Activating mu-opioid receptors in the lateral parabrachial nucleus increases c-Fos expression in forebrain areas associated with caloric regulation, reward and cognition.

The pontine parabrachial nucleus (PBN) has been implicated in the modulation of ingestion and contains high levels of mu-opioid receptors (MOPRs). In previous work, stimulating MOPRs by infusing the highly selective MOPR agonist [d-Ala2, N-Me-Phe4, Gly5-ol]enkephalin (DAMGO) into the lateral parabrachial region (LPBN) increased food intake. The highly selective MOPR antagonist d-Phe-Cys-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) prevented the hyperphagic action of DAMGO. The present experiments aimed to analyze both the pattern of neural activation and the underlying cellular processes associated with MOPR activation in the LPBN. Male Sprague-Dawley rats received a unilateral microinfusion of a nearly maximal hyperphagic dose of DAMGO into the LPBN. We then determined the level of c-Fos immunoreactivity in regions throughout the brain. MOPR activation in the LPBN increased c-Fos in the LPBN and in the nucleus accumbens, hypothalamic arcuate nucleus, paraventricular nucleus of the thalamus and hippocampus. Pretreatment with CTAP prevented the increase in c-Fos translation in each of these areas. CTAP also prevented the coupling of MOPRs to their G-proteins which was measured by [(35)S] guanosine 5'-O-[gamma-thio]triphosphate ([(35)S]GTPgammaS) autoradiography. Together, these data strongly suggest that increasing the coupling of MOPRs to their G-proteins in the LPBN disinhibits parabrachial neurons which subsequently leads to excitation of neurons in regions associated with caloric regulation, ingestive reward and cognitive processes in feeding.

Effects of sampling standardization on estimates of Phanerozoic marine diversification.

Global diversity curves reflect more than just the number of taxa that have existed through time: they also mirror variation in the nature of the fossil record and the way the record is reported. These sampling effects are best quantified by assembling and analyzing large numbers of locality-specific biotic inventories. Here, we introduce a new database of this kind for the Phanerozoic fossil record of marine invertebrates. We apply four substantially distinct analytical methods that estimate taxonomic diversity by quantifying and correcting for variation through time in the number and nature of inventories. Variation introduced by the use of two dramatically different counting protocols also is explored. We present sampling-standardized diversity estimates for two long intervals that sum to 300 Myr (Middle Ordovician-Carboniferous; Late Jurassic-Paleogene). Our new curves differ considerably from traditional, synoptic curves. For example, some of them imply unexpectedly low late Cretaceous and early Tertiary diversity levels. However, such factors as the current emphasis in the database on North America and Europe still obscure our view of the global history of marine biodiversity. These limitations will be addressed as the database and methods are refined.

Improved health-related quality of life with SSRIs and other antidepressants.

STUDY OBJECTIVE: To document the health-related quality of life (HRQOL) of depressed patients receiving antidepressant drugs. DESIGN: Cross-sectional study. SETTING: Community pharmacy-based setting. PATIENTS: Fifty-seven depressed patients. INTERVENTION: Independent pharmacist members of the Community Pharmacists Research Network in Georgia administered the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) to subjects. MEASUREMENTS AND MAIN RESULTS: Sixty-one percent of patients were treated with a selective serotonin reuptake inhibitor (SSRI) and 38.6% were treated with a non-SSRI. Those receiving SSRIs scored higher on the mean physical (PCS) and mental (MCS) health summary scores of the SF-36 than those not receiving the drugs. No significant differences were seen in PCS or MCS scores of men and women. CONCLUSION: Community pharmacists documented better HRQOL in patients receiving SSRIs than in those given other antidepressants.

Photoinduced ortho [2 + 2] cycloaddition of double bonds to triplet benzenes.

The triplet states of certain phenyl ketones and benzoic acid derivatives undergo regioselective and stereoselective intramolecular ortho cycloaddition to remote double bonds, triggering an array of photochemical and thermal pericyclic rearrangements among various novel polycyclic products.

Inferring and testing hypotheses of cladistic character dependence by using character compatibility.

