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Effective pain management in the terminally ill patient requires an understanding of pain control strategies. Ongoing assessment of pain is crucial and can be accomplished using various forms and scales. It is also important to determine if the pain is nociceptive (somatic or visceral pain) or neuropathic (continuous dysesthesias or chronic lancinating or paroxysmal pain). Nociceptive pain can usually be controlled with nonsteroidal antiinflammatory drugs or corticosteroids, whereas neuropathic pain responds to tricyclic antidepressants or anticonvulsants. Relief of breakthrough pain requires the administration of an immediate-release analgesic medication. If a significant amount of medication for breakthrough pain is already being given, the baseline dose of sustained-release analgesic medication should be increased. If pain does not respond to one analgesic medication, physicians should use an equianalgesic dose chart when changing the medication or route of administration. Opioid rotation can be used if pain can no longer be controlled on a specific regimen. The impact of unresolved psychosocial or spiritual issues on pain management may need to be addressed.

Electrical stimulation of vagal afferents or cardiopulmonary sympathetic afferent fibers excites C(1)--C(2) spinal neurons. The purposes of this study were to compare the responses of superficial (depth <0.35 mm) and deeper C(1)--C(2) spinal neurons to noxious chemical stimulation of cardiac afferents and determine the relative contribution of vagal and sympathetic afferent pathways for transmission of noxious cardiac afferent input to C(1)--C(2) neurons. Extracellular potentials of single C(1)--C(2) neurons were recorded in pentobarbital anesthetized and paralyzed male rats. A catheter was placed in the pericardial sac to administer a mixture of algogenic chemicals (0.2 ml) that contained adenosine (10(-3) M), bradykinin, histamine, serotonin, and prostaglandin E(2) (10(-5) M each). Intrapericardial chemicals changed the activity of 20/106 (19%) C(1)--C(2) spinal neurons in the superficial laminae, whereas 76/147 (52%) deeper neurons responded to cardiac noxious input (P < 0.01). Of 96 neurons responsive to cardiac inputs, 48 (50%) were excited (E), 41 (43%) were inhibited (I), and 7 were excited/inhibited (E-I) by intrapericardial chemicals. E or I neurons responsive to intrapericardial chemicals were subdivided into two groups: short-lasting (SL) and long-lasting (LL) response patterns. In superficial gray matter, excitatory responses to cardiac inputs were more likely to be LL-E than SL-E neurons. Mechanical stimulation of the somatic field from the head, neck, and shoulder areas excited 85 of 95 (89%) C(1)--C(2) spinal neurons that responded to intrapericardial chemicals; 31 neurons were classified as wide dynamic range, 49 were high threshold, 5 responded only to joint movement, and no neuron was classified as low threshold. For superficial neurons, 53% had small somatic fields and 21% had bilateral fields. In contrast, 31% of the deeper neurons had small somatic fields and 46% had bilateral fields. Ipsilateral cervical vagotomy interrupted cardiac noxious input to 8/30 (6 E, 2 I) neurons; sequential transection of the contralateral cervical vagus nerve (bilateral vagotomy) eliminated the responses to intrapericardial chemicals in 4/22 (3 E, 1 I) neurons. Spinal transection at C(6)--C(7) segments to interrupt effects of sympathetic afferent input abolished responses to cardiac input in 10/10 (7 E, 3 I) neurons that still responded after bilateral vagotomy. Results of this study support the concept that C(1)-C(2) superficial and deeper spinal neurons play a role in integrating cardiac noxious inputs that travel in both the cervical vagal and/or thoracic sympathetic afferent nerves.

Backbone dynamics of homodimeric apo-S100B were studied by (15)N nuclear magnetic resonance relaxation at 9.4 and 14.1 T. Longitudinal relaxation (T(1)), transverse relaxation (T(2)), and the (15)N-[(1)H] NOE were measured for 80 of 91 backbone amide groups. Internal motional parameters were determined from the relaxation data using the model-free formalism while accounting for diffusion anisotropy. Rotational diffusion of the symmetric homodimer has moderate but statistically significant prolate axial anisotropy (D( parallel)/D( perpendicular) = 1.15 +/- 0.02), a global correlation time of tau(m) = 7.80 +/- 0.03 ns, and a unique axis in the plane normal to the molecular symmetry axis. Of 29 residues at the dimer interface (helices 1 and 4), only one has measurable internal motion (Q71), and the order parameters of the remaining 28 were the highest in the protein (S(2) = 0.80 to 0.91). Order parameters in the typical EF hand calcium-binding loop (S(2) = 0.73 to 0.87) were slightly lower than in the pseudo-EF hand (S(2) = 0.75 to 0.89), and effective internal correlation times, tau(e), distinct from global tumbling, were detected in the calcium-binding loops. Helix 3, which undergoes a large, calcium-induced conformational change necessary for target-protein binding, does not show evidence of interchanging between the apo and Ca(2+)-bound orientations in the absence of calcium but has rapid motion in several residues throughout the helix (S(2) = 0.78 to 0.88; 10 < or = tau(e) < or = 30 ps). The lowest order parameters were found in the C-terminal tail (S(2) = 0.62 to 0.83). Large values for chemical exchange also occur in this loop and in regions nearby in space to the highly mobile C-terminal loop, consistent with exchange broadening effects observed.

The glial enzyme glutamine synthetase (GS) is critical for central nervous system catabolism of glutamate and glutamine production. Upregulation of GS is a hallmark of reactive astrocytosis, although such induction following spinal cord injury (SCI) has not been reported. This study's purpose was to determine if GS activity is increased following SCI. Experimental rats received a complete spinal transection at the T5 segment and control rats received a laminectomy only. GS activities were determined using an enzymatic microassay. Glutamine levels were resolved in semi-adjacent sections. At 7 days following SCI, GS activity increased an average of 170-190% in white matter and 15-25% in gray matter immediately adjacent to the transection, and 70-90% in white matter and 40-45% in gray matter from cervical and lumbar enlargements. Correlative increases in glutamine were observed also. These findings further characterize the astrocytic response to SCI, which may contribute to altered glutamine metabolism in injured spinal tissue.

