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To provide a potentially therapeutic intervention and to collect clinical and laboratory data during an outbreak of hantavirus pulmonary syndrome (HPS), 140 patients from the United States with suspected HPS were enrolled for investigational intravenous ribavirin treatment. HPS was subsequently laboratory confirmed in 30 persons and not confirmed in 105 persons with adequate specimens. Patients with HPS were significantly more likely than were hantavirus-negative patients to report myalgias from onset of symptoms through hospitalization, nausea at outpatient presentation, and diarrhea and nausea at the time of hospitalization; they were significantly less likely to report respiratory symptoms early in the illness. The groups did not differ with regard to time from the onset of illness to the point at which they sought care; time from onset, hospitalization, or enrollment to death was significantly shorter for patients with HPS. At the time of hospitalization, patients with HPS more commonly had myelocytes, metamyelocytes, or promyelocytes on a peripheral blood smear, and significantly more of them had thrombocytopenia, hemoconcentration, and hypocapnia. Patterns of clinical symptoms, the pace of clinical evolution, and specific clinical laboratory parameters discriminated between these 2 groups.

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Inherited defects in myocardial long-chain fatty acid metabolism are increasingly recognized as a cause of cardiomyopathy and sudden death in children. To evaluate whether the phenotypic expression of these genetic diseases could be delineated using positron emission tomography (PET), 11 patients with inherited defects in fatty acid metabolism were evaluated and results were compared with those of 6 nonaffected siblings. Myocardial perfusion, myocardial oxygen consumption (MVO2), and long-chain fatty acid metabolism were determined noninvasively with PET using quantitative mathematical models. There were no differences in haemodynamics, perfusion, MVO2 or plasma substrate levels between groups. Patients with defects in enzymes of fatty acid beta-oxidation (acyl-CoA dehydrogenase and 3-hydroxyacyl-CoA dehydrogenase deficiencies) (n = 5) had diminished myocardial palmitate oxidation compared with healthy siblings (3.2 +/- 3.0 vs. 13.0 +/- 5.6 nmol/g per min, p < 0.03) and a decrease in the percentage of MVO2 accounted for by palmitate (2% +/- 3% vs. 9% +/- 5%, p < 0.04). In these patients, extracted palmitate was shunted into a slow-turnover compartment (predominantly reflecting esterification to triglycerides) with expansion of palmitate in that pool (185 +/- 246 compared with 27 +/- 67 nmol/g in healthy siblings,p < 0.02). In contrast, myocardium of patients with carnitine deficiency (n = 6) (all on oral carnitine therapy) had normal palmitate extraction but expansion of the interstitial/cytosolic fatty acid pool (617 +/- 399 vs. 261 +/- 73 nmol/g in healthy siblings, p < 0.04), suggesting different mechanisms for handling upstream fatty acyl intermediates. Thus, PET can be used to noninvasively assess abnormal myocardial handling of fatty acids in patients with inherited defects of metabolism. This approach should be useful in the assessment of altered myocardial fatty acid metabolism associated with cardiomyopathy as well as for evaluating the efficacy of therapeutic interventions in affected patients.

