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Ventricular tachycardia caused by reentrant excitation can lead to cardiac arrest and sudden death. Drug treatment and surgical procedures have been used with limited effectiveness. Catheter ablation methods are more promising because they are less invasive than surgery. Although ablation has come to be highly effective in the treatment of supraventricular tachycardias, the overall success rate remains low for ventricular tachycardias, which may be due in part to an inaccurate localization of the reentrant pathway. The authors hypothesize that a site in the myocardium exists that is critical for the maintenance or reentry and that when ablated, will result in permanent cessation of the tachycardia. The authors also hypothesize that this is the same site where the reentrant impulse blocks during spontaneous termination of tachycardia. A series of experiments has been designed to determine if there are specific properties of extracellular electrograms recorded from reentrant circuits that would enable the circuits to be identified without activation maps and, more specifically, allow the site of block causing spontaneous termination to be localized. For quantitative analysis of electrograms, a paradigm is developed to characterize electrogram morphology using a canine infarct model. Changes in morphology (shape, size, and location of signal deflections) can be considered (1) motions of a coordinate system and/or (2) conformational changes of shape. To a first approximation, stationarity over short time segments is assumed so that the motions and conformations can be parameterized. These parameters were extracted for 50 cardiac cycles during an episode of nonsustained ventricular tachycardia, in which 196-bipolar electrode pairs were positioned in an array format across the epicardial surface of the heart. The results of these studies of changes in electrogram morphology suggest that during cycles 5 to 49 of ventricular tachycardia, in many electrograms near the circuit, the cycle length increases linearly, the amplitude increases, and the duration of activation decreases. During cycles 50 to 54, the cycle length increases much more markedly, the amplitude decreases, and the duration of activation increases. These observations suggest that cycle lengthening may be an important property of some spontaneous terminations, and moreover that other morphologic characteristics are affected differently at different stages of cycle lengthening. Further, all motion parameters tended to oscillate from cycle to cycle in either an alternans pattern or longer oscillation. The variations in morphology were typically only a few percent from cycle to cycle. Such variability would not be evident using only ruler-and-caliper measurements made by hand because of the lack of precision and the sheer volume of data. It is expected that this approach for characterization of electrogram morphology will be extremely useful clinically to (1) increase speed and accuracy of ablation site selection and (2) reduce multichannel electrogram recording complexity during ablation site selection.

Background: Intrathecal opioids routinely are administered to surgical patients to provide prolonged postoperative analgesia. This study evaluated the dose-response effects of intrathecal fentanyl in an elderly patient population undergoing lower extremity revascularization procedures., Methods: Surgical anesthesia was induced using a continuous spinal technique. No patient received perioperative antiemetics or opioids. Postoperatively, after complete regression of spinal anesthesia, patients received via the spinal catheter either 0, 5, 10, 20, 40, or 50 micrograms fentanyl. Blood pressure, heart rate, respiratory rate, oxyhemoglobin saturation, and visual analog pain scores were recorded approximately every minute for 15 min after study drug administration. After this initial observation period, blood pressure, heart rate, respiratory rate, oxyhemoglobin saturation were recorded every 15 min for the next 2 h, then every 30 min thereafter. A verbal analog pain score, with 0 equivalent to no pain and 10 the worst pain imaginable, was obtained with each set of vital signs. The study was concluded when the verbal analog pain score was > or = 3, the patient was medicated, and the time was recorded. Any side effects, such as respiratory depression, nausea, vomiting, and pruritus, were recorded., Results: Minimal analgesia was derived from the 0-, 5-, and 10-micrograms doses. Beginning at 20 micrograms, patients experienced the onset of satisfactory analgesia (visual analog pain scores < 3) within 4 min. All patients in the 40- and 50-micrograms groups had excellent analgesia (visual analog pain scores < 1) within 10 min. No patient experienced respiratory depression (respiratory rate < 9 breaths/min), hypoxemia (oxyhemoglobin saturation < 90%), or any hemodynamic alterations (20% change greater or less than baseline heart rate or blood pressure). In the 50-micrograms group, five of ten patients complained of pruritus., Conclusions: Results indicate that 40 micrograms intrathecal fentanyl provides satisfactory analgesia for approximately 5 h in an elderly patient population, with a low incidence of side effects.

We present a method for the localized statistical discrimination of class populations based on the Karhunen-Loève and Fukunaga-Koontz transforms. These transforms provide features that model the variance of a sample distribution. The spatial series of a 196 channel epicardial electrogram recording from an arrythmogenic postinfarct canine were analyzed. For each type of rhythm studied, Karhunen-Loève and Fukunaga-Koontz expansions were computed from five training sets of spatial data, corresponding to five locations across the surface of the heart. Nonparametric statistical tests were then used for discriminant analysis to compare properties representative of the distribution from each proposed class. In a comparison of properties from sinus rhythm to those of two ventricular tachycardias, several spatial regions exhibited statistically significantly different propagation characteristics. These areas were observed by visual inspection of electrogram activation maps to be characterized by conductive gradients, which differed in magnitude and direction from one rhythm to another. The regions in which the propagation characteristics are of greatest difference in each tachycardia were centered upon sites of conduction block, manifested by reentrant circuit rhythms. Therefore, the importance of the technique for the localization of specific electrophysiologic events is demonstrated. This study extends previous work of our group on biosignal pattern recognition to encompass localized spatial data.