The number of persons 65 years of age and older continues to increase dramatically in the United States. Comprehensive health maintenance screening of this population is becoming an important task for primary care physicians. As outlined by the U.S. Preventive Services Task Force, assessment categories unique to elderly patients include sensory perception and injury prevention. Geriatric patients are at higher risk of falling for a number of reasons, including postural hypotension, balance or gait impairment, polypharmacy (more than three prescription medications) and use of sedative-hypnotic medications. Interventional areas that are common to other age groups but have special implications for older patients include immunizations, diet and exercise, and sexuality. Cognitive ability and mental health issues should also be evaluated within the context of the individual patient's social situation-not by screening all patients but by being alert to the occurrence of any change in mental function. Using an organized approach to the varied aspects of geriatric health, primary care physicians can improve the care that they provide for their older patients.

The Centers for Disease Control and Prevention updated its guidelines for the treatment of sexually transmitted diseases. The guidelines include the following information: recommendations for hepatitis A immunization and expanded indications for hepatitis B vaccination; updated diagnostic criteria for pelvic inflammatory disease and parenteral treatment regimens; information on two additional antiviral agents for the treatment of genital herpes; a recommendation for use of a single 1-g dose of azithromycin (Zithromax) to treat urethritis and chlamydial cervicitis; information on the use of quinolones in the treatment of gonococcal infections; information on podofilox and imiquimod, which are both patient-applied medications, in the treatment of noncervical human papillomavirus infection; updated guidelines for the prevention and detection of congenital syphilis; and information on how to prevent the spread of sexually transmitted diseases by educating patients about the importance of changing their sexual behaviors. To have a significant impact on the current rate of transmission of sexually transmitted diseases, family physicians should develop a plan to integrate the guidelines into their practices.

First, a novel technique for calibration of a dynamic surface tension detector (DSTD) is described. The DSTD measures the differential pressure as a function of time across the liquid-air interface of growing drops that repeatedly form and detach at the end of a capillary tip. The calibration technique utilizes the ratio of pressure signals acquired from the drop growth of two separate solutions, i.e. a standard solution and a corresponding mobile phase, such as water, both of which have a known surface tension. Once calibrated, the dynamic surface tension of an analyte is obtained from the ratio of the pressure signals from the analyte solution to that of the mobile phase solution. Thus, this calibration technique eliminates the need to optically image the radius of the expanding drop of liquid. Accurate dynamic surface tension determinations were achieved for aqueous sodium dodecyl sulfate (SDS) solutions over a concentration range of 0.5-5.4 mM. The measured surface tensions for these SDS solutions range from 70.3 to 46.8 dyne/cm and were in excellent agreement with the literature. A precision of 0.2 dyne/cm (1 S.D.) was routinely obtained. Second, the DSTD with this calibration technique was combined with flow injection analysis (FIA) for the study of model protein solutions and polymer solutions. The kinetic surface tension behavior of aqueous bovine serum albumin (BSA) solutions as a function of concentration and flow rate is presented. Evaluation of the dynamic surface tension data illustrates that a protein such as BSA initially exhibits kinetically-hindered surface tension lowering, i.e. a time dependence, as BSA interacts with the liquid-air interface of an expanding drop. FIA/DSTD is then shown to be an effective tool for the rapid study of kinetically-hindered surfactant mixtures. It was found that mixtures of SDS and the polymeric surfactant Brij(R)-35 (lauryl polyoxyethylene ether with an average molecular weight of 1200 g/mol) result in essentially an additive lowering of the surface tension. Mixtures of polyethylene glycol (PEG), with an average molecular weight of 1470 g/mol, and Brij(R)-35, however, result in a competitive (non-additive) surface tension with the Brij(R)-35 dominating the response.

We have shown that stimulation of cardiopulmonary sympathetic afferent fibers activates relays in upper cervical segments to suppress activity of lumbosacral spinal cells. The purpose of this study was to determine if chemical excitation (glutamate) of upper cervical cell bodies changes the spontaneous activity and evoked responses of lumbosacral spinal cells to colorectal distension (CRD). Extracellular potentials were recorded in pentobarbital-anesthetized male rats. CRD (80 mmHg) was produced by inflating a balloon inserted in the descending colon and rectum. A total of 135 cells in the lumbosacral segments (L(6)-S(2)) were activated by CRD. Seventy-five percent (95/126) of tested cells received convergent somatic input from the scrotum, perianal region, hindlimb, and tail; 99/135 (73%) cells were excited or excited/inhibited by CRD; and 36 (27%) cells were inhibited or inhibited/excited by CRD. A glutamate (1 M) pledget placed on the surface of C(1)-C(2) segments decreased spontaneous activity and excitatory CRD responses of 33/56 cells and increased spontaneous activity of 13/19 cells inhibited by CRD. Glutamate applied to C(6)-C(7) segments decreased activity of 10/18 cells excited by CRD, and 9 of these also were inhibited by glutamate at C(1)-C(2) segments. Glutamate at C(6)-C(7) increased activity of 4/6 cells inhibited by CRD and excited by glutamate at C(1)-C(2) segments. After transection at rostral C(1) segment, glutamate at C(1)-C(2) still reduced excitatory responses of 7/10 cells. Further, inhibitory effects of C(6)-C(7) glutamate on excitatory responses to CRD still occurred after rostral C(1) transection but were abolished after a rostral C(6) transection in 4/4 cells. These data showed that C(1)-C(2) cells activated with glutamate primarily produced inhibition of evoked responses to visceral stimulation of lumbosacral spinal cells. Inhibition resulting from activation of cells in C(6)-C(7) segments required connections in the upper cervical segments. These results provide evidence that upper cervical cells integrate information that modulates activity of distant spinal neurons responding to visceral input.

