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PubMed2003

CCL28 has dual roles in mucosal immunity as a chemokine with broad-spectrum antimicrobial activity.

CCL28 is a CC chemokine signaling via CCR10 and CCR3 that is selectively expressed in certain mucosal tissues such as exocrine glands, trachea, and colon. Notably, these tissues commonly secrete low-salt fluids. RT-PCR analysis demonstrated that salivary glands expressed CCL28 mRNA at the highest levels among various mouse tissues. Single cells prepared from mouse parotid glands indeed contained a major fraction of CD3(-)B220(low) cells that expressed CCR10 at high levels and CCR3 at low levels and responded to CCL28 in chemotaxis assays. Morphologically, these cells are typical plasma cells. By immunohistochemistry, acinar epithelial cells in human and mouse salivary glands were strongly positive for CCL28. Furthermore, human saliva and milk were found to contain CCL28 at high concentrations. Moreover, the C terminus of human CCL28 has a significant sequence similarity to histatin-5, a histidine-rich candidacidal peptide in human saliva. Subsequently, we demonstrated that human and mouse CCL28 had a potent antimicrobial activity against Candida albicans, Gram-negative bacteria, and Gram-positive bacteria. The C-terminal 28-aa peptide of human CCL28 also displayed a selective candidacidal activity. In contrast, CCL27, which is most similar to CCL28 and shares CCR10, showed no such potent antimicrobial activity. Like most other antimicrobial peptides, CCL28 exerted its antimicrobial activity in low-salt conditions and rapidly induced membrane permeability in target microbes. Collectively, CCL28 may play dual roles in mucosal immunity as a chemoattractant for cells expressing CCR10 and/or CCR3 such as plasma cells and also as a broad-spectrum antimicrobial protein secreted into low-salt body fluids.

Adult↗
PubMed2005

The benzo[c]phenanthridine alkaloid, sanguinarine, is a selective, cell-active inhibitor of mitogen-activated protein kinase phosphatase-1.

Mitogen-activated protein kinase phosphatase-1 (MKP-1) is a dual specificity phosphatase that is overexpressed in many human tumors and can protect cells from apoptosis caused by DNA-damaging agents or cellular stress. Small molecule inhibitors of MKP-1 have not been reported, in part because of the lack of structural guidance for inhibitor design and definitive assays for MKP-1 inhibition in intact cells. Herein we have exploited a high content chemical complementation assay to analyze a diverse collection of pure natural products for cellular MKP-1 inhibition. Using two-dimensional Kolmogorov-Smirnov statistics, we identified sanguinarine, a plant alkaloid with known antibiotic and antitumor activity but no primary cellular target, as a potent and selective inhibitor of MKP-1. Sanguinarine inhibited cellular MKP-1 with an IC50 of 10 microM and showed selectivity for MKP-1 over MKP-3. Sanguinarine also inhibited MKP-1 and the MKP-1 like phosphatase, MKP-L, in vitro with IC50 values of 17.3 and 12.5 microM, respectively, and showed 5-10-fold selectivity for MKP-3 and MKP-1 over VH-1-related phosphatase, Cdc25B2, or protein-tyrosine phosphatase 1B. In a human tumor cell line with high MKP-1 levels, sanguinarine caused enhanced ERK and JNK/SAPK phosphorylation. A close congener of sanguinarine, chelerythrine, also inhibited MKP-1 in vitro and in whole cells, and activated ERK and JNK/SAPK. In contrast, sanguinarine analogs lacking the benzophenanthridine scaffold did not inhibit MKP-1 in vitro or in cells nor did they cause ERK or JNK/SAPK phosphorylation. These data illustrate the utility of a chemical complementation assay linked with multiparameter high content cellular screening.

Alkaloids↗
PubMed2005

Defining location in the mental health system: a case study of a consumer-run agency.

In this ethnographic study of a mental health service agency staffed by "consumers," or fellow "recipients" of services for serious mental illness, the concept of community narrative provides the framework for examining how such an agency preserves its consumer identity while providing services dictated by the established service system. Locating the agency's narrative in its "origins tale," analysis revealed five principles comprising the agency's identity: a normalizing view of mental illness, a commitment to helping, a dual-valued understanding of the mental health system, and beliefs in recovery and in the significance of employment as a criterion for recovery. Predicted consequences of narrative functioning emerged in social climate and staff expressions of cohesion and commitment. The local meaning of these narrative themes reveals the agency's view of the consumer element in its work and its solution to the dilemma of being both inside and outside of the mental health system.

