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Carboxysomes are organelle-like polyhedral bodies found in cyanobacteria and many chemoautotrophic bacteria that are thought to facilitate carbon fixation. Carboxysomes are bounded by a proteinaceous outer shell and filled with ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO), the first enzyme in the CO(2) fixation pathway, but exactly how they enhance carbon fixation is unclear. Here we report the three-dimensional structure of purified carboxysomes from Synechococcus species strain WH8102 as revealed by electron cryotomography. We found that while the sizes of individual carboxysomes in this organism varied from 114 nm to 137 nm, surprisingly, all were approximately icosahedral. There were on average approximately 250 RuBisCOs per carboxysome, organized into three to four concentric layers. Some models of carboxysome function depend on specific contacts between individual RuBisCOs and the shell, but no evidence of such contacts was found: no systematic patterns of connecting densities or RuBisCO positions against the shell's presumed hexagonal lattice could be discerned, and simulations showed that packing forces alone could account for the layered organization of RuBisCOs.

Purpose: To examine the relationship between change scores on the log mean Wolf Motor Function Test (lmWMFT) and the intensity of supervised Constraint Induced Movement Therapy (CIMT) in participants with subacute and chronic stroke., Methods: A retrospective analysis of data from 169 EXCITE participants who received CIMT either immediately after randomization or one year later was undertaken. During waking hours, participants wore a restraining mitt on the less affected extremity. The lmWMFT was administered before and after the two week treatment block., Results: Significant relationships were seen between the intensity of training and functional score in the immediate, lower functional group for whom more training in adaptive task practice resulted in poorer outcomes (p=0.01) and in the immediate, higher functioning group for whom more training in repetitive task practice resulted in poorer outcomes (p=0.02). Female participants in the immediate group showed less progress in lmWMFT scores with greater amounts of total training (p=0.01). Functional level, gender, and concordance did not modify any other relationship. Both higher functioning participants who trained within the normal ratio (N=50) and who were exposed to more than the prescribed adaptive task practice (N=11) experienced a significant improvement in the lmWMFT score (p=0.03 and p=0.02, respectively) compared to those higher functioning participants who experienced excessive repetitive task practice., Conclusion: Applying CIMT to a large sample of participants with stroke resulted in directionally inappropriate but significant relationships between intensity and lmWMFT scores in the immediate but not the delayed group. Our data also suggest that functional improvements observed in the EXCITE Trial might be attributable to training components other than the designated ratio of training approaches (adaptive and repetitive task practice).

This issue of the Emergency Medicine Clinics of North America focuses on the spectrum of public health issues that significantly impact the practice of emergency medicine and which are faced by practicing emergency physicians on daily basis. Topics include public health research in the emergency department; respiratory threats; emerging infectious diseases; emergency department overcrowding; end-of-life care; racial and ethnic disparities; issues of health promotion and disease prevention encompassing substance abuse, alcohol, and injury and violence; and public health surveillance; and the problems of homeless and disadvantaged patients. This article gives a brief introduction to the important relationship between emergency medicine and public health.

Participant recruitment is considered the most difficult aspect of the research process. Despite the integral role of recruitment in randomized clinical trials, publication of data defining the recruitment effort is not routine in rehabilitation initiatives. The recruitment process for the Extremity Constraint-Induced Therapy Evaluation (EXCITE) trial illustrates obstacles to and strategies for participant accrual and retention that are inherent in rehabilitation clinical trials. The purpose of this article is to increase awareness of the multiple facets of recruitment necessary for successful clinical trials, thus supporting the continued development of evidence-based practice in physical therapy. The Recruitment Index is presented as a variable to measure recruitment efficacy. In addition, ethical aspects of recruitment are explored, including informed consent and the concept of therapeutic misconception.

This article provides an overview of the role of the emergency department (ED) in the care of homeless and disadvantaged populations. It suggests that organized emergency medicine can have a significant impact on total community health by maintaining a universal "safety net" for the delivery of integrated health and human services. The epidemiology of social deprivation among ED patients is examined, with a particular focus on homelessness. Current research on the value of socio-medical integration in the ED setting is discussed, with emphasis on selected initiatives that have demonstrated feasibility, cost-effectiveness, and impact.

Recent years have seen a proliferation of animal and human studies that have associated significant changes in regional brain physiology with sustained altered environmental or somatic stimuli. The behavioral consequences in such instances can be adaptive or maladaptive. As would be expected, constraint-induced movement therapy (CI therapy), which has been found to be beneficial for chronic stroke hemiparesis, has been repeatedly associated with significant plastic brain changes in a variety of studies that have included transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI), or other approaches. In some instances, the initial degree of brain reorganization occurred in parallel with the improvement in spontaneous, real-world use by the more-affected hand, which suggests that plastic brain changes in some manner support therapeutic effects. However, the studies are also inconsistent with respect to whether the reorganization changes occur more in the lesioned vs unlesioned hemisphere. Interpreting the physiological outcomes post-treatment is compromised by inconsistencies in study design in the nature of treatment administered, participant recruitment, imaging modality, and extent of follow-up. Improved understanding of the biological basis for neuroplasticity in CI therapy may be obtained through rigorous control of study approaches and through evaluating treatment changes with more than one modality in the same patients concurrently. New quantitative structural brain imaging techniques may allow measuring morphological changes following CI therapy to test hypotheses of regional brain recruitment in use-dependent therapy while avoiding the variability of functional imaging and mapping techniques and the difficulties and assumptions imposed by requiring active limb movement during scanning.