Intraocular co-grafts of rat fetal spinal cord and dorsal root ganglia were used to examine the enhanced survival, growth, and differentiation of sensory neurons by nerve growth factor. E14 lumbar spinal segments were implanted into the anterior eye chamber of capsaicin-pretreated rats. Two weeks later, an E14 dorsal root ganglion was implanted beside the spinal cord graft. Nerve growth factor or vehicle was injected weekly for 4 weeks into the anterior eye chamber. Co-grafts were examined weekly and, at 6 weeks, processed for calcitonin gene-related peptide (CGRP) immunofluorescence. No differences in overall size were determined for the grafts. Co-grafts treated with nerve growth factor contained many more CGRP neurons (19.4 cells/20 microm) that were significantly larger (mean 764 microm2) than neurons from control co-grafts (8.6 cells/20 microm; mean 373 microm2). In co-grafts treated with nerve growth factor, CGRP-immunoreactive fibers were extensive in the dorsal root ganglion, adjacent iris, and spinal cord compared to control co-grafts. A few CGRP-positive motoneurons were observed in the spinal cord, but no differences in number or size of motoneurons were found. The current report demonstrates that spinal cord and dorsal root ganglia can be co-grafted in oculo for long periods of time. Many dorsal root ganglion neurons survive and send peripheral processes into the iris and central processes into the spinal cord under the influence of exogenous nerve growth factor. The intraocular graft paradigm can be of use to further examine the role of neurotrophic factors in regulating or modulating dorsal root ganglion and spinal cord neurons.

Outpatient detoxification of patients with alcohol or other drug addiction is being increasingly undertaken. This type of management is appropriate for patients in stage I or stage II of withdrawal who have no significant comorbid conditions and have a support person willing to monitor their progress. Adequate dosages of appropriate substitute medications are important for successful detoxification. In addition, comorbid psychiatric, personality and medical disorders must be managed, and social and environmental concerns need to be addressed. By providing supportive, nonjudgmental, yet assertive care, the family physician can facilitate the best possible chance for a patient's successful recovery.

Purpose: To determine whether high school athletic participation among adolescents in Western New York was associated with reduced rates of sexual behavior and pregnancy involvement., Methods: A secondary analysis of data from the Family and Adolescent Study, a longitudinal study of a random sample of adolescents (ages 13-16 years) from 699 families living in households in Western New York. A general population sample was obtained with characteristics closely matching the census distributions in the area. Interview and survey methods provided data on athletic participation, frequency of sexual relations during the past year, and risk for pregnancy. Bivariate correlations were used to examine relationships among athletic participation, demographic and control variables, and measures of sexual behavior and pregnancy rates. Next, path analyses were done in order to test for hypothesized relationships between athletic participation, sexual behavior, and pregnancy involvement while controlling for age, race, income, family cohesion, and non-athletic forms of extracurricular activity. Variables that were significantly associated with sexual behavior and/or pregnancy involvement were presented for both sexes within the resulting multivariate models., Results: Lower income and higher rates of sexual activity were associated with higher rates of pregnancy involvement for both sexes. Family cohesion was associated with lower sexual activity rates for both sexes. For girls, athletic participation was directly related to reduced frequency of sexual behavior and, indirectly, to pregnancy risk. Male athletes did not exhibit lower rates of sexual behavior and involvement with pregnancy than male non-athletes. Boys who participated in the arts, however, did report lower rates of sexual behavior and, indirectly, less involvement with pregnancy., Conclusions: Female adolescents who participated in sports were less likely than their non-athletic peers to engage in sexual activity and/or report a pregnancy. Among male adolescents, athletic participation was unrelated to sexual behavior and pregnancy involvement. Teen pregnancy prevention efforts for girls should consider utilizing sport as a strategic tool.

Isometric contractions and force-frequency relationships (FFR) were assessed in isolated ventricular preparations of 3- and 4-day chick embryos (EM) and posthatched (PH) chicks. Pacing protocols for the FFR assessment were applied in normal buffer, buffer with 50% and 25% of normal Na+ concentration, and in buffer with ryanodine. PH myocardium showed greater peak force and more prominent FFR than EM. 50% low Na+ superfusion induced positive inotropic effect and increase in the FFR in PH and EM. 25% low Na+ superfusion induced negative inotropic effect and suppressed FFR more prominent in EM. Ryanodine more suppressed FFR in PH myocardium. The observed age-dependent differences substantiate the fact that Na-Ca exchange plays a leading role in the FFR regulation in early embryonic myocardium and sarcoplasmic reticulum plays a leading role in PH myocardium.

Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G-protein-coupled receptors, including rhodopsin and beta2-adrenergic receptor. Unlike in human and cow, splice variants of this protein family in rat have not been studied extensively, and there has been no report on their existence at protein level. Hence, a previous report by others on the localization of both beta-arrestin-1 and -2 in a wide range of innervated rat tissues could imply their broad receptor specificity. In this report we show the presence of two alternatively spliced forms of beta-arrestin-1 in several rat tissues using both reverse transcription-polymerase chain reaction and Western immunoblot. Splicing of beta-arrestin-1 pre-mRNA appears to be subject to differential regulation between the rat CNS and peripheral tissues. In contrast, we detected no splice variants of beta-arrestin-2 in rat. A comparison of the genomic DNA sequences of bovine and rat beta-arrestin-2, where the splicing of bovine beta-arrestin-2 mRNA has been reported, revealed a high degree of homology in their organization of exons and introns as well as certain differences that might be responsible for the different processing of beta-arrestin-2 mRNA in the two species. Our two-dimensional isoelectric focusing gels using rat spinal cord and heart tissues demonstrate isoelectric heterogeneity of rat beta-arrestin-1, suggesting that beta-arrestin-1 is subject to post-translational modification unlike beta-arrestin-2.

Retrograde, transneuronal tracing with Bartha's strain of pseudorabies virus was used in rats to identify spinal cord, brainstem and hypothalamic loci of uterine-related neurons that could function in the regulation of uterine activity. Based on the premise that estrogen might influence such uterine-related neurons, the existence of estrogen receptors in neurons in these same loci was examined. Viral injections were made into the uterine cervix, body and cervical end of the uterine horns, and the rats allowed to survive for four to six days. After four days, mainly the spinal cord, medulla and pons contained virus-infected neurons. After longer survival times, progressively higher levels of the neuraxis contained viral-labeled neurons, so that by six days hypothalamic uterine-related neurons were identified. First-order virus-infected neurons were visualized by immunohistochemistry in the pelvic paracervical parasympathetic ganglia and in inferior mesenteric sympathetic ganglia. Preganglionic and putative interneurons were labeled in the lumbosacral spinal cord and thoracic spinal cord mainly in the lateral horn area (sacral parasympathetic nucleus and intermediolateral nucleus), lateral aspect of the dorsal horn, intermediate gray, lamina X and dorsal gray commissural area. In the brainstem, labeling was most evident and consistent in the nucleus tractus solitarius, ventrolateral medulla, raphe magnus and pallidus nuclei, parapyramidal area, A5 cell group, Barrington's nucleus of the pons and periaqueductal gray of the midbrain. In the hypothalamus, virus-infected neurons were most marked in the paraventricular nucleus, with fewer in the medial preoptic area and ventromedial hypothalamic nucleus. Estrogen receptor-immunoreactive neurons were most often present among the virus-labeled uterine-related neurons of the spinal cord, nucleus tractus solitarius, ventrolateral medulla, periaqueductal gray, medial preoptic area and ventromedial hypothalamic nucleus. These results identify a multisynaptic pathway of neurons whose eventual output is involved in uterine functions, whose distribution is similar to that revealed by pseudorabies virus tracing from other visceral organs, and which are often mixed among estrogen-responsive neurons.