The notion that two characters evolve independently is of interest for two reasons. First, theories of biological integration often predict that change in one character requires complementary change in another. Second, character independence is a basic assumption of most phylogenetic inference methods, and dependent characters might confound attempts at phylogenetic inference. Previously proposed tests of correlated character evolution require a model phylogeny and therefore assume that nonphylogenetic correlation has a negligible effect on initial tree construction. This paper develops "tree-free" methods for testing the independence of cladistic characters. These methods can test the character independence model as a hypothesis before phylogeny reconstruction, or can be used simply to test for correlated evolution. We first develop an approach for visualizing suites of correlated characters by using character compatibility. Two characters are compatible if they can be used to construct a tree without homoplasy. The approach is based on the examination of mutual compatibilities between characters. The number of times two characters i and j share compatibility with a third character is calculated, and a pairwise shared compatibility matrix is constructed. From this matrix, an association matrix analogous to a dissimilarity matrix is derived. Eigenvector analyses of this association matrix reveal suites of characters with similar compatibility patterns. A priori character subsets can be tested for significant correlation on these axes. Monte Carlo tests are performed to determine the expected distribution of mutual compatibilities, given various criteria from the original data set. These simulated distributions are then used to test whether the observed amounts of nonphylogenetic correlation in character suites can be attributed to chance alone. We have applied these methods to published morphological data for caecilian amphibians. The analyses corroborate instances of dependent evolution hypothesized by previous workers and also identify novel partitions. Phylogenetic analysis is performed after reducing correlated suites to single characters. The resulting cladogram has greater topological resolution and implies appreciably less change among the remaining characters than does a tree derived from the raw data matrix.

Alternative pharmacotherapy. Patterns of patient use and family physician practice.

BACKGROUND: The use of alternative pharmacotherapies is rapidly increasing. Many persons who use purchased or prepared alternative medications are also cared for by family physicians. We describe patient usage of alternative pharmacotherapies and examine how family physicians handle this in medical practice. METHODS: We recorded data from structured interviews of 178 patients in an academic family medicine practice in a midsized southern city. We then examined the medical records of each participant who reported using some form of alternative pharmacotherapy to determine whether there was discussion of this use with the physician. RESULTS: Approximately one third of the patients reported using some form of alternative pharmacotherapy for 1 year or less, learning about alternative medications mostly from the media, and being generally satisfied with the results. Eighty-four percent of the patients reported not having been asked by their physician about their use of these drugs on the day of their office visit, and more than half reported never having been asked about their use of them. Medical record reviews indicated that for the most part physicians did not document having discussed or making recommendations about the use of alternative pharmacotherapies at any point in their relationship with the patient. CONCLUSIONS: Since many of their patients are using alternative pharmacotherapies, family physicians are encouraged to learn more about what their patients use, to institute easy system-wide changes to facilitate discussion about this use with their patients, to document alternative drugs used, and to give recommendations regarding them.

Exhaustion of morphologic character states among fossil taxa.

Frequencies of new character state derivations are analyzed for 56 fossil taxa. The hypothesis that new character states are added continuously throughout clade history can be rejected for 48 of these clades. Two alternative explanations are considered: finite states and ordered states. The former hypothesizes a limited number of states available to each character and is tested using rarefaction equations. The latter hypothesizes that there are limited possible descendant morphologies for any state, even if the character has infinite potential states. This is tested using power functions. The finite states hypothesis explains states: steps relationships significantly better than does the ordered states hypothesis in 14 cases; the converse is true for 14 other cases. Under either hypothesis, trilobite clades show appreciably more homoplasty after the same numbers of steps than do molluscs, echinoderms, or vertebrates. The prevalence of the exhaustion pattern among different taxonomic groups implies that worker biases are not to blame and instead implicates biological explanations such as intrinsic constraints or persistent selective trends. Regardless of the source of increased homoplasy, clades appear to exhaust their available character spaces. Nearly all examined taxa show significant increases in proportions of incompatible character pairs (i.e., those necessarily implying homoplasy) as progressively younger taxa are added to character matrices. Thus, a deterioration of hierarchical structure accompanies character state exhaustion. Exhaustion has several implications: (1) the basic premise of cladistic analyses (i.e., that maximum congruence reflects homology rather than homoplasy) becomes increasingly less sound as clades age; (2) sampling high proportions of taxa probably is needed for congruence to discern homoplasy from homology; (3) stratigraphic data might be necessary to discern congruent homoplasy from congruent homology; and (4) in many cases, character states appear to have evolved in ordered patterns.