The worsening shortage of organ and tissue donors in the United States has led to new clinical and legislative initiatives designed to increase the number of organs and tissues available for donation. Inlight of these new initiatives, this article reexamines the relationship between hospitals and organ and tissue procurement agencies who coordinate the donation process.

As the AIDS pandemic enters its second decade, persons most at risk for developing the disease are low-income African-American women and their children. This group has been extremely difficult to reach with traditional "top-down" risk reduction programs developed by the federal government. The authors describe an ethnographic case study strategy, appropriate for and within the reach of many community-based organizations. This strategy can be used to identify barriers to risk-reducing behaviors; ultimately this strategy can be used to assist organizations to develop culturally relevant intervention programs.

Purpose: Despite reports of poor patient understanding and recall after cancer consultations, few doctors provide communication aids. We conducted a randomized trial comparing an audiotape of the consultation versus individualized summary letters to patients after their first consultation with a medical oncologist., Methods: One hundred eighty-two cancer patients were randomized to receive either (1) the audiotape followed 7 to 10 days later by the letter or (2) the letter followed by the audiotape. Outcome measures included patient recall, anxiety and depression, satisfaction with and use of the communication aids, and patient preferences for six communication options. Demographic and disease variables and information and involvement preferences were documented., Results: Eighty percent of patients wanted all information and 72% wanted to participate in treatment decisions. Patients listened to the tape on average 2.3 times and read the letter 2.8 times over 4 weeks, and 90% showed the tape or letter to a friend, relative, or doctor. Satisfaction with the tape and letter were uniformly high and they did not differentially affect recall, anxiety, or depression. When asked to rank six communication options, 46% of patients gave the highest rank to the tape and 21% to the letter., Conclusion: Patients use audiotapes of their cancer consultation and individualized letters to review the information given and communicate information to relatives and friends. They prefer audiotapes to letters. Clinicians should consider installing audiotape-recording facilities that could be used to tape new-patient consultations.

Because of its slow onset of action, intrathecal morphine may not be the optimal drug for intraoperative analgesia during short cases, such as cesarean sections. It is not known whether adding fentanyl to a morphine-lidocaine spinal solution would provide any benefits to patients undergoing cesarean sections. Sixty-two women scheduled for elective cesarean section received intrathecal 5% lidocaine with dextrose (50-70 mg), epinephrine 200 micrograms, preservative-free morphine 0.2 mg, and either 10 micrograms of fentanyl (study group) or preservative-free normal saline (placebo group) in a 0.2-mL volume. Patients were asked to rate their severity of pain on a visual analog scale (VAS) intraoperatively as the uterus was exteriorized and again when the dermatomal level had receded to L1. Intravenous fentanyl was administered if the patient experienced intraoperative discomfort. The VAS scores were 0.8 +/- 1.5 and 2.3 +/- 1.6 (mean +/- SD) in the placebo group at the time of uterine extrusion and in the post-anesthesia care unit (PACU). The corresponding scores in the fentanyl group were 0.4 +/- 1.1 and 2.7 +/- 2.2. There was a significant difference between the two groups in the VAS scores intraoperatively (P < 0.014) but not in the PACU (P not significant). There was also a significant difference (P < 0.015) in the need for supplementation with intravenous (i.v.) fentanyl. Six patients in the placebo group received i.v. fentanyl as compared with none of the patients in the fentanyl group.(ABSTRACT TRUNCATED AT 250 WORDS)

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor produced by mesenchymal and myeloid cells following activation by inflammatory stimuli. It has previously been shown that a region of the G-CSF promoter, (-200 to -165) containing the decanucleotide CK-1 element and two repeated sequences that resemble nuclear factor (NF)-interleukin-6 (IL-6) binding sites, is required for activation of the G-CSF gene by tumor necrosis factor-alpha (TNF-alpha) and IL-1 beta. We now show that the NF-kappa B p65 protein can bind to and activate this TNF response region. There are several unusual features of this p65 interaction with the TNF response region. First, NF-kappa B p65 but not the related NF-kappa B p50 binds to the CK-1 element and a p50/65 hybrid protein that relies on the p50 rel homology domain for DNA binding does not transactivate the TNF response region. Second, p65 transactivation of this region is cell specific and requires not only its own binding site but also the NF-IL6 consensus sites. NF-IL6 also binds to the TNF response region of the G-CSF promoter. Electrophoretic mobility shift studies show that p65 and NF-IL6 can bind cooperatively to the TNF response region. The ability of this region to respond to TNF-alpha or p65 is correlated with the ability to form the p65/NF-IL6 ternary complex.

Background: Active participation and asking questions are important ways in which patients can ensure they understand what the doctor has said. This study evaluated a question prompt sheet designed to encourage patients to ask questions in the cancer consultation., Patients and Methods: Patients (n = 142) were randomised to receive (i) a question prompt sheet or (ii) a general sheet informing patients of services available through the regional Cancer Council. Recall of information was assessed in a structured interview 4-20 days after the consultation. Questionnaires to assess patient satisfaction and adjustment to cancer were sent by mail., Results: The question prompt sheet had a significant effect in one content area: prognosis. Thirty-five percent of patients who received the question handout asked questions about prognosis compared to 16% of those receiving the information handout. The prompt sheet did not increase the mean number of questions asked overall. Age, in/out-patient status, gender and involvement preference were predictive of both number and duration of patient questions., Conclusions: A question prompt sheet has a limited but important effect on patient question asking behaviour in the cancer consultation.

