Continuous regional anaesthesia provides effective pain management and reduces opioid requirement following major lower limb amputation.

OBJECTIVES: Postoperative stump pain after major lower limb amputation is a significant impediment to the recovery of amputees. The vast majority of patients require opioid analgesics following surgery, which are associated with opioid-related side-effects. Here, we investigate whether intraoperative placement of a peripheral nerve stump catheter followed by continuous infusion of local anesthetic is as effective at pain control as current analgesic practices. If beneficial, this procedure could potentially reduce post-amputation opioid consumption and opioid-related adverse effects. METHODS: A retrospective chart review was conducted of 198 patients over a 4-year period who had undergone a major lower limb amputation for indications related to peripheral vascular disease. Postoperatively, 102 patients received a perineural catheter were compared to 96 patients who did not. The primary outcomes of this study were the amount of morphine equivalents used in the first 72 hours postoperatively and postoperative pain intensity in the first 24 hours. RESULTS: A total of 198 lower-limb amputations were selected for analyses. Multiple regression analyses indicated that perineural catheter use was associated with a lower cumulative postoperative opioid consumption over the first 72 hours but not postoperative pain scores at 24 hours. Perineural catheter use led to a 40% reduction in opioid use during the first 72 hours postoperatively. Mixed model repeated measures analysis demonstrated that this opioid reduction was consistent over time. Other variables related to total opioid use included age, pre-surgical chronic pain, pre-surgical opioid use, patient-controlled analgesia. CONCLUSIONS: Continuous perineural infusions of local anesthetic are a safe and effective method for reducing post-amputation opioid analgesic medications after major lower limp amputation.

Improving phylogenetic resolution of the Lamiales using the complete plastome sequences of six Penstemon species.

The North American endemic genus Penstemon (Mitchell) has a recent geologic origin of ca. 3.6 million years ago (MYA) during the Pliocene/Pleistocene transition and has undergone a rapid adaptive evolutionary radiation with ca. 285 species of perennial forbs and sub-shrubs. Penstemon is divided into six subgenera occupying all North American habitats including the Arctic tundra, Central American tropical forests, alpine meadows, arid deserts, and temperate grasslands. Due to the rapid rate of diversification and speciation, previous phylogenetic studies using individual and concatenated chloroplast sequences have failed to resolve many polytomic clades. We investigated the efficacy of utilizing the plastid genomes (plastomes) of 29 species in the Lamiales order, including five newly sequenced Penstemon plastomes, for analyzing phylogenetic relationships and resolving problematic clades. We compared whole-plastome based phylogenies to phylogenies based on individual gene sequences (matK, ndhF, psaA, psbA, rbcL, rpoC2, and rps2) and concatenated sequences. We also We found that our whole-plastome based phylogeny had higher nodal support than all other phylogenies, which suggests that it provides greater accuracy in describing the hierarchal relationships among taxa as compared to other methods. We found that the genus Penstemon forms a monophyletic clade sister to, but separate from, the Old World taxa of the Plantaginaceae family included in our study. Our whole-plastome based phylogeny also supports the rearrangement of the Scrophulariaceae family and improves resolution of major clades and genera of the Lamiales.

The natural history of encephalomyocarditis virus-induced myositis and myocarditis in mice. Viral persistence demonstrated by in situ hybridization.

Picornaviruses can initiate chronic inflammation that persists after the virus can no longer be cultured from inflamed tissues. In an attempt to understand this transition we have sought evidence for viral persistence by methods that detect viral genome independent of whether or not whole competent virus is present. In mice infected with a myotropic variant of encephalomyocarditis virus, EMC-221A, virus can be cultured in high yield at 1 wk and in low yield at 2 wk from skeletal muscle, heart, and brain; a small number of plaque-forming units could be cultured from brain at 4 wk. By contrast, in situ hybridization detected viral nucleic acid at least a week or two thereafter, often in single cells. In the skeletal muscle, inflammation disappeared by 3 wk, but in heart it remained for the full 12 wk of observation. In the brain, microglial nodules, sometimes with associated viral nucleic acid, were present for a long period. Application of this technique allows a more accurate assessment of the role of viral persistence in the pathogenesis of virus-initiated but apparently autoimmune inflammation.