Which medicines do our patients want from us?

BACKGROUND: The prescribing of medication, whether for infections or injuries, has come under the scrutiny of health maintenance organizations (HMOs). Our goal was to examine patient beliefs about the usefulness of certain classes of medications. METHODS: We surveyed 244 consecutive adult patients who presented to an urban private family medicine practice in Georgia. RESULTS: Regardless of who paid for prescriptions (an HMO or the patient), most people in the survey would be satisfied with over-the-counter medications and reassurance (84% for upper-respiratory infection, 72% for muscle strain, 56% for diarrhea). Few differences were attributable to payment status (prepaid as opposed to fee-for-service). African Americans are less likely than whites to accept reassurance as an appropriate treatment. CONCLUSIONS: Patients may be more willing to accept reassurance and over-the-counter medications than is commonly believed by physicians.

Age rank/clade rank metrics--sampling, taxonomy, and the meaning of "stratigraphic consistency".

Paleontologists frequently contrast clade rank (i.e., nodal or patristic distance from the base of a cladogram) with age rank (i.e., relative first known appearances of the analyzed taxa) to measure the degree of congruence between the estimated phylogeny and the fossil record. Although some potential biases of these methods have been examined (e.g., the effect of tree imbalance), other properties of age rank/clade rank (ARCR) comparisons have not been studied in detail. A basic premise of ARCR metrics is that outgroup taxa diverged earlier than ingroups and thus should first appear in older strata. For example, given phylogeny (A,(B,C)), then taxon A should be sampled before either taxon B or taxon C. We examine this premise in the context of (1) phylogenetic theory, (2) taxonomic practice, (3) sampling intensity (R), and (4) factors other than sampling intensity (including cladogram accuracy). Simulations combining clade evolution and sampling over time indicate a poor relationship between ARCR metrics and R when all taxa are apomorphy-based monophyletic groups. However, a good relationship exists when taxa are either stem-based monophyletic groups or if workers include taxa without a priori decisions about monophyly or paraphyly. These results are not surprising because cladograms predict the order in which lineages diverged (which applies to stem-based monophyletic taxa) and the order in which morphologic grades appeared (which applies to paraphyletic taxa relative to derived monophyletic groups). Other factors that increase ARCR metrics when the average R stays the same include high temporal variation in R, budding instead of bifurcating speciation patterns, low extinction rates, cladogram inaccuracy, and (to a much lesser extent) large clade size. These results suggest several plausible explanations for patterned differences in ARCR metrics among clades, thereby compromising their validity as measures of the quality of the fossil record.

The quality of the fossil record and the accuracy of phylogenetic inferences about sampling and diversity.

Because phylogenies can be estimated without stratigraphic data and because estimated phylogenies also infer gaps in sampling, some workers have used phylogeny estimates as templates for evaluating sampling from the fossil record and for "correcting" historical diversity patterns. However, it is not known how sampling intensity (the probability of sampling taxa per unit time) and completeness (the proportion of taxa sampled) affect the accuracy of phylogenetic inferences, nor how phylogenetically inferred estimates of sampling and diversity respond to inaccurate estimates of phylogeny. Both issues are addressed with a series of simulations using simple models of character evolution, varying speciation patterns, and various rates of speciation, extinction, character change, and preservation. Parsimony estimates of simulated phylogenies become less accurate as sampling decreases, and inaccurate trees chronically underestimate sampling. Biotic factors such as rates of morphologic change and extinction both affect the accuracy of phylogenetic estimates and thus affect estimated gaps in sampling, indicating that differences in implied sampling need not reflect actual differences in sampling. Errors in inferred diversity are concentrated early in the history of a clade. This, coupled with failure to account for true extinction times (i.e., the Signor-Lipps effect), inflates relative diversity levels early in clade histories. Because factors other than differences in sampling predict differences in the numbers of gaps implied by phylogeny estimates, inferred phylogenies can be misleading templates for evaluating sampling or historical diversity patterns.

Taking the edge off: why patients choose St. John's Wort.

