LDH) (65%). Of screening tests performed, only LDH was successful in detecting preclinical relapse, with a sensitivity of 42% and specificity of 85% for impending symptomatic relapse. These results indicate that conventional screening was ineffective in detecting preclinical relapse in LCL patients. We recommend prospective evaluation of a strategy that (1) screens with a frequency appropriate to a patient's risk of relapse, (2) uses sensitive test(s) not targeted to specific sites, and (3) limits aggressive screening to those high-risk patients eligible for potentially curative salvage therapy.
Antineoplastic Combined Chemotherapy Protocols↗
Hormonally mediated changes in simple reflex circuits during metamorphosis in Manduca.
During insect metamorphosis, the nervous system must be reorganized to allow the production of unique behaviors during each life stage. In the hawkmoth, Manduca sexta, it has been possible to follow this postembryonic phase of neuronal development at the level of identified neurons. Of particular interest in the present context are sensory neurons, motoneurons, and interneurons which persist through metamorphosis, but participate in different types of behavior at different stages of life. Many of these neurons undergo striking changes in their dendritic arborizations and axonal projection patterns, which can be correlated with changes in their synaptic interactions with other neurons. Manipulations of the ecdysteroid and juvenile hormone titers, both in vivo and in vitro, implicate these hormones in the regulation of metamorphic changes within the nervous system. Taking advantage of this endocrine control, it has been possible to create heterochronic mosaic animals that allow the relationship between specific cellular changes and behavioral alterations to be tested directly.
Animals↗
Postembryonic neuronal plasticity and its hormonal control during insect metamorphosis.
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Animals↗
Postsynaptic changes at a sensory-to-motoneuron synapse contribute to the developmental loss of a reflex behavior during insect metamorphosis.
The larval-pupal transformation of the tobacco hornworm, Manduca sexta, involves the loss of many larval-specific behaviors, including a simple withdrawal reflex of the abdominal prolegs. This reflex is mediated by monosynaptic excitatory connections between afferents that innervate mechanosensory hairs on the proleg [the planta hairs (PHs)] and motoneurons that innervate proleg retractor muscles. In response to hormonal cues during the final days of larval life, the dendritic arbors of proleg retractor motoneurons regress extensively. Intracellular recordings indicate that the synaptic depolarization evoked in proleg motoneurons by electrical stimulation of PH afferents decreases by 78% during the larval-pupal transformation, over the same time course that the motoneuron dendrites regress. During the same period the number of PH afferents and the extent of their central projections may decrease slightly. To test the relative contributions of developmental changes in the presynaptic afferents and postsynaptic motoneurons to the weakening of the reflex pathway, we generated heterochronic mosaic pupae that retained one larval proleg. The PH afferents on the retained proleg retained their larval characteristics while their postsynaptic targets, the proleg motoneurons, appeared to regress normally. In the mosaic hemisegments, electrical stimulation of PH afferents evoked only a small synaptic depolarization of the proleg motoneurons, similar in amplitude to that recorded in normally developing pupae; thus, the developmental status of the afferents was irrelevant to the loss of the reflex. These findings suggest that postsynaptic changes, e.g., structural regression of motoneuron dendrites, may cause the weakening of the reflex pathway. This is the first demonstrated correlation between the hormonally mediated regression of motoneuron dendrites and the loss of a specific behavior during metamorphosis.
Animals↗
Respecification of larval proleg motoneurons during metamorphosis of the tobacco hornworm, Manduca sexta: segmental dependence and hormonal regulation.
The principal locomotory appendages of the Manduca sexta caterpillar, the prolegs, are present on the third through sixth abdominal segments (anal prolegs located on the terminal segment were not included in this study). Previous studies have characterized some of the proleg retractor muscles and their motoneurons. In the present study we identified additional proleg motoneurons and their putative homologs in the non-proleg-bearing segments. One of the motoneurons present in the proleg-bearing segments is absent in the non-proleg-bearing segments. At pupation the prolegs are lost, their muscles degenerate, and some of their motoneurons regress structurally. Subsequently, subsets of the proleg motoneurons and their homologs in other segments die in a segment-specific pattern. This is the first report of segment-specific motoneurons, and of segment-specific death of identified motoneurons, in Manduca. During adult development the surviving proleg motoneurons innervate the tergosternal muscle (TSM) and grow bilateral dendritic arbors. Dendritic growth is completed by about the 12th of the 18 days of adult development. Following adult emergence all but one of the respecified proleg motoneurons dies. The hormonal dependence of dendritic outgrowth was tested by isolating abdomens to eliminate the ecdysteroid-secreting glands in the thorax. Between the second and fifth days after pupation the motoneurons became progressively more competent to undergo dendritic outgrowth following abdomen isolation. The extent of dendritic outgrowth paralleled the degree of morphological development attained by isolated abdomens. It is concluded that ecdysteroids are required for motoneuron outgrowth, but our findings suggest that, unless an abdominal source of ecdysteroids exists in pupae, a relatively small exposure may be sufficient.
