Phase coherence-A time-localized approach to studying interactions.

Coherence measures the similarity of progression of phases between oscillations or waves. When applied to multi-scale, nonstationary dynamics with time-varying amplitudes and frequencies, high values of coherence provide a useful indication of interactions, which might otherwise go unnoticed. However, the choice of analyzing coherence based on phases and amplitudes (amplitude-weighted phase coherence) vs only phases (phase coherence) has long been seen as arbitrary. Here, we review the concept of coherence and focus on time-localized methods of analysis, considering both phase coherence and amplitude-weighted phase coherence. We discuss the importance of using time-localized analysis and illustrate the methods and their practicalities on both numerically modeled and real time-series. The results show that phase coherence is more robust than amplitude-weighted phase coherence to both noise perturbations and movement artifacts. The results also have wider implications for the analysis of real data and the interpretation of physical systems.

"Goalkeeper's hip": acute haematogenous osteomyelitis secondary to apophyseal fractures.

We report two cases of acute haematogenous osteomyelitis in the anterior superior iliac spine (ASIS) in adolescent goalkeepers following trauma of the iliac crest apophysis. Both patients complained of pain over their right ASIS and were pyrexial. They were given antibiotics and were discharged from follow up without complication 64 and 90 days after starting treatment.

Conditioning of ictal and interictal behaviors in rats by amygdala kindling: context as the conditional stimulus.

The authors showed that conditional effects of the stimulation environment modulate both the ictal and interictal behaviors of rats subjected to amygdala kindling. Rats received 53 stimulations to the left basolateral amygdala in 1 conditional stimulus (CS) context (CS+) and 53 sham stimulations (the stimulation lead was attached but no current was delivered) in another context (CS-), quasirandomly over 54 days. Three kinds of conditional effects were observed. First, after several stimulations, less ambulatory activity, more freezing, and less rearing reliably occurred in the CS+ context than in the CS-context. Second, after 45 stimulations, all of the rats chose the CS- context over the CS+ context in a conditioned place preference test. Third, when the rats were finally stimulated in the CS- context, their motor seizures were less severe: Latencies were longer, motor seizures were shorter, convulsive patterns were of a lower class, and there were fewer falls.

Conditioned effects of kindling.

Mild periodic electrical stimulation to any one of many brain sites leads to the development and progressive intensification of elicited motor seizures. Since its discovery in 1969, this kindling phenomenon has been widely studied both as a model of epileptogenesis and as a form of neuroplasticity, and recently there has been increasing interest in kindling as a model of the interictal (i.e. between-seizures) changes in emotionality that accompany certain forms of epilepsy. Despite the extensive use of the kindling model, little consideration has been given to the role played by the cues regularly associated with the delivery of the kindling stimulations. However, we have recently demonstrated that cues associated with the standard kindling protocol (e.g. the stimulation environment) produce conditioned effects on both the motor seizures and interictal behavior of rats and that some kindling sites, such as the amygdala, produce conditioned interictal behaviors that are defensive in nature. The implications that these findings have for the study of interictal behavioral changes in particular and to kindling research in general are discussed.

Activation of transcription factors activator protein-1 and nuclear factor-kappaB by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD; dioxin), the prototype agonist of the aromatic hydrocarbon (Ah) receptor, is a potent tumor promoter as well as a complete liver carcinogen that produces an oxidative stress response in rodents and in cultured cell lines. It has been proposed that TCDD promotes neoplastic transformation through oxidative signal transduction pathways, which results in activation of immediate-early response transcription factors. To set the stage for a test of this hypothesis, we evaluated the effect of TCDD treatment on the activation of several transcription factors, including those in the nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) families, which are activated by changes in the redox state of cells. In an extension of prior results, we found that TCDD treatment produced a sustained overexpression of AP-1 for at least 72 hr in wild-type mouse hepatoma Hepa-1 cells, but not in the Ah receptor-deficient derivative c35 or in cytochrome P450-1A1 (CYP1A1)-negative c37 cells. In addition, TCDD treatment caused a significant increase in the DNA binding activity of NF-kappaB, but not in the activities of the other transcription factors tested. AP-1 and NF-kappaB activation were blocked by the thiol antioxidant N-acetylcysteine and by nordihydroguaiaretic acid, an antioxidant and lipooxygenase inhibitor and an inhibitor of the epoxygenase activity of CYP1A1, and did not take place in c35, c37, or in Ah nuclear translator-deficient c4 cells. Hence, sustained activation of these two transcription factors by TCDD is likely to result from a CYP1A1-dependent and Ah receptor complex-dependent oxidative signal. Electrophoretic mobility supershift analyses with specific antibodies showed that most of the increase in NF-kappaB binding activity could be accounted for by increases in p50/p50 complexes. Since these complexes are known to repress NF-kappaB-dependent gene transcription, our results delineate a second molecular mechanism, in addition to the recently found block of tumor necrosis factor-alpha-mediated p50/p65 activation, that may be responsible for the immunosuppresive effects of TCDD.