Human T cells require two discrete signals to initiate their proliferation. In Jurkat T cells the first signal can be provided by the phorbol ester TPA and the second by the calcium ionophore A23187. We have isolated a cDNA from Jurkat T cells representing mRNA induced by TPA but inhibited by simultaneous treatment of the cells with antibody, lectin, or A23187. Sequencing revealed identity of the Jurkat clone to a cDNA, termed ETR101, recently isolated from HL60 promyelocytic leukaemia cells and shown to be an immediate early gene expressed upon TPA stimulation of these cells [Shimizu et al.: J Biol Chem 266:12157, 1991]. The gene is also induced very rapidly upon TPA treatment of Jurkat cells and is superinduced by co-treatment with cycloheximide. The predicted amino acid sequence encoded by ETR101 has weak homology to JunB and JunD, therefore it is of some interest that these three genes share the chromosomal localization, 19p13.2. The divergent effects of TPA treatment upon cell proliferation and differentiation in different circumstances allow some speculation about a possible role for the ETR101 gene product upon cellular differentiation.

GABAA receptors have been solubilized from bovine brain membranes and, following purification by benzodiazepine affinity chromatography, have been reconstituted into phospholipid vesicles. Reconstituted vesicles were about 120 nm in diameter, and, on average, each vesicle contained fewer than one GABAA receptor which was reconstituted in an outside-out orientation. These preparations have been used in parallel studies of radiolabeled ligand binding and chloride flux, the latter being measured by following the fluorescence changes of a chloride-sensitive probe which was trapped within the vesicles at the time of reconstitution. The benzodiazepine [3H]flunitrazepam binds to an apparently homogeneous population of sites in these preparations (Kd of 5 nM) whereas the GABA analogue [3H]muscimol binds to both high- and low-affinity sites (KdS of 10 nM and 0.27 microM). Muscimol stimulated chloride flux with an EC50 of 0.2 microM and, at similar concentrations (EC50 = 0.16 microM), potentiated [3H]flunitrazepam binding, suggesting that occupancy of the low-affinity sites may be important for these effects. Diazepam shifted the dose-response curve for muscimol-stimulated flux to about 4-fold lower concentrations without affecting the maximum response. Diazepam did not, however, alter the equilibrium binding of [3H]muscimol. The purified receptor showed densensitization since flux responses were abolished by prior exposure to muscimol. The competitive antagonist bicuculline and the channel blocker picrotoxin completely inhibited ion flux mediated by 3 microM muscimol with EC50 values of 5.3 and 2.5 microM, respectively. These results are discussed in terms of possible mechanisms for activation, inhibition, and modulation of GABAA receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

This study investigates the effect of emotional behavior on the masseteric muscle EMG response patterns. Two experimental protocols are utilized: (1) does not elicit emotional behavior (stick chewing) and (2) elicits emotional behavior (hypothalamic stimulation). The Karhunen-Loève transform is used to compute features which exactly represent the correlated patterns of mean-zero observations, with data compression and noise immunity. Using nonparametric tests, it is found that the populations of biting and hissing features are significantly different (p < 0.05), with increased statistical significance as the size of the training set is increased. No statistically significant difference is seen in a test of the two biting populations.

Dental digital radiology is a rapidly changing field. The advantages and disadvantages are presented with an understanding that attention to fundamentals is paramount. The message for the near future is cautious optimism.

Purpose: Studies of tape recordings of cancer consultations have produced conflicting results. At the same time, audiotapes containing general information about cancer are poorly evaluated and are distributed to patients in an ad hoc manner. We compared the effects of both interventions on patient satisfaction, psychologic adjustment, and recall of information following their first consultation with a medical oncologist., Patients and Methods: Patients (n = 142) were randomized to receive (1) an audiotape of their consultation, (2) an audiotape describing cancer in general terms, or (3) no tape. Recall of information was assessed in a structured interview 4 to 20 days after the consultation., Results: Satisfaction with the consultation increased linearly from no tape to general tape to consultation tape. Satisfaction with the tape itself was higher in patients who received the consultation tape (satisfaction score, 61%) compared with those who received the general tape (43%). Average recall for all groups was 6.4 of the 25 items of information presented, and 2.4 of the six points identified as particularly important by the oncologist. The consultation tape did not improve recall over the no tape control, but the general tape caused a decrease of almost two items in total recall. Spontaneous (ie, unprompted) recall was significantly poorer with the general information tape. Psychologic adjustment to cancer was unaffected., Conclusion: We conclude that individual audiotapes have a limited potential to increase recall of information from the oncology consultation. General information tapes about cancer appear to inhibit recall actively.

Thrombolytic and anticoagulant therapies are used frequently in the cardiac patient. Bleeding complications and other coagulation defects, such as heparin-induced thrombocytopenia (HITP), can occur following the administration of these drugs. Nurses caring for the cardiac patient need to be aware of the potential for bleeding and know how to safely and effectively care for the patient who experiences a bleeding event.