Anthropology, Cultural↗
PubMed2001

Bone density measured by dual-energy X-ray absorptiometry in healthy Kuwaiti women.

A preliminary cross-sectional study of 623 healthy Kuwaiti women aged 20-79 years was carried out using dual-energy X-ray absorptiometry (DXA) to establish reference values of bone mineral density (BMD). Measurements were taken at the lumbar spine and proximal femur. The data were compared with normative data taken from Caucasian U.S./North European women over 6 decades of age. Our results showed the expected decline in BMD with age, especially for postmenopausal women. Despite differences in ethnicity, diet, and lifestyle no statistically significant differences in BMD were detected between the Kuwaiti subjects and the Caucasian normative data. Age-matched, clinically well-defined normative data for a given population must be used to diagnose osteoporosis and establish fracture risk. This study represents baseline data for Kuwaiti Arab females: it indicates that their BMD values are close to those of Caucasian females and higher than those reported recently for Lebanese and Saudi females. Further data is being collected to increase the statistical power of the study.

Absorptiometry, Photon↗
PubMed1989

Lipoxygenase and cyclooxygenase blockade by BW755C does not prevent the secondary phase of septic pulmonary hypertension.

The infusion of Group B beta hemolytic streptococci (GBS) in newborn animals generates a dual phase pulmonary hypertensive response. The initial, acute phase responds to cyclooxygenase or thromboxane inhibition, and appears to be thromboxane mediated. The second phase is characterized by a more moderate rise in pulmonary vascular resistance, accompanied by an increase in microvascular permeability. It has been speculated that this phase may be leukotriene mediated. In an attempt to clarify this, we have studied and compared the effects of the thromboxane synthetase inhibitor, Dazmegrel (DAZ), and the combined cyclooxygenase/lipoxygenase inhibitor, BW755C, on the cardiopulmonary hemodynamics of the secondary phase of GBS induced pulmonary hypertension in newborn piglets. Ten piglets were infused with GBS, and all animals developed a significant increase in pulmonary artery pressure (to 39 +/- 5 and 36 +/- 5 mmHg for DAZ and BW755C animals respectively). After one hour of GBS, either DAZ or BW755C was administered. Data were collected for another two hours following drug administration. GBS infusion was continued throughout. Both DAZ and BW755C were associated with transient, acute reductions in pulmonary artery pressure (to 22 +/- 5 and 22 +/- 8 mmHg, respectively). However, after 60 minutes, PAP again began to rise in both groups (PAP 30 +/- 5 and 30 +/- 11 mmHg respectively by 240 minutes). There were no differences between the groups at any time. These data do not support a significant role for lipoxygenase products in mediating the secondary phase of septic pulmonary hypertension.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed2006

Habituation of insulin-induced hypoglycemic transcription activation of lateral hypothalamic orexin-A-containing neurons to recurring exposure.

A CNS component of glucose counterregulatory collapse is supported by evidence for nonuniform genomic responsiveness of neurons in characterized central autonomic loci during recurring insulin-induced hypoglycemia (IIH). We have reported that exacerbated hypoglycemia and attenuated patterns of glucagon and epinephrine secretion in rats treated by daily sc injection of the intermediate-acting insulin formulation, Humulin NPH (NPH), are correlated with diminished immunodemonstrability of the AP-1 transcription factor, Fos, in several components of the central metabolic regulatory circuitry, including the lateral hypothalamic area (LHA). Neurons that synthesize the potent orexigenic peptide neurotransmitter, orexin-A, are restricted to the LHA and adjacent hypothalamic loci, and project throughout the central neuroaxis to structures that govern autonomic and behavioral motor output. Dual-label immunocytochemical and real-time RT-PCR techniques were utilized here to evaluate the functional status of this LHA phenotype during a single versus repetitive exposure to prolonged IIH. Tissue sections were collected at predetermined rostrocaudal levels of the LHA after acute or repeated NPH administration, and processed for nuclear Fos- and cytoplasmic orexin-A-immunoreactivity (-ir). Mean numbers of orexin-A-ir neurons were not different between treatment groups. Colabeling of these cells for Fos was increased relative to controls following a single injection of insulin, but numbers of Fos-ir-positive orexin-A neurons were significantly reduced after treatment with four versus one dose of insulin. Prepro-orexin mRNA levels in microdissected LHA tissue were upregulated during acute hypoglycemia, but were returned to control levels by repeated IIH. These data corroborate previous evidence that IIH is an activational stimulus for orexin-A-synthesizing neurons in the LHA, and further demonstrate that induction of cfos and prepro-orexin gene expression by acute hypoglycemia is attenuated by precedent exposure to hypoglycemia. The current results thus provide unique evidence for neurotransmitter-specific habituation of LHA neuronal sensitivity to IIH.