Electromagnetic Separation of Isotopes at Oak Ridge: An informal account of history, techniques, and accomplishments.

In 1960 I attended a European conference on isotope separation, after which I visited the Niels Bohr Institute in Copenhagen. A staff member there ventured the opinion that the separation of isotopes will be first on the list of important contributions to the peaceful uses of the atom when the Atomic Energy Commission's memoirs are written in the year 2000. In 1968 the AEC Division of Research contracted with the National Research Council of the National Academy of Sciences to conduct a review of the AEC program for the separation of stable isotopes by electromagnetic and thermal diffusion methods. This ad hoc panel comprised seven scientists from the fields of chemistry, classical physics, geochemistry, geophysics, medicine, and physics. In their final report on national uses and needs for separated stable isotopes (9), they referred to the store of separated isotopes as a "real national asset that attains increasing value as science and technology develop" and recommended "continuation of the program as a national resource of great value to the United States." Later, in a discussion of this report with A. M. Weinberg, J. Koch, himself a pioneer in electromagnetic isotope separation and member of the Danish Atomic Energy Program, said he would correct the statement that the Oak Ridge electromagnetic facility is a "national asset" to read "international asset." From my narrow viewpoint after an extended and complete engrossment with this program for so many years, it is gratifying to learn that such men as those mentioned above share my belief that the work has indeed been worthwhile.

Transport of equine ovaries for assisted reproduction.

Use of assisted reproduction to obtain foals from valuable mares post-mortem typically necessitates holding of ovaries during shipment to a laboratory. The present study evaluated whether holding ovaries briefly at a warm ( approximately 30 degrees C) temperature improves meiotic and developmental competence of oocytes, as determined after maturation in vitro and intracytoplasmic sperm injection. Ovaries were packaged in pairs in insulated containers, and held either at 24 or 25-35 degrees C for 4h, followed by cooling. Ovaries in both treatments were held for either a short (mean, 7-7.4h) or long (mean, 20.6-20.7h) duration before oocyte recovery. Control ovaries were collected en masse at the abattoir. The ovary temperature in this treatment slowly decreased to approximately 27 degrees C; oocyte recovery was performed after 3.5-7h total holding. There was no effect of temperature on oocyte meiotic or developmental competence within either treatment time period. Oocytes in the short duration holding group had similar meiotic competence to controls, but had a significantly decreased rate (P<0.05) of blastocyst development. Oocytes in the long duration holding group had decreased (P<0.05) meiotic competence and blastocyst development compared to controls. These findings indicate that storage of equine ovaries for only 7h may decrease blastocyst development, and that longer storage reduces both rate of oocyte maturation and blastocyst development. Further work is needed to determine if there is a critical time before 7h post-mortem by which equine oocytes should be recovered to maximize developmental competence.

Holding bovine oocytes in the absence of maturation inhibitors: kinetics of in vitro maturation and effect on blastocyst development after in vitro fertilization.