Research on monkeys with a single forelimb from which sensation is surgically abolished demonstrates that such animals do not use their deafferented limb even though they possess sufficient motor innervation to do so, a phenomenon labeled learned nonuse. This dissociation also occurs after neurological injury in humans. Instruments that measure these two aspects of motor function are discussed. The effects of a neurological injury may differ widely in regard to motor ability assessed on a laboratory performance test in which movements are requested and actual spontaneous use of an extremity in real-world settings, indicating that these parameters need to be evaluated separately. The methods used in Constraint-Induced Movement therapy (CI therapy) research to independently assess these two domains are reliable and valid. We suggest that these tests have applicability beyond studies involving CI therapy for stroke and may be of value for determining motor status in other types of motor disorders and with other types of treatment. The learned nonuse formulation also predicts that a rehabilitation treatment may have differential effects on motor performance made on request and actual spontaneous amount of use of a more affected upper extremity in the life situation. CI therapy produces improvements in the former, but focuses attention on the latter and, in fact, spontaneous use of the limb is where this intervention has by far its greatest effect. The evidence suggests that this result is driven by use of a ''transfer package'' of techniques, which can be used with other therapies to increase the transfer of improvements made in the clinic to the life situation. The use of CI therapy in humans began with the upper extremity after stroke and was then extended for the upper extremity to cerebral palsy in young children (8 months to 8 years old) and traumatic brain injury. A form of CI therapy was developed for the lower extremities and was used effectively after stroke, spinal cord injury, and fractured hip. Adaptations of CI therapy have also been developed for aphasia (CI aphasia therapy), focal hand dystonia in musicians and phantom limb pain. The range of these applications suggests that CI therapy is not only a treatment for stroke, for which it is most commonly used, but for learned nonuse in general, which manifests as excess motor disability in a number of conditions which until now have been refractory to treatment.

Constraint-induced movement therapy (CI therapy) is a rehabilitation treatment approach that improves more-affected extremity use following a stroke, especially in the life situation. The originators of the approach describe CI therapy as consisting of a family of therapies including a number of treatment components and subcomponents. When thinking of CI therapy, rehabilitation researchers and clinicians frequently cite a restraining mitt on the less affected arm as the main active ingredient behind improvements in motor function. However, substantial data suggest that restraint makes actually a relatively small contribution to treatment outcome. This paper provides a detailed description of the multiple treatment elements included in the CI therapy protocol as used in our research laboratory. Our aim is to improve understanding of CI therapy and the research supporting its use.

A volunteer sample of 22 participants with chronic traumatic brain injury (TBI) (onset >1 year) and relative hemiplegia that revealed moderate disability in the more-affected upper limb (UL) participated. Constraint-induced (CI) movement therapy (CI therapy) was employed for a 2-week period; treatments included massed practice, shaping of the more-affected UL, behavioral contracts, and other behavioral techniques for affecting transfer to a real-world setting. We used the Wolf Motor Function Test, the Fugl-Meyer Motor Performance Assessment, and the Motor Activity Log to measure outcomes. All outcome measures improved significantly as a result of the intervention. More-adherent participants had more improvement compared with less-adherent participants. These preliminary results suggest that CI therapy may be effective for improving UL motor function following chronic TBI.

The Wolf Motor Function Test (WMFT) has been used in rehabilitation studies of chronic stroke patients, but until now its psychometric properties have not been evaluated in patients with subacute stroke. Two hundred twenty-nine participants with subacute stroke (3-9 months postinjury) at 7 research sites met inclusion criteria for the EXCITE Trial and were randomized into immediate or delayed (by 1 year) constraint-induced movement therapy treatment. All evaluations were undertaken by assessors standardized in the administration of the WMFT and masked to treatment designation. Participants were also assessed using the Fugl Meyer Motor Assessment (FMA). Delayed group members had measurements repeated 2 weeks following baseline assessment to determine learning or exposure effects. The results demonstrate that the WMFT differentiated higher from lower functioning participants across sites; scores were uninfluenced by hand dominance or affected side. Women exhibited slower performance times than men. The Functional Ability scale (FAS) portion of the WMFT also revealed lower scores among lower functioning participants and women. Minimal changes were observed after repeating the WMFT among delayed group participants 2 weeks later. The FMA revealed similar results when the total group was divided into higher and lower functional levels at its midpoint score of 33. The WMFT discriminates higher from lower functioning participants tested across research sites. Comparable findings using the FMA support the criterion validity of the WMFT.

A novel T*(2)-weighted contrast-preparation scheme is described for use with segmented k-space cardiac sequences. This approach frees the imaging phase from the requirement of a long TE and, hence, a relatively long TR. A [90 degrees (x)-tau-90 degrees (rho)] preparation scheme is used to acquire four image data sets with the phase rho of the second pulse set to x, y, -x, and -y. The rho = x raw data is subtracted from the rho = -x data to form the "x" image, with a similar subtraction to generate the "y" image. These images are added in quadrature to obtain the T*(2)-weighted image. The method results in reduced artifact compared to a simple two-image scheme with rho = x, and y. T*(2) was measured in the myocardial septum in six normal volunteers by comparing tau = 7 and 28 ms images, and it was found to be 44 +/- 5 ms at 0.95 T., (Copyright 2003 Wiley-Liss, Inc.)

Constraint-Induced Movement therapy (CI therapy) has been demonstrated to improve motor function and upper extremity (UE) use of persons with hemiparesis resulting from chronic stroke through two separate but linked mechanisms, overcoming learned nonuse, and facilitating use-dependent cortical reorganization. The principles of CI therapy and adaptations of the basic techniques have been used successfully with diagnostic categories other than stroke that involve disability greater than what is warranted by the organic condition of the individual. Because neuroimaging and transcranial magnetic stimulation studies indicate that many of these conditions involve abnormalities of cortical organization, CI therapy might therefore be viewed as a technique that achieves clinical efficacy by correcting disorders of brain plasticity. CI therapy constitutes a new approach to neurorehabilitation and, with continued investigation, elaboration, and application to clinical settings, it seems to hold considerable promise.