Animals↗
PubMed1993

Current concepts of the classification of affective disorders.

The introduction of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III), which uses a descriptive approach to operational definitions of psychiatric diagnostic groups, is an important step forward. Still the present classification systems of DSM or the International Classification of Diseases (ICD) are preliminary. A systematic descriptive approach based on data collection as a foundation for diagnostic definitions is strongly recommended. Data-based definitions have a good change of surviving later changes of diagnostic fashion. Treatment studies will be more valuable when the course of a disorder is included in its definition. The diagnosis of depression has to include operationalized subthreshold syndromes, such as minor depression and recurrent brief depression. In the face of the elementary importance of the distinction between uni- and bipolar disorders, a development of the definition of hypomania is proposed. Based on this definition, bipolar disorders are more prevalent in the normal population than is commonly assumed. Most diagnostic subgroups of depression are artificial. They are not diagnostic entities, but subtypes of the same spectrum disorder. During his/her lifetime, a patient may therefore receive two or more diagnoses, but still suffer from a single disorder. Dual diagnoses, such as double depression and combined depression, define more severely affected patients with major depression, characterized by higher suicide attempt rates. Thus the differentiation of subgroups is more than an academic exercise but has a practical use.

Bipolar Disorder↗
PubMed1996

Treatment of Helicobacter pylori infection: a review of the world literature.

BACKGROUND: None of the currently used anti-Helicobacter pylori drug regimens cures the infection 100%, and cure results still vary considerably. The present article reviews the effectiveness of currently used antimicrobial regimens, aimed to cure H. pylori infection. METHODS: Data collection started from the beginning of the anti-H. pylori-therapy era until May 1995. No attempt at formal metanalysis has been made, because many studies have been published only in abstract form. Attempts were made to exclude duplicates of studies by comparison to previously reported ones; the authors of suspected duplicates were contacted. After amalgamation of the number of included patients and the number of successfully treated patients, the mean values of eradication rates and the 95% confidence intervals were calculated. RESULTS: A total of 237 treatment arms were analyzed. Bismuth triple therapy continues to reach high eradication rates worldwide (78-89%). Side effects leading to diminished patient compliance and the marked decline of eradication efficacy in cases of metronidazole resistance are considered to be the major drawbacks of this therapy. Proton pump inhibitor (PPI) dual therapy is better tolerated with fewer side effects than is bismuth triple therapy. The mean eradication rates vary from 55 to 75%, and the extremes lie between 24 and 93%. PPI triple therapies have been shown to be very effective against H. pylori (eradication rates, 80-89%). Quadruple therapy leads to a mean eradication rate of 96%. CONCLUSION: Based on efficacy, PPI triple or bismuth triple therapy are recommended as first-line treatment for H. pylori infection. Quadruple therapy could serve as second-line treatment for eradication of initial failures and in case of metronidazole resistance.

Amoxicillin↗
PubMedDate not supplied

[Use of condoms by adolescents seeking oral contraceptives in the Montreal area].

