Bone Disease in the Common Marmoset: Radiographic and Histological Findings.

The common marmoset (Callithrix jacchus) is a New World primate that is used in biomedical research due to its small size and relative ease of handling compared with larger primates. Although bone disease in common marmosets is well recognized, there are very few detailed descriptions in the literature that cover the range of lesions seen in these animals. For all animals used to model human disease, it is important to be aware of background lesions that may affect the interpretation of study findings. This retrospective study details bone diseases encountered in marmoset breeding colonies at 2 different institutions. Affected marmosets at Johns Hopkins University had lesions compatible with diagnoses of rickets, fibrous osteodystrophy and osteopenia. Affected marmosets at the Wisconsin National Primate Research Center exhibited severe lesions of osteoclastic bone resorption and remodeling that had an unusual distribution and were not easily categorized into a known disease entity. The purpose of this report is to document these naturally occurring skeletal lesions of common marmosets and suggest an approach to evaluating skeletal disease in prospective studies of these animals that will allow the most accurate diagnoses.

Obstructive sleep apnoea and perioperative complications in bariatric patients.

BACKGROUND: The objective of this study was to determine the relationship between perioperative complications and the severity of obstructive sleep apnoea (OSA) in patients undergoing bariatric surgery who had undergone preoperative polysomnography (PSG). METHODS: The records of 797 patients, age >18 yr, who underwent bariatric operations (442 open and 355 laparoscopic procedures) at Mayo Clinic and were assessed before operation by PSG, were reviewed retrospectively. OSA was quantified using the apnoea-hypopnoea index (AHI) as none (≤ 4), mild (5-15), moderate (16-30), and severe (≥ 31). Pulmonary, surgical, and 'other' complications within the first 30 postoperative days were analysed according to OSA severity. Logistic regression was used to assess the multivariable association of OSA, age, sex, BMI, and surgical approach with postoperative complications. RESULTS: Most patients with OSA (93%) received perioperative positive airway pressure therapy, and all patients were closely monitored after operation with pulse oximetry on either regular nursing floors or in intensive or intermediate care units. At least one postoperative complication occurred in 259 patients (33%). In a multivariable model, the overall complication rate was increased with open procedures compared with laparoscopic. In addition, increased BMI and age were associated with increased likelihood of pulmonary and other complications. Complication rates were not associated with OSA severity. CONCLUSIONS: In obese patients evaluated before operation by PSG before bariatric surgery and managed accordingly, the severity of OSA, as assessed by the AHI, was not associated with the rate of perioperative complications. These results cannot determine whether unrecognized and untreated OSA increases risk.

Rates of DNA-mediated electron transfer between metallointercalators.

Ultrafast emission and absorption spectroscopies were used to measure the kinetics of DNA-mediated electron transfer reactions between metal complexes intercalated into DNA. In the presence of rhodium(III) acceptor, a substantial fraction of photoexcited donor exhibits fast oxidative quenching (>3 x 10(10) per second). Transient-absorption experiments indicate that, for a series of donors, the majority of back electron transfer is also very fast (approximately 10(10) per second). This rate is independent of the loading of acceptors on the helix, but is sensitive to sequence and pi stacking. The cooperative binding of donor and acceptor is considered unlikely on the basis of structural models and DNA photocleavage studies of binding. These data show that the DNA double helix differs significantly from proteins as a bridge for electron transfer.

Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease.

REM sleep behaviour disorder (RBD) is a parasomnia characterized by the loss of normal skeletal muscle atonia during REM sleep with prominent motor activity accompanying dreaming. The terminology relating to RBD, and mechanisms underlying REM sleep without atonia and RBD based on data in cat and rat are presented. Neuroimaging data from the few published human cases with RBD associated with structural lesions in the brainstem are presented, in which the dorsal midbrain and pons are implicated. Pharmacological manipulations which alter RBD frequency and severity are reviewed, and the data from human neuropathological studies are presented. An anatomic framework and new schema for the pathophysiology of RBD are proposed based on recent data in rat regarding the putative flip-flop switch for REM sleep control. The structure in man analogous to the subcoeruleus region in cat and sublaterodorsal nucleus in rat is proposed as the nucleus (and its associated efferent and afferent pathways) crucial to RBD pathophysiology. The association of RBD with neurological disease ('secondary RBD') is presented, with emphasis on RBD associated with neurodegenerative disease, particularly the synucleinopathies. The hypothesized pathophysiology of RBD is presented in relation to the Braak staging system for Parkinson's disease, in which the topography and temporal sequence of synuclein pathology in the brain could explain the evolution of parkinsonism and/or dementia well after the onset of RBD. These data suggest that many patients with 'idiopathic' RBD are actually exhibiting an early clinical manifestation of an evolving neurodegenerative disorder. Such patients may be appropriate for future drug therapies that affect synuclein pathophysiology, in which the development of parkinsonism and/or dementia could be delayed or prevented. We suggest that additional clinicopathological studies be performed in patients with dementia or parkinsonism, with and without RBD, as well as in patients with idiopathic RBD, to further elucidate the pathophysiology and also characterize the clinical and pathophysiological relevance of RBD in neurodegenerative disease. Furthermore, longitudinal studies in patients with idiopathic RBD are warranted to characterize the natural history of such patients and prepare for future therapeutic trials.