Holding immature oocytes before maturation simplifies the transport of oocytes and aids in scheduling later manipulations. We examined the effect of holding bovine oocytes in the absence of meiotic inhibitors on their subsequent meiotic and developmental competence. Oocytes were matured immediately after recovery (control) or were held in a mixture of 40% TCM 199 with Earle's salts, 40% TCM 199 with Hanks' salts, and 20% FBS, at room temperature for 16 to 18 h (EH-held) and then matured. Chromatin status was determined at 0, 10, 14, 18, and 22 h of maturation culture. Oocytes were fertilized in vitro after either 18 or 22-24h maturation. The EH treatment maintained oocytes at the germinal vesicle stage (79.3%, vs. 87.7% for control oocytes at 0 h; P>0.05). Upon culture, held oocytes matured more quickly than did control oocytes. The proportions of mature oocytes were not significantly different between groups at 18 h (EH-held, 80.6% and control, 79.3%); however, after 22 h significantly more EH-held than control oocytes had degenerated (24.1% vs. 4.5%, P<0.0001). Blastocyst development was similar between groups for oocytes fertilized after 18 h maturation (EH-held, 29.6% and control, 27.8%). When oocytes were fertilized after 22-24h maturation, EH-held oocytes yielded lower blastocyst development than did control oocytes (16.5% vs. 29.3%, P<0.05). In conclusion, bovine oocytes may be effectively held in the EH treatment before maturation without adversely affecting meiotic or developmental competence. However, holding affects the kinetics of maturation and this must be taken into account when subsequent manipulations are performed.

Pathological and immunological effects of ingesting L-tryptophan and 1,1'-ethylidenebis (L-tryptophan) in Lewis rats.

The eosinophilia-myalgia syndrome (EMS) has been associated with ingestion of L-tryptophan (L-TRP) produced by a single manufacturer. Epidemiological data implicated 1,1'-ethylidenebis (L-tryptophan) (EBT) (peak 97 or peak E) as a possible etiologic agent. We showed previously that Lewis rats treated with the L-TRP implicated in EMS develop fasciitis and perimyositis similar to those seen in human EMS. We now report the pathology associated with the treatment of Lewis rats with synthetic EBT and/or L-TRP. All animals treated for 6 wk with case-associated L-TRP or EBT developed significant myofascial thickening, compared with animals in the vehicle control and control L-TRP groups. However, even those animals receiving the control L-TRP showed a mild but significant increase in the thickness of the myofascia, compared with vehicle-treated control animals. All animals except vehicle controls also exhibited significant pancreatic pathology, including fibrosis and acinar changes. Only animals treated with case-associated L-TRP for 6 wk showed evidence of immune activation with increased frequency of CD8, Ia, and IL-2 receptor-positive cells in the peripheral blood. Animals receiving L-TRP or EBT for < 6 wk did not show significant differences in myofascial thickness, although these animals did show pancreatic acinar changes. Although these results demonstrate for the first time the pathological effects of EBT, they do not rule out the possibility that other impurities in the EMS-case-associated L-TRP may also contribute to some of the features of EMS.

Teaching teamwork during the Neonatal Resuscitation Program: a randomized trial.

OBJECTIVE: To add a team training and human error curriculum to the Neonatal Resuscitation Program (NRP) and measure its effect on teamwork. We hypothesized that teams that received the new course would exhibit more teamwork behaviors than those in the standard NRP course. STUDY DESIGN: Interns were randomized to receive NRP with team training or standard NRP, then video recorded when they performed simulated resuscitations at the end of the day-long course. Outcomes were assessed by observers blinded to study arm allocation and included the frequency or duration of six team behaviors: inquiry, information sharing, assertion, evaluation of plans, workload management and vigilance. RESULT: The interns in the NRP with team training group exhibited more frequent team behaviors (number of episodes per minute (95% CI)) than interns in the control group: information sharing 1.06 (0.24, 1.17) vs 0.13 (0.00, 0.43); inquiry 0.35 (0.11, 0.42) vs 0.09 (0.00, 0.10); assertion 1.80 (1.21, 2.25) vs 0.64 (0.26, 0.91); and any team behavior 3.34 (2.26, 4.11) vs 1.03 (0.48, 1.30) (P-values <0.008 for all comparisons). Vigilance and workload management were practiced throughout the entire simulated code by nearly all the teams in the NRP with team training group (100% for vigilance and 88% for workload management) vs only 53 and 20% of the teams in the standard NRP. No difference was detected in the frequency of evaluation of plans. CONCLUSION: Compared with the standard NRP, NRP with a teamwork and human error curriculum led interns to exhibit more team behaviors during simulated resuscitations.

