In vivo evidence that endogenous dopamine modulates sympathetic activity in man.

Dopamine receptors type 2 (D2)-like receptor blockers cause an increase in the norepinephrine response to intense physical exercise. However, during intense physical exercise, D2-like antagonists also cause an increase in the epinephrine response, which itself might cause an increase in plasma norepinephrine through the activation of beta2 presynaptic receptors. Therefore, we evaluated the effect of domperidone, a D2-like antagonist, on the norepinephrine response to physical exercise in 6 Addison patients (3 were adrenalectomized and 3 had adrenal tuberculosis). In these patients, the norepinephrine increase observed during exercise was significantly higher after the administration of domperidone than a placebo (F=4,328; P<0.001). Because peripheral plasma norepinephrine does not reflect the sympathetic tone to the heart accurately, we evaluated the effect of domperidone administration (20 mg orally) on the sympathovagal balance, which was measured by the ratio between the high- and low-frequency components of heart rate variability, in 9 normal volunteers in the supine and sitting positions. When compared with placebo, domperidone caused a significant increase in the low/high frequency ratio (P<0.05) in the sitting position without modifying basal and stimulated norepinephrine plasma levels or blood pressure. These data support a role for endogenous dopamine in modulating norepinephrine release by human sympathetic nerves in vivo.

Inability of serum myocyte death markers to predict acute cardiac allograft rejection.

Acute cardiac rejection involves myocyte necrosis. Hence, markers of myocyte death may be useful in diagnosing rejection. Creatine kinase MB, MB isoforms, and troponins I and T were measured in 186 patients undergoing 365 endomyocardial biopsies. No differences were noted with rejection (rejectors vs. nonrejectors: CK=63.8 U/L and 86.6 U/L, P=0.0881; CK MB=2.04 ng/ml and 2.06 ng/ml, P=0.949; troponin T=0.134 ng/ml and 0.0881 ng/ml, P=0.374; troponin I=0.216 ng/ml and 0.707 ng/ml, P=0.357). The time course of troponins T and I levels in rejectors and nonrejectors do not differ with both groups having early elevations. Markers of myocyte death are inadequate predictors of acute rejection in cardiac allografts. The time course of troponins T and I suggests a possible role as prognostic indicators of outcome.

Diagnosis of pancreatic allograft rejection by measurement of urinary radioimmunoreactive insulin.

The accurate, early, and sensitive diagnosis of pancreatic allograft rejection is one of the major problems in clinical pancreas transplantation today. Pancreaticocystotomy is a popular technique for pancreas transplantation that permits simple and frequent urinary chemistry examinations. In this experiment, 20 mongrel dogs with a bladder-drained pancreatic transplant had serial monitoring of urinary amylase (UA) and urinary insulin (UI). The mean UI in the nonrejection state was 9.6 +/- 12 mIU/L. In eight dogs varying degrees of rejection were documented by histopathology. All three animals having severe acute rejection had high levels of IU (all greater than 300-800 mIU/L). Of the five animals with mild-to-moderate rejection, all had significant UI elevations to greater than 100 mIU/L but none had elevations above 200 mIU/L (P less than 0.05 for all groups). Ten animals were treated with prednisone, Imuran, and cyclosporine (CsA), and five of these dogs had good graft function for greater than 14 days, during which the mean UI was extremely low (11 +/- 6.4 mIU/L, P less than 0.05). These values were not significantly different from the 0-14-day values for three pancreas autotransplants with bladder drainage (8.9 +/- 7.2 mIU/L, P less than 0.05). All rejections were preceded by significant rises of UI occurring two to five days prior to rejection. In seven animals, early graft dysfunction (1-4 days) developed, with total graft necrosis by five days. This graft injury was presumably caused by preservation damage or early vascular thrombosis and was associated with early (1-4 days) marked elevations of the UI (greater than 300 mIU/L). None of the animals with grafts surviving to rejection at seven days or more had these early severe elevations, and thus these early UI rises are pathognomonic of graft damage. In contrast, UA and lipase showed inconsistent association with rejection or early damage, although falls in UA generally occurred at or following the time of rejection. Marked daily variations in UA measurements were the most difficult aspect of UA monitoring. Serial electromagnetic flow probe studies of blood flow to the pancreas graft showed a good correlation between loss of blood flow and rises in UI associated with early graft injury. These results suggested that the UI assay gives a sensitive, early, accurate, and specific differential prediction of pancreas graft dysfunction. Specifically, the UI assay appears to be of value not only in the early differential diagnosis of graft injury and graft rejection, but also in the assessment of the severity of rejection.(ABSTRACT TRUNCATED AT 400 WORDS)