OBJECTIVES: To examine female adolescents' use of condoms before and after seeking their first prescription of oral contraceptives and to identify variables associated with use of oral contraceptives. METHOD: This longitudinal study was conducted among 350 female adolescents recruited from 8 CLSCs in the Montreal Metropolitan Area. Data were collected at the first medical visit and again three months later. RESULTS: At the 3-month follow-up, a decrease of 41% was observed in the systematic use of condoms with an inadequate use of condoms reported in 44% of subjects. In the last year, the variables associated with irregular use of condoms were low intention to use simultaneously the pill and the condom in the next 12 months, higher frequency of intercourse, a larger number of sexual partners, and alcohol or drug use before or during sexual intercourse. CONCLUSION: Our results indicate that female adolescents stop using condoms when they adopt oral contraceptives. At the first visit, the lack or inadequate use of condoms seemed related to other STD risk behaviours. These results should encourage clinicians to revise their counselling approach with adolescents and promote dual protection in the context of serially monogamous relationships with known partners or with partners they trust.

Adolescent↗
PubMed1987

Surgical operations in the United States: 1979 to 1984.

With data from the National Center for Health Statistics, an in-depth analysis of the number of surgical operations performed in the United States from 1979 to 1984 was carried out. During the study period, there was a 9% increase in the total number of surgical procedures. For the same time period, the number of surgeons grew 20%. By 1984 general surgical operations were greatest in number. However, the 5-year increase in the number of general surgical operations was just 7%. Although obstetric and gynecologic operations declined 1%, the most common inpatient surgical operation performed in the United States is cesarean section. Orthopedic surgical operations grew 24% and arthroscopy has become this country's sixteenth most frequent operation. Cataract extraction is the fourth most common operation and represents 60% of all ophthalmologic surgery. Cardiothoracic operations had the largest increase, 34%. This study demonstrates the dynamics of surgical practice in the United States and conveys a dual message. There is reassuring news concerning "unnecessary" surgery due to supplier-induced demand for operations. Despite recent large increases in the number of surgeons, there have not been parallel increases in the number of surgical operations. The belief that more surgeons necessarily means more surgery is not noted. The disturbing news concerns surgical case loads. The prospect of more surgeons performing fewer operations has become a major problem. The surgical community will have to address this growing inbalance.

Data Collection↗
PubMed1997

Obstetricians' receptiveness to teen prenatal patients who are Medicaid recipients.

OBJECTIVE: To test the accuracy of various physicians' participation in Medicaid models. DATA SOURCES/STUDY SETTING: Primary data on 221 obstetricians and gynecologists in the Chicago area by telephone interviews over a four-month period. These data were combined with secondary data from the American Medical Association Master File (1993) and U.S. Census data (1990). STUDY DESIGN: Telephone interviewers posing as the older sisters of a pregnant teenager who is a Medicaid recipient sought information regarding the care provided in a first prenatal care appointment (e.g., appointment duration, tests administered, delivery privileges, appointment availability). DATA COLLECTION/EXTRACTION METHODS: A "receptionist helpfulness" variable was developed through pretesting on obstetricians in another city. Inter-interviewer reliability was enhanced through common interview technique education. PRINCIPAL FINDINGS: Only 81 obstetricians (36.7 percent) accepted new Medicaid patients. This finding is lower than previous research on physician participation in Medicaid. There was strong empirical support for both dimensions-cost containment and limited access-of the physicians' receptiveness model, the model introduced with this research. There was limited support for the dual market and residential segregation models of physician participation in Medicaid. CONCLUSIONS: It is argued that this study's research design is more accurate in reflecting the barriers that a pregnant Medicaid-eligible patient encounters when seeking office-based prenatal care. As such, combining the physicians' receptiveness model with other physician participation in Medicaid models provides a more complete picture of access barriers to prenatal care for our most needy populations.

Adolescent↗
PubMed2001

Biodistribution and dosimetry of 99mTc-BTAP-annexin-V in humans.