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PURPOSE OF THE STUDY: After total hip replacement, the initial stability of the cementless femoral stem is a prerequisite for ensuring bone ingrowth and therefore long term fixation of the stem. For custom made implants, long term success of the replacement has been associated with reconstruction of the offset, antero/retro version of the neck orientation and its varus/valgus orientation angle. The goals of this study were to analyze the effects of the extra-medullary parameters on the stability of a noncemented stem after a total hip replacement, and to evaluate the change of stress transfer. MATERIAL AND METHODS: The geometry of a femur was reconstructed from CT-scanner data to obtain a three-dimensional model with distribution of bone density. The intra-medullary shape of the stem was based on the CT-scanner. Seven extra-medullary stem designs were compared: 1) Anatomical case based on the reconstruction of the femoral head position from the CT data; 2) Retroverted case of - 15 degrees with respect to the anatomical reconstruction; 3) Anteverted case with an excessive anteversion angle of + 15 degrees with respect to the anatomical case; 4) Medial case: shortened femoral neck length (- 10 mm) inducing a medial shift of the femoral head offset; 5) Lateral case: elongated femoral neck length (+ 10 mm) inducing lateral shift of the femoral head offset 6) Varus case with CCD angle 127 degrees; 7) Valgus case with CCD angle 143 degrees. The plasma sprayed stem surface was modeled with a frictional contact between bone and implant (friction coefficient: 0.6). The loading condition corresponding to the single limb stance phase during the gait cycle was used for all cases. Applied loads included major muscular forces (gluteus maximus, gluteus medius, psoas). RESULTS: Micromotions (debonding and slipping) of the stems relative to the femur and interfacial stresses (pressure and friction) were different according to the extra-medullary parameters. However, the locations of peak stresses and micromotions were not modified. The highest micromotions and stresses corresponded to the lateral situation and to the anteverted case (micro-slipping and pressure were increased up to 35 p.100). High peak pressure was observed for all designs, ranging from anatomical case (34 MPa) to anteverted case (44 MPa). The peak stresses and micromotions were minimal for the anatomical case. The maximal micro-debonding was not significantly modified by the extra-medullary design of the femoral stem. DISCUSSION: The extra-medullary stem design has been shown to affect the primary stability of implant and the stress transfer after THR. Most interfacial regions present small micro-slipping which normally allows the occurrence of bone ingrowth. The anatomical design presents the lowest micromotions and the lowest interfacial stresses. The worst cases correspond to the anteverted and lateralized cases. Probably, the anteverted situation involves higher torsion torque, which in turn may induce high torsion shear micromotions and higher stress at the interface. Moreover, the lever arm of the weight bearing force on the femoral head is augmented for the augmented neck length situation. This increases the bending moment, and therefore may increase the stresses as well as the stem shear micromotions. In summary, the present results could be taken as biomechanical arguments for the requirement of anatomical reconstruction of not only the intra-medullary shape but also the extra-medullary parameters (reconstruction of the normal hip biomechanics).

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Intravenous ribavirin was provided non-selectively for investigational open-label use among persons with suspected hantavirus pulmonary syndrome (HPS) in the United States between 4 June 1993 and 1 September 1994. Therapy was initiated prior to laboratory confirmation of hantavirus infection because most deaths from HPS occur within 48 h of hospitalization. Thirty patients with confirmed HPS, 105 patients without HPS and 5 patients without adequate diagnostic testing for HPS were enrolled. This observational study arguably provides the most complete information available on ribavirin-associated adverse effects. Although ribavirin was generally well tolerated, 71% of recipients became anaemic and 19% underwent transfusion. An apparent excess of hyperamylasaemia/pancreatitis was either therapy-associated or due to enrollment bias. The 30 enrolled HPS patients had a case-fatality rate of 47% (14/30). It is not possible to assess efficacy with this study design. However, comparison of survival curves for the 30 enrolled HPS patients and 34 patients who developed HPS during the same time period but were not enrolled did not suggest an appreciable drug effect. A randomized, placebo-controlled trial that enrolls patients during the prodrome phase would be necessary to assess the efficacy and further define the safety of intravenous ribavirin for HPS.

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BACKGROUND: Contractile reserve, improvement in contractile function during inotropic stimulation, is a proposed marker of viable myocardium. This study was designed to address, in patients with left ventricular dysfunction due to chronic coronary artery disease, whether contractile reserve depends on myocardial blood flow. METHODS AND RESULTS: We studied 19 patients, at rest and during dobutamine, with 2D echocardiography for regional mechanical function and PET for regional myocardial blood flow ([(15)O]water) and oxygen consumption ([11C]acetate). Of 166 myocardial segments, 21 had normal systolic function, 56 were dysfunctional but contractile reserve-positive, and 89 were dysfunctional and contractile reserve-negative. Myocardial blood flow at rest was lower in contractile reserve-negative (0.41+/-0.18 mL x g(-1) x min(-1)) than in contractile reserve-positive (0.50+/-0.22 mL x g(-1) x min(-1)) and normal segments (0.55+/-0.20 mL x g(-1) x min(-1), P<.009). After dobutamine infusion, blood flow increased less in contractile reserve-negative (0.63+/-0.38 mL x g(-1) x min(-1)) than in contractile reserve-positive (1.28+/-0.65 mL x g(-1) x min(-1)) and normal segments (1.93+/-0.83 mL x g(-1) x min(-1), P<.0001). Likewise, myocardial oxygen consumption was lower at rest in contractile reserve-negative (clearance rate of [11C]acetate, 0.043+/-0.012 min(-1)) than in contractile reserve-positive (0.048+/-0.01 min(-1)) and normal segments (0.058+/-0.008 min(-1), P<.02). Myocardial oxygen consumption with dobutamine increased less in contractile reserve-negative (0.060+/-0.013 min(-1)) than in contractile reserve-positive (0.077+/-0.016 min(-1)) and normal segments (0.092+/-0.024 min(-1), P<.0001). Of segments defined as viable by PET, 54% were contractile reserve-negative and exhibited lower blood flow with dobutamine (0.72+/-0.36 mL x g(-1) x min(-1)) than with viable, contractile reserve-positive segments (1.29+/-0.70 mL x g(-1) x min(-1), P<.0001). CONCLUSIONS: Contractile reserve depends, in part, on the level of myocardial blood flow at rest and during inotropic stimulation.