The binding of agonists, antagonists, and the acetylcholinesterase inhibitor, eserine, to the nicotinic acetylcholine receptor from Torpedo californica has been monitored by the fluorescence changes of two extrinsic probes that have been covalently attached to the receptor protein. Although both probes, 5-(iodoacetamido)salicylic acid (IAS) and 4-[N-[(2-iodoacetoxy)ethyl]-N-methylamino]-7-nitrobenz-2-oxa-1,3-diaz ol e (IANBD) react with sulfhydryl groups, they do not react at the same location. The conditions for IAS labeling and competition studies have shown that, following reduction of the receptor, this fluorophore reacts with the same cysteines on each of the two alpha subunits that may be labeled by the alkylating agonist, [3H]bromoacetylcholine. The fluorescence of this probe is sensitive to the binding of agonists and competitive antagonists to two high-affinity sites on the receptor. IANBD does not react with the same cysteines as IAS, and its fluorescence is unchanged by the high-affinity binding of agonists and antagonists. The fluorescence of this probe is, however, specifically and saturably enhanced by the binding of agonists to distinct low-affinity sites. Heterogeneity in the NBD fluorescence changes induced by the bis-quaternary agonist, suberyldicholine, has indicated that the stoichiometry of low-affinity sites is also two per receptor. Stopped-flow studies of agonist binding to receptor preparations that had been doubly labeled by both fluorophores demonstrate that the conformational changes detected by IAS occur on slow time scales of seconds to minutes whereas a much faster conformational change is revealed by changes in NBD fluorescence.(ABSTRACT TRUNCATED AT 250 WORDS)

Affinity labeling techniques have been used to investigate the location of high-affinity binding sites for cholinergic agonists on the Torpedo acetylcholine receptor and the extent of overlap of these sites with those for long alpha-neurotoxins. Following reduction of the receptor by dithiothreitol, reaction with [3H]bromoacetylcholine leads to covalent incorporation into each of the two alpha subunits. At high concentrations of [3H]bromoacetylcholine (240 microM) and with prolonged incubation times (1-2 h), this labeling was not inhibited by either alpha-bungarotoxin or alpha-najatoxin. Following maximum labeling by [3H]bromoacetylcholine, no residual high binding sites for [125I]-alpha-bungarotoxin could be detected in the membrane-bound receptor, but 50% of the original sites were recovered by receptor solubilization. Since it has previously been reported that one of the two sites for alpha-bungarotoxin in the membrane-bound receptor is readily reversible but is converted to a high-affinity state by solubilization [Conti-Tronconi, B. M., Tang, F., Walgrave, S., & Gallagher, W. (1990) Biochemistry 29, 1046-1054], these results demonstrate that the covalently bound agonist inhibits the binding of alpha-bungarotoxin only to its higher affinity site in the membrane. When [3H]bromoacetylcholine labeling was carried out after reduction of the receptor by sodium borohydride rather than dithiothreitol, both alpha and gamma subunits of the receptor were labeled. Labeling of both subunits was completely inhibited if the receptor was first reduced with dithiothreitol and the alpha subunit sites were previously covalently labeled by unlabeled bromoacetylcholine.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of sulfhydryl modification on benzodiazepine binding to gamma-aminobutyric acid type A (GABAA) receptors have been studied in membrane preparations from bovine cerebral cortex. After reduction of membranes with increasing concentrations of dithiothreitol, the binding of the partial inverse agonist [3H]Ro15-4513 (2.5 nM) was inhibited with an IC50 of 4.6 mM, while the binding of the classical agonist [3H]flunitrazepam was affected only at much higher concentrations (> 30 mM). Prior desensitization of the GABAA receptor by incubation with 10 microM muscimol had no effect on dithiothreitol inhibition of [3H]Ro15-4513 binding. In equilibrium assays, 10 mM dithiothreitol increased the KD for [3H]Ro15-4513 binding by more than three-fold and reduced the density of binding sites by more than one-third. The binding sites for [3H]Ro15-4513 were protected from the effects of dithiothreitol by carrying out the reduction step in the presence of 10 microM Ro15-4513 or 10 microM flunitrazepam. Alkylation of brain membranes by N-ethylmaleimide inhibited the binding of both [3H]Ro15-4513 and [3H]flunitrazepam with a similar concentration dependence. Equilibrium binding assays in the presence of 10 mM N-ethylmaleimide showed that both the affinity and number of binding sites for [3H]Ro15-4513 were reduced, whereas only the KD for [3H]flunitrazepam binding was affected. These results demonstrate that sulfhydryl modification of GABAA receptors has different effects on the binding of a classical benzodiazepine agonist and a partial inverse agonist, suggesting differences in the modes of binding of the two ligands.

Calcium flux responses mediated by voltage-dependent calcium channels have been studied in transverse tubule membrane vesicles from rabbit skeletal muscle. Vesicles were loaded with 45Ca2+, and membrane potentials were generated by establishing potassium gradients across the membrane in the presence of valinomycin. After the membranes were polarized to an estimated -80 mV to approximate the resting state of the cell, a significant 45Ca2+ efflux occurred upon subsequent depolarization to -60 mV. The efflux response was modulated by activators and inhibitors of slow, dihydropyridine-sensitive calcium channels, being inhibited by inorganic calcium channel blockers, verapamil, nifedipine, and (-)-SDZ 202-791 and potentiated by the dihydropyridine agonists (+/-)-Bay K8644 and (+)-SDZ 202-791. These results demonstrate that calcium channels in transverse tubule membranes can open to mediate calcium flux in the same range of membrane potential as the late afterpotentials that occur during tetanic contractions of intact muscle fibres.

The dental radiograph is a diagnostic tool that is used to view internal structures without any invasive procedures. A difference radiograph, i.e. one showing the changes that occurred over time, is the best tool for diagnosing slow or small changes. The difficulty in creating a meaningful difference radiograph, or its digital image, is that the imaging geometry of the image pair must be identical. This paper addresses the problem of reproducing imaging geometry. A new technique for registering digital images of radiographs based on the correspondence of 3D anatomical structures (such as root apices and the cemento-enamel junction) was compared with a registration method using occlusal stents. In a pilot study of 30 volunteers, difference images were created by three different registration techniques (no registration, mathematical methods and occlusal stents). The standard deviations of the difference images were used to compare the registration techniques. The results show that this new mathematical technique applied to digital images of radiographs can be used to establish correspondence between pairs of clinical images taken at different projection angles and to produce reconstructed images comparable with images taken with occlusal stents.

