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PubMed2004

Interleukin-1beta and TNF-alpha act in synergy to inhibit longitudinal growth in fetal rat metatarsal bones.

UNLABELLED: We hypothesized that pro-inflammatory cytokines can act locally in the growth plate to impair longitudinal growth. In a model of cultured fetal rat metatarsal bones, we found that IL-1beta and TNF-alpha act in synergy to inhibit longitudinal growth, an effect linked to decreased proliferation and increased apoptosis of growth plate chondrocytes. IGF-I could partially reverse all these effects. INTRODUCTION: Children with chronic inflammatory conditions, such as Crohn's disease or rheumatoid arthritis, experience impaired longitudinal growth. The inflammatory process itself, which includes upregulation of the pro-inflammatory cytokines interleukin (IL)-1beta, IL-6, and TNF-alpha, is believed to be at least partly responsible for the poor growth in these patients. This study aimed to clarify whether these cytokines can act locally in the growth plate to suppress longitudinal growth and whether any negative effects can be reversed by insulin-like growth factor-I (IGF-I). MATERIALS AND METHODS: The effects of cytokines on longitudinal bone growth were studied in fetal (day E20) rat metatarsal bones kept in culture. After a 7-day culture, the bones were sectioned, and chondrocyte proliferation was assessed by bromodeoxyuridine (BrdU) incorporation and apoptosis by TUNEL. RESULTS: When added separately, IL-1beta and TNF-alpha impaired longitudinal bone growth only at a high concentration (100 ng/ml each; p < 0.05 versus control). In contrast, when added in combination, IL-1beta and TNF-alpha potently inhibited growth at far lower concentrations (from 3 ng/ml each; p < 0.001 versus control) and also decreased chondrocyte proliferation and increased apoptosis. Growth failure induced by the combination of IL-1beta and TNF-alpha (10 ng/ml each) could be counteracted by anti-IL-1beta (100 ng/ml; p < 0.001), anti-TNF-alpha (100 ng/ml; p < 0.001), or IGF-I (100 ng/ml; p < 0.01). IL-6 did not affect longitudinal growth even when added in combination with IL-1beta or TNF-alpha (10 ng/ml each). CONCLUSIONS: We show that IL-1beta and TNF-alpha act in synergy to locally suppress longitudinal growth, an effect that can be partially reversed by IGF-I. Although growth hormone (GH)/IGF-I may improve longitudinal growth in children with chronic inflammatory diseases, our results suggest that the inflammatory process itself must be targeted to achieve normal growth.

Animals↗
PubMed1990

Effects of teat cistern mural biopsy and teatoscopy stab versus longitudinal incision with or without tube implant on incisional healing in lactating dairy cattle.

Effects of teat cistern mural biopsy and full-thickness stab and longitudinal incisional healing were evaluated experimentally on clinically normal teats in 12 lactating dairy cattle. Each teat on each cow was assigned by Latin-square design to 1 of 4 surgical interventions: (I) teatoscopy only; (II) teatoscopy, stab incision, and mural biopsy; (III) longitudinal incision and mural biopsy; and (IV) longitudinal incision, mural biopsy, and tube implantation. Teatoscopy was done with a 4-mm OD arthroscope introduced through the teat canal and attached to a television camera. Teatoscopy was quicker to perform and provided a more detailed videotaped examination of the teat and gland cistern, compared with gross inspection through a longitudinal incision. In intervention-II cows, the Ferris-Smith biopsy instrument jaws introduced through a longitudinal 1-cm midteat stab incision were easy to visualize and manipulate accurately. Stab incisions closed with only 1 or 2 skin sutures healed without complications in all 12 teats. On palpation, stab incisions were significantly (P less than 0.01) less thick than longitudinal incisions at 8 weeks and were microscopically indistinguishable from the normal tissue. However, in 24 teatoscopically examined teats, 9 (38%) had microscopic evidence of teat canal injury and 12 (50%) of the quarters developed mastitis. This was attributed to trauma resulting from introduction of the arthroscope through the teat canal. Intervention III yielded satisfactory results with the least complications. All 12 longitudinal incisions healed by primary intention, and all teats remained patent. Mastitis developed in 4 (33%) quarters. Intervention IV caused considerable complications associated with the tube implant and no improvement in biopsy site healing, compared with interventions II and III. Eleven longitudinal incisions healed by primary intention. One incision dehisced, 2 (17%) tube implants dislodged, 2 (17%) became obstructed proximally, and irritations of the mucous membrane developed in 2 teats proximally and in 6 teats distally. Mastitis developed in 6 (50%) quarters. Longitudinal incisions healed with moderate submucosal fibrosis. All sutured incisions had multifocal microgranulomata in which suture material was in various stages of degradation. At 8 weeks, localized teat wall thickening could be detected at incisional and biopsy sites, but did not obstruct milk flow. Excessive granulation tissue was at the biopsy sites (72 total) at 2 weeks, and at this time, the sites were partially covered by metaplastic squamous epithelium. However, by 8 weeks, 71 (98%) of the areas were replaced by fibrous tissue with minimal protrusion into the teat cistern.