Reversible lesions of the rhinal cortex produce delayed non-matching-to-sample deficits in rats.

Rats with cannulae guides implanted in the rhinal cortex were tested on a delayed non-matching-to-sample task, following either lidocaine or sham microinfusions. Bilateral lidocaine microinfusions to the rhinal cortex produced significant delayed non-matching-to-sample deficits. These results are consistent with the putative role of the rhinal cortex in object recognition but because the deficits were not shown to be time dependent, non-mnemonic interpretations cannot be ruled out. These results also illustrate the utility of reversible lidocaine lesions in the study of the neuroanatomical basis of delayed non-matching-to-sample.

Aromatic hydrocarbon receptor interaction with the retinoblastoma protein potentiates repression of E2F-dependent transcription and cell cycle arrest.

Polyhalogenated aromatic hydrocarbons, of which 2,3,7, 8-tetrachloro-p-dioxin (TCDD) is the prototype compound, elicit a variety of toxic, teratogenic, and carcinogenic responses in exposed animals and in humans. In cultured cells, TCDD shows marked effects on the regulation of cell cycle progression, including thymocyte apoptosis, induction of keratinocyte proliferation and terminal differentiation, and inhibition of estrogen-dependent proliferation in breast cancer cells. The presence of an LXCXE domain in the dioxin aromatic hydrocarbon receptor (AHR), suggested that the effects of TCDD on cell cycle regulation might be mediated by protein-protein interactions between AHR and the retinoblastoma protein (RB). Using the yeast two-hybrid system, AHR and RB were in fact shown to bind to each other. In vitro pull-down experiments with truncated AHR peptides indicated that at least two separate AHR domains form independent complexes with hypophosphorylated RB. Coimmunoprecipitation of whole cell lysates from human breast carcinoma MCF-7 cells, which express both proteins endogenously, revealed that AHR associates with RB in vivo only after receptor transformation and nuclear translocation. However, the AHR nuclear translocator and transcriptional heterodimerization partner, is not required for (nor is it a part of) the AHR.RB complexes detected in vitro. Ectopic expression of AHR and RB in human osteosarcoma SAOS-2 cells, which lack endogenous expression of both proteins, showed that AHR synergizes with RB to repress E2F-dependent transcription and to induce cell cycle arrest. Furthermore, AHR partly blocked T-antigen-mediated reversal of RB-dependent transcriptional repression. These results uncover a potential function for the AHR in cell cycle regulation and suggest that this function may be that of serving as an environmental sensor that signals cell cycle arrest when cells are exposed to certain environmental toxicants.

A framework for strategic information systems implementation in the United Kingdom health sector.

The implementation of information technologies in the United Kingdom health sector is a relatively recent phenomenon. Many of the developments have followed the patterns in the United States. One such example is that of Case Mix, introduced strategically as part of the Resource Management Initiative and aimed at the facilitation of both clinical and financial audit. Moreover, Case Mix was implemented alongside significant changes in hospital structure and culture, requiring clinicians to get involved in management tasks and decision making within the structure of the hospital, supported by a new information infrastructure. The success of such systems has varied significantly. A number of lessons can be learned from the way that the implementation was approached. This article stems from a research project focusing longitudinally on the implementation of Case Mix in four UK hospitals. It draws a number of findings from the cases, and importantly, explicates a framework for strategic information systems implementation, as generated from the cases and supported by the extant literature. Such a framework has implications for both theory and practice, and assists in the understanding of what is often a dynamic and poorly understood situation.