The purpose of this study was to assess the functional outcomes of first-time cerebrovascular accident survivors 1 to 5 years after rehabilitation. Subjects (n=68) consisted of individuals discharged from a regional rehabilitation center between 1992 and 1996 with the diagnosis of first-time cerebrovascular accident. The Adult Functional Independence Measure (FIM), an on-site outcomes measurement tool, was used to assess subjects' admittance and discharge total FIM scores. The Adult Functional Independence Measure, a phone interview methodology, was used to assess individuals' functional levels from 1 through 5 years after discharge from rehabilitation. Motor (Rasch Motor) and cognitive (Rasch Cognitive) components of the FIM also were analyzed over time. Data pertaining to differences in function between genders, site of lesion, family support, and whether therapy was received after discharge were collected. Data were analyzed to determine changes in function over time. Significant increases in total FIM and motor and cognitive scores occurred between admittance and discharge and between discharge and 1 year after discharge. Although not significant, slight increases were noted in all three measures up to 3 years after discharge. From 3 to 5 years after discharge, a steady decline was noted. First-time cerebrovascular accident survivors who did not experience additional medical problems continued to improve during the first 3 years after discharge from a rehabilitation center. After this time, however, declines were noted in total FIM, Rasch Motor, and Rasch Cognitive scores.

The class III antiarrhythmic agent, azimilide, has been shown to inhibit dihydroalprenolol binding to the beta-adrenergic receptor of rat brain and heart in an in-vitro ligand-binding assay. Azimilide, was assessed for beta-adrenergic activity, either agonist or antagonist, in the isolated perfused guinea pig heart in comparison with class III reference agents and the class II agent, propranolol. Varying concentrations of compound (0.03-100 microM) were retrogradely perfused and the effects on corrected QT interval, baseline heart rate, and isoproterenol-stimulated heart rate were measured. Propranolol, dl-sotalol, azimilide, and d-sotalol inhibited isoproterenol-induced tachycardia with IC50 values (the concentration giving 50% inhibition of isoproterenol-stimulated heart rate) of 0.12, 1.4, 14.6, and 38.0 microM, respectively. Clofilium, dofetilide, and sematilide did not affect the action of isoproterenol. Dofetilide, clofilium, azimilide, sematilide, dl-sotalol, and d-sotalol increased the QTc interval approximately 20 ms at concentrations of 0.1, 0.3, 1.0, 3.0, 30.0, and 100.0 microM, respectively. The class III antiarrhythmic agents also slowed baseline heart rate and exhibited linear R-R and QT-interval relationships of similar slope. Azimilide's antagonism of isoproterenol in this isolated heart model may reflect a direct receptor interaction or a contribution from the bradycardic action of the compound, which distinguishes it from several other pure IKr-blocking class III antiarrhythmic agents.

Ganglion cysts are commonly seen in orthopedic and general practice. Compression of the common peroneal nerve by a ganglion cyst is rare in children; to the authors' knowledge, only five cases in patients younger than 18 years have been reported. A ganglion cyst was found in a 3-year-old child who was brought in for an evaluation of intoeing and was found subsequently to have a mass in the proximal aspect of the right leg. The literature is reviewed with attention to specific recommendations for the evaluation of soft tissue masses and the utility of imaging modalities.

A reliable serum assay that can discriminate between cardiac and skeletal muscle injury is not available for diagnostic use in laboratory animals. We tested and supported the hypotheses that serum cardiac troponin T (cTnT) was widely applicable in laboratory animals as a biomarker of cardiac injury arising from various causes; that it increased in proportion to severity of cardiac injury; and that it was more cardiospecific than creatine kinase (CK) or lactate dehydrogenase (LD) isozyme activities. In canine and rat models of myocardial infarction, cTnT concentration increased 1,000- to 10,000-fold and was highly correlated with infarct size within 3 h of injury. Serum CK and LD isozymes were substantially less effective biomarkers and, in contrast to cTnT, were ineffective markers in the presence of moderate skeletal muscle injury, with resulting serum CK activity > 5,000 U/L. Using these animal models, and mouse and ferret models, we also showed cTnT to be an effective biomarker in doxorubicin cardiotoxicosis, traumatic injury, ischemia, and cardiac puncture. Reference range serum concentrations for all species were at the detection limit of the assay, except those for mice, in which they were slightly increased, possibly because mice were used to generate assay monoclonal antibodies. We conclude that cTnT is a powerful biomarker in laboratory animals for the sensitive and specific detection of cardiac injury arising from various causes.

We present a model that predicts the maximum axonal length from the apparent velocity of slow axonal transport and cytoskeletal protein half-life. The model assumes that in mature axons the apparent velocity of slow transport varies with position, but that the density of cytoskeletal proteins and protein degradation are uniform. The model predicts that the apparent transport velocity of cytoskeletal proteins if highest near the cell body and decreases linearly along the axon, and that when axons branch the apparent velocity of transport decreases across the branch point. The predictions of this model are shown to be consistent with experiments. These results explain the variation in these fundamental metabolic parameters in different axons and species.

When providing health care for women, one of the more common problems facing the primary care physician is sexually transmitted diseases (STDs). It is important to be able to develop an accurate diagnosis and appropriate treatment plan for STDs to reduce the potential long-term sequelae of these infections. It is also vital for the primary care physician to provide counseling for patients with STDs to improve compliance with the treatment regimens and prevent any further risk-taking behavior.