Insights into REM sleep behavior disorder pathophysiology in brainstem-predominant Lewy body disease.

BACKGROUND AND PURPOSE: Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia reflecting changes in the brain, but which specific neuronal networks are involved in human RBD pathogenesis has not yet been determined. To date, only one case of idiopathic RBD has undergone autopsy, in which "incidental Lewy body disease" was found. Due to the severe neuronal loss and gliosis in the substantia nigra (SN) and locus ceruleus (LC) in this case, degeneration of brainstem monoaminergic neurons was postulated as the underlying substrate for RBD. Additional cases of idiopathic RBD with neuropathologic examination may help clarify which key brainstem structures are involved. PATIENT AND METHODS: Case report with neuropathologic analysis. RESULTS: A man with polysomnographically proven RBD (onset age 57 years), but no other neurologic signs or symptoms, underwent neuropathologic examination upon his death at age 72. Histopathologic analysis showed Lewy body disease, but no significant neuronal loss or gliosis was present in the SN or LC. CONCLUSIONS: This case represents another example of Lewy body disease associated with RBD. The minimal degenerative changes in the SN and LC call into question the role of these nuclei in RBD, at least in our case. We suggest additional cases of idiopathic RBD undergo neuropathologic analyses to better delineate the neurologic substrate of this intriguing parasomnia.

Active calcium and strontium transport in human erythrocyte ghosts.

Both calcium and strontium could be transported actively from erythrocytes if adenosine triphosphate, guanosine triphosphate, or inosine triphosphate were included in the hypotonic medium used to infuse calcium or strontium into the cells. Acetyl phosphate and pyrophosphate were not energy sources for the transport of either ion. Neither calcium nor strontium transport was accompanied by magnesium exchange, and the addition of Mg(++) to the reaction medium in a final concentration of 3.0 mmoles/liter did not promote the transport of either ion. In the absence of nucleotide triphosphates, the addition of 1.5 mmoles/liter of Sr(++) to the reaction solution did not bring about active calcium transport and similarly 1.5 mmoles/liter of Ca(++) did not bring about active strontium transport. The inclusion of 1.5 mmoles/liter of Ca(++) or Sr(++) in the reaction medium did not interfere with the transport of the other ion when the erythrocytes were infused with adenosine triphosphate.

Investigation of the accompaniment of calcium during active calcium transport from human erythrocyte ghosts.

To determine whether a cell metabolite was involved in active calcium transport, the cell contents of human erythrocytes were subjected to high dilutions and the resultant ghosts were checked for their ability to actively transport calcium. It was found that the diluted erythrocyte ghosts did retain their capacity to actively transport calcium and that the characteristics of this transport process appeared to be unaltered by the high dilutions. Calcium analysis of the cell membrane and cell supernatant indicated that almost all of the calcium was lost from the cell solution rather than the cell membrane as active calcium transport proceeded. Therefore it appeared that calcium was able to cross the cell membrane without the aid of a cell metabolite. Investigations with layered erythrocytes indicated that the active transport of calcium was not assisted by centrifugation. Neither inorganic phosphate, pyrophosphate, nor an adenine nucleotide appeared to accompany calcium across the membrane as indicated by total phosphate and inorganic phosphate analysis and 260-nm readings of the deproteinized supernatant.

REM sleep behavior disorder and degenerative dementia: an association likely reflecting Lewy body disease.