The effect of lysed platelets on neutralization of heparin in vitro with protamine as measured by the activated coagulation time (ACT)

The effect of lysed platelets on the activated coagulation time (ACT) was studied in heparinized whole blood during titration with protamine. Frozen-thawed washed platelet suspension, or a chromatography fraction thereof, or autologous frozen-thawed platelet-rich plasma was added in various dilutions to freshly drawn blood anticoagulated with 3,000 USP units/l heparin. After a 10 min incubation, the amount of protamine needed to restore the ACT to baseline ("protamine titration dose") was determined. We found that the protamine titration dose decreased in proportion to the amount of lysed platelet material added; expressed as a percentage of the total number of platelets present, each unit increase in lysed platelets produced a 1.7% +/- 0.8 (SD) reduction in the protamine dose needed to normalize the ACT. A heparin activity assay showed that this effect was not due to anti-heparin activity of lysed platelets such as platelet factor 4 (PF4). Our data indicate that the procoagulant activity of platelet membranes reduced the sensitivity of the ACT to heparin. These findings suggest that membranous platelet microparticles may cause an inaccurate calculation, based on the ACT, of a protamine dose to reverse heparin anticoagulation in cardiopulmonary bypass procedures.

Large and small airway responses to procaterol hydrochloride administered through different extension devices in asthmatic patients.

The effects of spacer devices on the magnitude and velocity of large and small airway bronchodilator responses in asthmatic patients who can correctly operate a metered dose inhaler (MDI) remain unclear. According to a double-blinded, randomized, crossover protocol, 14 asthmatic patients were studied on seven separate occasions. On each occasion, patients inhaled doubling methacholine concentrations until forced expiratory volume in 1 second (FEV1) had fallen by 20% of baseline. Changes in forced expiratory flow between 25% and 75% of vital capacity (FEF25-75) were also evaluated. Subsequently, patients were administered 20 or 50 micrograms of procaterol from an MDI either alone or in conjunction with a small- or large-volume spacer device. Changes in FEV1 and FEF25-75 corrected for baseline forced vital capacity (isoFEF25-75) were assessed at 3-minute intervals for 15 minutes and at 30 minutes. Spontaneous recovery was similarly evaluated. The time required to attain significant increases in both FEV1 and isoFEF25-75 was calculated in bronchodilator trials. With 20 micrograms of procaterol, both spacers allowed larger and faster FEV1 increases than the MDI alone (P < 0.01); with 50 micrograms, the velocity and magnitude of FEV1 increases were further enhanced in trials with the MDI alone. The lower procaterol dose via the large-volume spacer determined larger and faster isoFEF25-75 increases than the higher dose via both the small-volume spacer and the MDI alone (P < 0.01). Spacers enhance bronchodilation even in patients using MDIs optimally. Compared with both the small-volume device and the MDI alone, the large-volume spacer allows faster and larger small airway dilation with less than half of the procaterol dose.

[Physical exercise in the thromboembolism of the pulmonary artery]. / L'esercizio fisico nella tromboembolia dell'arteria polmonare.

In order to evaluate post-embolic pulmonary gas exchange responses to exercise, we studied 7 patients who had previously suffered from an acute pulmonary embolism but were presently free from clinical and functional signs of cardiorespiratory diseases. Patients came to the laboratory on two occasions, 30 and 120 days following the episode of acute embolism, respectively, and performed an incremental ramp exercise test up to the maximum attainable workload. On both occasions, the dead volume/tidal volume (VD/VT) ratio at rest increased. During the first exercise test performed 30 days after the acute pulmonary embolism, mean VD/VT decreased from a resting value of 62.5% to 38.6% at the maximum workload. During the second exercise test, VD/VT decreased, at the same workload, from 71.3% to 35.5%. There was no significant difference in exercise-related VD/VT decrease between the two exercise tests. The results suggest that in patients who have suffered from an acute pulmonary embolism, a considerable pulmonary blood flow redistribution may occur during incremental ramp exercise performed 30 and 120 days after the acute event.