Animals↗
PubMed1983

Relaxation and Ca-spike suppression in circular and longitudinal muscles of hog bile duct ampulla by CCK-C-terminal peptides.

The mechanisms by which cholecystokinin (CCK)-C-terminal peptides relax biliary smooth muscles were investigated using circular and longitudinal muscles of hog bile duct ampulla. In normal Tyrode's solution the concentration-contraction curves for acetylcholine (ACh) were in a higher range in circular muscle than in longitudinal muscle. In K+-depolarized muscles the concentration-contraction curves for Ca2+ were in a lower range in circular than in longitudinal muscle. When the Ca2+ concentration in Tyrode's solution was decreased, circular muscle showed concentration-dependent relaxation of normal tone from 1.8 mM to zero calcium, but longitudinal muscle did not show any relaxation. Concentrations of CCK-4, CCK-6 and CCK-7 producing 50% relaxation of normal tone in circular muscles were 19 microM, and 53 nM, respectively; concentrations producing 50% inhibition of ACh-induced contraction in longitudinal muscle were 20, 13 and 47 microM, respectively. The effects of calcium removal on the membrane potential were hyperpolarization in circular muscle but depolarization in longitudinal muscle, although there was cessation of calcium spikes in both muscles. In longitudinal muscle, CCK-4 suppressed spontaneous spikes and evoked spikes. In circular muscle, CCK-4 did not suppress evoked spikes even in a concentration that caused relaxation and hyperpolarization of the membrane. In conclusion, CCK-C-terminal peptides may induce relaxation of circular muscle, not by direct suppression of calcium influx during the action potential, but by intracellular decrease in Ca2+ levels probably arising from increased calcium uptake into the sarcoplasmic reticulum or the plasma membrane. On the other hand, the peptides do not induce relaxation of longitudinal muscle, but suppress only the calcium influx (resulting in cessation of spontaneous contraction). Therefore, CCK-4 may cause a relaxation of normal tone in circular muscle, and an inhibition in the spontaneous contraction, induced by some transmitters, of longitudinal muscle.

Acetylcholine↗
PubMedDate not supplied

Cross-sectionally and longitudinally balanced effects of processing speed on intellectual abilities.

The processing speed theory of cognitive aging states that declines in intellectual abilities other than processing speed are mainly due to a slowing of processing speed. Cross-sectional studies have provided support for the processing speed theory as for age-related cognitive differences. Longitudinal studies, in turn, have provided weaker support for the processing speed theory as for cognitive age changes. The present study aims to reconcile this discrepancy of cross-sectional and longitudinal results by constructing a "fair" test of the processing speed theory, i.e., a test that balances the cross-sectional age range and the time period covered longitudinally. Data from 83 older adults came from the Bonn Longitudinal Study on Aging. Using hierarchical linear models, it is shown that, although cross-sectional age differences and longitudinal changes in the intellectual abilities were equal, processing speed only attenuated cross-sectional age effects in cognition but virtually did not reduce longitudinal change effects in cognition. This persisting difference in the explanatory power of processing speed regarding age-related differences and age-related changes is discussed with reference to other longitudinal studies and statistical issues regarding cross-sectional and longitudinal studies of aging.

Aged↗
PubMed1997

Morphologic evaluation and surgical simulation of ossification of the posterior longitudinal ligament using helical computed tomography with three-dimensional and multiplanar reconstruction.