BACKGROUND: The number of visits to alternative medicine practitioners in this country is estimated at 425 million, which is more than the number of visits to allopathic primary care physicians in 1990. Patients' use of St. John's Wort (SJW) has followed this sweeping trend. The purpose of our study was to examine the reasons people choose to self-medicate with SJW instead of seeking care from a conventional health care provider. METHODS: We used open-ended interviews with key questions to elicit information. Twenty-two current users of SJW (21 women; 20 white; mean age = 45 years) in a Southern city participated. All interviews were transcribed, and descriptive participant quotes were extracted by a research assistant. Quotes were reviewed for each key question for similarities and contextual themes. RESULTS: Four dominant decision-making themes were consistently noted. These were: (1) Personal Health Care Values: subjects had a history of alternative medicine use and a belief in the need for personal control of health; (2) Mood: all SJW users reported a depressed mood and occasionally irritability, cognitive difficulties, social isolation, and hormonal mood changes; (3) Perceptions of Seriousness of Disease and Risks of Treatment: SJW users reported the self-diagnosis of "minor" depression, high risks of prescription drugs, and a perception of safety with herbal remedies; and (4) Accessibility Issues: subjects had barriers to and lack of knowledge of traditional health care providers and awareness of the ease of use and popularity of SJW. Also of note was the fact that some SJW users did not inform their primary care providers that they were taking the herb (6 of 22). Users reported moderate effectiveness and few side effects of SJW. CONCLUSIONS: SJW users report depression, ease of access to alternative medicines, and a history of exposure to and belief in the safety of herbal remedies. Users saw little benefit to providing information about SJW to primary care physicians.

Practice patterns in managing the difficult airway by anesthesiologists in the United States.

UNLABELLED: Despite the availability of several techniques and devices for the management of the difficult airway, little information has been published regarding the prevalence of their use by anesthesiologists in the United States. To determine current practice patterns, we surveyed clinicians using a questionnaire consisting of 14 difficult airway scenarios. Anesthesiologists were requested to indicate their likely approach to anesthetic induction (e.g., awake but sedated, general anesthesia with spontaneous ventilation, general anesthesia with apnea after assuring a patent airway, or general anesthesia with apnea) and the primary device they would use to intubate (e.g., direct laryngoscopy [DL], flexible fiberoptic bronchoscope [FOB], rigid fiberoptic device, surgical airway, retrograde intubation kit, laryngeal mask airway, gum elastic bougie, or Combitube). The availability of these devices was also determined (in room at all times, available "stat," available if arranged preoperatively, or not available). The survey was mailed to 1000 randomly chosen active members of the American Society of Anesthesiologists. Second and third surveys were mailed to non responders. Four hundred seventy-two completed surveys were returned. Responses by demographic groups were compared by using chi 2 analysis. DL and FOB-aided tracheal intubation techniques were chosen for most cases by most anesthesiologists (P < 0.05). Anesthesiologists with > 10 yr of clinical experience and those older than 55 yr of age preferred DL with apneic conditions (P < 0.05). Anesthesiologists who had attended workshops within the last 5 yr had greater availability of retrograde guidewire equipment and FOBs (P < 0.05). There was little use of newer alternative airway devices. IMPLICATIONS: Although the teaching of alternative methods of securing a difficult airway has become ubiquitous, most anesthesiologists rely on direct laryngoscopy and fiberoptic-aided intubation in most clinical circumstances. Although workshops in the management of the difficult airway may have resulted in increased use of the fiberoptic bronchoscope and the availability of retrograde guidewire intubation equipment, other devices have not enjoyed such an increase.

Validating the concept of abuse: women's perceptions of defining behaviors and the effects of emotional abuse on health indicators.

OBJECTIVES: To validate the construct of abuse in 2 ways: first, to examine female patients' perceptions of abusive behaviors that are typically used in standardized abuse scales; and second, to determine health status symptom and medical utilization differences between women who report emotional abuse and women who are not abused. DESIGN: Cross-sectional interviews and medical record reviews. MAIN OUTCOME MEASURES: Modified directions to the Conflict Tactics Scale were used to identify women's perceptions of abusive behaviors. Personal history of abuse was determined by self-report. Health status was measured using the Medical Outcomes Study Short-Form Health Survey-36 and medical services utilization was determined from medical records. The Wahler Physical Symptom Inventory was used to measure symptom experience. SETTING: Patients were interviewed in either a rural primary care practice or an urban medical university practice. PATIENTS: Four hundred seven women older than 18 years were interviewed. Half were from an urban and half from a rural setting. Sixty-four percent of the sample was black. RESULTS: Women saw more behaviors as abusive than are typically identified by the Conflict Tactics Scale and abused women identified more abusive behaviors than nonabused women. Significant health status differences were found between women who reported emotional abuse with no concurrent physical or sexual abuse and nonabused women on 7 of the 8 dimensions of the Short-Form Health Survey health status scales and on 25% of measured symptoms. CONCLUSIONS: These findings reflect the idea that women consider many behaviors to be abusive and that abused women perceive more behaviors as abusive than do nonabused women. Given that significant health status differences are shown between emotionally abused and nonabused women, emotional abuse can be viewed as a critical variable in patient health behavior.