Purpose: In this study we tested some assumptions about the use of euphemism in communicating with cancer patients. Does an explicit statement about the diagnosis of cancer cause patients to respond with greater anxiety than when uncertainty or ambiguity is allowed to persist? Do patients believe they cope better with cancer when the diagnosis is explicit?, Methods: A heterogeneous sample of 165 cancer patients completed a new measure of emotional adjustment to cancer using random assignment among four testing variables: agent (self-report v interview), terminology (the words cancer v illness), identification (patient identified v anonymous), and supervision (clinic v home). Internal consistency (Cronbach's alpha) for the 39-item set was 0.74 and face and content validity were determined using the focus-group technique and preliminary factor analysis. After answering the adjustment measures, subjects completed the Spielberger State-Trait Anxiety Inventory (STAI)., Results: Overall anxiety levels were significantly lower in the sample than published norms for general medical and surgical patients. Exposure to the word cancer as distinct from illness increased anxiety, but did not alter adjustment scores. Supervision and agent conditions did not affect anxiety, but reported adjustment was poorer in the interview condition compared with the self-report condition. Ambiguous instructions, such as asking patients to complete the questionnaire anonymously but return it in person to staff in the clinic, resulted in poorer adjustment, which was reversed by the consistent instruction to complete the questionnaire anonymously at home and return it by mail., Conclusion: Use of the word cancer generated anxiety to levels similar to those reported in general medical and surgical patients, but did not produce any distortion in reported adjustment. However, any ambiguity associated with the conditions under which adjustment is assessed may lead to distortion and an increase in the patient's reported psychologic distress.

The purpose of this paper is to clarify the distinction between the recognition of form, i.e. pattern recognition, and the interpretation of visual scenes, i.e. image understanding. Pattern recognition is part of image understanding, but the latter also includes cognitive tasks such as learning and inference. The key to developing image-understanding systems is to concentrate on the representation and use of models. This paper is a brief outline of the components of a model-based image-understanding system. First, the notions of iconic, categorical and symbolic knowledge are described. Although they appear to be disparate, the common notion is that the image understanding is based on recognizing concepts and not recognizing form. Next, the notion of a concept is defined, followed by representation techniques and control strategies for using concepts. Last, an example is given of an image-understanding system that learns to recognize concepts such as radiographic projections of teeth in panoramic radiographs.

The dental radiograph is a non-invasive tool that is used to view internal structures for the diagnosis of caries, periapical lesions and periodontal disease. The requirement for a standardized image is most prominent in periodontal disease since the diagnosis is best done with a difference radiograph. The difficulty is that exact registration for subtraction requires exact reproduction of imaging geometry. A new model of imaging geometry, based on the correspondence of 3D structures, to describe the radiograph formation process is presented. The experimental results show that 3D measurements can be made in dental radiographs (P < 0.01) with up to 16-mm translation errors and angulation errors of up to 32 degrees.

Trabecular pattern, the radiographic projection of trabecular bone, is a repeated structure that appears in a dental radiograph. Texture analysis, the computer image analysis of repeated patterns, is a technique that can be used to automate the diagnosis of periapical lesions with the detection of the absence of the texture that corresponds to the trabecular bone. The purpose of this study was to determine whether it is feasible to use texture analysis to identify the presence of the trabecular pattern in radiographs and to detect a periapical bone lesion based on a local absence of this pattern. Thirty-two mandibular periapical films, 16 with and 16 without periapical lesions, were used in this study. Texture analysis was carried out on the digital images of these radiographs. In the 16 films with lesions, they were all correctly identified, and no lesions were found in the 16 films without lesions. This result is based on the a prior knowledge of the user about the localization of the disease. Locating periapical regions without user interaction is a goal for future research.

Background and Objectives: We postulated that epidural sufentanil alone would provide adequate analgesia for labor and delivery. We also considered the possibility that a combination of epidural sufentanil and bupivacaine would demonstrate superior analgesia and fewer side effects when compared with either agent alone., Methods: Using a randomized, double-blind design, parturients were prospectively assigned to receive intermittent 10-ml doses of 3 micrograms/ml sufentanil in saline (Group S), 1.5 micrograms/ml sufentanil in 0.125% bupivacaine (Group SB), or 0.25% bupivacaine (Group B). Lumbar epidural catheters were placed during the first stage of labor, and a test dose (3 ml 2% lidocaine with 15 micrograms epinephrine) was given, followed by coded study solution. Subsequent doses of study solution were given at the patient's request. Those parturients who remained uncomfortable after 30 minutes were given 10 ml 2% lidocaine and were designated efficacy failures. Patients were evaluated for quality and duration of analgesia for each dose. Neonates were assessed using Apgar scores and the neonatal behavioral assessment scale. Maternal and umbilical venous sufentanil concentrations were measured at the time of delivery., Results: All patients received satisfactory analgesia of similar duration after the first epidural dose. After subsequent doses, women in Group S experienced more efficacy failures (Groups S, SB, and B, respectively, 12 of 26, 5 of 22, and 1 of 25; p less than 0.005) and received briefer, less intense analgesia compared to the other groups. Instrumental delivery was performed more frequently for women in Group B (Groups S, SB, and B, respectively, 0 of 14, 2 of 17, and 7 of 24; p = 0.04). No serious maternal side effects occurred. Apgar and neurobehavioral scores were comparable for all groups, with the exception that Group B infants had higher irritability scores at 1 hour of age (p = 0.003). Neither maternal nor umbilical venous sufentanil concentrations bore a consistent relationship to clinical outcomes., Conclusions: Epidural sufentanil alone does not reliably provide satisfactory analgesia for labor and delivery. Addition of small amounts of local anesthetic to bolus doses of sufentanil enhances and prolongs the analgesic effect.