STUDY DESIGN: Using helical computed tomography with three-dimensional and multiplanar reconstruction, ossification of the posterior longitudinal ligament in the cervical and thoracic region was observed. Preoperative simulation also was performed, and the availability of these methods was evaluated. OBJECTIVE: To use preoperative evaluation and simulation with helical computed tomography to enhance the accuracy of excision of ossification of the posterior longitudinal ligament lesion. SUMMARY OF BACKGROUND DATA: Ossification of the posterior longitudinal ligament lesion is sometimes so complicated that preoperative morphologic evaluation and excision of the lesion are difficult when using only conventional imaging techniques. METHODS: Seven cases of cervical and two cases of thoracic ossification of the posterior longitudinal ligament were scanned using helical computed tomography at 2-mm or 5-mm slice thickness. Three-dimensional and multiplanar reconstruction were performed at 0.7-mm or 2-mm intervals in the bone window. Surgical simulation of the anterior approach for cervical lesion and posterior approaches for thoracic lesion was performed. RESULTS: Preoperative direct observation of the ossification of the posterior longitudinal ligament lesion was possible, and the complicated structures could be understood more easily than with other conventional methods. When surgical simulation was performed in the workstation, the ossification of the posterior longitudinal ligament lesion was removed sufficiently on arbitrarily reconstructed view in the spinal canal. When the viewpoint then was changed to the approaching side, the location and dimension of the removed area were determined. In all cases, surgical approach and excision of the ossification of the posterior longitudinal ligament lesion were performed more easily and more precisely than in the surgery with no three-dimensional images. CONCLUSION: Helical computed tomography with three-dimensional, multiplanar reconstruction would be a valuable tool for evaluation and surgical simulation of ossification of the posterior longitudinal ligament lesion by enhancing the accuracy of the surgical procedure.

Adult↗
PubMed1997

An ultrastructural study of calcitonin gene-related peptide-immunoreactive nerve fibers innervating the rat posterior longitudinal ligament. A morphologic basis for their possible efferent actions.

STUDY DESIGN: The present study investigated ultrastructural characteristics of calcitonin gene-related peptide-immunoreactive nerve fibers in the posterior longitudinal ligament of the rat lumbar spine. OBJECTIVES: To provide a morphologic basis for assessment of the afferent and, in particular, efferent functions of calcitonin gene-related peptide immunoreactive nerves in the posterior longitudinal ligament and their eventual role in degenerative spondylarthropathies and low back pain. SUMMARY OF BACKGROUND DATA: Previous studies using light-microscopic localization of sensory neuronal markers such as calcitonin gene-related peptide have reported the presence of sensory fibers in the supporting structures of the vertebral column. Meanwhile, accumulating research data have suggested efferent properties for calcitonin gene-related peptide, i.e., a trophic action that alters the intrinsic properties of target cells not through transient action of synaptic transmission, but through long-lasting signal transmission by the secreted neuropeptides. To verify such trophic, paracrine actions of the calcitonin gene-related peptide-containing fibers in the posterior longitudinal ligament, however, ultrastructural details of the terminals and their spatial relationship to their eventual target structures have to be elucidated. METHODS: Rat posterior longitudinal ligaments were stained immunohistochemically for calcitonin gene-related peptide. Light-microscopic analysis of the semithin sections facilitated subsequent electron microscopy of specific sites of the posterior longitudinal ligament to determine ultrastructural details and nerve fiber-target relationships. RESULTS: The rat lumbar posterior longitudinal ligament was found to be innervated by two distinctive calcitonin gene-related peptide immunoreactive nerve networks. In immunoelectronmicroscopy, the fibers of the deep network had numerous free nerve endings, whereas those of the superficial network showed spatial associations with other non-calcitonin gene-related peptide immunoreactive components of the network. In both systems, naked axons not covered by the Schwann cells made close spatial contact with smooth muscle cells: of blood vessels and resident posterior longitudinal ligament fibroblasts. CONCLUSIONS: The ultrastructural characteristics of the innervation of the rat posterior longitudinal ligament would be compatible not only with a nociceptive function, but also with neuromodulatory, vasoregulatory, and trophic functions, as has already been established in some visceral organs.

Animals↗
PubMed1998

Quantitative anthropometry of the subatlantal cervical longitudinal ligaments.