Background: It has been documented in the literature that hypocalcemia, hypoaminoacidemia, and hyperaminoaciduria are sequelae of trauma. The aminoaciduria of patients with different types and severity of traumatic injuries was investigated., Methods: Eight severely traumatized patients (ISS range, 20-43 years) and eight age-, gender-, and weight-matched controls were studied. Plasma and urine were collected 2.5-72 h after admission. Quantification of 28 amino acids in plasma and urine was performed by reversed-phase high-performance liquid chromatography. Urine concentrations of amino acids were indexed to creatinine., Results: The patients' mean serum concentrations of 4 amino acids (arginine, threonine, isoleucine, and glutamine) were significantly decreased, 2 others (tryptophan and glutamic acid) were significantly increased, and 22 were unchanged (p-value< or =0.05). Fractional (urinary) excretion of 11 amino acids was increased in the patients. The patients' serum total calcium and albumin concentrations were decreased, but the mean ionized calcium concentration was not significantly different from the controls., Conclusions: The results of this study showed that aminoaciduria involving many amino acids is common for patients with different traumatic injuries and that the aminoaciduria is correlated with a reduction of the total serum calcium concentration.

Traditional rehabilitation programs for persons with neurologic dysfunction emphasize a compensation, true recovery, or substitution approach to improve functional abilities. Constraint-induced (CI) movement therapy substantially increases more-affected extremity use in the life situation due to the influence of two different underlying mechanisms: overcoming learned nonuse and inducing use-dependent cortical reorganization. In this way, it bypasses the debate over whether a compensation, true recovery, or substitution approach should be used. The purposes of this article are to describe the CI therapy approach, discuss its proposed modes of action, and discuss other unique aspects of CI therapy as a rehabilitation technique.

A therapeutic approach to rehabilitation of movement after stroke, termed constraint-induced (CI) movement therapy, has been derived from basic research with monkeys given somatosensory deafferentation. CI therapy consists of a family of therapies; their common element is that they induce persons with stroke to greatly increase the use of a more-affected upper extremity (UE) for many hours a day over a 2- to 3-week period. These therapies have significantly improved quality of movement and substantially increased amount of use of a more-affected UE in the activities of daily living in life situations. A number of neuroimaging and transcranial magnetic stimulation studies have shown that the massed practice of CI therapy produces a massive use-dependent cortical reorganization that increases the area of cortex involved in the innervation of movement of the more-affected UE. The intensity and schedule of delivery of this very efficacious therapy is quite different from that of more traditional physical rehabilitation approaches. As a result, to be clinically applicable, the CI therapy approach to rehabilitation will likely require a paradigm shift in the delivery of physical rehabilitation services.

Objective: To examine the reliability of the Wolf Motor Function Test (WMFT) for assessing upper extremity motor function in adults with hemiplegia., Design: Interrater and test-retest reliability., Setting: A clinical research laboratory at a university medical center., Patients: A sample of convenience of 24 subjects with chronic hemiplegia (onset >1yr), showing moderate motor impairment., Intervention: The WMFT includes 15 functional tasks. Performances were timed and rated by using a 6-point functional ability scale. The WMFT was administered to subjects twice with a 2-week interval between administrations. All test sessions were videotaped for scoring at a later time by blinded and trained experienced therapists., Main Outcome Measure: Interrater reliability was examined by using intraclass correlation coefficients and internal consistency by using Cronbach's alpha., Results: Interrater reliability was.97 or greater for performance time and.88 or greater for functional ability. Internal consistency for test 1 was.92 for performance time and.92 for functional ability; for test 2, it was.86 for performance time and.92 for functional ability. Test-retest reliability was.90 for performance time and.95 for functional ability. Absolute scores for subjects were stable over the 2 test administrations., Conclusion: The WMFT is an instrument with high interrater reliability, internal consistency, test-retest reliability, and adequate stability.

A phase III study was performed to compare the efficacy and safety of lamotrigine (Lamictal), desipramine (Norpramin), and placebo in the treatment of unipolar depression. Desipramine is extensively metabolized by cytochrome P450 2D6 (CYP2D6), and kinetics of this compound are altered in poor metabolizers. Genotyping was utilized to exclude poor metabolizers in order to increase subject safety and to eliminate the need to continuously monitor plasma desipramine levels. As part of screening, subjects were genotyped for the *3(A), *4(B), and *5(D) alleles, which identify approximately 95% of poor metabolizers. Extensive metabolizers were eligible for randomization to the lamotrigine, desipramine, or placebo arm. Follow-up genotyping for the *6(T) and *7(E) alleles was performed after study enrollment and was used to identify poor metabolizers who may have been incorrectly identified as extensive metabolizers upon initial three-allele screening. Of 628 subjects screened for *3(A), *4(B), *5(D) alleles, 590 (93.9%) were classified as extensive metabolizers. The remaining 38 (6.1%) subjects were poor metabolizers and excluded. Subsequent *6(T) and *7(E) testing revealed that two poor metabolizers had been enrolled, and the follow-up genotyping provided an explanation for the high desipramine plasma concentrations in one subject. No differences in phenotypic or allelic frequencies were found between the study population and literature populations. However, the frequency of poor metabolizers varied among clinical sites (0-15%). For a compound that is extensively metabolized by CYP2D6, prescreening subjects for *3(A), *4(B), *5(D), *6(T) and *7(E) alleles can increase subject safety and eliminate the need to continuously monitor drug plasma concentrations.

Background: Little is known about the changes that occur in antioxidant levels in response to surgical trauma. The antioxidant system may influence recovery and healing after operation. Miller et al described a reliable assay for total antioxidant capacity of serum. We studied changes in antioxidant levels secondary to operation using this assay., Methods: Twenty-seven patients were studied: 14 abdominal and 13 breast cancer operations. Initial blood samples were obtained when starting the preoperative intravenous line, the second in the recovery room, and every 6 hours thereafter., Results: Levels did not correlate with diagnosis, extent of operation, age, body mass index, or complications. Differences between preoperative and postoperative values in the down and up groups were significant at P = 0.002 and P = 0.023, respectively. Differences in initial levels between the down and up groups were significant at P = 0.005. Levels 12 hours after operation were stable., Conclusions: Rapid return to a baseline of approximately 1 micromole/L, regardless of the direction of initial response, supports the concept of a set point for regulation of serum's antioxidant capacity.