Update in regional anesthesia for shoulder surgery.

Recent advances in the application of regional anesthesia to the care of patients undergoing shoulder surgery are discussed. New techniques for the management of postoperative pain are highlighted, with an emphasis on interscalene patient-controlled analgesia and suprascapular block. New developments in the safety and effectiveness of brachial plexus block are presented. The technique of interscalene block used at our institution is discussed in detail. Intraoperative hypotension and bradycardia caused by activation of the Bezold-Jarisch reflex is considered. The ongoing debate regarding the use of paresthesia versus nerve-stimulator techniques is examined.

Mechanical ocular trauma.

Mechanical ocular trauma remains a leading cause of visual loss and blindness and often affects young individuals. Approximately 75% of people with trauma-induced visual impairment are monoculary blind. Furthermore, the human, social, and economic consequences of eye injuries are enormous in all parts of the world. Because most eye injuries are preventable, efforts could be spent much more effectively on preventing eye injuries rather than treating them. It is important to make the public aware of the benefits of using protective equipment, which is almost universally available, and was the main concern of most of the authors reporting on ocular trauma in the past year. Of great importance seems to be the introduction of an international standardized classification of ocular trauma.

Experience of abuse in primary care patients. Racial and rural differences.

OBJECTIVE: To examine the experience of abuse in rural, urban, black, and white women on the following dimensions: prevalence, symptom experience, health status, medical services utilization, and coping mechanisms. DESIGN: Retrospective study using patient interviews. SETTING: Half the subjects were recruited from a large medical university family medicine center and half from a rural family medicine center, both in the Southeast. PATIENTS: Four hundred seven women were interviewed. Groups were distributed as follows: urban white, 24.9% (n = 99); urban black, 25.6% (n = 102); rural white, 11.1% (n = 44); and rural black, 38.4% (n = 153). MAIN OUTCOME MEASURES: Self-report of abuse (sexual, physical, and emotional) was related to symptom history, current health status, medical services utilization, and coping styles. RESULTS: Sixty-six percent of the total sample reported some kind of abuse. Black, rural women reported the least (52.3%). Presence of greater numbers of symptoms, greater medical services utilization, and lower health status were found in the abused population. Abused women used all types of coping mechanisms to a greater extent than non-abused women. Black women were more likely to use confrontation (F = 8.82 [P = .003]), problem solving (F = 8.24 [P = .004]), and reappraisal (F = 4.13 [P = .04]) than white women. Rural women were more likely to use psychological distancing (F = 5.25 [P = .02]) and escape (F = 5.67 [P = .02]) than urban women, although abused women in general use those coping methods more than nonabused women. CONCLUSIONS: The experience of abuse remains similar across black, white, rural, and urban women; however, coping mechanisms appear to be influenced by group membership.

Psychological considerations in colonoscopy.

In summary, psychological issues around the colonoscopy procedure have not yet been fully studied or even formulated. The framework taken here is to consider psychological preconditions to disease, psychological barriers to screening, and ways to maximize the psychological strength of patients when presenting serious diagnoses. Two common themes are present in this review. First, the idea of hopelessness and loss of personal control is present throughout the research in terms of personality predispositions, decisions to seek care, and outcome of disease when present. Physicians need to address the question, what can I do to maximize the hopefulness of this person before, during, and after screening? Are we encouraging an optimistic perspective in the lives of others? The second theme is closely related and that is the critical nature of the patient/physician relationship in all stages of health/illness behavior. It is often the positive, empathic strength of this relationship that affects patient behavior and ultimately the patient's medical outcome. Future research as well as physician self-examination and increased knowledge in this area are truly important. It is in this way that the procedure of colonoscopy truly becomes part of the total patient care.