Animals↗
Somatotopic mapping of sensory neurons innervating mechanosensory hairs on the larval prolegs of Manduca sexta.
The abdominal prolegs are the principal locomotory appendages of the larval tobacco hornworm, Manduca sexta. The prolegs bear numerous mechanosensory bristle sensilla, each innervated by an afferent neuron that arborizes within the central nervous system (CNS). Based on their positions on the proleg, we have divided the sensilla into planta hairs (PHs), lateral hairs (LHs), and medial hairs (MHs). Previously, we found that PH afferents produce monosynaptic excitatory postsynaptic potentials (EPSPs) in proleg retractor muscle motoneurons, the size of which depends on the position of the hair in the PH array. In this paper we examined the central arbors of the proleg afferents to determine whether there was an anatomical correlate to the pattern of synaptic strengths. We found that the afferent arbors are arranged somatotopically within the CNS in a pattern similar to that for bristle afferents elsewhere on the abdomen; i.e., the anterior-posterior and medial-lateral position of a hair on the proleg was reflected in the location of the afferent arbor along the corresponding axes within sensory neuropil. All afferents terminated within a similar ventral region of neuropil. The arbors of PH, MH, and to a lesser extent, LH afferents, were enlarged as compared to afferents innervating hairs elsewhere on the abdomen. This feature, combined with the dense innervation of the proleg, causes the proleg region to be relatively overrepresented in sensory neuropil. We also examined the afferents innervating a pair of ventral midline hairs (VMHs) present in each abdominal segment, which, unlike the other afferents, showed segment-specific central arbors. We conclude that the somatotopic mapping of afferent arbors may contribute to the specificity of synaptic connections in this system.
Afferent Pathways↗
A reflex behavior mediated by monosynaptic connections between hair afferents and motoneurons in the larval tobacco hornworm, Manduca sexta.
In the tobacco hornworm caterpillar, tactile stimulation of sensory hairs located on the tip of a proleg (the planta) evokes ipsilateral or bilateral retraction of the prolegs in that segment. We have used electrophysiological and anatomical methods to investigate the excitatory neural pathways linking the planta hair afferents and the proleg retractor motoneurons (MNs). An important technical innovation was the development of an isolated proleg and desheathed ganglion preparation that permits rapid and reversible ionic manipulations and drug applications. Action potentials (spikes) in individual planta hair afferents produce time-locked excitatory postsynaptic potentials (EPSPs) in ipsilateral proleg MNs which appear to be chemically-mediated and monosynaptic: the EPSPs have a short and constant latency, they follow afferent spikes without failure, they are reversibly abolished in elevated Mg++ saline, and they persist in saline with elevated Mg++ and Ca++ levels. Planta hair afferents also excite ipsilateral MNs by polysynaptic pathways, and their excitation of contralateral proleg MNs is exclusively polysynaptic. Cobalt-staining of the proleg MNs and planta hair afferents shows that the afferents terminate in ventral neuropil, and the proleg MNs have an unusual ventral projection into this region. The ventral projection is on the ipsilateral side, which is consistent with the electrophysiological finding that time-locked EPSPs are found only from ipsilateral hairs. Two factors that contribute to the strong monosynaptic excitation of proleg MNs by ipsilateral planta hairs are the convergence of many hair afferents onto each MN, and the facilitation shown at each afferent-MN synapse. At least 6 afferents converge on each MN, and at short interspike intervals the afferent-evoked EPSPs are enhanced by as much as 400% by homosynaptic facilitation. The EPSP is abolished reversibly by the cholinergic antagonists curare and atropine, suggesting that the neurotransmitter at the synapse is acetylcholine (ACh). This is of particular interest because the ACh receptors of tobacco-feeding Manduca larvae are reported to be less nicotine-sensitive than those of other insects.
Acetylcholine↗