To compare the training effects of doing high intensity intervals at 1,840 m in a normoxic vs. hyperoxic environment, eight cyclists (NORM) performed intervals on ergometers 3d/wk while breathing normoxic gas (P1O2 = 128 Torr), and seven subjects (HYPER) performed identical intervals at the same relative workload while breathing hyperoxic gas (P1O2 = 156 Torr). HYPER subjects were able to train at a higher percentage of their altitude lactate inflection point than were NORM subjects (HYPER = 126+/-2%, NORM = 109+/-3% p<0.05). Improvements in power output at maximal steady state (NORM = 8 W, HYPER = 20 W,) and improvement in time to complete a 120 kJ cycling performance test (NORM = 2 s, HYPER = 15 s) were significant in the HYPER group pre- vs. post-training (p<0.05) while the NORM group exhibited no significant changes. No significant changes in power output at lactate inflection point were seen in either group (NORM = -12 W, HYPER = +11 W). The results demonstrate that while training at moderate altitude, breathing hyperoxic gas vs. ambient air allows for higher training intensities and this higher intensity training results in significant improvements in maximal steady state power output and time to complete a 120 kJ performance test.

The mechanisms by which heparin protects the liver during induced episodes of liver ischemia-reperfusion are poorly understood. Previous work in a swine model demonstrated that serum levels of glycohydrolases and lipid peroxide peaked within 3 h after 45 minutes of hepatic ischemia followed by reperfusion. Serum levels of lactate dehydrogenase and aspartate aminotransferase peaked 20-24 h later. The aim of this study was to evaluate the effect of heparin on these two-phases of enzyme release, using a pig model of hepatic ischemia-reperfusion injury. Twenty male swine were divided into control (n = 8) and heparin (n = 12) groups. In the heparin group, heparin was administered prior to and concurrent with ischemia-reperfusion. Following 45 min of hepatic ischemia, the levels of beta-galactosidase, beta-glucosidase, acid phosphatase, purine nucleoside phosphorylase, lipid peroxides, lactate dehydrogenase, and aspartate aminotransferase in serum were monitored for up to 166 h and compared to pre-ischemic and control levels. With heparin infusion, the peak levels of beta-galactosidase, beta-glucosidase, and the lipid peroxide were reduced to 50-60% of the control levels. Acid phosphatase and purine nucleoside phosphorylase activities in serum were reduced to 25% and 60%, respectively. The peak concentrations of lactate dehydrogenase and aspartate aminotransferase were reduced to about 25% of the control level. In addition, the serum enzymes of control pigs did not return to pre-ischemic levels until 2 weeks after hepatic ischemia, while they normalized in less than 1 week in the heparin-treated animals. Systemic heparinization had different protective effects on the first and secondary phases of liver injury. These differences may reflect heparin protection of different types of liver cells. The protection of the parenchymal cells may be the combined result of reduced sinusoidal cell injury and the anticoagulant properties of heparin.

A single-center, open-label, three-way crossover study was conducted in 24 healthy subjects to assess (1) the bioequivalence of a combined lamivudine 150 mg/zidovudine 300 mg tablet relative to the separate brand-name components administered concurrently and (2) the effect of food on the bioavailability of the drugs from the combination tablet. The subjects were randomly assigned to receive each of the following three treatments, separated by a 5- to 7-day washout period: one lamivudine/zidovudine combination tablet after an overnight fast, one lamivudine 150 mg tablet and one zidovudine 300 mg tablet simultaneously after an overnight fast, or one lamivudine/zidovudine combination tablet 5 minutes after completing a standardized high-fat breakfast (67 g fat, 58 g carbohydrate, and 33 g protein). Serial blood samples were collected up to 24 hours postdose for the determination of lamivudine and zidovudine plasma concentrations. Standard pharmacokinetic parameters were estimated. Treatments were considered bioequivalent if 90% confidence intervals for the ratio of least squares (LS) means for the lamivudine and zidovudine area under the plasma concentration-time curve (AUC infinity) and maximum observed plasma concentration (Cmax) fell entirely within 0.80 to 1.25 for log-transformed parameters. The combined lamivudine/zidovudine tablet was bioequivalent in the extent (AUC infinity) and rate of absorption (Cmax and time of Cmax [tmax]) to the individual brand-name drug components administered concurrently under fasted conditions. Geometric LS mean ratios and 90% confidence intervals for AUC infinity and Cmax were 0.97 (0.92, 1.03) and 0.94 (0.84, 1.06), respectively, for lamivudine and 0.99 (0.91, 1.07) and 0.97 (0.82, 1.15), respectively, for zidovudine. The extent of absorption of lamivudine and zidovudine from the combination tablet was not altered by administration with meals, indicating that this formulation may be administered with or without food. However, food slowed the rate of absorption, delayed the tmax, and reduced the Cmax of lamivudine and zidovudine. These changes were not considered clinically important. All formulations were well tolerated under fasted and fed conditions.

Hernia repair may involve the use of an implant to augment or replace autologous tissue, but the best material for use in this application has not been established. We developed a dog model to evaluate the mechanical strength of fascial defects repaired using carbon fibers, compared with the strength of similar defects repaired using polypropylene mesh (Marlex). Unrepaired defects were included as an additional control. Bilateral defects (1 cm square) were made in the fascia of the back, and the ultimate mechanical strength and stiffness at the repair sites were measured 3-12 months after operation. Defects repaired with carbon fibers were significantly stronger 12 months after operation compared with defects repaired with polypropylene mesh and compared with unrepaired defects. It is concluded that carbon fibers are biocompatible and significantly increase mechanical strength at the repair site. A randomized clinical trial involving patients undergoing hernia repair seems justified to determine whether carbon fibers are superior to standard therapy., (Copyright 1998 Academic Press.)