STUDY DESIGN: The quantitative anthropometry of the cervical longitudinal ligaments was determined in 20 human cadaveric subatlantal cervical spines at the limits of flexion and extension. OBJECTIVES: To provide measurements of cervical anterior and posterior longitudinal ligament lengths, widths, and cross-sectional areas at segmental levels. SUMMARY OF BACKGROUND DATA: Although mathematical models of the cervical spine require specific data to predict kinematics, the anthropometry of the cervical spine has not been examined in detail. The dimensional changes of ligaments in physiologic motion are not well characterized. METHODS: Segmental lengths and widths of the cervical longitudinal ligaments were measured in sagittal plane flexion and extension, using a three-dimensional electromagnetic digitizer. The cross-sectional areas of the ligaments at resting length were measured with a laser micrometer system. Comparisons between anterior and posterior location and among segmental levels were made. Several ligaments were examined histologically to determine the insertion sites and, thus, to define the segmental length. RESULTS: The anterior longitudinal ligaments were shorter in flexion than in extension. In extension, they were longer than the posterior longitudinal ligaments in flexion. The resting isolated ligaments were longer than the longest in situ lengths at several vertebral levels. The anterior longitudinal ligaments were wider at the disc than at the body. The cross-sectional area at C2-C3 was smaller than at subaxial levels. The longitudinal ligaments were observed to insert along the entire underlying vertebral body. CONCLUSIONS: The quantitative anthropometry of the cervical longitudinal ligaments is important in the development of accurate mathematical models of the cervical spine. The in situ ligaments may not be under tension in the physiologic range of motion.

Aged↗
PubMed2005

Bone displacement and the role of longitudinal ligaments during balloon vertebroplasty in traumatic thoracolumbar fractures.

STUDY DESIGN: In a human cadaveric burst fracture model with and without longitudinal ligament damage, the amount of anterior and posterior bone displacement (ABD, PBD) during balloon vertebroplasty after pedicle-screw instrumentation was investigated quantitatively. OBJECTIVES: To investigate, in a burst fracture model with and without longitudinal ligament damage, the amount of ABD, PBD, and cement leakage at various phases during balloon vertebroplasty in combination with pedicle-screw instrumentation. SUMMARY OF BACKGROUND DATA: The role of intact longitudinal ligaments in traumatic spine fractures, for prevention of bone retropulsion and subsequent reduction, has been discussed in several studies but is still up for debate. In a recent human cadaveric burst fracture study, inflatable bone tamps and calcium phosphate cement were used for the augmentation of the anterior column after pedicle-screw instrumentation. The additional balloon vertebroplasty procedure was found to be feasible and safe, but no data pertaining to unwarranted bone displacement or cement leakage during the procedure are available for burst fractures with damaged longitudinal ligaments. METHODS: Ten thoracic and 10 lumbar burst fractures, with rotation or flexion components, were created, and balloon vertebroplasty with calcium phosphate cement was performed after pedicle-screw instrumentation. Volumetric datasets (using the 3-dimensional (3D) rotational x-ray imaging technique) of the fractures were obtained during the following phases: intact, fractured, after reduction and stabilization with pedicle-screws, after inflation of the balloons, after deflation and removal of the balloons, and after injection of the cement. The amount of ABD and PBD was measured on reconstructed sagittal images and recorded together with the presence of extracorporal cement leakage. The continuity of the longitudinal ligaments was assessed after anatomic dissection. RESULTS: During the balloon vertebroplasty procedure, a significant (P < 0.05) increase of ABD (at both thoracic and lumbar level) and PBD (thoracic level) occurred after inflation of the balloons. After deflation and subsequent injection of the cement, however, the ABD and PBD returned to the preinflation levels. The absolute amount of ABD and PBD (<1 mm) during inflation was considered of little clinical importance. No differences in ABD or PBD were observed for specimens with or without continuity of the corresponding longitudinal ligament, irrespective of the level, at any of the phases during the experiment (P > 0.5 in all cases). A small amount of cement leakage was observed in the psoas compartment of one specimen with intact longitudinal ligaments. CONCLUSIONS: It is suggested that balloon vertebroplasty after pedicle-screw instrumentation may safely be used, in terms of bone displacement and cement leakage, in fracture types where damage to longitudinal ligaments is to be expected.

Aged↗
PubMed2005

Accelerated longitudinal decline of aerobic capacity in healthy older adults.