BACKGROUND: REM sleep behavior disorder (RBD) has been reported with various neurodegenerative disorders, most frequently in disorders with Lewy body pathology. RBD often precedes the onset of PD, and a recent prospective study showed that 38% of patients with RBD eventually developed PD. METHODS: We identified 37 patients with degenerative dementia and a history of bursts of vigorous movement of the arms and legs with vocalization during sleep and associated with dream recall. Patients with and without two or more signs of parkinsonism were compared. Clinical, laboratory, and neuropsychometric features were analyzed, and criteria for the clinical diagnosis of dementia with Lewy bodies (DLB) were applied to all patients. RESULTS: Thirty-four of the 37 patients were male with mean age at onset of 61.5 years for RBD and 68.1 years for cognitive decline. RBD commenced before or concurrently with dementia in all patients but two. Parkinsonism (two or more signs) occurred in 54% of the sample (20/37), with a mean age at onset of 69.1 years. Polysomnography (PSG) confirmed RBD in all patients studied. Neuropsychological testing demonstrated impaired perceptual-organizational skills, verbal fluency, and marked constructional dyspraxia in more than one-half the patients. There were no statistically significant differences in the frequency of clinical features or in neuropsychological performance between patients with and without parkinsonism. Thirty-four patients (92%) met criteria for clinically possible or probable DLB. Three patients were autopsied; all had limbic with or without neocortical Lewy bodies. CONCLUSIONS: We report a group of predominantly male patients with a characteristic association of RBD and degenerative dementia. The clinical and neuropsychometric features of the groups of patients with and without parkinsonism are similar. We hypothesize that the underlying pathology in these patients is DLB.

Fungal beta-glucans modulate macrophage release of tumor necrosis factor-alpha in response to bacterial lipopolysaccharide.

Tumor necrosis factor-alpha (TNF alpha) is a potent cytokine believed to participate in the development of endotoxin-induced shock and the adult respiratory distress syndrome. Treatment of animals with beta-glucan prior to bacterial challenge reduces TNF alpha release and prevents death. We therefore hypothesized that beta-glucan might regulate TNF alpha secretion from macrophages in response to lipopolysaccharide (LPS). Rat alveolar macrophages were cultured in the presence of beta-glucan alone and the TNF alpha secretion quantified using an L929 cytotoxicity assay. Concentrations of beta-glucan less than 500 micrograms/ml were found to stimulate TNF alpha release from macrophages. However, concentrations of beta-glucan greater than 500 micrograms/ml resulted in suppression of the TNF alpha activity released. This reduction in TNF alpha release was not mediated by a toxic effect of beta-glucan, as large concentrations of beta-glucan had no effect on macrophage viability. We further observed that the incubation of macrophages with large concentrations of beta-glucan (500 micrograms/ml) also inhibited the secretion of TNF alpha induced by bacterial LPS. Furthermore, interferon-gamma (IFN gamma), a potent activator of TNF alpha expression, failed to overcome the inhibition of TNF alpha caused by beta-glucan. These data suggest an immunomodulatory role for beta-glucan which may explain both the TNF alpha-stimulating and -inhibiting effects of fungal beta-glucans during infection.

Clinical recognition of pulmonary embolism: problem of unrecognized and asymptomatic cases.

Dyspnea, pleuritic chest pain, and tachypnea are widely appreciated as common initial features of pulmonary embolism (PE). This knowledge is derived primarily from prospective studies evaluating diagnostic tests or therapeutic interventions in which the study patients are suspected to have PE based on their initial symptoms. Autopsy studies, however, continue to show that most cases of fatal PE are unrecognized and undiagnosed. Data from studies screening for PE in patients with deep venous thrombosis and in postoperative patients suggest that many patients with PE are asymptomatic and that PE is unrecognized. We believe that the current concepts regarding the initial clinical features of PE are too narrow and biased toward symptomatic cases. High clinical suspicion may be insufficient in recognizing PE. Herein we summarize the available data and explore the implications for clinical practice.

Diagnosis of pulmonary embolism with use of computed tomographic angiography.

Pulmonary embolism (PE) is a common diagnostic problem, particularly in hospitalized patients. It remains a frequent cause of unexpected deaths. Traditionally, the diagnostic work-up for suspected PE has centered on the use of ventilation-perfusion (V-P) radionuclide lung scanning. However, V-P scanning does not provide adequate confirmation or exclusion of the diagnosis in the majority of patients who undergo this test. Although published guidelines advise further diagnostic testing after nondiagnostic V-P scans, clinicians infrequently perform such testing, and management decisions are commonly based on clinical judgment. In recent years, there has been an increasing interest in the use of computed tomographic (CT) angiography in the diagnostic evaluation of patients with suspected PE. Although there are unresolved issues regarding its sensitivity in detecting small peripheral emboli, CT angiography is more accurate than V-P scanning in the diagnosis of PE and yields other intrathoracic diagnoses. Herein we summarize the problems with the traditional approach centered on the use of V-P scanning in the diagnosis of PE and propose an alternative diagnostic strategy based primarily on the use of CT angiography.

