Cognitive-behavioral therapy for persistent pain: Does adherence after treatment affect outcome?

It is a tenet of cognitive behavioral treatment of persistent pain problems that ex‐patients should adhere to treatment methods over the longer term, in order to maintain and to extend treatment gains. However, no research has quantified the causal influence of adherence on short‐term outcome in this field. The aims of this study are to assess determinants of adherence to treatment recommendations in several domains, and to examine the extent to which cognitive and behavioral adherence predicts better outcome of cognitive behavioral treatment for persistent pain. Longitudinal data from a sample of 2345 persistent pain patients who attended a multicomponent treatment programme were subjected to structural equation modeling. Adherence emerged as a mediating factor linking post‐treatment and follow‐up treatment outcome, but contributed only 3% unique variance to follow‐up outcomes. Combined end‐of‐treatment outcomes and adherence factors accounted for 72% of the variance in outcome at one‐month follow‐up. Notwithstanding shortcomings in the measurement of adherence, these findings question the emphasis normally given to adherence in the maintenance of behavioral and cognitive change, and clinical implications are discussed.     

Male-male competition magnifies inbreeding depression in wild house mice

The detrimental effects of inbreeding on vertebrates are well documented for early stages of the life cycle in the laboratory. However, the consequences of inbreeding on long-term survival and reproductive success (Darwinian fitness) are uncertain for vertebrates in the wild. Here, we report direct experimental evidence for vertebrates that competition increases the harmful effects of inbreeding on offspring survival and reproduction. We compared the fitness of inbred (from full-sib matings) and outbred wild house mice (Mus domesticus) in large, seminatural enclosures. Inbred males sired only one-fifth as many surviving offspring as outbred males because of their poor competitive ability and survivorship. In laboratory conditions, inbreeding had relatively minor effects on male reproductive success and no effect on survivorship. Seminatural conditions did not increase inbreeding depression for females, probably because females were not competing for any critical resources. The overall reduction in fitness from inbreeding was 57%, which is 4.5 times as great as previous estimates from the laboratory. These results have important implications for medicine, conservation, evolutionary biology, and functional genomics.     

Thinking about vaginal microbicide testing

A vaginal microbicide could slow the spread of HIV. To date, volunteers in placebo-controlled trials of candidate microbicides have been counseled to use condoms. This does not reduce the number of volunteers exposed to possible risk, but it shifts the allotment of risk from those conducting the trial to those women who may be least able to make autonomous decisions. Alternative ways of meeting the obligation to offer volunteers active benefits are explored. Counseling the use of condoms prolongs clinical trials and could cause tens of thousands of otherwise avoidable deaths.     

Early experience with the selective splenocaval shunt for variceal bleeding

Selective variceal decompression is the operative method of choice in the definitive management of recurrent hemorrhage from gastroesophageal varices. The distal splenorenal shunt is the recommended procedure for selective variceal decompression, but its use may be limited in patients who have undergone left nephrectomy, in patients with an anatomically aberrant relationship between the splenic and left renal veins and in patients with preoperative visceral angiographic findings suggesting that they are at risk for development of the postoperative syndrome of renal vein hypertension. In these clinical situations, selective variceal decompression can be obtained with a splenocaval shunt, constructed by directly anastomosing the splenic vein to the infrarenal vena cava. Seven patients who have undergone the selective splenocaval shunt are reviewed in this report. Early experience with these patients demonstrates the use of the selective splenocaval shunt when an alternative to the distal splenorenal shunt is needed.     

Neural circuits controlling cardiorespiratory responses: baroreceptor and somatic afferents in the nucleus tractus solitarius

1. A vast array of peripheral receptors provide the central nervous system (CNS) with sensory signals that coordinate autonomic motor outflow to cardiovascular organs, such as the heart and peripheral vasculature, during locomotion. 2. Much of this sensory input is mediated by cardiovascular receptors located in blood vessels (arterial baroreceptors) and skeletal muscle (skeletal muscle ergoreceptors). 3. Several medullary nuclei are targets for cardiovascular receptors, including the nucleus tractus solitarius (NTS). 4. In the present review, the interaction between arterial baroreceptor and somatosensory receptor afferents in the NTS is examined while placing particular emphasis on the neurochemical and electrophysiological mechanisms involved in processing these signals. 5. Data from anaesthetized animals, as well as from an innovative working heart-brainstem preparation, will illustrate the potential role of GABAergic transmission on baroreceptor signalling in the caudal NTS during locomotion.     