Background: Recommendations regarding therapeutic use of (131)I for patients with well-differentiated thyroid cancer remain controversial. Between 1969 and 1993, 1171 patients with papillary (including mixed) or follicular thyroid cancer were reported to the New Mexico Tumor Registry. Of these, 1075 cases (77.6% female, median age 41 years) were available for analysis of survival plots and previously recognized risk factors. Extent of operation was documented for 344 patients., Methods: One hundred twenty-seven (37%) patients underwent postoperative (131)I ablation. Median follow-up was 99 months. A proportional hazards model was constructed using age, gender, stage, histology, and use of radioiodine. The same variables plus extent of operation were examined in the smaller group., Results: Kaplan-Meier survival estimates at 12 years were 96.2% for patients younger than 45 years and 68.6% for those older than 45 years. Age, gender, and histology, but not stage, were important survival variables (P <.05). Adjusting for other risk factors, there was no apparent survival benefit associated with radioiodine following clinically appropriate thyroidectomy. Findings from the small group mirrored those of the large group., Conclusions: (131)I may not be as efficacious as previously believed for patients with well-differentiated thyroid cancer confined to the neck.

This study evaluated the ability of a commercially available accelerometer (Tritrac-R3 D) to measure energy expenditure in 16 subjects at rest (pre- and post-exercise) and during three different intensities of steady-state exercise (40-70% of peak oxygen consumption [VO2peak]) while ambulating on a treadmill (no grade). Oxygen consumption and the respiratory exchange ratio from indirect calorimetry and the vector magnitude of triaxial accelerations were used to estimate energy expenditure using the manufacturers' equations. There was a significant relationship between indirect calorimetry-derived energy expenditure and the energy expenditure derived from the accelerometer (r=0.96). Using analysis of variance, there was no difference in the energy expenditure derived by the two methods at rest before exercise and during the three different intensities of ambulatory exercise. There was a significant difference between energy expenditure derived via indirect calorimetry and with the accelerometer during rest after exercise, probably due to the failure of the accelerometer to accurately estimate the energy expenditure associated with the progressive decline in post-exercise oxygen consumption. Thus, this commercially available accelerometer appears to provide statistically acceptable estimates of energy expenditure at rest and during zero-grade treadmill ambulation up to about 70% VO2peak. This may indicate its acceptable utility for large-scale population studies of physical activity involving this mode of movement. The failure of the accelerometer to accurately estimate energy expenditure during recovery from exercise may contribute to an underestimation of energy expenditure in some physically active individuals.

Managed care is affecting the business of medical practices. Many physicians are joining with larger organizations and employee benefits are even more significant in each physician's financial security. Background on benefit issues and common areas of caution when contemplating joining a large entity are addressed.

The purpose of this investigation was to determine the effects of various crank arm lengths on oxygen consumption for trained cyclists. Secondary purposes were, if optimal crank arm lengths existed, to determine if these lengths could be predicted based on an individual's leg length. Six trained cyclists completed four experimental protocols riding at a workload of approximately 68% of VO2 max using crank arm lengths of 165, 170, and 175 mm. During each protocol, the cadence, oxygen consumption, and distance traveled were determined, and values were combined to give a VO2.m-1.min-1 value. The values then were placed in either a high, medium, or low efficiency category. Significant differences were found among the three protocols. No significant correlations were found between each subject's most efficient crank arm length and leg length. The results of the study suggest that each subject has a most efficient crank arm length, but it does not appear that optimal crank arm length can be predicted by leg length.

Background: A number of prognostic factors for thyroid carcinoma have been identified, including sociodemographic characteristics, such as age and gender, and tumor characteristics, such as histology and stage. The relative importance of these factors as independent predictors of survival for patients with papillary, follicular, anaplastic, and medullary thyroid carcinoma has been extensively studied but remains uncertain., Methods: The authors used data collected by the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute between 1973 and 1991 to investigate prognostic factors for each of the major histologic types of thyroid carcinoma in a population-based patient series and to assess the effect of these factors as predictors of survival., Results: Both tumor and sociodemographic characteristics were independently associated with survival. Patients with papillary carcinoma had the highest 10-year relative survival (0.98), followed by those with follicular carcinoma (0.92) and medullary carcinoma (0.80). Anaplastic tumors had the lowest 10-year relative survival (0.13). Stage at diagnosis and differentiation status were strong independent prognostic factors for each histologic type. Advanced stage at diagnosis was a stronger prognostic factor for medullary carcinoma than for other histologic types. Increasing age was associated with lower relative survival for each histologic type. Gender, marital status, and ethnicity were significant, but weaker, predictors of survival., Conclusions: Survival varied markedly among patients with different histologic types of thyroid carcinoma. Stage at diagnosis and tumor differentiation were important prognostic factors for each histologic type. Age at diagnosis was a stronger predictor of survival for patients with follicular and medullary carcinoma than for patients with papillary carcinoma.

The contributions of amino acids to the overall osmotic activity of cyst fluids were sought in this comparative study of fluids from the cysts of autosomal dominant polycystic disease (ADPKD) and gross cystic disease of the breast (GCDB). Fluids (n = 18) from 18 women with GCDB and from 8 patients with ADPKD (n = 25), grouped on the basis of sodium concentrations, were analyzed for potassium, chloride, protein, and osmolality by routine methods and for amino acids by reversed-phase high-pressure liquid chromatography. Similarities between kidney and breast cyst fluids included relative isosmolality, a wide range of sodium concentrations, an inverse relationship between sodium and potassium concentrations, higher concentrations of amino acids in low-sodium fluids, and significant correlations between sequential concentrations of amino acids in cyst fluids versus blood and some of its components. Therefore, cyst fluids in ADPKD and GCDB share compositional characteristics, and amino acids, possibly of blood protein origin, accumulate in small but osmotically significant amounts in some, particularly low-sodium, cysts of kidney and breast.