Persistence of the interictal emotionality produced by long-term amygdala kindling in rats.

Long-term amygdala kindling in rats results in large and reliable increases in emotional behaviour that model the interictal emotionality often observed in temporal lobe epileptics [Kalynchuk L. E. et al. (1997) Biol. Psychiat. 41, 438-451; Pinel J. P. J. et al. (1977) Science 197, 1088-1089]. These experiments investigated the persistence of these kindling-induced increases in emotional behaviour after the cessation of the kindling stimulations. In Experiment 1, rats received 99 amygdala or sham stimulations. Then, they were tested on three tests of emotionality (i.e. activity in an unfamiliar open field, resistance to capture from the open field, and activity in an elevated-plus maze) either one day, one week, or one month after the final stimulation. The rats tested one day after the last stimulation displayed substantial decreases in open-field activity, increases in resistance to capture and increases in open-arm activity on the elevated-plus maze; these effects decreased, but not to control levels, in the rats tested one month after the final stimulation. In Experiment 2, rats received 99 amygdala or sham stimulations, and their resistance to capture was assessed one day later. Then, after a 60-day stimulation-free period, the rats received another zero, one, 10, or 30 amygdala stimulations and their resistance to capture was reassessed one day later. The high levels of resistance to capture observed in the rats tested one day after the 99 stimulations declined significantly during the 60-day stimulation-free period, but it remained significantly above control levels. However, the administration of 30 additional stimulations reinstated asymptotic levels of resistance to capture. These results provide the first systematic evidence that kindling-induced increases in emotional behaviour persist at significant levels for at least two months following the termination of kindling stimulations. Thus, they suggest that the neural changes underlying the genesis of interictal emotionality may be closely related to those mediating epileptogenesis itself.

Rapid haemodynamic improvement following saruplase in recent massive pulmonary embolism.

In a single centre pilot study, saruplase (20 mg bolus plus 60 mg infusion over 1 h) was administered to twenty patients with an angiographically documented recent massive pulmonary embolism: Miller index of at least 20 and mean pulmonary artery pressure of at least 20 mmHg. The lytic ability of saruplase to cause normalization of haemodynamic parameters over the first 12 h and reperfusion of pulmonary arteries at 24 h was assessed. A decrease of 25 +/- 10% in total pulmonary resistance was evident at 30 min. Haemodynamic parameters continued to improve with total pulmonary resistance decreasing by 29 +/- 8% and 40 +/- 11% at 1 and 12 h respectively. Relative improvement in Miller index 24 +/- 6 h after saruplase treatment was 38 +/- 9%. Two patients suffered recurrent pulmonary embolism, two severe bleeding events were observed. One patient died following a haemorrhagic stroke.

Efficacy of a belly board device with CT-simulation in reducing small bowel volume within pelvic irradiation fields.