Central mechanisms underlying short- and long-term regulation of the cardiovascular system

1. Sympathetic vasomotor nerves play a major role in determining the level of arterial blood pressure and the distribution of cardiac output. The present review will discuss briefly the central regulatory mechanisms that control the sympathetic outflow to the cardiovascular system in the short and long term. 2. In the short term, the sympathetic vasomotor outflow is regulated by: (i) homeostatic feedback mechanisms, such as the baroreceptor or chemoreceptor reflexes; or (ii) feed-forward mechanisms that evoke cardiovascular changes as part of more complex behavioural responses. 3. The essential central pathways that subserve the baroreceptor reflex and, to a lesser extent, other cardiovascular reflexes, have been identified by studies in both anaesthetized and conscious animals. A critical component of these pathways is a group of neurons in the rostral ventrolateral medulla that project directly to the spinal sympathetic outflow and that receive inputs from both peripheral receptors and higher centres in the brain. 4. Much less is known about the central pathways subserving feed-forward or 'central command' responses, such as the cardiovascular changes that occur during exercise or that are evoked by a threatening or alerting stimulus. However, recent evidence indicates that the dorsomedial hypothalamic nucleus is a critical component of the pathways mediating the cardiovascular response to an acute alerting stimulus. 5. Long-term sustained changes in sympathetic vasomotor activity occur under both physiological conditions (e.g. a change in salt intake) and pathophysiological conditions (e.g. heart failure). There is evidence that the paraventricular nucleus in the hypothalamus is a critical component of the pathways mediating these changes. 6. Understanding the central mechanisms involved in the long-term regulation of sympathetic activity and blood pressure is a major challenge for the future. As a working hypothesis, a model is presented of the postulated central mechanisms that result in sustained changes in sympathetic vasomotor activity that are evoked by different types of chronic stimulation.     

Design,synthesis, and SAR of tachykinin antagonists: modulation of balance in NK(1)/NK(2) receptor antagonist activity

Through optimization of compounds based on the dual NK(1)/NK(2) antagonist ZD6021, it was found that alteration of two key regions could modulate the balance of NK(1) and NK(2) potency. Substitution of the 2-naphthalene position in analogues of ZD6021 resulted in increased NK(1) potency and thus afforded NK(1) preferential antagonists. Alterations of the piperidine region could then increase NK(2) potency to restore dual NK(1)/NK(2) selectivity. Through these efforts, three novel receptor antagonists from a single chemically related series were identified; two are dual NK(1)/NK(2) antagonists, and the third is an NK(1) preferential antagonist. In this paper, the factors affecting the balance of NK(1) and NK(2) selectivity in this series are discussed and the in vitro and in vivo properties of the novel antagonists are described.     

Relations between offending,injury and illness

The objectives of this study were to determine relations between offending and health, and how illness and injury relate to concurrent offending--whether offending predicts health or vice versa, and whether relations persist after adjustment for childhood predictors of offending. Data collected in the Cambridge Study in Delinquent Development were analysed. This is a prospective longitudinal survey of 411 South London males first recruited at age 8. Information about injuries and illnesses between ages 16 and 18 was set against information on offending and other types of antisocial behaviour. Males who were injured (especially in assaults) tended to be convicted, to be violent, to have unskilled manual jobs and to be generally antisocial. Respiratory tract illnesses were negatively related to convictions and antisocial behaviour in general. Drug users were significantly likely to be ill. Adult convictions were predicted by childhood troublesome behaviour, daring/hyperactivity, low IQ/attainment, a convicted parent, family disruption/poor supervision and poverty. Assault injuries and respiratory tract illnesses did not predict adult convictions independently of these childhood factors. It was concluded that injury is one symptom of an antisocial personality that arises in childhood and persists into adulthood. Therefore, measures that lead to a reduction in offending should also lead to a reduction in concurrent injuries. Negative relations between a range of antisocial behaviours and respiratory tract illness deserve further study.     

Tracing of projection neurons from the cervical dorsal horn to the medulla with the anterograde tracer biotinylated dextran amine

In addition to the well-defined role of dorsal horn neurons in pain transmission, neurons in the superficial laminae also provide a rich source of synaptic input to cardiovascular and respiratory centers in the medullary reticular formation. In this study, ascending projection neurons from the superficial laminae of the cervical enlargement were studied in the rat using the anterograde tracer biotinylated dextran amine (BDA). Ipsilateral microinjection of BDA into the cervical spinal cord (C6-C8) resulted in extensive labeling of dorsal horn neurons in laminae I-V. Axons and terminal processes of cervical dorsal horn cells projecting to the medulla were present in the cuneate nucleus (Cu), the nucleus of the solitary tract (NTS), the lateral reticular nucleus, (LRt) as well as the caudal and rostral ventrolateral medulla (VLM). The highest density of BDA labeling was found ipsilaterally in the Cu, LRt, caudal and rostral VLM, while a moderate density of labeling was present in the NTS caudal to the area postrema (AP). Moderate-to-weak labeling was also found in the LRt, the caudal and rostral VLM contralateral to the BDA injection. These results support the existence of a spinomedullary pathway that transmits noxious and innocuous Adelta and C fiber-mediated sensory signals to the medulla. Neurons in this ascending spinal pathway likely participate in the patterning of autonomic responses evoked by pain or during exercise.