A 20-item self-administered questionnaire with Likert scale responses was developed to measure quality of life in adult subjects with asthma. A total scale score together with subscale scores for breathlessness, mood disturbance, social disruption and concerns for health were calculated by addition of item scores. Items for the scale were selected by principal components analysis of the responses of 283 subjects to a preliminary pool of 69 items. In 58 subjects with stable asthma, good short term test-retest reliability was demonstrated with the intraclass correlation coefficient for the total scale being 0.80. The questionnaire was internally consistent in a sample of outpatients (Cronbach's alpha 0.92 in 77 subjects) and in a community sample with asthma (Cronbach's alpha 0.94 in 87 subjects). Weak correlations in the expected direction were seen with three medical markers of asthma severity. This supports the construct validity of the questionnaire and emphasizes that quality of life represents a separate dimension of asthma.

The fluorescence changes accompanying the binding of the fluorescent calcium channel antagonist, felodipine, to transverse tubule membranes from rabbit skeletal muscle have been used to characterize low-affinity binding sites for 1,4-dihydropyridine derivatives in these preparations. In competition experiments, felodipine inhibited the high-affinity binding of (+)-[3H]PN200-110 to transverse tubule membranes with an apparent Ki of 5 +/- 2 nM. Binding of felodipine to additional low-affinity sites resulted in a large, saturable (Kd = 6 +/- 2 microM) increase in its fluorescence which could be excited either directly (380 nm) or indirectly via energy transfer from membrane protein (290 nm). The observed fluorescence enhancement was competitively inhibited by other 1,4-dihydropyridines with inhibition constants of 3-21 microM but was unaffected by the structurally unrelated calcium channel antagonists, diltiazem and verapamil, or by Ca2+, Cd2+, and La3+. Both high- and low-affinity binding sites appear to be localized in the transverse tubular system, since the magnitude of the observed fluorescence enhancement was higher in these membranes than in microsomal preparations and was directly proportional to the density of high-affinity sites for (+)-[3H]PN200-110. Furthermore, both high- and low-affinity sites appear to be conformationally coupled since, over the same concentration range that the fluorescence changes were observed, felodipine accelerated the rate of dissociation of [3H]PN200-110 previously bound to its high-affinity sites. Similar behavior has previously been reported for other 1,4-dihydropyridines [Dunn, S. M. J., & Bladen, C. (1991) Biochemistry 30, 5716-5721].(ABSTRACT TRUNCATED AT 250 WORDS)

The GABAA/benzodiazepine receptor has been solubilized from bovine brain membranes and purified by benzodiazepine affinity chromatography. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate revealed two major protein species of 53 and 56 kDa. The purified protein has been reconstituted, in a functionally active form, into phospholipid vesicles. Chloride flux responses of the reconstituted preparations were investigated in stopped-flow experiments by monitoring fluorescence changes of a chloride-sensitive dye trapped within the vesicles. Flux was rapidly stimulated by muscimol and this response was potentiated by diazepam and blocked by desensitization of the receptor and by preincubation with the channel blocker, picrotoxin.

Detailed kinetic studies of the binding of the calcium channel antagonist (+)-[3H]PN200-110 to membrane preparations from rabbit skeletal muscle have demonstrated that, in addition to the high-affinity sites (Kd = 0.30 +/- 0.05 nM) that are readily measured in equilibrium and kinetic experiments, there are also dihydropyridine binding sites with much lower affinities. These sites were detected by the ability of micromolar concentrations of several dihydropyridines to accelerate the rate of dissociation of (+)-[3H]-PN200-110 from its high-affinity sites. The observed increase in rate was dependent on the concentration of competing ligand, and half-maximal effects occurred at approximately 10 microM for the agonist (+/-)-Bay K8644 and for the antagonists nifedipine, (+/-)-nitrendipine, and (+)-PN200-110. The low-affinity sites appear to be stereospecific since (-)-PN200-110 (1-200 microM) did not affect the dissociation rate. The possible involvement of guanine nucleotide binding proteins in dihydropyridine binding has been investigated by studying the effects of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) and guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) on binding parameters. At a concentration of 10 microM, neither GTP gamma S nor GDP beta S significantly affected the binding of dihydropyridines to their high-affinity sites. GTP gamma S did, however, increase the ability of (+/-)-Bay K8644, but not of (+/-)-nitrendipine, to accelerate the rate of dissociation of tightly bound (+)-[3H]PN200-110. GDP beta S did not affect the dose dependence of either the agonist or the antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Dental digital subtraction radiography requires accurate repositioning of the patient and X-ray source in order to facilitate correct diagnostic of bone loss. Present mechanical repositioning systems do not allow radiography of posterior teeth, and are uncomfortable for the patient. A new repositioning system that utilizes a six degrees of freedom position sensor and a robot arm with X-ray source is proposed. A mathematical model for the system is given, and the robot arm solution is obtained based on patient position. An error analysis is performed in order to determine the influence of sensor and robot errors on system accuracy. A series of experiments to determine sensor noise and accuracy are described. These tests showed relatively small errors over the work envelope of the sensor. Further tests showed that there is no adverse effect due to the presence of metal work in the patient's mouth. The high bandwidth of the sensor may allow real time tracking of small movements of the patient's head.