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In the field of uncemented hip arthroplasties, secondary biologic fixation of femoral implants depends directly on the quality of the primary stability. Metaphyseal filling and a good fit between the implant and the proximal femur improve initial stabilization and optimize the transmission of forces to the bone. Precise knowledge of the three-dimensional femoral shape is essential to the design and selection of adapted implants. Three hundred ten femurs in 300 patients suffering from primary hip osteoarthritis were analyzed by computed tomography scanning. After three-dimensional reconstruction, several measurements were extracted, and the parameters essential to the characterization of the diverse femoral morphologies encountered were identified. A new classification of the proximal femur is proposed. The consequences on the design and the preoperative selection of femoral implants are discussed.

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The purpose of the study is to investigate the influence of psychosocial stress, maternal schooling, social support, psychological well-being, alcohol and smoking on intrauterine growth retardation and premature delivery. At a Copenhagen university hospital 2432 consecutive Danish-speaking women in 20th week of pregnancy completed a questionnaire including the General Health Questionnaire and Severity of Psychosocial Stressor Scale and questions about social network, education, smoking and drinking habits. In 212 cases (8.7%) the women delivered before day 259 of gestation. In a multiple logistic regression model, pre-term delivery proved to be associated with psychosocial stress and poor school education. In 152 cases (6.3%) infants had a birth weight below the defined 10th percentile. In a multiple logistic regression model, IUGR was associated with smoking. In preventive programmes, such as anti-smoking campaigns, it should be kept in mind that women who smoke are also the least educated and have the poorest support from a social network.

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In patients with chronic coronary artery disease, preservation of myocardial oxidative metabolism measured by positron emission tomography (PET) with 11C-acetate is a more accurate predictor of subsequent myocardial functional recovery than is maintenance of glucose metabolism estimated with 18F-fluorodeoxyglucose. However, whether measurements of myocardial oxidative metabolism are more accurate than measurements of glucose metabolism in predicting functional recovery in patients with recent myocardial infarction is unknown. Myocardial oxidative metabolism was measured within 10 days of infarction in 19 patients by analysis of the rate of myocardial clearance of 11C-acetate. Metabolism of glucose was assessed by analysis of the uptake of 18F-fluorodeoxyglucose. Criteria for prediction of the recovery of function based on measurements of oxidative metabolism and glucose metabolism were compared. Threshold criteria with 11C-acetate exhibited superior positive and negative predictive values (89% and 73%, respectively) compared with the criteria of 18F-fluorodeoxyglucose (65% and 57%, respectively) (p <0.025). In addition, the magnitude of functional recovery after revascularization correlated with the severity of the metabolic abnormality present initially. In patients with recent myocardial infarction, the extent of functional recovery can be predicted accurately by measurement of regional oxidative metabolism by PET with 11C-acetate, and these measurements are superior to those of 18-fluorodeoxyglucose.