Sleep apnea in heart transplant recipients: type, symptoms, risk factors, and response to nasal continuous positive airway pressure.

BACKGROUND: We determined the type, symptoms, and risk factors for sleep apnea in heart transplant recipients and the response to nasal continuous positive airway pressure. METHODS: A retrospective study on heart transplant recipients with sleep apnea was conducted in a tertiary care medical center with follow-up telephone interviews. Between February 1988 and August 1998, 147 patients underwent orthotopic heart transplantation at our institution. Seventeen patients (11.6%) who were suspected of having sleep apnea underwent polysomnography at a mean interval of 17.5 months after transplantation. RESULTS: All were diagnosed with sleep apnea: 13 had obstructive sleep apnea and 4 had mixed sleep apnea. Mean age at polysomnography was 50.8 years (range, 24-67 years). The patients presented with snoring (100%), excessive daytime somnolence (65%), witnessed apneas (53%), and morning fatigue (53%). Sixteen (94%) had a mean weight gain of 10.4 kg after transplantation, and 1 patient lost 14.6 kg. In the 11 patients with obstructive sleep apnea who underwent nasal continuous positive airway pressure titration, significant improvements occurred in the apnea-hypopnea index (decreased from 37.6 to 10.4; p = 0.01) and mean arousal index (decreased from 44.5 to 19.4; p = 0.01). Only 2 of the 8 patients with sleep apnea for whom nasal continuous positive airway pressure was recommended continued to use it at the time of telephone follow-up. CONCLUSIONS: Sleep apnea, especially obstructive sleep apnea, occurs frequently in heart transplant recipients. Obstructive sleep apnea appears to present in the typical manner, and although a positive response to nasal continuous positive airway pressure can be documented by polysomnography, long-term use of nasal continuous positive airway pressure may be low.

The tibiofibular syndesmosis. Evaluation of the ligamentous structures, methods of fixation, and radiographic assessment.

Twenty-five fresh-frozen cadaveric specimens were used to evaluate the role of the syndesmotic ligaments when the ankle is loaded with external rotation torque. An apparatus was constructed that allowed pure external-rotation torque to be applied through the ankle with the foot in neutral flexion. The apparatus provided solid fixation of the tibia while allowing free movement of the fibula in all planes. The syndesmotic ligaments were incrementally sectioned, and direct measurements of anatomical diastasis were made. Mortise and lateral radiographs were made at each increment under both loaded (5.0 newton-meters) and unloaded conditions. After all structures of the syndesmosis had been divided, the syndesmosis was reduced and was repaired with one or two screws. The strength of the repair was measured with incremental increases in torque of 1.0 newton-meter. The radiographs were measured by three independent observers in a blind fashion. In order to evaluate intraobserver error, each observer was randomly given forty radiographs to reinterpret. Diastasis and rotation were found to be related to the amount of injury of the ligament (p < 0.0001). After the entire syndesmosis had been divided, application of a 5.0-newton-meter torque resulted in a mean diastasis of 7.3 millimeters. The subsequent repair of the anterior tibiofibular ligament with suture failed at a mean of 2.0 newton-meters (range, 1.0 to 6.0 newton-meters) of torque. Repair with two screws was found to be stronger than repair with one, with the first construct failing at a mean of 11.0 newton-meters (range, 5.0 to 15.0 newton-meters) and the second, at a mean of 6.2 newton-meters (range, 2.0 to 10.0 newton-meters) (p = 0.0005). Failure of the screw fixation was not associated with the maximum previous diastasis (p = 0.13). Measurements of anatomical diastasis were compared with measurements made on the mortise and lateral radiographs. Measurements on the stress mortise radiographs had a weak correlation with diastasis (r = 0.41, p < 0.0001). However, measurements on the stress lateral radiographs had a higher correlation (r = 0.81, p < 0.0001). Additionally, interobserver correlation was significantly higher for the measurements on the lateral radiographs (r = 0.87, p < 0.0001) than for those on the mortise radiographs (r = 0.56, p < 0.0001). Intraobserver correlation for the three observers was poor with regard to the measurements on the mortise radiographs (r = 0.12, 0.42, and 0.25). The respective correlations for the measurements on the lateral radiographs were r = 0.81, 0.90, and 0.89.(ABSTRACT TRUNCATED AT 400 WORDS)

Tendon-healing to cortical bone compared with healing to a cancellous trough. A biomechanical and histological evaluation in goats.