The purpose of this study was to determine the biodistribution and the associated radiation dose of technetium-99m 4,5-bis(thioacetamido)pentanoyl-annexin-V (99mTc-Apomate), a tracer proposed for the study of apoptosis. Eight patients (including two females) with normal kidney and liver functions were included in the study. An activity of 580 +/- 90 MBq of 99mTc-Apomate was injected intravenously, immediately followed by a dynamic study of 30 frames of 1 min each. At about 1 h, 4 h and 20 h p.i., whole-body scans were acquired. All activity distributions were measured using a dual-head gamma camera. Before injection of activity, a transmission scan with a cobalt-57 flood source had been performed to determine patient attenuation. Blood samples were taken every 10 min during the first hour after injection, and at about 4 and 20 h. Urine and faeces were collected during the first 20 h. Organ uptake was estimated after correction for body background activity, attenuation and scatter. Residence times were calculated from the dynamic and whole-body studies and used as input in the Mirdose 3.1 program to obtain organ doses and effective dose. It was found that radioactivity strongly accumulated in the kidneys and the liver [at 70 min p.i., 28% +/- 8% and 20% +/- 4% of the injected dose (ID), respectively]. Uptake in the target tissues (lymphomas or heart) was negligible from a dosimetric point of view. Extrapolating data from the first 20 h, one finds that approximately 73% of the ID will be excreted in the urine, and 27% in the faeces. The biological half-life of the activity in the total body was 16 +/- 7 h. Some organ doses +/- standard deviation (SD) in microGy/MBq were: kidneys 63 +/- 22, urinary bladder 20 +/- 6, spleen 15 +/- 3, liver 13 +/- 3, upper large intestine 12 +/- 6, lower large intestine 8 +/- 4, testes 6 +/- 2 and red bone marrow 4 +/- 0.7. The effective dose was 7.6 +/- 0.5 microSv/MBq, corresponding to a total effective dose of 4.6 +/- 0.3 mSv for a nominal injected activity of 600 MBq. In conclusion, 99mTc-Apomate has a high uptake in the kidneys and liver--in fact a factor of 1.3-1.6 higher than that found for the previously studied 99mTc-(n-1-imino-4-mercaptobutyl)-annexin-V. The biological half-life is shorter, however, but still long compared with the physical half-life of 99mTc. The faster appearance of activity in the intestines may preclude imaging of apoptosis in the abdomen. The effective dose is within the lower range of values reported for typical 99mTc compounds.

Adult↗
PubMed2005

Carbon-13 NMR method for the detection of correlated hydrogen exchange at adjacent backbone peptide amides and its application to hydrogen exchange in five antiparallel beta strands within the hydrophobic core of Streptomyces subtilisin inhibitor (SSI).

A novel method for monitoring proton-deuteron (H/D) exchange at backbone amides is based on the observation of H/D isotope effects on the (13)C NMR signals from peptide carbonyls. The line shape of the carbonyl (13)C(i) signal is influenced by differential H/D occupancy at the two adjacent amides: the H(N)(i)(+1) (beta site) and the H(N)(i) (gamma site). At a carbon frequency of 75.4 MHz, the H --> D isotope shifts on the (13)C signal are about 5-7 Hz for exchange at the beta site and 2 Hz or less for exchange at the gamma site. Because the effects at the two sites are additive, the time dependence of the line shape of a particular carbonyl resonance can report not only the exchange rates at the individual sites but also the level of dual exchange. Therefore, the data can be analyzed to determine the rate (k(c)) and degree of correlated exchange (X(betagamma)) at the two sites. We have applied this approach to the investigation of the pH dependence of hydrogen exchange at several adjacent residues in Streptomyces subtilisin inhibitor (SSI). Two selectively labeled SSI proteins were produced: one with selective (13)C' labeling at all valyl residues and one with selective (13)C' labeling at all leucyl residues. This permitted the direct observation by one-dimensional (13)C NMR of selected carbonyl signals from residues with slowly exchanging amides at the i and i + 1 positions. The residues investigated were located in an alpha helix and in a five-stranded antiparallel beta sheet. Samples of the two labeled proteins were prepared at various pH values, and (13)C NMR spectra were collected at 50 degrees C prior to and at various times after transferring the sample from H(2)O to (2)H(2)O. Most of the slowly exchanging amides studied were intramolecular hydrogen-bond donors. In agreement with prior studies, the results indicated that the exchange rates of the amide hydrogens in proteins are governed not only by hydrogen bonding but also by other factors. For example, the amide hydrogen of Thr34 exchanges rapidly even though it is an intramolecular hydrogen-bond donor. Over nearly the whole pH range studied, the apparent rates of uncorrelated exchange (k(beta) and k(gamma)) were proportional to [OH(-)] and the apparent rates of correlated exchange at two adjacent sites (k(c)) were roughly proportional to [OH(-)](2). This enabled us to extract the pH-independent exchange rates (k(beta) degrees , k(gamma) degrees , and k(c) degrees ). In all cases in which correlated exchange could be measured, the observed sigmoidal pH dependence of X(betagamma) could be replicated roughly from the derived pH-independent rates.