Effect of holding technique and culture drop size in individual or group culture on blastocyst development after ICSI of equine oocytes with low meiotic competence.

The effect of medium-to-embryo ratio on blastocyst development of equine embryos from oocytes with compact cumuli was evaluated in the present experiment. In addition, two methods for holding oocytes before in vitro maturation were compared. In Experiment 1, oocytes cultured with roscovitine for 16-18h before maturation were fertilized by intracytoplasmic sperm injection and cultured individually in 2.5, 5, 10 or 50microl droplets. In Experiment 2, oocytes were either cultured with roscovitine or held in a modified M199 with 20% serum at room temperature (EH treatment) for 16-18h, then matured, fertilized and cultured in groups at 5microl medium per embryo. In Experiment 3, oocytes were held in the EH treatment, then were matured and fertilized. In Study 3.1, injected oocytes were cultured individually in drop sizes as for Experiment 1; in Study 3.2, groups of 2-7 oocytes were cultured in fixed drop sizes of 5 or 50microl. Blastocyst development rates of individually-cultured embryos were not significantly different among drop sizes in either Experiment 1 or 3 (15-29%). In Experiment 2, blastocyst rates were not significantly different between holding treatments (17-23%). In Experiment 3, for group-cultured oocytes, blastocyst development was not significantly different between 5 and 50microl drops (39 and 27%, respectively). In conclusion, compact-cumulus oocytes may be effectively held in the EH treatment before maturation, and single culture of equine embryos yields acceptable blastocyst development. The greatest blastocyst rate (39%) was obtained with group culture in a 5microl droplet.

Holding immature equine oocytes in the absence of meiotic inhibitors: effect on germinal vesicle chromatin and blastocyst development after intracytoplasmic sperm injection.

Holding immature oocytes before the onset of maturation simplifies oocyte transport and aids in scheduling later manipulations. We report here a method for holding equine oocytes in the absence of meiotic inhibitors. In Experiment 1, immature oocytes with expanded cumuli were cultured at 38.2 degrees C in medium containing cycloheximide, or were held at room-temperature in M199 with Hanks' salts, for 16-18 h before maturation. Control oocytes were matured immediately after recovery. Oocytes were fertilized by intracytoplasmic sperm injection and cultured for 4d. Embryo development was not different among treatments. In Experiment 2, oocytes were treated as in Experiment 1, but embryos were cultured for 7.5d. Blastocyst development was significantly lower in the cycloheximide-treated group than in controls (7% versus 30%) with the room-temperature group intermediate (16%). In Experiment 3, oocytes were cultured at 38.2 degrees C in medium containing roscovitine, or were held at room temperature in sealed glass vials in a mixture of 40% M199 with Earle's salts, 40% M199 with Hanks' salts, and 20% FBS (EH treatment) for 16-18 h, before maturation, sperm injection, and embryo culture for 7.5d. Blastocyst development of oocytes in the EH treatment was significantly higher than that for roscovitine-treated oocytes (34% versus 12%), but not significantly different from that for controls (25%). Oocytes in the EH treatment did not mature during holding (70% germinal vesicle stage after 18 h holding). Whereas culture with cycloheximide or roscovitine of equine oocytes with expanded cumuli reduced subsequent blastocyst formation, these oocytes could be held in a modified M199 at room temperature overnight without adverse affecting meiotic or developmental competence.

Effect of intestinal microflora suppression on liver carcinogenicity of dimethylnitrosamine in Syrian hamsters.

Liver tumors induced by dimethylnitrosamine showed an increased incidence in Syrian hamsters with intestinal microflora suppressed by antibiotics, as compared with the incidence in animals not treated with antibiotics. The possible mechanisms, including metabolic alterations caused by changes in the normal microflora population, were discussed.

Chaparral-associated hepatotoxicity.