Changes in concentrations of C-reactive protein in serum after kidney or heart transplantation.

C-reactive protein (CRP) concentrations were serially determined in serum after kidney or heart transplantation. The initial postsurgical CRP response in these patients was compared with that of control patients undergoing related procedures but not subjected to immunosuppressive therapy. Immunosuppression clearly depressed the postsurgical CRP response in transplant recipients. The effect is greatest with the administration of cyclosporine. In addition, we found serial CRP determinations to be a sensitive indicator of renal but not cardiac allograft rejection. The specificity of CRP as such a predictor was affected by non-rejection-based inflammation. We conclude that serial determination of CRP, interpreted by the extent by which its concentration increases between sequential samples, may be a useful adjunct to biochemical monitoring of renal transplants, but a similar approach to monitoring heart transplants is not possible.

Robotic sample preparation evaluated for the immunochemical determination of cardiac isoenzymes.

A general-purpose bench-top laboratory robot was programmed to perform sample preparation for immunoprecipitative and immunoinhibitory determinations of cardiac isoenzymes with commercial kits. Run size could be varied from 1 to 24 patients' samples, and was determined by the robot without prompting. The robot placed the processed samples into a sample rotor for dried transfer to a batch centrifugal analyzer. Robotic precision compared well with that of manual performance of the same procedures at four concentrations of lactate dehydrogenase (EC 1.1.1.27) isoenzyme 1 activity and at one of two concentrations of creatine kinase (EC 2.7.3.2.) isoenzyme MB activity; for the other creatine kinase MB concentration, use of the robot significantly improved precision. Results for 100 samples from patients after open-heart surgery were highly correlated with manually obtained results for both isoenzyme determinations (r less that 0.96 each). Time to completion for small run sizes for either approach was comparable about 25 min. For larger batches, robotic run time increased rapidly, to 169 min for 24 patients' samples vs 41 min by manual assay.

Comment: Applications of robotics in the clinical laboratory.

The implementation of a robotic workstation in the clinical laboratory involves considerations and compromises common to any instrument design and development activity. The trade-off between speed and flexibility not only affects the way the instrument interacts with human operators and other devices (the 'real-world interface'), but also places limitations on the adaptation of chemistries to the given instrument. Mechanical optimization for speed and reproducibility places restrictions on the imprecision of consumables. Attempts to adapt a robot to a constrained system may entail compromises that either degrades the theoretically-attainable quality of results, or requires human interaction to compensate for physical or mechanical limitations. The general considerations of function and workflow, programming and support, and reliability place practical limits on the implementation of robotic workstations in the clinical laboratory.

Anaerobic threshold: reproducibility out from ventilatory parameter estimation.

Anaerobic threshold (AT) during exercise is usually noninvasively determined by assuming a two-segment mathematical relationship between two ventilatory parameters. In the literature, all the possible pairs of segments are first considered, and the most appropriate pair is then selected according to at least-squares method. In such a model, the AT is considered to be related to the joining point of the two segments. In order to test the reliability of the model, we compare the results of the least-squares method to those based on maximum probability method in discriminating the two regression coefficients. In order to test the reproducibility of the two different criteria, comparisons have been repeated after data have been filtered. A paired t test was used to carry out comparisons. Ventilatory parameters were collected in 10 healthy subjects during the use of a bicycle ergometer. The required power was increased every 15 s by steps of 30 W, starting from 50 W. Ve, VO2 and VCO2 have been sampled every 15 s, then the three functions--Ve versus VO2, Ve versus VCO2 and VCO2 versus VO2--were considered. Each function was stylized with two linear segments. Each segment was estimated by using a second-kind linear fitting. We verified that: (i) the AT may be reliably appreciated depending on the pair of selected parameters; (ii) only when data are smoothed is no difference between the two criteria documented (Ve vs. VO2, p = 0.99; Ve vs. VCO2, p = 0.54); (iii) no significant difference, related to smoothing, is documented both in using the least-squares method (Ve vs. VO2, p = 0.61; Ve vs. VCO2, p = 0.15) and the maximum p level criterion (Ve vs. VO2, p = 0.59; Ve vs. VCO2, p = 0.19).