BACKGROUND: The ability of older persons to function independently is dependent largely on the maintenance of sufficient aerobic capacity and strength to perform daily activities. Although peak aerobic capacity is widely recognized to decline with age, its rate of decline has been estimated primarily from cross-sectional studies that may provide misleading, overly optimistic estimates of aging changes. METHODS AND RESULTS: To determine longitudinal rate of change in aerobic capacity and the influence of age, gender, and physical activity on these changes, we performed serial measurements of peak treadmill oxygen consumption (peak VO2) in 375 women and 435 men ages 21 to 87 years from the Baltimore Longitudinal Study of Aging, a community-dwelling cohort free of clinical heart disease, over a median follow-up period of 7.9 years. A linear mixed-effects regression model was used to calculate the predicted longitudinal 10-year rate of change in peak VO2, expressed in milliliters per minute, for each age decade from the 20s through the 70s after adjustment for self-reported leisure-time physical activity. A longitudinal decline in peak VO2 was observed in each of the 6 age decades in both sexes; however, the rate of decline accelerated from 3% to 6% per 10 years in the 20s and 30s to >20% per 10 years in the 70s and beyond. The rate of decline for each decade was larger in men than in women from the 40s onward. Similar longitudinal rates of decline prevailed when peak VO2 was indexed per kilogram of body weight or per kilogram of fat-free mass and in all quartiles of self-reported leisure-time physical activity. When the components of peak VO2 were examined, the rate of longitudinal decline of the oxygen pulse (ie, the O2 utilization per heart beat) mirrored that of peak VO2, whereas the longitudinal rate of heart rate decline averaged only 4% to 6% per 10 years, and accelerated only minimally with age. CONCLUSIONS: The longitudinal rate of decline in peak VO2 in healthy adults is not constant across the age span in healthy persons, as assumed by cross-sectional studies, but accelerates markedly with each successive age decade, especially in men, regardless of physical activity habits. The accelerated rate of decline of peak aerobic capacity has substantial implications with regard to functional independence and quality of life, not only in healthy older persons, but particularly when disease-related deficits are superimposed.

Adult↗
PubMedDate not supplied

Longitudinal research and data collection in primary care.

PURPOSE: This article reviews examples of and experience with longitudinal research in family medicine. The objective is to use this empirical information to formulate recommendations for improving longitudinal research. METHODS: The article discusses 3 longitudinal studies from the Nijmegen academic family practice research network: 1 on the prognosis of depression and 1 each on the prognosis of and outcomes of care for type 2 diabetes mellitus. The Nijmegen network has recorded all episodes of morbidity encountered in Dutch family medicine since 1971 in a stable practice population. This network's experience is evaluated to identify lessons that may help other practice-based research networks (PBRNs) in pursuing longitudinal research. RESULTS: In terms of external conditions (conditions related to the general setting), the stability of a population and a high level of continuity of care substantially enhance the ability to perform longitudinal research. In terms of internal conditions (conditions related to the PBRN), motivation of family physicians and their staff to conduct ongoing data collection, and their ownership of the data are key for success. Other critical internal conditions include standardization of data; collection of data by clinician-friendly means; training of family physicians and their staff in data collection, as well as meetings for discussion of this task; provision of feedback to practices on the research findings; use of standard procedures to promote adherence to data collection; availability of facilities for regular measurement of patients' health status or chart review; and use of mechanisms for tracking patients who leave the practice area. CONCLUSIONS: Insight from existing experience suggests that longitudinal research can be enhanced in PBRNs. The best way forward is to build longitudinal data collection by drawing on lessons from successful studies. Primary care research policy should advocate for a role of longitudinal research and stimulate its development in PBRNs under favorable population circumstances.

Biomedical Research↗
PubMed2026

Pilot study identifying distinct circulating proteomic profiles associated with longitudinal CT-defined fibrotic and inflammatory sarcoidosis.