PURPOSE/OBJECTIVE: Acute and chronic small bowel toxicity associated with pelvic irradiation limits dose escalation for both chemotherapy and radiotherapy for rectal cancer. Various surgical and technical maneuvers including compression and belly board devices (BBD) have been used to reduce small bowel volume in treatment fields. However, quantitative dose volume advantages of such methods have not been reported. In this study, the efficacy of BBD with CT-simulation is presented with dose-volume histogram (DVH) analyses for rectal cancer. METHODS AND MATERIALS: Twelve consecutive patients referred to our department with rectal cancer were included in this study. Patients were given oral contrast 1.5 h prior to scanning and instructed not to empty their bladder during the procedure. The initial CT scan without BBD was taken in the prone position with an immobilization cast. A second CT study was performed with a commercially available BBD consisting of an 18-cm thick hard sponge with an adjustable opening (maximum 42 x 42 cm2). All patients were positioned prone over the BBD so that the opening was above the treatment volume and usually extended from the diaphragm to the bottom of the fourth lumbar spine. Image fusion between both sets of CT scans (with and without BBD) was performed using common bony landmarks to maintain the same target volume. The critical structures including small bowel and bladder were delineated on each slice for DVH analysis. On each study, a three-field optimized plan with conformal blocks in beams-eye-view was generated for volumetric analysis. The DVHs with and without BBD were evaluated for each patient. RESULTS: The median age and body weight of 12 patients (4 females and 8 males) were 57.5 years and 82.7 kg, respectively. The changes in posterior-anterior (PA) and lateral separation with and without BBD at central axis slices were analyzed. The changes in lateral separation were minimal (<0.8 cm); however, the PA separation was reduced by 11.3 +/- 3.3% when BBD was used. The reduction in PA separation was directly related to the reduction in small bowel volume. The small bowel volume was significantly reduced with a median reduction of 70% (range 10-100%) compared to the small bowel volume without BBD. The small bowel volume reduction did not correlate either with body weight, age, gender, or sequence of radiation treatment with surgery (pre-op vs. post-op). The DVH analysis of small bowel with BBD showed significant volume reduction at each dose level. For 50% patients, the DVH analysis demonstrated an increase in bladder volume with BBD. All patients treated with the BBD completed their treatment without any break and without significant acute gastrointestinal or genitourinary toxicity. CONCLUSIONS: For rectal cancers, small bowel is the dose-limiting structure for acute and chronic toxicity. The use of the BBD should improve the tolerance of aggressive combined modality treatment by reducing the small bowel volume within the pelvis compared to the prone position alone. The BBD provides an easy, economical, comfortable, and noninvasive technique to displace small bowel from pelvic treatment fields. The small bowel volume is dramatically reduced at each dose level. The volume reduction does not correlate with gender, age, weight, pelvic separation, and sequence of radiation treatment vs. surgery.

Management of problematic behavioral symptoms associated with dementia: a cognitive developmental approach.

The purpose of this 3-year study was to test the efficacy of using a theoretical model based on Piaget's cognitive developmental stages for consistent behavioral and environmental interventions for persons at all stages of Alzheimer's disease and related disorders (ADRD) in nursing home and special care units. The specific aims were to reduce problematic behavioral symptoms and the number, amount and frequency of use of psychotropic medications. After 18 months, problem behaviors and some types of psychotropic medications significantly decreased in the treatment group but not in the control group. Results of the study indicate that using behavioral and environmental interventions based on Piaget levels of cognitive development may be an effective method of managing problematic behavioral symptoms and decreasing the use of psychotropic medications in institutionalized ADRD patients.

The relationship between Piaget and cognitive levels in persons with Alzheimer's disease and related disorders.

Clinical observations and research studies have documented that people with Alzheimer's disease and related disorders (ADRD) appear to regress developmentally during the course of the disease. The purpose of this study was to prospectively determine the association between changes in Piaget levels of cognitive development and cognitive decline in nursing home residents in various stages of ADRD. Fifty-seven people were tested three times at yearly intervals, using the Folstein Mini-Mental State Exam to determine cognitive levels and a set of 14 Piaget tasks to determine cognitive developmental levels: 1) Formal Operations; 2) Concrete Operations; 3) Preoperational; and 4) Sensorimotor. Mean MMSE scores declined from 12.7 to 9.4, and there was a downward trend in Piaget levels over the study period. ANOVA showed significant differences (p < 0.0005, Years 1, 2, 3) in MMSE scores among all Piaget levels, and Spearman rho analysis showed significant correlations between Piaget levels and MMSE for each year (p < 0.0005, Years 1, 2, 3). The results suggest that there is a concurrent decline in cognitive developmental levels and cognition in people in various stages of Alzheimer's disease and related disorders.

Cognitive developmental approach to dementia.

Systematic observations of people suffering from dementia of the Alzheimer's type (DAT) reveal they regress in behavior and become childlike. These observations have been used to structure clinical research and therapeutic interventions for dementia patients. However, no concise framework explains successful caregiving. Models for care exist but they lack an adequate framework for the long-term care of a person with DAT. This state of the science review describes what is known about cognitive functioning in people with DAT. It examines studies based on cognitive functioning. It also then relates this information to an emerging theory tentatively identified as a "cognitive developmental approach" which may be useful for understanding people with dementia and for predicting caregiver requirements.