This study was performed to test the hypothesis that attaching a tendon to a trough in cancellous bone results in tendon-healing that is biomechanically superior to that after direct fixation of a tendon to cortical bone. Twenty adult female goats were treated with a bilateral tenotomy of the infraspinatus tendon with subsequent reattachment of the tendon. In shoulders randomized to the cancellous-fixation group, a cancellous bed was prepared with a motorized burr and a template measuring twenty by five by five millimeters. The repair in the shoulders randomized to the cortical-fixation group was performed in the same manner, except that the tendon was attached to cortical bone. Three outcome measures were assessed, six and twelve weeks after the repair, with the Student paired t test and analysis of variance: load to failure, energy to failure, and stiffness. The types of repair were not significantly different with regard to any of the three outcomes. When the six and twelve-week data were combined, an average difference in load to failure of 3.9 per cent in favor of cancellous repair was observed but it was not significant (p = 0.78). The associated 95 per cent confidence interval for the difference ranged from 10.5 per cent in favor of cortical repair to 18.3 per cent in favor of cancellous repair. Histological analysis at six and twelve weeks revealed progressive maturation and reorganization of the bone-tendon interface with re-establishment of collagen-fiber continuity between the tendon and bone. This process was indistinguishable between the cortical and cancellous specimens. This study demonstrated no significant benefit from the creation of a trough to expose the tendon to cancellous bone. In this model, at both six and twelve weeks, the tendon-to-bone healing process of the two groups appeared similar and the biomechanical properties were approximately equal.

Vertebral column allografts for the treatment of segmental spine defects. An experimental investigation in dogs.

Vertebral column allografts, with their intervertebral discs, were implanted into thoracic spine defects (T7-T9) in 11 dogs in an attempt to re-establish spinal stability and preserve spinal biomechanics. Before implantation, the allografts were harvested under sterile conditions from similar-sized dogs and deep frozen at -80 C. The animals were followed for 18 months postoperatively. Radiographs demonstrated gradual loss of intervertebral disc height. Biomechanical analysis showed that the dogs with allografts had no significant difference in spine stiffness compared with normal spines in compression, flexion, and extension testing. Control spines that had been fused were significantly stiffer than the allograft spines in all modes tested (P less than 0.05). Histologic analysis showed incorporation of the allograft but with incomplete revascularization of the allograft's eighth thoracic body. This investigation found that vertebral body allografts with intervertebral discs can function successfully for 18 months in a canine model. This research may assist in the development of physiologic treatment for spinal deficiencies in humans.

The biochemical and histological effects of artificial ligament wear particles: in vitro and in vivo studies.

Growing evidence suggests that biochemical mechanisms play a role in the pathogenesis of arthritis. Cartilaginous wear particles have been shown to induce destructive enzymes and cytokines. To assess the biocompatibility of artificial ACL replacements, the effects of wear particles from the following ligaments were analyzed biochemically and histologically: GORETEX, Stryker Dacron Ligament Prosthesis, Versigraft carbon, Kennedy LAD, Xenograft, Leeds-Keio, and human patellar tendon allograft. Ligaments were frozen and ground to produce wear particles similar to those seen clinically and were added to lapine synovial cell cultures. The resulting conditioned medium was analyzed for collagenase, gelatinase, and chondrocyte activating factor (CAF) production. All of the ligaments induced significantly elevated enzyme and CAF production by the synoviocytes, with Xenograft and carbon inducing significantly higher enzyme levels than those of the other five ligaments. Five milligrams of wear particles were injected into the knees of 4 kg to 5 kg rabbits that were analyzed histologically after 14 weeks. Wear particles accumulated in the periarticular synovial folds and induced modest to severe macrophage infiltration in the synovium. A hypothetical model explaining the role of artificial ligament wear particles in the pathogenesis of arthritis is presented.

Ultrastructural and lectin-histochemical differences between the scolex/strobila and bladder teguments of the Taenia taeniaeformis strobilocercus.