Bacterial Proteins↗
PubMed2004

Tissue transglutaminase triggers oligomerization and activation of dual leucine zipper-bearing kinase in calphostin C-treated cells to facilitate apoptosis.

Although tissue transglutaminase (tTG) has been recognized as a mediator of apoptosis in various experimental models, little is currently known about the molecular mechanisms by which this protein modulates cell death. Recent work from our laboratory has shown that activation of tTG in cells exposed to the apoptotic inducer calphostin C triggers the crosslinking of dual leucine zipper-bearing kinase (DLK), a proapoptotic kinase acting as an essential component of the c-Jun amino-terminal kinase (JNK) signaling pathway. As a consequence of this observation, we have undertaken experiments to investigate the functional relevance of DLK oligomerization in tTG-mediated apoptosis. Our results indicate that, in cells undergoing calphostin C-induced apoptosis, tTG-dependent DLK oligomerization occurs early in the apoptotic response. Both immunocomplex kinase assays and immunoblotting with phosphospecific antibodies revealed that oligomer formation by tTG-mediated crosslinking reactions significantly enhanced the kinase activity of DLK and its ability to activate the JNK pathway. Moreover, functional studies demonstrate that tTG-mediated oligomerization of wild-type DLK sensitizes cells to calphostin C-induced apoptosis, while crosslinking of a kinase-inactive variant of DLK does not. Collectively, these data strongly suggest that tTG facilitates apoptosis, at least partly, by oligomerization and activation of the proapoptotic kinase DLK.

Animals↗
PubMed1998

Caring for patients at the end of life in an HMO.

BACKGROUND: Increasing numbers of Americans are receiving care within managed care organizations (MCOs), and the ability of MCOs to provide high-quality end-of-life care is under greater scrutiny. Although many anecdotal reports have been published, almost no research has been published on patient/family experiences with end-of-life care in MCOs. METHODS: We undertook a qualitative study of end-of-life care during 1996 and 1997 in the closed-panel staff-model, not-for-profit, health center division of Harvard Pilgrim Health Care. We collected and analyzed data from five focus groups composed of family members of patients who had died during the preceding year (n = 22) and four focus groups composed of clinicians and administrators who routinely care for dying patients and/or have responsibility for managing end-of-life care resources and systems (n = 31). RESULTS: Problems noted in this setting that are also reported in other health care settings included divergent expectations and unclear primary care/specialist roles and hospice/primary physician roles, difficulties in transitions across care settings, ineffective communication between physicians and patients/families about end-of-life care preferences, and lack of systematic attention to bereavement care. More unique to managed care settings were problems related to the absence of a consistently applied hospice benefit and concerns about the impact of cost containment on the quality of care, reflecting the conflict between the dual roles of MCOs as both insurers and providers of care. CONCLUSIONS: Our findings highlight specific issues involved in providing quality end-of-life care in MCOs and suggest areas for further exploration.

Journal Article↗
PubMed1998

An algorithm for automatic measurement of stimulation thresholds: clinical performance and preliminary results.