A new therapeutic approach to rehabilitation of movement after stroke, termed Constraint-Induced (CI) Movement Therapy, has been derived from basic research with monkeys given somatosensory deafferentation. CI consists of a family of therapies; their common element is that they induce stroke patients to greatly increase the use of a more affected upper extremity for many hours a day over a 10-14 consecutive-day period. These therapies have significantly improved quality of movement and substantially increased amount of use of a more affected extremity in the activities of daily living in the life situation. The purpose of this paper is to describe the protocol used by the investigative team that developed the family of CI therapies and examined them as an effective rehabilitation approach.

Lamivudine is a novel cytosine nucleoside analog, reverse transcriptase inhibitor that has shown activity against human immunodeficiency virus (HIV) types 1 and 2 and hepatitis B virus in vitro. This study was conducted to compare the absolute bioavailability, pharmacokinetics, and absorption characteristics of oral solution, 100-mg capsule, and 100-mg tablet formulations of lamivudine with those of intravenous lamivudine. Twelve patients with HIV were enrolled in a single-center, randomized, open-label, four-way cross-over study. Treatment arms consisted of 100 mg intravenous lamivudine (administered over 1 hour), 100 mg oral lamivudine (1 mg/mL), a 100-mg capsule, and a 100-mg tablet, each followed by a 3- to 14-day washout period. Serial blood samples over 24 hours were obtained after each dose administration. Serum concentration data were analyzed to determine pharmacokinetic parameter estimates including area under the curve (AUC), terminal half-life (t1/2), mean residence time (MRT) for each formulation, systemic clearance, oral clearance, and apparent volume of distribution (Vd). Absolute bioavailability and in vivo mean absorption time (MAT) and mean dissolution time (MDT) were calculated for the oral formulations. Deconvolution techniques were used to calculate the input rate for the oral solution, capsule, and tablet. The two one-sided t test was used to determine bioequivalency among oral formulations with respect to logarithmic transformed estimates of AUC and maximum peak concentration (Cmax). Mean (CV) systemic clearance and Vdss after intravenous administration of lamivudine were 22.6 L/h (15%) and 99 L (28%), respectively; mean t1/2 ranged from 8.41 to 9.11 hours for all formulations; and MRT ranged from 4.42 to 5.77 hours for all formulations. Mean absolute bioavailability ranged from 86% to 88% for the oral solution, capsule, and tablet. All oral formulations were considered bioequivalent for AUC and Cmax. The MAT was 1.32 hour for the oral solution, and MDT was 0.03 and -0.11 hours for the capsule and the oral solution, respectively. The oral formulations of lamivudine examined in this study demonstrated acceptable bioavailability for oral administration. The solid oral formulations (capsule and tablet) show rapid dissolution properties with an absorption rate similar to or exceeding those observed with the oral solution. This suggests that dissolution is not an important factor for the rate of absorption of lamivudine. The use of deconvolution techniques using PCDCON provides valuable insight into the absorption characteristics of lamivudine.

GG167 is a novel compound which selectively inhibits viral neuraminidase and has demonstrated activity against influenza A and B. A liquid chromatography (LC) method for the determination of GG167 in human urine has been developed and validated. The method allows direct injection of urine (7 microliters) using LC column switching followed by UV detection. Initial chromatography is performed using a Nucleosil-Diol column (7 microns, 250 mm x 4.6 mm), eluted with 20 mM phosphate buffer (pH 2.5):acetonitrile (18:82, v/v) at 2.0 ml min-1. GG167 is "heart-cut" to a Spherisorb-SCX column (5 microns, 100 mm x 4.6 mm) and eluted with 35 mM phosphate buffer (pH 2.5):acetonitrile (50:50, v/v) at 1.5 ml min-1 for final separation. GG167 is detected by UV absorbance at lambda = 238 nm. UV detection and peak shape are enhanced at pH < 2.5. The quantitation range of the assay is 0.3-100 micrograms ml-1. The method has demonstrated sufficient ruggedness to be used in support of GG167 clinical trials.

Objective: A study was performed to determine the appropriate time for the initiation of therapy for thyroid carcinoma first diagnosed during pregnancy., Data Sources: Material on thyroid cancer cases was obtained from the New Mexico Tumor Registry, Albuquerque, a computerized population-based registry for the state of New Mexico, and the Indian reservation facilities in New Mexico and Arizona (a Surveillance, Epidemiology, and End Results Registry funded by the National Cancer Institute, Bethesda, Md) for the period 1970 to 1991., Study Selection: All cases of thyroid cancer, except medullary and anaplastic, in patients aged 18 to 46 years were evaluated. Subgroups were established for (1) all women who were noted to be pregnant at the time of their initial diagnosis and (2) all women with thyroid cancer in the 18- to 46-year-old age group., Data Extraction: The information was extracted by a certified tumor registrar for age, sex, thyroid cancer, specific type of thyroid cancer, period, race, year of diagnosis, accession date, last date seen, tumor status, treatment, and patient status., Data Synthesis: There have been no deaths in the pregnant group with a follow-up ranging from 0.5 to 20 years. There was no statistically significant difference in observed survival rates between the pregnant group and 465 women, aged 18 to 46 years, with comparable thyroid cancers or in the death rates of women aged 18 to 67 years in the general population., Conclusions: Surgical treatment for patients with well-differentiated thyroid cancer diagnosed during pregnancy can be delayed until after parturition.

It is now possible to adminster doses of chemotherapy several-fold those used in standard treatment regimens. This can be done with relative safety, and in patients with metastatic breast cancer or refractory nonHodgkin's lymphoma such treatment produces a high complete-remission rate. Some patients enjoy a long-term disease-free survival following dose-intensive therapy. Chemotherapy intensified to this degree produces prolonged periods of myelosuppression. This can be managed rather well with progenitor-cell infusion and cytokine support. There is little experience with such regimens in the treatment of locally advanced or locally aggressive breast cancer. However, early experience in several institutions, including our own is encouraging. In this article the rationale for dose intensity, the experience in metastatic breast cancer, and the available information on outcomes in locally advanced cancer are reviewed. The appropriate role for dose-intensive chemotherapy in locally advanced breast cancer treatment remains to be defined.