Major depression is a common disorder. Historically, tricyclic antidepressants have been the standard pharmacologic agents in the treatment of this disorder. Unfortunately, the occurrence of significant side effects has limited the use of these drugs. In the past decade, however, antidepressants that are pharmacologically distinct from the tricyclics have been introduced. These newer drugs are tolerated better than the tricyclics and have been reported to have similar efficacy. Thus, because these newer agents provide effective, well-tolerated treatment of mild to moderate depression, they are now generally preferred to the tricyclic antidepressants, despite their greater cost.

The purpose of this study was to examine barriers family physicians face when providing hospice care. A questionnaire was developed by the authors, and was mailed to 1,013 randomly selected AAFP members. The questionnaire addressed the various hospice care barriers. The respondents felt comfortable with hospice care, but felt that they did not receive adequate education in this area. They stated that they do have access to hospice programs. There is a general belief on the part of the respondents that their education in death and dying issues, and in hospice care was inadequate. The respondents, however, did feel comfortable in providing hospice care.

Azimilide exhibited antiarrhythmic activity in several rodent models of ventricular arrhythmias. In the mouse chloroform model, azimilide provided limited efficacy by the i.p. route (50% at 100 mg/kg versus 20% by vehicle), and no efficacy by the oral route (300 mg/kg). In a rat model in which arrhythmias are induced by ligation and reperfusion of the left descending coronary artery (CALR model), azimilide provided dose-dependent (1-18 mg/kg) efficacy by the intravenous route. The estimated dose that suppressed ventricular fibrillation (VF) was 5.0 mg/kg i.v. At 18 mg/kg i.v. azimilide also partially suppressed ventricular tachyarrhythmia (VT) and extrasystoles (VES). Rats dosed orally (100 mg/kg) were fully protected from VF. In isolated guinea pig hearts exposed to 1 microM ouabain, azimilide at 10 microM prevented the VT and VF seen in 69% and 23%, respectively, of control hearts. In anesthetized guinea pigs, azimilide at 10 and 30 mg/kg i.v. increased the dose of ouabain required to induce VES. While sematilide, dofetilide, and E-4031 significantly increased sensitivity to the arrhythmogenic actions of ouabain (by lowering the dose that caused VF), azimilide did not. Azimilide's antiarrhythmic profile in these rodent models differs from that of other class III agents, since azimilide had less efficacy in the mouse chloroform model, could suppress VT and VES as well as VF in the CALR rat model, and protected from or did not aggravate cardiac glycoside-induced arrhythmias in guinea pigs. These results demonstrating the antiarrhythmic efficacy of azimilide in the intact animal suggest that the compound has a different profile than other class III agents.

This study examined the mental health and psychosocial development of 58 Guatemalan Mayan Indian children living in 2 refugee camps in the Mexican state of Chiapas. Conventional assessment instruments were adapted for use in this unique context, and semistructured interviews were utilized to gather phenomenological data from children regarding various developmental, sociocultural, and political topics. Data are presented that show minimal evidence of psychological trauma in this sample, and various factors are suggested to account for this finding. In addition, data are presented showing a positive relationship between children's mental health and the health status (physical and mental) of their mothers. In particular, a strong association was found between depressive symptomatology in girls and poor health status in their mothers. Qualitative data from the interviews are presented, focusing on children's understandings of why their families fled Guatemala, the nature and causes of the violence, and their thoughts and feelings regarding the prospect of returning to Guatemala at some future point.

Background: Many studies have attempted to determine what factors influence medical students' career selections. This study determined students' perceptions of family practice, examined what variables influenced these perceptions, and measured whether medical students' perceptions were similar to or different from those of practicing family physicians., Methods: The two populations studied were students sampled at an Ohio medical school over the first 3 years of their training and a random sample of Ohio family physicians. Each subject was asked to complete a questionnaire that asked about perceptions of family practice and demographic information., Results: A total of 719 (69%) students and 295 (59%) family physicians responded to the survey. Sixty-seven percent of the physician responders were actively involved in medical student teaching. More than 94% of the students had exposure to family physicians during their preclinical education. Students' perceptions were different than physicians' perceptions about lifestyle issues, patient care, and practice characteristics; over time, these approached the physicians' perceptions. However, the perceptions of family physicians and students about professional issues were similar., Discussion: Medical students and family physicians have different perceptions about family practice. Students' perceptions become similar to physicians' perceptions as they progress through the educational system, while, at the same time, their interest in family practice declines.

A pull-out program for gifted students was evaluated in reports (qualitative evaluations) from a sample of 60 program participants from the fourth, fifth, and sixth grades. The students identified six areas in their evaluations: cognitive aspects, program satisfaction, self-expression, self-esteem, boredom, and learning environment. Students who identified cognitive aspects of their program also were likely to identify program satisfaction and not being bored. Statements about opportunities to be self-expressive were made more by girls than by boys and more by fifth and sixth graders than by fourth graders.

Formal mentoring programs have been suggested as one strategy to increase student interest in primary care. Mentoring has long been a part of the business world but has only recently become a formal part of family medicine training. This paper reviews the literature on mentoring and provides applications to family practice. Mentoring has been found to develop a deeper relationship than role modeling or preceptoring and should benefit the student and mentor. The mentor's roles and functions are varied and numerous; the mentor guides, assists, and counsels students longitudinally through their development as professionals. Mentoring is based in the present but is directed toward the future. Mentors need to have charisma, leadership and motivational skills, inspiration, competence, compassion, empathy, and willingness to share with the student. Strategies used when developing a mentoring program need to incorporate the positive qualities of mentoring while minimizing the negative components, as described in this paper. The tasks of mentoring are of less importance than the personal characteristics of the mentor. Mentors should not be involved in formally evaluating the student. Faculty development and monitoring of the relationships on a regular basis are important aspects of a successful program.

Adaptation and implementation of a primary mental health project based on work with children affected by political repression in Guatemala and Argentina are described. This intervention model utilizes a variety of expressive arts techniques to help children express their thoughts and feelings about growing up in exile. The model emphasizes the training of community members in the theory and methods of the intervention.