Cholera toxin and dibutyryl cyclic adenosine 3',5'-monophosphate sensitize gonadotropin-releasing hormone-stimulated inositol phosphate production to inhibition in protein kinase-C (PKC)-depleted cells: evidence for cross-talk between a cholera toxin-sensitive G-protein and PKC.

The present study assesses the relationship between G-proteins and protein kinase-C (PKC) in the gonadotrope. Cells were depleted of PKC with 1 microM phorbol 12-myristate 13-acetate for 12 h, followed by medium 199-BSA for 6 h before treatment with vehicle, pertussis toxin (PTX), cholera toxin (CTX), or (Bu)2cAMP (dBcAMP) for 18 h. PTX (10 ng/ml) significantly decreased GnRH-stimulated inositol phosphate (IP) production over a range of 10(-8)-10(-6) M GnRH. The degree of this inhibition was the same in control cells and PKC-depleted cells. Pretreatment with CTX (0.5 microgram/ml) significantly decreased GnRH-stimulated IP production over a range of 10(-9)-10(-6) M GnRH in PKC-depleted cells. This effect was mimicked by pretreatment with 3 mM dBcAMP. Although CTX and dBcAMP both decreased GnRH-stimulated IP production in control cells, this effect was enhanced in PKC-depleted cells. CTX (0.1 microgram/ml) and dBcAMP (3 mM) both enhanced GnRH-stimulated LH release, whereas PTX (100 ng/ml) had no effect. This was observed in control as well as PKC-depleted cells. Both PKA and PKC are capable of regulating IP turnover by phosphorylating phospholipase-C at distinct sites. CTX activates a G-protein that increases cAMP. cAMP can then activate PKA. In PKC-depleted cells, CTX inhibits GnRH-stimulated IP production. This effect is mimicked by dBcAMP, which suggests a role for PKA in the gonadotrope. The results of this study provide evidence for cross-talk between a CTX-sensitive G-protein and PKC.

Repair of avulsed insertion of biceps. A new technique in four cases.

We report the use of the Mitek anchor with a limited approach for repair of avulsion of the biceps tendon from the radius in four middle-aged men. All regained a full range of movement with minimal loss of power.

Flash burns to the face.

A characteristic 'crow's foot' pattern is seen around the eye in many flash burns. The protective blink reflex underlies this, and the injury is due to convected rather than radiant energy.

A new spectrophotometric assay for citrate synthase and its use to assess the inhibitory effects of palmitoyl thioesters.

We have demonstrated that citrate synthase may be assayed by a simple, discontinuous, spectrophotometric procedure based on the measurement of oxaloacetate utilization with 2,4-dinitrophenylhydrazine. The assay is applicable both to the purified enzyme and to cell extracts, and has the advantage that it can be used in the presence of high concentrations of thiols and thioesters. We have used this new assay in part of our investigations into the inhibitory effects of palmitoyl thioesters on diverse citrate synthases. Both palmitoyl-CoA and palmitoyl thioglycollate inhibit citrate synthases from pig heart, Bacillus megaterium and Escherichia coli, the E. coli enzyme showing the greatest sensitivity to these effectors. With palmitoyl-CoA the extent of inhibition is time-dependent, but the enzymes can be protected from the effect by the substrates oxaloacetate and acetyl-CoA. Using the dinitrophenylhydrazine assay, we have shown that the thioester bond is essential for inhibition; that is, if the palmitoyl thioesters are cleaved to give a mixture of palmitate and a thiol compound, the inhibitions of pig heart and B. megaterium citrate synthases are eliminated and that of the E. coli enzyme is markedly decreased.

Hip fractures in healthy patients: operative delay versus prognosis.

One hundred and forty five women who had undergone hemiarthroplasty for a subcapital fracture of the femoral neck but who were otherwise fit were studied to determine whether undue delay between injury and operation influenced their social circumstances three months after surgery. The median delay for those patients who showed good rehabilitation at three months was 29 hours, but for those who showed poor rehabilitation it was 57 hours. This difference was significant. It is suggested that a subcapital fracture in an otherwise fit elderly patient should therefore be regarded as a surgical emergency.