A high-performance liquid chromatographic method for the determination of 2'-deoxy-3'-thiacytidine (3TC), a novel dideoxy-nucleoside analogue, in human serum is described. 3TC was extracted from serum samples using Bond Elut Certify solid-phase extraction cartridges prior to reversed-phase chromatography with UV detection. The method has been shown to be valid over the concentration range 10-5000 ng/ml using a 1-ml sample volume, both before and after heat treatment of the samples at 60 degrees C for 3 h. The method has been automated using a Zymark robot and used in the analysis of serum samples from HIV positive patients.

We retrospectively reviewed 70 cases of perforated appendicitis in children to examine the relationship between postoperative antibiotic selection and culture results from the peritoneal cavity. Initial antibiotic therapy chosen for the children consisted of a three-drug combination in 54 (77%) patients. Peritoneal cultures were performed in 58 (83%) patients. Escherichia coli and Bacteriodes fragilis were the most common bacterial isolates from the peritoneal culture. Only 7 (10%) patients had their antibiotic regimen changed after the culture results were available, of which 2 changes brought drug therapy into compliance with the cultures and 5 changes were inappropriate with respect to the peritoneal cultures. Of the remaining 51 patients with culture data available, 39 should have had changes to bring the antibiotic therapy into compliance with the observed culture results. These data indicate that surgeons select antibiotic therapy for perforated appendicitis in children based on assumptions of which organisms should be present in the infection and not on culture data. There appears to be no clinical usefulness to the routine culturing of the peritoneal cavity in children with perforated appendicitis.

3TC (GR109714X) is a cytidine dideoxynucleoside analogue which has been shown to have in vitro activity against a variety of strains of HIV-1 and is currently being investigated in clinical trials as a treatment for HIV infection. An HPLC method for the determination of 3TC in human urine has been developed and validated. The method allows direct injection of urine (10 microliters) using HPLC column switching followed by UV detection. On-line extraction is performed using a Spherisorb-SCX (5 microns, 20 x 4.0 mm) eluted with deionized water at 1 ml min-1. 3TC is retained while the bulk of urine constituents are eluted to waste. The SCX column is then backflushed to a BDS-Hypersil-C18 (5 microns, 250 x 4.6 mm) and eluted with 100 mM acetate pH 4.5-methanol (95:5, v/v) for final separation. 3TC is detected by UV absorbance at lambda = 285. The quantitation range of the assay was 0.5-500 micrograms ml-1. The method has demonstrated sufficient ruggedness to be used in support of 3TC clinical trials. Application to other cytidine analogues including DDC has been demonstrated.

Patients with neurological disorders present therapists with complex challenges for treatment, including weakness, hypertonicity, voluntary movement deficit, limited range of motion, sensory loss, incoordination, and postural instability. The presence of one or more of these impairments negatively influences these patients by contributing to problems in walking, transferring, and reaching. Aquatic rehabilitation offers a unique, versatile approach to the treatment of these disabilities. This article examines the problems encountered by patients with neurological disorders, general principles guiding neurotreatment, and aquatic neurorehabilitation approaches.

Electrical potentials were measured on the breast and at other sites in 110 women with palpable breast masses. The tumor site was significantly electropositive compared with control sites only when the tumor was a cancer, as determined by a subsequent biopsy; the electrical potentials were not influenced by age or menstrual cycle. The results indicate that, on average, altered electrical potentials detected by a noninvasive measurement on the skin reflect the presence of transformed cells in patients with breast cancer. Previous in vitro studies of breast tissue and breast epithelial cells suggest that the observed effect was due to a change in interstitial K+ concentration that arose from alterations in the activity of K+ channels. Electrical potentials may be suitable for diagnosis of individual patients if refinements are made in the measurement technique.

Twenty-two consecutive critically ill surgical patients who had a Swan-Ganz thermodilution catheter inserted as part of their intensive care unit therapy were studied prospectively. Patients were divided into two groups. Group I consisted of 17 patients whose pulmonary artery diastolic pressure minus pulmonary artery wedge pressure (PADP-PAWP) gradient was less than 5 mm Hg or if greater than 5 mm Hg persisted for less than 12 hours. Group II was composed of 5 patients whose PADP-PAWP gradient was greater than 5 mm Hg for at least 12 hours or more. The two groups were equally matched in terms of risk factors that predispose to an elevated gradient or factors that falsely lower the gradient. Nine other physiologic parameters were measured in patients in Group II during the period of the elevated gradient and were compared with the same parameters measured in patients in Group I. An elevated pulmonary vascular resistance was the only parameter associated with an elevated gradient. An elevated PADP-PAWP gradient greater than 5 mm Hg that persisted for 12 hours or more was associated with a 60 per cent mortality rate.

Anastomotic leak is the main complication after Whipple procedures. We reviewed retrospectively our experience with pancreatic cancer patients treated with Whipple resection and reconstruction with a pancreaticogastrostomy (PG) or a pancreaticojejunostomy (PJ). Ten patients operated between 1966 and 1990 composed the PJ group. Eight patients operated recently made up the PG group. Data on age, length of stay (LOS), survival, and complications (early and late) were noted from patient's charts. Patients in the PJ group had an average age of 58.3 years, a mean LOS of 60.3 days (median, 48 days), and a mean survival of 14.5 months. PG group patients had a mean age of 64.5 years, an average LOS of 14.3 days (median, 14 days), and an average survival of 10+ months. None of these differences were significant. Major complications in the PJ group included 2 leaks, 2 cases of pancreatic insufficiency, and 2 deaths related to the anastomotic leaks. Eleven other major complications occurred. The PG group patients did not have any leaks. One developed pancreatic insufficiency. Complications in the PG group were much less serious than those in PJ group. The longest hospital stay in the PG group was 20 days (range, 2-20) and 144 days (range, 11-144) in the PJ group. We conclude that PG is superior to PJ because of the decreased incidence of anastomotic leaks and the less serious nature of the complications associated with PG.