BACKGROUND: Personal health care practices that may include the use of dietary supplements are common in the United States. Products marketed as dietary supplements are diverse and may include botanicals, vitamins, and/or minerals. Chaparral (Larrea tridentata) is a botanical dietary supplement made from a desert shrub and used for its antioxidant properties. Several reports of chaparral-associated hepatitis have been published since 1990, but a complete picture of the clinical presentation is still unclear. MATERIALS AND METHODS: We reviewed the 18 case reports of adverse events associated with the ingestion of chaparral reported to the Food and Drug Administration between 1992 and 1994. These reports were from health care professionals, state health departments, and individual consumers. RESULTS: Of 18 reports of illnesses associated with the ingestion of chaparral, there was evidence of hepatotoxicity in 13 cases. Clinical presentation, characterized as jaundice with a marked increase in serum liver chemistry values, occurred 3 to 52 weeks after the ingestion of chaparral, and it resolved 1 to 17 weeks after most individuals stopped their intake of chaparral. The predominant pattern of liver injury was characterized as toxic or drug-induced cholestatic hepatitis; in 4 individuals, there was progression to cirrhosis; and in 2 individuals, there was acute fulminant liver failure that required liver transplants. CONCLUSIONS: These data indicate that the use of chaparral may be associated with acute to chronic irreversible liver damage with fulminant hepatic failure, and they underscore the potential for certain dietary supplement ingredients to cause toxic effects on the liver. Health professionals should be encouraged to inquire routinely about the use of dietary supplements and other products, to be alert to potential adverse effects that may be associated with these products, and, finally, to report any serious adverse events associated with these products through the MEDWatch Program of the Food and Drug Administration.

A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define useful homogeneous patient groups.

The IIM are a heterogeneous group of systemic rheumatic diseases which share the common features of chronic muscle weakness and mononuclear cell infiltrates in muscle. A number of classification schemes have been proposed for them, but none takes into consideration the marked immunologic, clinical, and genetic heterogeneity of the various clinical groups. We compared the usefulness of myositis-specific autoantibodies (anti-aminoacyl-tRNA synthetases, anti-SRP, anti-Mi-2 and anti-MAS) to the standard clinical categories (polymyositis, dermatomyositis, overlap myositis, cancer-associated myositis, and inclusion body myositis) in predicting clinical signs and symptoms, HLA types, and prognosis in 212 adult IIM patients. Although patients with inclusion body myositis (n = 26) differed in having significantly more asymmetric and distal weakness, falling, and atrophy than other patients, there were few other significant differences among the other clinical groups. In contrast, autoantibody status defined distinct sets of patients and each patient had only 1 myositis-specific autoantibody. Patients with anti-amino-acyl-tRNA synthetase autoantibodies (n = 47), compared to those without these antibodies, had significantly more frequent arthritis, fever, interstitial lung disease, and "mechanic's hands"; HLA-DRw52; higher mean prednisone dose at survey, higher proportion of patients receiving cytotoxic drugs, and higher death rates. Those with anti-signal recognition particle antibodies (n = 7) had increased palpitations; myalgias; DR5, DRw52; severe, refractory disease; and higher death rates. Patients with anti-Mi-2 antibodies (n = 10) had increased "V-sign" and "shawl-sign" rashes, and cuticular overgrowth; DR7 and DRw53; and a good response to therapy. The 2 patients with anti-MAS antibodies were the only ones with alcoholic rhabdomyolysis preceding myositis; both had insulin-dependent diabetes mellitus, and both had HLA-B60, -C3, -DR4, and -DRw53. These findings suggest that myositis-specific autoantibody status is a more useful guide than clinical group in assessing patients with myositis, and that specific associations of immunogenetics, immune responses, and clinical manifestations occur in IIM. Thus the myositis-specific autoantibodies aid in interpreting the diverse symptoms and signs of myositis patients and in predicting their clinical course and prognosis. We propose, therefore, that an adjunct classification of the IIM, based on the myositis-specific autoantibody status, be incorporated into future studies of their epidemiology, etiology, and therapy.