INTRODUCTION: Pulmonary sarcoidosis exhibits heterogeneous clinical trajectories ranging from self-limited disease resolution to chronic progressive fibrosis, yet reliable biomarkers capable of distinguishing these disease patterns remain lacking. Whether longitudinal CT-defined sarcoidosis phenotypes are associated with distinct circulating molecular signatures remains unknown. METHODS: We performed high-throughput plasma proteomics (SomaScan 11K) in participants with pulmonary sarcoidosis classified into longitudinal chest CT-defined progressive fibrosis, progressive nodular inflammatory disease, or resolving disease trajectories, along with healthy controls. CT phenotypes were assigned based on predefined longitudinal changes in reticulation, traction bronchiectasis, nodular involvement, and mediastinal lymphadenopathy across serial CT scans. One plasma sample per participant was selected from the study visit corresponding to the CT time point at which criteria for the assigned longitudinal phenotype were met. Principal component analysis, hierarchical clustering, pathway enrichment, and correlation-based analyses linking protein expression to quantitative CT features were used to evaluate whether distinct longitudinal CT phenotypes were associated with divergent proteomic signatures. RESULTS: Principal component analysis and hierarchical clustering suggested partial segregation by CT-defined phenotype. Longitudinal CT phenotypes were associated with distinct pathway-level proteomic signatures, with progressive fibrosis enriched for epithelial-mesenchymal transition signaling, and progressive nodular inflammatory disease enriched for mTORC1, MYC, oxidative phosphorylation, adipogenesis, and fatty acid metabolism pathways. Correlation analyses showed coordinated protein-expression patterns associated with fibrotic CT features and mediastinal lymph node enlargement. DISCUSSION: These findings suggest that longitudinal CT-defined fibrotic and inflammatory sarcoidosis phenotypes are associated with distinct pathway-level proteomic signatures. This pilot study provides preliminary proof-of-concept evidence that integrating longitudinal CT imaging phenotypes with plasma proteomics may serve as a framework for future mechanistic studies and biomarker discovery in pulmonary sarcoidosis.

Humans↗
PubMedDate not supplied

Longitudinal residency training: a survey of family practice residency programs.

BACKGROUND AND OBJECTIVES: Most family practice residency training consists of 2-4-week block rotations in specific curricular areas, supplemented by training in the family practice center. An alternative model, longitudinal residency training, emphasizes training in curricular areas over a 3-year time period. This study determined the frequency of longitudinal training in family practice residency programs. METHODS: We conducted a survey of 477 residency program directors listed in the American Academy of Family Physicians 2000 Directory of Family Practice Residency Programs. RESULTS: Sixty-eight percent (n=320) of program directors responded to the survey. A total of 3.6% of program directors described their program as "mostly longitudinal," and 14.2% described their program as "half block/half longitudinal." An additional 15% of program directors indicated interest in adopting or moving toward a longitudinal program in the next 2 wears. Responses suggest some inconsistencies in program directors' understanding of what constitutes a longitudinal curriculum. CONCLUSIONS: Longitudinal residency training is reported in 18% of family practice residency programs. Further work is needed to develop a definition of longitudinal residency training.

Adult↗
PubMedDate not supplied

Longitudinal versus traditional residencies: a study of continuity of care.

BACKGROUND AND OBJECTIVES: Continuity of care is one of the presumed advantages of longitudinal residencies. However, it is not clear how well such residencies provide continuity of care, and, further, there is no recognized acceptable rate of good continuity. We compared traditional and longitudinal residencies to determine the extent to which the residents provided their patients with continuity of care. METHODS: We conducted a systematic chart review at three longitudinal and three matched traditional block-rotation programs. In total, 628 charts were reviewed, and 6,256 visits were evaluated. Continuity with a primary resident was evaluated over a 2-year period, with continuity defined as the percentage of visits for which the patient saw the same resident. RESULTS: There was no significant difference in overall rates of continuity between longitudinal and traditional programs (59.6% versus 57.8%). One longitudinal program, however, had a 74.8% rate of continuity, which was significantly higher than the rates in the otherfive programs. CONCLUSIONS: There was no significant difference found in continuity of care provided by residents at longitudinal programs, compared with those at traditional programs. Our results do not support the hypothesis that longitudinal residency programs achieve superior rates of continuity of care. Further comparison studies of longitudinal and traditional programs would be useful.

Analysis of Variance↗
PubMed2002

Predicting time to prostate cancer recurrence based on joint models for non-linear longitudinal biomarkers and event time outcomes.