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BACKGROUND: Cardiac transplantation is an increasingly important treatment for patients with end-stage heart failure. Rejection is one of the major limitations, and currently, serial endomyocardial biopsies are required to diagnose rejection. In the year after transplantation, patients routinely undergo 12, 14, or more biopsies. Infiltration of lymphocytes into the graft is a central feature of rejection. Previous studies from our laboratory have demonstrated the feasibility of detecting early rejection noninvasively with gamma scintigraphy after administration of autologous lymphocytes labeled with 111In. METHODS AND RESULTS: Eight patients were studied at the time of routine biopsy an average of 4.5 months after cardiac transplantation. Autologous lymphocytes were isolated and labeled with 111In. Forty-eight to 72 hours later, patients underwent planar scintigraphic imaging. Myocardial accumulation of labeled lymphocytes was quantified (indium excess, IE) with a previously described and validated technique. Animal studies have shown that an IE > or = 0.07 is associated with rejection. Two of four patients with biopsy grade 0 or 1A rejection had no excess accumulation of labeled lymphocytes. The other two patients with biopsy grade 0 or 1A had an average IE of 0.13 +/- 0.04 (SD), which may actually represent the higher sensitivity of the scintigraphic approach, since the whole myocardium is interrograted. All four patients with biopsy grade 1B rejection had increased accumulation of labeled lymphocytes (IE = 0.18 +/- 0.06, P = .06 compared with all patients with grade 0 or 1A biopsies). CONCLUSIONS: The development of a sensitive, specific, and noninvasive method of diagnosing cardiac allograft rejection in humans might obviate the need for endomyocardial biopsy as well as improve the accuracy of diagnosis. The results suggest that scintigraphic detection of labeled lymphocytes is a promising approach for the noninvasive detection of cardiac transplant rejection. In addition, the approach should permit the assessment of the efficacy of antirejection therapy.

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The purpose of this study was to examine the differential myocardial signal responses due to the blood oxygen level dependent (BOLD) effect in magnetic resonance imaging (MRI) under differing conditions of myocardial oxygen supply and demand. The signal response was measured when myocardial blood flow was increased in excess of oxygen demand or when flow was increased in response to increased myocardial oxygen demand. Normal volunteers were studied using a segmented, interleaved, double-echo, gradient-echo sequence at baseline conditions and during pharmacological stress with either dipyridamole (n = 5) or dobutamine (n = 6). Changes in T2* in the myocardium during stress were calculated. Peak coronary flow velocity was measured at rest and during stress using a breath-hold phase contrast technique. Administration of dipyridamole induced a 124 +/- 27% increase in coronary blood flow which resulted in a 46 +/- 22% increase in T2*, consistent with a decrease in myocardial venous deoxyhemoglobin concentration as myocardial oxygen supply exceeds demand. In contrast, the administration of dobutamine resulted in a 41 +/- 25% increase in coronary blood flow but no significant change in T2* (-5 +/- 19%), consistent with a lack of change in myocardial venous deoxyhemoglobin concentration and balanced oxygen supply and demand. Thus, alterations in the relationship between myocardial oxygen supply and demand appear to be detectable using BOLD MRI.

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Forty-five patients with schizophrenia or schizophreniform disorder admitted to hospital for the first time had a neurological examination, including integrative sensory and complex motor acts, by a trained neurologist. The patients were studied by CT and regional cerebral blood flow as well. A control group of 24 healthy volunteers was included. The patients had significantly more neurological abnormalities (NA) than the healthy volunteers. Medication did not explain the discrepancy. The NA were associated with sulcal enlargement and smaller brains as visualized by CT but not with ventricular enlargement. There was no association between the regional flow values and NA.

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During knee flexion, the human patella moves along a complex path resulting from the combined actions of articular contact and soft-tissue stabilization. The current study is an attempt to characterize the role of these soft structures on patellar kinematics. To this end, the three-dimensional patellar motion during full knee flexion was accurately measured before and after partial dissection of the joint. The guiding role of the femoral groove prevailed over soft-tissue action through most of the range of motion. At full extension, however, when the patella and the femur were not in contact, the influence of the retinaculi was most noticeable, highlighting the unstable behavior of the patella near extension. The differences between the intact and dissected knee kinematics suggested that control over patellar motion is ensured by the transverse soft-tissue structures near extension and by the patellofemoral joint geometry during further flexion.

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A numerical model of a femoral total hip component based on the finite element method is developed to evaluate the relative micromotions at the bone-implant interface and the stress distribution in the femoral bone. The interface is modelled as unilateral contact involving Coulomb's dry friction between the bone and the implant. In addition, the model includes inhomogeneity, anisotropy as well as plasticity of both cortical and spongious bones. An automatic data processor coupled to a three-dimensional mesh generator is designed to extract cortical bone geometry and inhomogeneous distribution of trabecular bone density from data obtained with quantitative computed tomography (QCT). A preliminary application is conducted to evaluate the mechanical behaviour of an existing bone-prosthesis structure for two typical loadings: a load simulating the single leg stance and a load simulating the stair climbing stance. The obtained results are subdivided in two parts. Firstly, the characterization of stress transfer and micromotions at the bone-stem interface. The peak value of the shear micromotions reaches 600 microns in the proximal medial region with a friction coefficient equal to 0.6. An analysis of the influence of the friction coefficient reveals that the shear and distractive micromotions as well as the shear and normal stresses depend strongly on this coefficient. Secondly, the representation of stresses in the femoral bone. Determination of complementary invariants such as the hydrostatic pressure, the deviatoric stress and anisotropic stresses brings additional insights in the evaluation of the stress field in the femoral bone.