Diabetes patient education has emerged as an integral component of comprehensive diabetes care during the past 50 years. The medical model of information transfer is now inadequate to support the variety of effective techniques which have been shown to influence patients' knowledge and health behavior. To cope with rapidly changing patterns of diabetes care, diabetes education must develop new models and modes. This article presents a re-evaluation of the traditional concepts of diabetes education and identifies new challenges and new directions for the 1990s.

Inconsistent findings on the efficacy of psychosocial interventions in cancer may be due to their lack of specificity. The aim of this study was to identify priorities of psychosocial need among cancer patients currently receiving treatment in Western Sydney (NSW) as a prelude to targeted intervention. A sample of 188 patients (129 female, median age 52 years, median time since diagnosis 12 months), with various solid tumours, completed a self-report ranking questionnaire listing eight major areas of psychosocial need based on a literature search of relevant studies. The resulting ranking of priorities was: family (1), dealing with emotional stress (2), getting information (3), money (4), work (5), social life (6), sex life (7), and dealing with hospital staff (8). These priorities were independent of demographic characteristics, including time since diagnosis, suggesting that support in the areas of major need may be just as important during follow-up as it is at diagnosis. Males reported less distress than females, and patients with cancer of the head/neck or breast reported most distress. To be maximally effective, psychosocial intervention for cancer patients should focus on the principal areas of family interaction, effective stress management, and access to information.

Evaluation of diabetes education programs (DEPs) has provided minimal empirical support for a relationship between improved knowledge and better metabolic control. We hypothesized that improved knowledge in specific areas is predictive of changes in specific measures of diabetes control. Patients (n = 558) attending one of five DEPs completed a diabetes knowledge questionnaire at baseline and post-DEP. Glycosylated hemoglobin (GHb) was measured at baseline and at 3 months follow-up. Total diabetes knowledge (DKN) scores increased significantly by 18%, but improvement was uncorrelated with changes in GHb (r = 0.03). Improvement in nine specific content areas failed to predict changes in GHb (all P greater than 0.05) and improvement in knowledge of the causes of hypoglycemia did not predict changes in frequency of hypoglycemia (chi 2 = 1.54; P greater than 0.05). We conclude that neither global nor specific knowledge improvement predicts metabolic control in diabetes and suggest that evaluation of diabetes education should focus more intensively on behavioral and attitudinal outcomes.

In the absence of ligands, dihydrofolate reductase from Escherichia coli exists in at least two interconvertible conformations, only one of which binds NADPH with high affinity. This equilibrium is pH dependent, involving an ionizable group of the enzyme (pK approximately 5.5), and the proportion of the NADPH-binding conformer increases from 42% at pH 5 to 65% at pH 8. The role of specific amino acids in enzyme conformation has been investigated by studying the kinetics of NADPH binding to three dihydrofolate reductase mutants: (i) a mutant in which Asp-27, a residue that is directly involved in the binding of folates and antifolates but not NADPH, has been replaced by a serine, (ii) a mutant in which Phe-137 on the exterior of the molecule and distant from the binding sites has been replaced by a serine, and (iii) a mutant in which both Asp-27 and Phe-137 have been replaced by serines. Mutation of the Asp-27 residue reduces the affinity for NADPH by approximately 7-fold. Kinetic measurements have suggested that this is due mainly to an increase in the rate of dissociation of the initial complex and a slight shift in the enzyme equilibrium to favor the nonbinding conformation. The pH dependence of the conformer equilibrium is also shifted by approximately one pH unit to higher pH (pK approximately 6.5). In addition, the pH profile suggests the involvement of a second ionizable group having a pK of about 8 since, above pH 7, the proportion of the NADPH-binding form decreases.(ABSTRACT TRUNCATED AT 250 WORDS)

Randomized trials of formal diabetes education have proven that education in isolation from other aspects of diabetes care has limited impact on metabolic control through the simple transfer of information. Comprehensive programme evaluation requires assessment of the process by which knowledge and attitude change affect subsequent control of diabetes. This study examined the impact of a formal diabetes education programme on diabetes-specific knowledge and attitude, and the relationship between these characteristics and metabolic control of the disease over a 15-month period. Knowledge and attitude were assessed using parallel forms of the DKN and ATT39 scales presented randomly as pre-test and post-test to 309 patients attending a 2-day diabetes education programme. Mean knowledge scores increased by 25% (P less than 0.0001) and standardized ATT scores showed a small but significant positive shift after the programme (P less than 0.01) and remained stable in a subset of 177 patients at 3-month follow-up. ATT scores showed a marked convergence towards normal during the intervention (ANOVA, P less than 0.0001). Glycosylated haemoglobin (HbAlc), a medium-term measure of blood glucose control, was recorded in 209 cases for 6 months preceding the programme, and for 15 months following, at intervals of 3 months. The mean HbAlc improvement, from 11.3 to 9.0% (P less than 0.001), was predicted by stepwise regression from initial diabetes control (57% variance) and psychosocial factors (17% variance) including attitude scores and personality characteristics. Diabetes knowledge did not predict improvement in the control of diabetes.