Biological markers that are both sensitive and specific for tumour regrowth or metastasis are increasingly becoming available and routinely monitored during the regular follow-up of patients treated for cancer. Obtained by a simple blood test, these markers provide an inexpensive non-invasive means for the early detection of recurrence (or progression). Currently, the longitudinal behaviour of the marker is viewed as an indicator of early disease progression, and is applied by a physician in making clinical decisions. One marker that has been studied for use in both population screening for early disease and for detection of recurrence in prostate cancer patients is PSA. The elevation of PSA levels is known to precede clinically detectable recurrence by 2 to 5 years, and current clinical practice often relies partially on multiple recent rises in PSA to trigger a change in treatment. However, the longitudinal trajectory for individual markers is often non-linear; in many cases there is a decline immediately following radiation therapy or surgery, a plateau during remission, followed by an exponential rise following the recurrence of the cancer. The aim of this article is to determine the multiple aspects of the longitudinal PSA biomarker trajectory that can be most sensitive for predicting time to clinical recurrence. Joint Bayesian models for the longitudinal measures and event times are utilized based on non-linear hierarchical models, implied by unknown change-points, for the longitudinal trajectories, and a Cox proportional hazard model for progression times, with functionals of the longitudinal parameters as covariates in the Cox model. Using Markov chain Monte Carlo sampling schemes, the joint model is fit to longitudinal PSA measures from 676 patients treated at Massachusetts General Hospital between the years 1988 and 1995 with follow-up to 1999. Based on these data, predictive schemes for detecting cancer recurrence in new patients based on their longitudinal trajectory are derived.

Bayes Theorem↗
PubMed2001

Projections of excitatory and inhibitory motor neurones to the circular and longitudinal muscle of the guinea pig colon.

The aim of this study was to identify myenteric pathways to the circular and longitudinal muscle of the guinea pig proximal colon. To identify excitatory and inhibitory muscle motoneurones, we applied the neuronal retrograde tracer DiI onto the circular or longitudinal muscle layer and performed additional immunohistochemistry for nitric oxide synthase (NOS) and choline acetyltransferase (ChAT). On average 166 +/- 81 circular muscle motoneurones (CMMN) and 100 +/- 74 longitudinal muscle motoneurones (LMMN) were labelled by DiI tracing. Myenteric pathways innervating the muscle were either ascending (DiI-labelled neurones with oral projections) or descending (DiI-labelled neurones with anal projections). The circular muscle was preferentially innervated by ascending pathways (66.0 +/- 9.1%). Most ascending CMMN were ChAT-positive (87.2 +/- 8.5%), whereas descending CMMN were mainly NOS-positive (82.3 +/- 14.6%). Most ascending (62.2 +/- 11.1%) and descending (82.0 +/- 12.5%) CMMN had circumferential projection preferences (circumferential projections were longer than projections along the longitudinal gut axis). In contrast to the polarised projections to the circular muscle, the longitudinal muscle was equally innervated by ascending (46.2 +/- 15.1%) and descending (53.9 +/- 15.1%) neurones. Ascending and descending pathways to the longitudinal muscle consisted predominantly of ChAT-positive neurones (98.1 +/- 1.9% and 68.0 +/- 8.5%, respectively), and both pathways had prominent longitudinal projection preferences. Only 25.5% of the descending LMMN were NOS-positive. In conclusion, the circular muscle in the proximal colon is innervated by descending inhibitory (NOS-positive neurones) and ascending excitatory (ChAT-positive neurones) pathways. In contrast, the longitudinal muscle is primarily innervated by ascending and descending excitatory motoneurones, and only a small proportion of the descending pathway consisted of inhibitory motoneurones.

Animals↗
PubMed1989

Effects of leu-enkephalin on the mechanical activity of longitudinal and circular muscles of the small intestine of the cat.

The effects of leu-enkephalin on the spontaneous and electrically-evoked activity were studied in the longitudinal and circular strips isolated from the duodenum, jejunum and ileum of the cat. Leu-enkephalin affected the spontaneous activity of both longitudinal and circular strips, with the exception of the circular strips from the ileum, in a naloxone-dependent manner. Elimination of the neural input to the smooth muscle cells with tetrodotoxin blocked the effects of leu-enkephalin in the longitudinal and circular strips from the jejunum and in the longitudinal strips from the ileum. In the longitudinal strips from the duodenum the effect was resistant to tetrodotoxin, while in the circular strips a tetrodotoxin-sensitive component of the effect of leu-enkephalin was observed. Since leu-enkephalin evoked opposite effects in the longitudinal and circular layers of one and the same region, it is concluded that leu-enkephalin-induced modulation of the motility of the small intestine in the cat is a physiological phenomenon. Electrical stimulation, at a frequency of 5 Hz, evoked contractile responses in the longitudinal strips and relaxant, as well as low-amplitude, contractile responses in the circular strips. Rebound contractions developed after the end of stimulation in all preparations tested, with the exception of the longitudinal strips from the duodenum. Leu-enkephalin decreased the contractile components and tended to potentiate the relaxant components of the responses in a naloxone-dependent manner. Atropine inhibited the contractile components of the responses and significantly depressed the rebound contractions. Leu-enkephalin, applied after atropine, was ineffective suggesting that leu-enkephalin-induced modulation was mediated mainly through interaction with cholinergic transmission.