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During the past decades the possibility of measuring regional brain structure and function by computed tomography, magnetic resonance, single photon emission computed tomography and positron emission tomography has brought the biological research on schizophrenia into focus. Structural changes with enlargement of the lateral and third ventricle and broader sulci on the brain surface compared to those of healthy volunteers have been reproducible findings. Functionally, the reduced activity in the prefrontal cortex especially during activation tests has been the most reliable finding. However, the etiology and specific meaning of the brain changes remains unsolved. Furthermore, in all the studies performed there is a considerable overlap in the measurements in the schizophrenic patients and in the controls.

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A numerical model based on the finite element method was developed for the load transfer analysis at the tibial bone-implant interfaces in total knee replacement. A transverse isotropic material model, based on a quadratic elastic potential and on Hill's quadratic yield criterion, was next developed for bone constitutive laws. The bone-cement and bone-prosthesis interfaces were both assumed to be discontinuous. A dry friction model based on Coulomb's criterion was adopted for the interfaces friction. The model was shown to be able to give compressive and shear stresses distributions and distractive and relative shear micromotions at these interfaces. A preliminary application was conducted for cemented metal tray total condylar (MTTC) and for cemented and uncemented porous coated anatomic (PCA) tibial plateaus. The PCA plateaus were found to be more deformable and had greater global displacements than the MTTC one. Debonding of the bone-peg interface was observed for the uncemented PCA. Correspondingly, the stress peaks at the interface beneath the tray were lower for the uncemented PCA. Correspondingly, the stress peaks at the interface beneath the tray were lower for the PCA than for the MTTC. Shear micromotions appeared under the tray for both the two prostheses. We observed that bone anisotropy and interface discontinuity affected the results sensibly.

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Investigation of the development in the incidence of suicide among psychiatric patients is reviewed and it is concluded that the majority of investigations have demonstrated an increasing suicide rate even when the increasing numbers of admissions and discharges are taken into consideration. It is concluded that altered circumstances for psychiatric patients have played a part in relation to the increase in the suicide rate. Investigation of the suicide rates related to diagnoses suggest that manic-depressive patients, alcoholics and schizophrenics have the highest suicide rates. In investigations of patients who died from suicide as compared with patients who did not die from suicide but who were otherwise comparable, it appears that unmarried status, male sex and previous attempted suicide and suicidal thoughts are more frequently correlated with subsequent suicide. Medical audit in connection with suicide among psychiatric patients is discussed as a possible method of improving the training and competence of psychiatric staff in relation to suicidal behaviour.

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Biological fixation of cementless femoral implants requires primary stability by optimal fit in the proximal femur. The anatomy of the bone must then be known precisely. We analysed in vitro the accuracy of bone measurements of 32 femurs and compared the dimensions obtained from radiographs and CT scans with the true anatomical dimensions. Standard radiographs gave only a rough approximation of femoral geometry (mean difference: 2.4 +/- 1.4 mm) insufficiently accurate to allow selection of the best fitting prosthesis from a range of sizes and altogether inadequate to design a custom-made prosthesis. CT scans give greater accuracy (mean difference: 0.8 +/- 0.7 mm) in our experimental conditions, but in clinical practice additional sources of error exist.

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Twelve anatomical values of the proximal femur and theirs variations in rotation (internal 12 degrees, neutral, external 12 degrees) have been measured radiologically by digitalization on a group of ten anatomical units. A computerized analysis has been performed considering the errors in the X-ray amplification and dispersion factors, as well as the methodological imprecisions. It came out that, except for the width of the medullary canal in AP view, all anatomical parameters were very sensitive to the different positions of the femur in rotation and were subject to significant variations. These fluctuations lead the authors to the following conclusion: during the pre-operating planning of cementless hip arthroplasties, the radiology still allows to choose the size of the femoral component so as to improve the fitting with the internal geometry of the femur. However, the radiology still remains insufficient as a basis to conceive and design a custom implant.

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