Transmission of Toxoplasma gondii infection by liver transplantation.

Toxoplasmosis is an important disease in immunocompromised hosts, particularly in patients with AIDS and in heart transplant recipients. Infection with Toxoplasma is less commonly seen in recipients of other solid organ transplants. We report a case of fulminant disseminated infection with Toxoplasma after liver transplantation. Despite numerous diagnostic studies including open lung biopsy, toxoplasmosis was diagnosed only at the time of autopsy and involved the brain, spinal cord, pituitary gland, lungs, and heart. Toxoplasmosis should be considered in the differential diagnosis of multiorgan failure in the early period after liver transplantation. If mismatched serologies could be identified then clinical suspicion might be higher and prophylactic or empirical therapy could be instituted. The United Network for Organ Sharing (Richmond, VA) should consider including serology for Toxoplasma in the testing of donors.

Adherence to structured physical exercise in overweight and obese subjects: a review of psychological models.

Regular physical exercise is a widely accepted means of reducing mortality and improving a number of health outcomes, which is also efficacious in the treatment of obesity. Unfortunately, despite the evidence of favourable short- and long-term effects, the results seem to be affected by a lack of adherence, particularly over the long term. It is very important to evaluate and predict good adherence in order to be able to assess the real efficacy of physical activity in the treatment of various diseases. In this paper, we describe most of the psychological models used to evaluate such adherence, and investigate the physiological and psychological bases of physical activity, the most suitable type of exercise for obese patients and some useful strategies for ensuring long-term adherence.

Application of the EXPERT consultation system to accelerated laboratory testing and interpretation.

The EXPERT consultation system-building tool, a knowledge-based artificial intelligence program developed at Rutgers University, has been applied to the development of a laboratory consultation system facilitating sequential laboratory testing and interpretation. Depending on the results of a basic panel of laboratory tests, the system requests that specific secondary tests be performed. Input of these secondary findings can result in requests for tertiary testing, to complete the database necessary for interpretation. Interpretation of all results is based upon final inferences from the collected findings through a series of rules, a hierarchical network that yields an efficient production system not easily obtained through conventional programming. The rules included in this model are based upon initial results for total protein, calcium, glucose, total bilirubin, alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase, thyroxin, hemoglobin, mean corpuscular volume, and the concentrations of four drugs. Pertinent clinical history items included are jaundice, diabetes, thyroid disease, medications, and ethanol. Implementing this system in a laboratory-based accelerated testing program involving outpatients maximized the effective use of laboratory resources, eliminated useless testing, and provided the patient with low-cost laboratory information.

Pulmonary involvement in juvenile systemic lupus erythematosus: a study on lung function in patients asymptomatic for respiratory disease.

Pleuro-pulmonary involvement has been well recognized in adults affected with systemic lupus erythematosus (SLE), but few studies have been carried out in children. A longitudinal study on a group of 15 children affected with juvenile SLE (JSLE), asymptomatic for lung disease, was performed, and the prevalence and the features of respiratory function alterations, over a period of 12 months, were analysed. Moreover, a possible correlation between any pulmonary function test (PFT) and disease duration, disease activity, visceral involvement and immunological pattern was evaluated. At baseline, a significant functional lung impairment was present in 40% of patients, with a significantly reduced FVC, VA and DLCO in 26% of them; in 60% of patients at 6 months and in 33% of patients at 12 months. At 6 and 12 months, our data did not show any significant modification in PFTs and the restrictive pattern, observed at baseline, remained unchanged. No correlation between altered PFTs and disease duration, activity and/or immunological findings was found. At baseline, the presence of neurological involvement was the only extra-pulmonary feature correlated to reduced FVC.

Effect on lung function of methotrexate and non-steroid anti-inflammatory drugs in children with juvenile rheumatoid arthritis.