Animals↗
PubMedDate not supplied

The effect of technical factors on the quality of pulmonary venous flow from the transverse and longitudinal imaging planes with transesophageal echocardiography.

Right and left upper pulmonary venous flow is usually assessed with monoplane transesophageal echocardiography (TEE) in the transverse imaging plane. Pulmonary venous flow in the transverse imaging plane may be relatively difficult to record because of the larger angle between the pulmonary vein and the transducer beam. To compare the quality of echocardiographically derived Doppler flows of the right and left upper pulmonary veins between the longitudinal and transverse imaging planes with TEE, we performed pulsed-wave Doppler TEE of both upper pulmonary veins in transverse and longitudinal imaging planes in 36 patients with various diseases. We also recorded a quality index for each flow profile and the angle between the transducer beam and the pulmonary vein. The quality index of the left pulmonary venous flow assessed with the longitudinal and transverse imaging planes was similar in 35 (95%) of 36 patients, whereas the longitudinal imaging plane was superior to the transverse plane in one patient (3%). In contrast, the quality index of the right pulmonary venous flow assessed with the longitudinal and transverse imaging planes was similar in only 19 (53%) of 36 patients, whereas in 17 patients (47%) the longitudinal imaging plane was superior to the transverse imaging plane. The quality index had a significant effect on the Doppler flow recordings; suboptimal-quality flow recordings significantly underestimated the pulmonary venous diastolic flow integrals. The left atrium was larger in those patients with unobtainable flows than in those patients with exclusively obtainable flows (p < 0.001). The angle between the sample volume and the right pulmonary vein was larger in the transverse imaging plane than in the longitudinal plane (p < 0.001). In conclusion, the longitudinal imaging plane is generally superior to the transverse imaging plane for assessing right pulmonary venous flow and is recommended for performing a comprehensive assessment of pulmonary venous flow. The ability to obtain quality images and accurate assessment of flow may be related to the size of the left atrium and angle of the pulmonary vein.

Adult↗
PubMed2002

Discrimination by SZL49 between contractions evoked by noradrenaline in longitudinal and circular muscle of human vas deferens.

The effects of irreversible alpha1-adrenoceptor antagonists, SZL-49 (an alkylating analogue of prazosin), dibenamine and benextramine on contractions to noradrenaline (NA) in longitudinal and circular muscle of human epididymal vas deferens were investigated. Competitive alpha1-adrenoceptor antagonists were also used to further characterize the alpha1-adrenoceptor subtype stimulated by NA in longitudinal and circular muscle. NA evoked concentration-dependent contractions of both muscle types (pD2; 5.4 and 5.2 respectively). The contraction of circular muscle was comparatively more sensitive than that of longitudinal muscle to pretreatment with SZL-49. In contrast, dibenamine or benextramine produced comparable effects in both muscle types. The relationship between receptor occupancy and contraction in either longitudinal or circular muscle was nonlinear, with half-maximal response requiring similar receptor occupancy (longitudinal muscle 14%, circular muscle 16%). Maximal response in both muscle types occurred with little or no receptor reserve (<10%). The competitive alpha1-adrenoceptor antagonists produced dextral shifts of the dose-response curves to NA in longitudinal and circular muscle. The inhibitory potencies, estimated from the apparent pKB values were significantly different in longitudinal and circular muscle respectively for either WB 4101 (pKB, 8.6 and 9.5) or RS-17053 (pKB, 7.1 and 9.0) but not for Rec 15/2739 (pKB, 9.2 and 9.8) or HV 723 (pKB, 8.3 and 8.4). In conclusion, the potency profile of the competitive alpha1-adrenoceptor antagonists and the lack of different receptor reserves for NA in the muscle types suggest that the discriminatory effects of SZL-49 is primarily due to a predominance of the alpha1L-adrenoceptor subtype in longitudinal muscle and alpha1A-subtype in circular muscle.

Adrenergic alpha-Antagonists↗