Improved prognosis for granulocytopenic patients with gram-negative bacteremia.

The grave prognosis associated with gram-negative bacteremia occurring in granulocytopenic patients with cancer suggests that granulocyte transfusions are frequently indicated. We have evaluated 67 episodes of gram-negative bacteremia, studied in four consecutive antibiotic trials, in order to correlate prognostic determinants of recovery. These patients had a median absolute granulocyte count of 100/microliter at the time of bacteremia. Empiric antibiotic regimens were begun at the first evidence of suspected infection. Granulocyte transfusions were employed only as clinically indicated by inadequate patient response to antibiotic therapy. Among the 29 patients who had an increase in their granulocyte count of greater than or equal to 100/microliter over the subsequent 14 days, 27 (93 per cent) recovered whereas among 38 patients who had no appreciable increase in their granulocyte count, 21 (55 per cent) improved (p = 0.006). In this latter group of patients with no granulocyte recovery, the susceptibility of the pathogen(s) to the initial empiric antibiotic regimen was of major importance. None of four patients responded when the pathogen was resistant to both antibiotics initially utilized, six of 14 (44 per cent) patients responded when there was susceptibility to one antibiotic, and 15 of 20 (75 per cent) patients responded when there was susceptibility to both antibiotics (p less than 0.025). We conclude that patients with gram-negative bacteremia and persistent granulocytopenia will often respond to antimicrobial therapy alone provided the initial choice of empiric antibiotics is appropriate and that their use is instituted promptly. Granulocyte transfusions need not be added unless clinical evaluation indicates inadequate response.

Randomized trial of empiric antibiotic therapy with ticarcillin in combination with gentamicin, amikacin or netilmicin in febrile patients with granulocytopenia and cancer.

A randomized trial of ticarcillin plus gentamicin (group 1), ticarcillin plus amikacin (group 2) and ticarcillin plus netilmicin (group 3) as empiric antibiotic therapy in patients with granulocytopenia and cancer was carried out at the Baltimore Cancer Research Center. The response rate for all infections was 97 per cent in group 1, 91 per cent in group 2 and 95 per cent in group 3. Patients with bacteremias showed improvement in 93 per cent (group 1), 78 per cent (group 2) and 82 per cent (group 3) of cases. All failures were among patients with gram-negative bacteremias. Both antibiotic susceptibility of the bacteremic organism and granulocyte recovery correlated with patient improvement. Nephrotoxicity and ototoxicity were rare and were not significantly different in three groups of patients. Therefore, ticarcillin plus gentamicin, ticarcillin plus amikacin and ticarcillin plus netilmicin appear to be equally efficacious and minimally toxic in this patient population. Excellent over-all results can be expected with these combinations provided the etiologic agent is susceptible.

Drug therapy of the idiopathic inflammatory myopathies: predictors of response to prednisone, azathioprine, and methotrexate and a comparison of their efficacy.

PURPOSE: To identify factors associated with responses to treatment with prednisone, methotrexate, or azathioprine in patients with idiopathic inflammatory myopathy, and to compare the efficacy of these drugs. PATIENTS AND METHODS: Data were collected on 113 adult patients meeting criteria for definite idiopathic inflammatory myopathy in this retrospective cohort study. Patients were categorized as responding completely, partially, or not at all to each therapeutic trial based upon clinical and laboratory criteria. RESULTS: Clinical group, presence of certain myositis-specific autoantibodies, and time from disease onset to diagnosis influenced rates of complete clinical response to these therapeutic agents. Patients with inclusion body myositis responded comparatively poorly to prednisone and the other drugs: 43% had no clinical response to prednisone and none responded completely to any medication. Patients with autoantibodies to aminoacyl-tRNA synthetases or to signal recognition particle proteins were likely to respond partially, but not completely, to prednisone. No patient with a long delay to diagnosis (greater than 18 months) responded completely, compared with 34% of those with a short delay (less than 3 months). A patient's response to the first course of prednisone predicted subsequent responses to prednisone and to azathioprine better than response to methotrexate. Men responded to methotrexate better than women. Among certain subgroups of patients, responses to methotrexate were better than to either azathioprine or retreatment with prednisone. CONCLUSION: Determining the clinical group, autoantibody status, and time from disease onset to diagnosis of patients with myositis provides useful information in predicting clinical responses to therapy, and these factors should be considered in designing future therapeutic trials. Methotrexate therapy may be superior to either azathioprine or further steroid treatment alone in certain patients who do not respond completely to an initial adequate course of prednisone.