The GABAA/benzodiazepine receptor has been solubilized from membrane preparations of bovine cerebral cortex and has been reconstituted, in a functionally active form, into phospholipid vesicles. In preliminary experiments, the receptor was labeled with the photoactive benzodiazepine [3H]flunitrazepam prior to solubilization. A peptide of apparent molecular weight 53,500 was specifically labeled by this method, and this was used as a marker for the receptor during the reconstitution procedures. The labeled protein was solubilized with approximately 40% efficiency by 1% beta-octyl glucoside. Reconstitution was achieved by mixing the solubilized proteins with a 4:1 mixture of soybean asolectin and bovine brain phospholipids, followed by chromatography on Sephadex G-50-80 to remove detergent. The incorporation of the GABAA receptor into membrane vesicles has been verified by sucrose gradient centrifugation in which the [3H]-flunitrazepam-labeled peptide comigrated with [14C]phosphatidylcholine used as a lipid marker. Vesicles prepared without labeled markers retained the ability to bind both [3H]flunitrazepam and the GABA analogue [3H]muscimol. Furthermore, the binding parameters were very similar to those measured using native membrane preparations. A novel fluorescence technique has been used to measure chloride transport mediated by the GABAA receptor in reconstituted vesicles. Chloride influx was rapidly stimulated in the presence of micromolar concentrations of muscimol and was blocked by preincubation of the membranes with muscimol (desensitization). Flux was also blocked by pretreatment with the competitive GABAA receptor blocker bicuculline or with the noncompetitive GABAA receptor antagonist picrotoxin.

The effects of sulfhydryl group modification on ligand binding and functional properties of the membrane-bound acetylcholine receptor from Torpedo californica have been investigated. Agonist binding kinetics were monitored by changes in fluorescence of the probe 5-(iodoacetamido)-salicylic acid which was covalently bound to the receptor after reduction of a reactive disulfide bond(s) by low concentrations of dithiothreitol. These labeling procedures did not affect either the equilibrium binding constant for [3H]acetylcholine or the number of high-affinity binding sites measured in centrifugation experiments. Further reduction of these labeled receptor preparations by higher concentrations of dithiothreitol and subsequent alkylation by excess iodoacetamide resulted in a more than 10-fold decrease in the affinity of the receptor for [3H]acetylcholine. This reduction and alkylation did not, however, radically alter the observed kinetics of acetylcholine binding. The fluorescence signal change on binding consisted of at least three phases similar to those observed for the control preparations, and the ligand concentration dependencies of the measured rate constants could be described by the same kinetic mechanism involving sequential binding of two ligand molecules and three conformational changes. Variation in the values of some of the kinetic parameters describing the formation of the monoliganded complex adequately accounted for the measured decrease in affinity for [3H]acetylcholine. Stopped-flow fluorescence experiments showed that extensive reduction and alkylation resulted in an apparent loss of the ability of the acetylcholine receptor to mediate agonist-induced cation flux. These results show that reduction of disulfide bonds by high concentrations of dithiothreitol followed by alkylation with iodoacetamide seriously perturbs receptor function although the receptor can still undergo its characteristic conformational changes on the binding of acetylcholine but with altered concentration dependence accounting for the reduced affinity for agonist.

The intercellular adhesion molecule (ICAM-1) is a cell-surface molecule which binds to leukocyte function antigen-1 (LFA-1) and regulates both leukocyte adhesion to endothelial cells and immune functions requiring cell-cell contact. Membrane expression of ICAM-1 is highly regulated on all hematopoietic lineages. Cell membrane antigen is significantly expressed on a small subset of bone marrow (BM) progenitors but is weak or absent on all cell lineages once they enter the circulation. However, strong expression on tissue macrophages and germinal center B cells suggested that activated cells may show upregulated expression. When B cells, T cells, macrophages, or granulocytes were activated in vitro by suitable mitogens, ICAM-1 expression was induced in all cases. Parallel studies of hematopoietic tumors demonstrated a heterogeneity of expression which correlated with expression on their normal cellular counterparts. In particular, a striking correlation between expression on B-cell tumors and corresponding stages of B-cell differentiation was noted. The widely varying expression of ICAM-1 contrasts with LFA-1 which, while variable, is nevertheless significantly positive at all stages of differentiation. This suggests that the major regulation of homotypic adhesion mediated by the LFA-1/ICAM-1 linkage occurs through control of ICAM-1 expression. In keeping with this notion, ICAM-1 expression was also correlated with the "adhesiveness" of B-lymphoid tumors. Large solitary lymphoma masses showed intense expression of ICAM-1. Conversely, chronic lymphocytic leukemia (CLL) cells and lymphoma cells from tumors exhibiting diffuse, widespread lymph node disease showed weak expression. These observations are discussed in relation to the role of ICAM-1 in regulation of lymphoid recirculation and the biology of lymphoid tumors.

During October and November, 1978, gastroenteritis developed in 17 of 24 young children aged between eight months and two years from an R.A.F. station in the U.K. The illness, in which diarrhoea was always the predominant symptom, had an incubation period of eight to ten days and lasted about a week. It seemed to be transmitted from child to child, and in all but one instance parents and older siblings remained well. Stool specimens from 14 of the affected children were examined bacteriologically and virologically, and a highly significant association was found between the presence of adenovirus particles in stools, identified by electron microscopy, and the acute stage of the illness. This evidence suggests that an adenovirus was the cause of this outbreak of gastroenteritis.