A tetrasaccharide related to the blood group oligosaccharides, known as sialyl LewisX, has been proposed as the receptor for the lectin responsible for leukocyte adhesion named alternatively as E-selectin or ELAM-1. The 13C- and 1H-nmr spectra have been completely assigned for a tetrasaccharide model of this receptor, Neu5Ac alpha-(2-->3)-Gal beta-(1-->4)-[Fuc alpha-(1-->3)-]GlcNAc beta-NHAc. Quantitative nuclear Overhauser data (NOESY) have been recorded and analyzed by a complete spin matrix simulation method. Conformational space was exhaustively searched and all conformational models whose simulated NOESY spectra matched the experiment were found. Molecular mechanics and molecular dynamics calculations were carried out to test whether the experimental conformations are low energy and thus likely to represent true single conformations for the tetrasaccharide. It was concluded that while the LewisX trisaccharide portion of the compound adopts a single conformation, there is likely to be some flexibility about the Neu5Ac alpha-(2-->3)-linkage. A model featuring fast exchange between two different conformations of this linkage is found to be consistent with both the nmr experiments and the molecular dynamics simulations.

Background: The risk of occupational exposure to the human immunodeficiency virus (HIV) may be one of the important issues facing family physicians in the 1990s. The use of universal precautions has been shown to reduce the incidence of exposures to bloodborne pathogens. Studies indicate, however, that these guidelines are not being followed consistently by physicians or their staffs., Methods: A survey of 3568 randomly sampled members of the American Academy of Family Physicians was performed using a questionnaire that was designed by the authors. Three mailings were conducted., Results: The total response rate was 39%. Approximately 80% of the respondents reported that they used gloves appropriately and disposed of sharp instruments in a puncture-resistant container. Only 39% "always" or "almost always" used eye protection when indicated, and only 35% "almost never" or "never" recapped used needles. There was a significant number of physicians who reported that they or their office staff had had an occupational exposure to bloodborne pathogens within the last year., Conclusions: Family physicians and their staffs do not uniformly follow universal precaution guidelines and, as a result, many have been exposed to blood products. If the physician or the office staff would not recap used needles and would place used sharp instruments in a puncture-resistant container, the greatest risks of occupational exposure would be reduced.

The Lewis x (Lex) determinant is a trisaccharide fragment that has been implicated as a specific differentiation antigen, as a tumor antigen, and as a key component of the ligand for the endothelial leukocyte adhesion molecule, ELAM-1. High-resolution nuclear magnetic resonance spectroscopy shows it to have a relatively rigid structure. Only a small range of glycosidic dihedral angles in the trisaccharide produce simulated nuclear Overhauser effect spectra agreeing with data measured for the human milk pentasaccharide, lacto-N-fucopentaose-3, which contains the Lex determinant. Independently, the same average structure for the Lex determinant arises from in vacuo molecular dynamics simulations. The proposed conformation of the Lex trisaccharide is very similar to that recently determined for the closely related Lea trisaccharide. In agreement with the recent finding that both sialylated Lea and Lex react with ELAM-1, the results presented here show that the Lea and Lex determinants contain very similar carbohydrate domains.

This study examined the extent to which adolescents' perceptions of their family environments were associated with suicidal behavior. Fifteen suicidal adolescents, 14 psychiatric controls, and 14 normal controls rated their families on cohesiveness, adaptability, parent-adolescent communication, parental caring, and parental over-protectiveness. Suicidal adolescents rated their families as the least cohesive and most rigid of the 3 groups, suggesting that adolescent suicidal behavior may occur when isolation is experienced within an inflexible family system. Suicidal and psychiatric control adolescents rated their families as similarly dysfunctional along the remaining variables, and as more dysfunctional than families of normal control adolescents. The implications of these findings are discussed, and it is suggested that several characteristics commonly attributed to families of suicidal adolescents may actually be general risk factors for adolescent psychopathology, rather than for suicidal behavior specifically.

An estimated 13,500 cases of invasive cervical cancer and 6,000 related deaths occur each year in the United States. These numbers can be significantly reduced if all women are regularly screened with Papanicolaou (Pap) smears and undergo colposcopy when abnormalities are detected. Screening with Pap smears should begin at age 18 or at the age of first sexual intercourse and should be repeated every one to three years, depending on individual risk factors, until age 65. Screening may be discontinued in women over age 65 who have had normal findings on two consecutive Pap smears. Risk factors for cervical cancer include sexual intercourse before age 20, more than two sexual partners in a lifetime, cigarette smoking and genital human papillomavirus (HPV) infection. Use of a spatula and Cytobrush for cervical sampling will improve the chances of collecting an adequate sample containing endocervical cells. Family physicians must know the significance of various cervical abnormalities reported by the laboratory. In women with cervical or genital HPV infection and persistent inflammatory cervical changes unresponsive to appropriate therapy, colposcopy is necessary to screen for underlying dysplasia.

The spinal cord contains mu, delta and kappa opioid receptors which mediate the antinociceptive effects of opioid agonists administered onto the spinal cord. In this study, we characterized the binding sites for highly-selective mu, delta and kappa opioid radioligands and quantified the distribution of opioid binding sites in rat lumbosacral spinal cord using autoradiography. In sections of rat brain mounted on glass slides, the mu ligand, [3H]sufentanil, bound with high affinity with an apparent Kd of 0.46 nM. The delta ligand, [3H]DPDPE [( D-Pen2.5]-enkephalin), bound with a Kd of 4.31 nM, and the kappa-ligand, [3H]U69593, bound with a Kd of 2.27 nM. Three regions of the spinal gray were targeted for quantification of binding sites by autoradiography. The data indicate that when considered as a percentage of the total opioid binding capacity within a region, the contribution of mu sites in laminae I-II was about 90%, with delta and kappa sites 7% and 3%, respectively. In lamina V, the mu sites comprised about 70% of the total opioid sites, with delta and kappa sites comprising 28% and 2%, respectively. In the area adjacent to the central canal, mu sites contributed about 65% of the total opioid sites followed by delta sites at 33% and kappa sites at 2% of total opioid sites. These results demonstrate a differential distribution of mu, delta and kappa binding sites with respect to the organization of the spinal gray matter. The preferential occurrence of all 3 opioid binding sites in the superficial dorsal horn is noteworthy since many fine caliber primary afferent fibers mediating nociception establish synaptic contact in this region.