The strobilocercus stage of the cat tapeworm Taenia taeniaeformis is surrounded by a single syncytial sheet of cytoplasm called the tegument. The outer membrane of the tegument covers both the scolex/strobila (S/S) and the bladder portions of the strobilocercus, but only the S/S region is resistant to intestinal digestion. It has been suggested that the glycocalyx, the surface-exposed glycoconjugates of the outer membrane, may serve to insulate underlying surface membrane components from digestion. In this study, we used lectin binding to test the hypothesis that the glycocalyx of the S/S is different from that of the bladder and that this may serve as the resistance mechanism of the S/S to digestion. Biotin-labeled lectins and an avidin-glucose oxidase detection system were applied to whole strobilocerci and to 1-microm epon-araldite plastic-embedded sections. Lectins bound to either both regions of the strobilocerci, to the S/S regions only, or did not bind at all. The restriction of some glycoconjugates to the glycocalyx of the S/S region only is consistent with our hypothesis.

The distribution of copper in sickling erythrocytes as determined by an IBM cell separator.

Elevated levels of copper have been found in sickling erythrocytes. Since this copper may inhibit sickling or induce hemolysis the authors decided to investigate the distribution of copper in sickling erythrocytes to gain some insight into its origin. When samples of sickling erythrocytes were fractionated by density gradient centrifugation with an IBM cell separator and the fractions analyzed for copper, it was found that the copper to hemoglobin ratio of the different fractions varied several fold. This finding indicated that the copper in sickling erythrocytes did not equilibrate with the copper in serum or other cells and that the copper was present in the cells when they were released into the blood stream. When erythrocytes were obtained from a sickle cell patient four days post-crises, a large amount of residual copper could be observed in the first (youngest) fraction. It was suspected that this copper was in mitochondrial residues. It was also observed that copper levels tended to be higher in control and sicklings erythrocytes during the winter months. The predominance of the first fraction in samples of sickling erythrocytes taken during the winter months suggests that the turnover of sickling erythrocytes is accelerated at this time.

Effects of an allicin-based product on cryptosporidiosis in neonatal calves.

OBJECTIVE: To evaluate effectiveness of an allicin-based product in neonatal calves inoculated with Cryptosporidium parvum. DESIGN: Randomized controlled study. ANIMALS: 43 neonatal calves. PROCEDURE: Calves were inoculated with 1.5 x 10(8) or 7.5 x 10(5) C parvum oocysts within 2 days after birth. Calves were given an allicin-based product once after inoculation or daily for 7 days after inoculation or were not treated. Calves that developed diarrhea were treated by administration of the product. Fecal consistency scores and weight gains were statistically evaluated. RESULTS: Mean daily weight gain and severity of diarrhea in calves 4 to 21 days old were unaffected by prophylactic use of the product. However, intensive prophylactic administration may have delayed onset of C parvum-induced diarrhea in calves inoculated with the lower dose of oocysts. CLINICAL IMPLICATIONS: Administration of an allicin-based product did not alter duration of C parvum-induced diarrhea or enhance weight gain in neonatal calves. However, intensive prophylactic administration of an allicin-based product may delay onset of diarrhea in calves exposed to C parvum oocysts.

No room at the inn: a snapshot of an American emergency room.

The emergency rooms of American hospitals have frequently become the principal suppliers of nonurgent primary care to the under- and uninsured. Canvassing published reports and using original data obtained from a representative urban hospital, Erik Olson examines the demographics of the American emergency room and analyzes its finances. The costs of providing primary care are shifted, to the extent possible, to those who can pay. The result is escalating health care costs and a deterioration of quality of care due to overcrowding, leading some hospitals to close their emergency rooms and others to turn away ambulances or "dump" patients who still require critical care. Mr. Olson explains that state antidumping laws and the federal COBRA statute have been ineffective at stemming these practices in the face of severe economic pressure to continue them. Pointing out that emergency rooms are an excessively expensive method of treating uninsured nonemergency patients, he proposes a system of primary care clinics created through a public/private partnership between municipalities and existing private health care providers. The partnership is designed to maintain a high standard of care at the clinics. As an incentive to stimulate the appearance of such clinics, a tax would be imposed on private health care providers; the tax on a given provider would be reduced to the extent that provider subsidizes a local primary care clinic that offers universal coverage, regardless of insurance status. Because the existence of such clinics would reduce inefficient use of hospital emergency rooms, in the long run hospitals should find it less expensive to finance local primary care clinics than to continue to sustain unreimbursed expenses due to improper use of their emergency departments.