We evaluated lung function in a group of patients affected by juvenile rheumatoid arthritis (JRA), without clinical and/or radiological signs of respiratory involvement. We compared the effects on pulmonary function of methotrexate (MTX) therapy combined with non-steroid anti-inflammatory drugs (NSAIDs) to those of NSAIDs alone and correlated lung function to subtype onset, disease duration and disease activity. Our patients were 27 JRA children, subdivided into two groups according to the therapy (group A = 14 patients, treated with a low dose of MTX and NSAIDs; group B = 13 patients, treated with NSAIDs alone). Clinical evaluation, haematological data and pulmonary function tests (PFTs) were obtained in each group at baseline (time 0) and at 1 year (time 1). At time 0 and time 1 PFTs were altered in 51.8% of JRA patients. The restrictive pattern (reduced forced vital capacity, FVC) was the most frequent feature, observed in 22.2% of patients. In group A the mean values of FVC, FEV1 (forced expiratory flow in 1 s), FRC (functional residual capacity), TLC (total lung capacity) and DLCO (diffusing lung capacity of carbon monoxide) were significantly lower compared to those of group B, at time 0 and at time 1. No functional parameter was correlated to subtype, duration or activity of the disease. Our study confirms that abnormalities in PFTs may be detected in JRA patients, even in the absence of clinical and/or radiological signs of lung disease; MTX in combination with NSAIDs does not seem to affect lung function at 1 year more than NSAIDs alone.

Effect of reticulocytosis on lactate dehydrogenase isoenzyme distribution in serum: in vivo and in vitro studies.

We investigated the effect of reticulocytosis on the lactate dehydrogenase (LD; EC 1.1.1.27) isoenzyme LD1/LD2 ratio in patients with and without evidence of hemolytic disease. Analysis of sera from patients with reticulocytosis and in vivo hemolysis showed a mean LD1/LD2 ratio of 0.92 compared with a ratio of 0.69 in patients with in vivo hemolysis and normal reticulocyte counts. Determination of LD isoenzymes in erythrocyte lysate revealed significantly increased LD1/LD2 ratios for patients with marked reticulocytosis compared with those for patients with normal-to-minimal increases in reticulocytes. Finally, separation of mature erythrocytes and reticulocytes by flow cytometry revealed marked differences in the LD1/LD2 isoenzyme distribution between these two cell types. The ability of hemolysis to cause a "flipped" LD1/LD2 ratio is dependent on the proportion of the hemolyzed cells that are reticulocytes.

Plasmacytoma of the ovary: a case report and literature review.

BACKGROUND: Ovarian plasmacytomas are a unique and unusual presentation of extramedullary plasmacytomas (EMP). A report of the seventh such case is presented with review of the previous six cases. METHODS: Surgical and medical staging were performed on the present case. The literature is reviewed. RESULTS: EMP involving the ovary is usually large at the time of presentation, more likely involving the left side, and without evidence of disseminated disease. As in other plasma cell dyscrasia, IgG paraprotein is more frequently involved. CONCLUSION: Adjuvant treatment for ovarian plasmacytomas is not clearly established; however, if complete surgical resection is achieved and no evidence of multiple myeloma is found, observation should be strongly considered.

Fog-induced respiratory responses are attenuated by nedocromil sodium in humans.

Fog inhalation induces cough and bronchoconstriction in patients with asthma, but only cough in normal subjects; whether it also influences the pattern of breathing is unclear. Nedocromil sodium (NCS) inhibits the cough response to inhalation of several pharmacological agents but its effects on fog-induced cough and changes in the pattern of breathing are unknown. We evaluated the effects of no drug, placebo, and 4- and 8-mg NCS administration on the cough threshold and changes in the pattern of breathing during fog inhalation in 14 healthy subjects. Measurements of tidal volume (VT), duration of inspiratory and expiratory times (TI and TE, respectively), total duration of the respiratory cycle (TT), mean inspiratory flow (VT/TI), duty cycle (TI/TT), respiratory frequency (f, 60/TT), and inspiratory minute ventilation (V I) were obtained by inductive plethysmography. Median cough threshold values were unaffected by placebo, but were increased (p < 0.01) by both NCS doses. In no-drug and placebo trials, inhalation of the threshold fog concentration caused increases in both VT/TI and V I (p always < 0.05) due to selective increases (p < 0.01) in VT. These changes were markedly attenuated by both NCS doses administration. Thus, fog induces coughing and increases in VT, VT/ TI, and V I in healthy subjects; NCS possesses antitussive effects and attenuates fog-induced changes in the pattern of breathing, possibly through inhibition of rapidly adapting "irritant" receptors.