We have developed an algorithmic method for automatic determination of stimulation thresholds in both cardiac chambers in patients with intact atrioventricular (AV) conduction. The algorithm utilizes ventricular sensing, may be used with any type of pacing leads, and may be downloaded via telemetry links into already implanted dual-chamber Thera pacemakers. Thresholds are determined with 0.5 V amplitude and 0.06 ms pulse-width resolution in unipolar, bipolar, or both lead configurations, with a programmable sampling interval from 2 minutes to 48 hours. Measured values are stored in the pacemaker memory for later retrieval and do not influence permanent output settings. The algorithm was intended to gather information on continuous behavior of stimulation thresholds, which is important in the formation of strategies for programming pacemaker outputs. Clinical performance of the algorithm was evaluated in eight patients who received bipolar tined steroid-eluting leads and were observed for a mean of 5.1 months. Patient safety was not compromised by the algorithm, except for the possibility of pacing during the physiologic refractory period. Methods for discrimination of incorrect data points were developed and incorrect values were discarded. Fine resolution threshold measurements collected during this study indicated that: (1) there were great differences in magnitude of threshold peaking in different patients; (2) the initial intensive threshold peaking was usually followed by another less intensive but longer-lasting wave of threshold peaking; (3) the pattern of tissue reaction in the atrium appeared different from that in the ventricle; and (4) threshold peaking in the bipolar lead configuration was greater than in the unipolar configuration. The algorithm proved to be useful in studying ambulatory thresholds.

Adult↗
PubMed2005

Management of chest pain: exploring the views and experiences of chiropractors and medical practitioners in a focus group interview.

BACKGROUND: We report on a multidisciplinary focus group project related to the appropriate care of chiropractic patients who present with chest pain. The prevalence and clinical management, both diagnosis and treatment, of musculoskeletal chest pain in ambulatory medical settings, was explored as the second dimension of the focus group project reported here. METHODS: This project collected observational data from a multidisciplinary focus group composed of both chiropractic and medical professionals. The goals of the focus group were to explore the attitudes and experiences of medical and chiropractic clinicians regarding their patients with chest pain who receive care from both medical and chiropractic providers, to identify important clinical or research questions that may inform the development of 'best practices' for coordinating or managing care of chest pain patients between medical and chiropractic providers, to identify important clinical or research questions regarding the diagnosis and treatment of chest pain of musculoskeletal origin, to explore various methods that might be used to answer those questions, and to discuss the feasibility of conducting or coordinating a multidisciplinary research effort along this line of inquiry. The convenience-sample of five focus group participants included two chiropractors, two medical cardiologists, and one dual-degreed chiropractor/medical physician. The focus group was audiotaped and transcripts were prepared of the focus group interaction. Content analysis of the focus group transcripts were performed to identify key themes and concepts, using categories of narratives. RESULTS: Six key themes emerged from the analysis of the focus group interaction, including issues surrounding (1) Diagnosis; (2) Treatment and prognosis; (3) Chest pain as a chronic, multifactorial, or comorbid condition; (4) Inter-professional coordination of care; (5) Best practices and standardization of care; and (6) Training and education. CONCLUSION: This study carries implications for chiropractic clinical training relative to enhancing diagnostic competencies in chest pain, as well as the need to ascertain and improve those skills, competencies, and standards for referrals and sharing of clinical information that may improve cross-disciplinary coordination of care for chest pain patients.

Journal Article↗
PubMedDate not supplied

Hydroxyapatite composites designed for antibiotic drug delivery and bone reconstruction: a caprine model.

The purpose of this study was to investigate the feasibility of fabricating a drug delivery system that serves a dual function, to eradicate infection as well as to provide a scaffold for osseous integration. Two porous composite systems were fabricated using hydroxyapatite (HA) as the carrier for gentamicin sulfate (GS), an aminoglycoside antibiotic. Structural and mechanical properties of porous HA-GS composites were characterized and the in vitro release behavior of GS from fabricated composites was monitored and compared with the well-known polymethylmethacrylate (PMMA)-GS delivery system. Scanning electron microscopy revealed a macropore range of 150 to 200 microm and 100 to 190 microm for the sintered and unsintered HA-GS composites, respectively. The effect of GS inclusion on bone apposition and ingrowth was assessed using a caprine model. Plugs 10 mm x 6 mm of cylindrical tricalcium phosphate, sintered HA, and sintered HA-GS were implanted in the femoral diaphysis for a period of 6 weeks. Data collected during the in vitro study showed that GS can successfully be incorporated into HA and used as a drug delivery system to eradicate Staphylococcus aureus. In vivo data confirmed that the inclusion of GS within a ceramic matrix did not stimulate or inhibit osteointegration or bone apposition. In conclusion, the fabricated sintered HA-GS composite may be beneficial in the treatment of infected osseous sites as a drug delivery system.

Animals↗