The continued functioning of organ transplantation depends on obtaining the permission of the next of kin. This communication process between medical or transplant professionals and a donor family hinges heavily on the understanding of certain critical terms like brain dead, life support, and transplantation. Communication issues in obtaining organ donation consent were examined, with particular focus on what are literally life-and-death decisions. Using an experimental simulation methodology, data are offered in support of the claim that much miscommunication occurs in such situations. Directions for improving such communication by allaying latent fears and more carefully defining crucial terminology are offered.

Platelets from normal and malignant hyperthermia (MH)-susceptible pigs were evaluated for differences in 45calcium uptake in the absence or presence of caffeine (2-16 mM), halothane (0.05-0.5%), or halothane and caffeine together. There were no statistically significant differences in basal or halothane-inhibited calcium uptake by platelets from either source. There was a small statistically significant difference in calcium uptake between platelets from normal and MH-susceptible pigs in the presence of 16 mM caffeine and 0.5% halothane. Calcium uptake by platelets from one pedigree of MH-susceptible pigs were stimulated in a concentration-dependent manner by caffeine. These data suggest that exposure of platelets to caffeine may have potential for identifying MH-susceptibility.

Selectivity of captopril, enalapril (MK-421), enalaprilat (MK-422), ketoace, and SA-300 for inhibiting kininase II when angiotensin (ANG) I versus bradykinin (BK) is the substrate has been studied in vitro. Potency for inhibiting purified rabbit lung ANG I-converting enzyme (ACE) using a tripeptide substrate with an ANG I-like (hippurylhistidylleucine, HHL) or a BK-like (hippurylphenylalanylarginine, HPA) cleavable dipeptide was determined. Inhibition of ANG I-induced and potentiation of BK-induced contractions of isolated guinea pig ileum strips was measured. For the enzyme assay, the inhibitor concentration which reduced the rate of HHL and HPA hydrolysis 50% (IC50) from the control value was estimated. All tested compounds more potently inhibited hydrolysis of the ANG I-related tripeptide by the purified enzyme. Ketoace, with a selectivity ratio (HPA IC50:HHL IC50) of 23, was the most substrate-dependent inhibitor. For the isolated ileum assay, the inhibitor concentration which augmented the contractile response to BK by 50% (AC50) or inhibited the contractile response to ANG I by 50% (IC50) was calculated. Only enalaprilat retained a selectivity ratio (BK AC50:ANG I IC50) in the guinea pig ileum system greater than one. Ketoace, with a ratio of 0.038, was the least ANG I-selective by this criterion. In vivo selectivity data on captopril seem more in accord with the ileum, rather than the enzyme, results. It was concluded that converting enzyme inhibitors differ in their relative selectivity for inhibiting kininase II reactions using different substrates.

The caudal neurosecretory complex (CNc) of poecilids has previously been shown to receive serotonergic inputs. In the present study, immunohistochemical techniques were applied at the light and electron microscopic levels to characterize serotonergic terminals in the neuroendocrine nucleus. A dense plexus of varicose fibers observed in the rostral CNc neuropil was absent in the spinal cords of deafferented fish, indicating that the origin of this input was extranuclear. Ultrastructural study revealed no direct contacts between labeled structures and neuroendocrine cells. Non-synaptic terminals (varicosities) were the predominantly labeled structures in the neuropil. Synaptic terminals were observed on cellular and axonal targets in the CNc. Small cells containing 70 nm dense-core vesicles received serotonergic input on their perikarya. Labeled synapses were also found on unlabeled axon terminals which made axo-axonal synapses on neuroendocrine processes. Non-synaptic terminals may be responsible for a variety of serotonin-mediated effects in the CNc. Synaptic interactions with local catecholaminergic and afferent cholinergic inputs to the CNc are likely.

A double-peroxidase procedure was used to study the ultrastructural relationships between terminals and fibers containing three putative neurotransmitters and retrogradely identified sympathetic preganglionic neurons (SPNs) located in the intermediolateral cell column (IML) of the rat. SPNs with axons in the cervical sympathetic trunk were retrogradely labeled with horseradish peroxidase. In addition, terminals and fibers containing substance P, enkephalin, and serotonin were detected using immunohistochemistry. Sections containing both retrogradely labeled SPNs and immunoreactive processes were processed for electron microscopy. Ultrastructural examination revealed synaptic contacts between terminals containing each of these three neurotransmitters and retrogradely labeled dendrites from SPNs. Also, immunoreactive terminals were apposed to retrogradely labeled cell bodies. Therefore, these transmitters may alter sympathetic function by their direct action on SPNs.

Several a-pyrones have been synthesized and investigated for their in vitro inhibitory activity using a-chymotrypsin (a-CT), porcine pancreatic elastase (PPE) and human leukocyte elastase (HLE). 4-Hydroxy-6-undecyl-2H-pyran-2-one 4, 4-Hydroxy-6-[(1-butyl)heptyl]-2H-pyran-2-one 5 and 4-Methoxy-6-[(1-butyl) heptyl]-2H-pyran-2-one 6 were found to be specific inhibitors of HLE. These compounds constitute a promising new class of HLE inhibitors.

This study compared the distribution of methionine enkephalin-, dynorphin A 1-8-, and neurotensin-immunoreactive (IR) perikarya in laminae I and IV-VII of selected segments of lumbar spinal cord of cat(L5) and rat(4). Immunoreactive neurons for each peptide were found throughout the dorsal horn and dorsal lamina VII but were quantified only within laminae I and IV-VII. In lamina I, both large (greater than 20 micron) and small (less than 20 micron) IR neurons were identified. Large IR neurons for each peptide in both species resembled Waldeyer neurons studied by Golgi stain and were outnumbered by small IR neurons. Comparison among the laminae of the distribution of met-enkephalin IR neurons showed a similar pattern in the two species with the majority of IR neurons (greater than 65%) in laminae V and VI. Differences in laminar distribution occurred between species for the other peptides. Dynorphin IR neurons were greatest in number in lamina V in rat but greatest in number in laminae I and V in cat. Neurotensin IR neurons occurred predominantly in cat lamina I but were nearly equal in density in rat laminae I and VI. The topographic distribution of each peptide in laminae V and VI was similar between the two species with IR neurons occurring laterally in lamina V and more medially in lamina VI. Comparisons between species of the numbers of IR neurons/segment indicated distinct relationships for each peptide. The number of met-enkephalin IR neurons in laminae of cat L5 was generally two times greater than the number of IR neurons in the same laminae of rat L4, except in laminae I and IV, where the numbers were nearly equal. In contrast, the number of dynorphin IR neurons in cat laminae was generally one-half the number in rat, except in lamina I, where the number in cat was two times greater than rat. A high degree of variability occurred in laminar comparisons of neurotensin IR neurons. Neurotensin IR neurons in lamina I of cat outnumbered those of rat 2:1, but in laminae IV-VII, the ratio of cat to rat IR neurons varied from 1:1 to 1:20. The met-enkephalin, dynorphin, and neurotensin IR neurons quantified in this study may be interneurons or may serve as projection neurons to brainstem and/or thalamic nuclei. The observed differences in distribution may be relevant to differences in spinal cord physiology in the two species.