We evaluated the effect of direct electrical current on large tumors in mice. Lewis lung carcinoma greater than 1 cm in the shortest dimension was treated percutaneously with 20 mA for 15 min. Separate groups were given one or more than one (two or three) percutaneous electrical treatments (PET). A third group was given sham electrical treatment, and a fourth group had surgical excision of the tumor. Animals in both PET groups survived longer and had smaller primary tumors at death compared with the sham group. PET did not alter the systemic course of the disease, judged by lung and spleen weights and by histological observation of the extent of metastatic burden in the lung. Surgery resulted in long-term survival of 17% and an increase in average survival time compared with both PET and sham treatment. PET produced rapid and polarity-dependent alterations in physiological solutions in vitro, and it is likely that similar electrochemical processes mediated the observed reduction in tumor growth. PET is potentially useful as an adjuvant modality because it reduces local tumor mass but does not alter the extent of metastasis.

In a randomized, controlled study of the Treatwell work-site nutrition intervention program, which focused on promoting eating patterns low in fat and high in fiber, 16 work sites from Massachusetts and Rhode Island were recruited to participate and randomly assigned to either an intervention or a control condition. The intervention included direct education and environmental programming tailored to each work site; control work sites received no intervention. A cohort of workers randomly sampled from each site was surveyed both prior to and following the intervention. Dietary patterns were assessed using a semiquantitative food frequency questionnaire. Adjusting for work site, the decrease in mean dietary fat intake was 1.1% of total calories more in intervention sites than in control sites (P less than .005). Mean changes in dietary fiber intake between intervention and control sites did not differ. This study provides evidence that a work-site nutrition intervention program can effectively influence the dietary habits of workers.

Esophageal perforation remains a difficult diagnostic and management problem. Recommendations regarding treatment remain controversial. A 15-year experience with perforation of the esophagus from all causes was reviewed at Louisiana State University and Veterans Administration, Medical Centers (Shreveport, LA). The majority of the injuries involved the thoracic esophagus (28 or 54%), followed by the cervical (21 or 40%), and the intraabdominal esophagus (3 or 6%). Iatrogenic causes constituted most of the injuries (52%), followed by external trauma (23%), barogenic rupture (15%), and ingested foreign bodies (10%). Diatrizoate methylglucamine 66 per cent, sodium diatrizoate 10 per cent (Gastrografin; Squibb, Princeton, NJ) contrast studies and flexible esophagoscopy were performed in 44 and 22 patients, respectively. In the cervical esophagus, contrast studies were more sensitive and specific than endoscopy (P less than .01), but both studies were equally effective as diagnostic methods in thoracic perforations. Cervical perforations were treated with either drainage alone (7 patients) or primary repair with drainage (14 patients) with an operative mortality of 4.8 per cent. Several procedures were used in thoracic perforations, which carried a mortality of 36 per cent and were more lethal than cervical tears (P less than 0.2). Any thoracic esophageal perforation treated more than 24 hours after the onset of symptoms, irrespective of what procedure was used, was associated with a significantly higher mortality than if operated on earlier (P less than .001). Five patients with perforated carcinomas were treated by esophageal resection with no mortality. Significantly higher mortality was seen with a delay in diagnosis, thoracic perforations, and Boerhaave's Syndrome. A subset of patients with perforated carcinomas may benefit from esophageal resection with delayed reconstruction.

The charts of 480 patients with secondary bacterial peritonitis were reviewed. The antibiotics used were compared with the culture and sensitivity data obtained at surgery, and the outcomes of patients were evaluated. Patients treated with a single broad-spectrum antibiotic had a better outcome than patients treated with multiple drug treatment. Inadequate empiric antibiotic treatment was associated with poorer outcome than any other type of treatment. The outcome of this inadequate treatment group could not be improved by any antibiotic response to culture and sensitivity information after operation. Those patients treated with antibiotic coverage for anticipated organisms and having no cultures taken did as well as patients having cultures taken. Surgeons typically ignore culture data after operation, and only 8.8% of patients in this study had an appropriate change in antibiotic treatment after operation. A benefit from obtaining operative cultures could not be identified.

Temporary colostomy is a mainstay in the treatment of patients with colon injuries. Common teaching is that loop colostomies are not totally diverting. We performed this study to determine whether loop colostomies are totally diverting. Twenty-three patients presenting for closure of loop colostomies were given barium by mouth. Serial abdominal films were obtained at intervals over 24 hours. Scout films were obtained after bowel preparation to see if flushing the colon could cause passage of barium into distal bowel. We could not demonstrate passage of barium into the distal limb of the colon in any patient studied. This was true even in long-established loop colostomies. Bowel preparation did not cause passage of barium into the distal colon. Loop colostomies constructed over a rod and matured immediately totally divert the fecal stream. Most surgeons would agree that this type of colostomy is more easily and quickly created and closed. Since it fulfills the criteria for fecal diversion, the use of divided colostomies should be abandoned when a loop colostomy can be utilized.

We retrospectively reviewed cases of pancreatic cancer to determine the benefit of various methods of biliary decompression and the role of prophylactic gastroenterostomy (GE) in management. Twenty-seven patients had only biliary bypass, and 26 had biliary bypass and GE. Operative mortality was similar for both groups (22% and 19%, respectively). The complication rates were almost identical (37% and 35%). Differences in operative mortality, incidence of cholangitis, and recurrence of jaundice were not statistically significant between patients having biliary decompression via the common bile duct or the gallbladder. Operative mortality associated with choledochoenterostomy was 33% versus 17% for cholecystoenterostomy. Gastric outlet obstruction developed in 5% of patients who did not have GE. We conclude that cholecystojejunostomy is an effective method of biliary bypass. Because its addition did not seem to increase operative morbidity or mortality, we advocate GE at the initial exploration to prevent gastric outlet obstruction.