Quantitation of fluorescence fading phenomena for identifying intracellular biopolymers.

The fading behavior of the 670 nm fluorescence emission band produced by unfixed rat mast cells stained with acridine orange (AO) has been found to be in excellent agreement with the behavior predicted by second order chemical kinetics. The reciprocal of fluorescence intensity plotted against time yields a straight line. When due account is taken of dye/cell ratio and the intensity of fluorescence-exciting radiation, Io (measured with the standard phosphor particle), the slope of this straight line is a constant, k'', which is independent of dye/cell ratio and Io. k'' differs from the second order photochemical rate constant by a constant factor. The fading of a given AO-biopolymer complex is described by a particular value of k''. Two values of k'' have been found for rat mast cell granules, indicating the presence of two different AO-biopolymer complexes. Fading of fluorescence may serve to identify particular intracellular biopolymers in individual cells even when present in a heterogeneous population.

Lymphocyte fluorescent profiles (LFP): a possible screening technique in neoplasia.

A technique involving fluorescent protein staining and microfluorometry has been developed for measuring the lymphocyte fluorescent profile (LFP) of peripheral blood lymphocytes. In contrast to normal humans who display a regular bell-shaped curve, the profile from patients with cancer is irregular, showing a bimodal distribution of fluorescence, with a significant population of cells fluorescing at a higher relative intensity. It is suggested that this elevation in protein concentration is due to an immune response to the presence of a neoplasm, and thus this technique may prove to be a useful indicator of malignancy.

Energy expenditure in obstructive sleep apnea.

Patients with obstructive sleep apnea (OSA) are often obese and, in common with obese patients generally, find it difficult to lose weight. Obstructive sleep apnea may be associated with changes in total daily energy expenditure that could contribute to obesity and complicate its management. To determine whether resting metabolic rate and the thermogenic effect of food are reduced in OSA, we have compared postabsorptive resting energy expenditure (REE) and dietary thermogenesis (DT) in 14 patients with moderate to severe symptomatic OSA and 14 control subjects matched for obesity. Anthropometrics, body composition analysis using bioelectrical impedance and indirect calorimetry using a metabolic cart and canopy system were performed in all subjects. Dietary thermogenesis after a liquid meal equivalent to 35% of REE was measured in 13 patients and 8 control subjects. Measurements were repeated after chronic (mean +/- SD 12 +/- 5 weeks) nasal continuous positive airway pressure (CPAP) therapy in 10 patients with OSA. Energy expenditure was expressed in terms of metabolic body size. The patients with OSA were heavier and had larger necks and a larger lean body mass (LBM) than controls, but the two groups were well matched for body mass index (BMI) and percent body fat. REE was greater in OSA patients than controls, but when corrected for LBM there was no difference between the two groups (27 +/- 3 vs. 28 +/- 4 kcal/kg). DT was similar in patients and controls (17 +/- 6 vs. 15 +/- 10%). REE/LBM was quite consistent among patients with OSA, regardless of body weight. REE and DT did not change following chronic nasal CPAP therapy. (ABSTRACT TRUNCATED AT 250 WORDS)