To determine specificity of rodent models of arrhythmia for different Vaughan Williams classes of antiarrhythmic drugs, we tested 17 drugs from the four classes in one in vitro and four in vivo models. In the mouse chloroform-induced ventricular fibrillation model and in the guinea pig ouabain-induced arrhythmia model, drugs of classes I (amefalone, aprindine, lidocaine, mexiletine, phenytoin, procainamide, or quinidine), II (metoprolol or propranolol), and IV (bepridil) were active. Class III drugs (bretylium, clofilium, or melperone did not suppress ouabain arrhythmias, but were active in the mouse chloroform model. In the rat coronary artery ligation model, disopyramide (class I), amefalone and melperone significantly (P less than 0.05) reduced the number of extrasystoles. Propranolol, sotalol, and verapamil (class IV) were less effective. In the rat coronary artery ligation/reperfusion model, all four classes of antiarrhythmic agents were active in vitro (isolated heart) and in vivo (anesthetized rat). Thus, one model of automaticity, the guinea pig ouabain model, detected class I, II, and IV drugs, whereas another automaticity model, the mouse chloroform model, also detected class III agents. The model of reentry induced by ischemia plus reperfusion (rat coronary artery ligation reperfusion) can be recommended as a screen for new antiarrhythmic agents based on its sensitivity to all four classes of antiarrhythmic drugs. The Vaughan Williams class of an antiarrhythmic agent must be determined, however, by additional mechanism studies.

Calcified intraluminal meconium is a rare finding in newborn infants that is often associated with communication between the urinary and gastrointestinal tracts. Frequently such infants die because of respiratory problems. An illustrative case is presented, and pulmonary hypoplasia is suggested as an etiology of the respiratory difficulties observed.

A 4 1/2-month-old male infant with systemic candidiasis had anuria secondary to Candida albicans fungus balls impacted in the renal pelves. The patient was treated with temporary urinary diversion, amphotericin B, and flucytosine. Six weeks after therapy had been concluded, the patient had C albicans arthritis of the right hip and responded to a second course of amphotericin B and flucytosine therapy. This article discusses immunologic evaluation and presents a literature review.

Over a 3-year-period, standard treatment with hydrostatic pressure from a contrast enema failed to reduce ileocolic intussusception in 31 of 62 children. With the child anesthetized in the operating room, a second contrast enema was given before laparotomy. Of the 31 intussusceptions, 21 (68%) were reduced without complication, thereby avoiding the discomfort, longer hospitalization, complications, and expense of surgery. Nine of the remaining 10 intussusceptions were difficult to reduce manually during surgery or required resection. The overall nonoperative reduction rate for the 3-year period was 84%; for the last 2 years it was 90%. Success with the second enema may be related to the effects of general anesthesia. In addition, partial reduction with the first enema may improve blood flow from the intussusceptum so that it becomes smaller and easier to reduce with the second enema. Because it can easily be added to standard management protocols without increased risk, routine use of this second enema with anesthesia is recommended.

Brain stem projections to the neurons in the caudal neurosecretory complex (CNC) of Poecilia sphenops (molly) have been studied with HRP retrograde tracing. Using light microscopic procedures, HRP-labelled neurons were located in the reticular nucleus of the medulla (RMN) and in the vicinity of the nucleus of the medial longitudinal fascicle (NMLF). The present study was undertaken to examine the cytology of the brain stem neurons that project to the caudal neurosecretory complex using combined HRP-electron microscopic methods. Cells in the midbrain NMLF containing HRP-filled profiles were located bilaterally close to the midline and just beneath the ependyma. HRP reaction product was found additionally in the neurosecretory cells of the midbrain dorsal tegmental magnocellular nucleus (DTMN) located dorsal to the NMLF. Cells containing HRP-labelled profiles were also seen in the RMN and in neurons dorsal-lateral to the RMN. This latter group of neurons contained small dense core vesicles in addition to HRP labelled dense bodies.

Classically, multicystic kidneys have been described as having no functioning renal parenchyma that, consequently, should not be seen on excretory urography. However, during the last several years, sufficient concentration of contrast medium permitted radiographic visualization of renal tissue in 4 cases of pathologically typical multicystic kidneys.

Glutamate has been shown to be a neurotransmitter in the central nervous system of vertebrates, and it has been hypothesized that glutamate is functional as a neurotransmitter in the spinal cord dorsal horn. A monoclonal antibody to fixative-modified glutamate was used in this study to examine the light microscopic and ultrastructural profiles of glutamate-like immunoreactivity in the superficial dorsal horn of the rat spinal cord. Glutamate-like immunoreactivity was observed in neurons, fibers, and terminals of both laminae I and II. Marginal zone immunoreactive neurons ranged from 10 to 30 micron in diameter and received many nonimmunoreactive somatic synapses. In substantia gelatinosa, immunoreactive neurons were observed in both inner and outer layers, ranged 5 to 10 micron in diameter, and received few nonimmunoreactive somatic synapses. Glutamate-like immunoreactive dendrites were observed in both laminae and were contacted primarily by nonimmunoreactive synaptic terminals that generally contained small clear vesicles. Both myelinated and unmyelinated immunoreactive axons were observed in Lissauer's tract. Immunoreactive terminals contained small (40 nm) clear vesicles and generally formed simple synaptic contacts with nonimmunoreactive dendrites in laminae I and II. The results of this study corroborate the importance of glutamate as a neurotransmitter in spinal sensory mechanisms.