Fractionation studies of copper in erythrocytes from normal, sickle cell anemia, and hemoglobin C disease.
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Biomedical subjects
Publications and source records attributed to S M Howell.
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The effect of an 80-mg intravenous dose of furosemide on the urinary excretion of digoxin was determined in three adult men with normal renal function, each of whom was taking 0.25 mg digoxin daily on a chronic basis. On two separate days, serum samples were taken and urine was collected every 2 hours over an 8-hour period for determination of digoxin, creatinine, calcium, and sodium concentrations. On the first day of study, a saline bolus was given intravenously, and on the second day, furosemide was given. In all subjects, urinary digoxin excretion increased after furosemide in direct proportion to the increase in urine volume. No consistent correlation was seen between digoxin excretion and creatinine, calcium, or sodium output. No significant changes in serum digoxin were found in this active study. These results are consistent with the hypothesis that increasing glomerular filtration rate or total urine volume increases the renal excretion of digoxin and may result in increased total urinary output of this glycoside.
Epidemiologic studies link plasma cholesterol reduction to increased mortality rates as a result of suicide, violence, and accidents. Deficient central serotonergic activity is similarly associated with violence and suicidal behavior. We investigated the relationship among dietary and plasma cholesterol, social behavior, and the serotonin system as a possible explanation for these findings. Juvenile cynomolgus monkeys (eight female and nine male) were fed a diet high in fat and either high or low in cholesterol. We then evaluated their behavior over an 8-month period. Plasma lipids and cerebrospinal fluid metabolites of serotonin, norepinephrine, and dopamine were assessed on two occasions, at 4 and 5.5 months after the initiation of behavioral observations. Animals that consumed a low-cholesterol diet were more aggressive, less affiliative, and had lower cerebrospinal fluid concentrations of 5-hydroxyindoleacetic acid than did their high-cholesterol counterparts (p < .05 for each). The association among dietary cholesterol, serotonergic activity, and social behavior was consistent with data from other species and experiments and suggested that dietary lipids can influence brain neurochemistry and behavior; this phenomenon could be relevant to our understanding of the increase in suicide and violence-related death observed in cholesterol-lowering trials.
The goal of this study was to determine how well a medial meniscal allograft restores the normal contact mechanics of the medial tibial plateau at the time of implantation. We measured maximum pressure, mean pressure, and contact area of the intact human cadaveric knee, the knee after meniscectomy, the knee with the original meniscus removed and reimplanted as an autograft, and the knee with an allograft. Measurements were made using pressure-sensitive film in 10 specimens loaded in compression to 1000 N at 0 degrees, 15 degrees, 30 degrees, and 45 degrees of flexion. The autograft and the allograft were identically implanted by cementing bone plugs attached to the meniscal horns in anatomic transtibial tunnels and suturing the outer edge of the meniscus to the remnant of the original meniscus. A medial meniscal allograft did not consistently restore normal contact mechanics because the process of implantation and the degree of match between the original and allograft meniscus affected the immediate load-bearing performance of the transplant. However, the allograft did significantly reduce the contact pressure compared with the knee after meniscectomy. If the results from this study can be extrapolated to patients, then using an allograft to restore contact mechanics to normal may require improvements in surgical technique and graft selection.
Tension in an anterior cruciate ligament graft is greater with the knee in flexion when the angle of the tibial tunnel in the coronal plane is vertical or more perpendicular to the medial joint line of the tibia; however, the relationship of the angle of the tibial tunnel to knee function has not been studied. Greater graft tension may limit knee flexion or stretch the graft and increase anterior laxity. Five surgeons treated 119 subjects by reconstructing a torn anterior cruciate ligament using a double-looped semitendinosus and gracilis graft and a standardized technique. The femoral tunnel was drilled through the tibial tunnel. Radiographs were analyzed for tibial tunnel placement and a clinical evaluation was made 4 months postoperatively. Knees were assigned to subgroups according to the angle of the tibial tunnel in the coronal plane (65 degrees to 69 degrees, 70 degrees to 74 degrees, 75 degrees to 79 degrees, 80 degrees to 84 degrees, and 85 degrees to 89 degrees), with the angle of the latter subgroup being most vertical. Loss of flexion increased significantly from 0.5 degrees to 6.5 degrees and anterior laxity increased significantly from 0.5 to 2.2 mm as the tunnel angle was increased. The average angle of the tibial tunnel varied significantly, 11 degrees between surgeons (range, 69 degrees to 80 degrees). We found a tibial tunnel angle of 75 degrees or more is associated with greater loss of flexion and anterior laxity. Surgeons do not drill the angle of the tibial tunnel in the coronal plane accurately. We now routinely drill the tibial tunnel at an angle of 65 degrees to 70 degrees in the coronal plane because it may reduce loss of flexion and anterior laxity.
Quadriceps exercises are used sparingly in the early rehabilitation of ACL reconstructions because of concern about prematurely stretching the ACL graft. The aim of this study was to determine if a maximum isometric quadriceps contraction significantly translates the tibia anteriorly at 15 degrees, 30 degrees, 45 degrees, 60 degrees, and 75 degrees of flexion. Secondly, the role of the ACL in knee stability was analyzed by comparing the amount of tibial translation in normal, ACL deficient, and reconstructed knees. Thirdly, the location in the motion arc where a quadriceps contraction produces anterior tibial translation was determined. Anterior tibial translation was measured using an arthrometer (KT-1000) during an 89 N and manual maximum translation applied to the knee at rest. The manual maximum translation test determines the magnitude of anterior tibial translation produced by a high anterior force applied directly to the proximal calf. These translations were compared to the tibial translation intrinsically induced by a quadriceps contraction. Testing was performed in normal (N = 22), ACL deficient (N = 10), and reconstructed (N = 10) knees. Anterior tibial translation produced by a maximum quadriceps contraction was measured at 15 degrees, 30 degrees, 45 degrees, 60 degrees, and 75 degrees of flexion. The extension exercise resulted in less anterior tibial displacement than an 89 N drawer and half the translation produced by a manual maximum translation (P less than 0.001). Instrumented laxity testing produced greater anterior translation of the tibia than a maximum isometric quadriceps contraction. Anterior tibial translation was the same during maximum isometric knee extension in all tested knees.(ABSTRACT TRUNCATED AT 250 WORDS)
A prospective, observational study was performed to document the serial changes in the magnetic resonance signal of devascularized, hamstring ACL autografts during the 1st year of implantation. Twenty-one ACL deficient knees (14 chronic, 7 acute) were reconstructed. Instability developed in five knees within the first 6 months of graft implantation (24%). Magnetic resonance examinations were performed at 1, 6, 12, 24, 36, and greater than 48 weeks postoperatively (repetition time 1500, echo delay time = 50). A total of 104 scans were reviewed (average, five per knee). The ACL graft was divided into four unequal size zones for analysis. The proximal, middle, and distal thirds of the intraarticular portion of the graft and the portion of the graft within the tibial tunnel were independently analyzed. The magnetic resonance signal in each portion of the graft was graded on a scale with (I) being a normal signal, (II) greater than 50% of the total volume of the graft having a normal signal, (III) less than 50% of the graft having a normal signal, and (IV) 100% of the graft having an increased signal. The increased magnetic resonance signal of the ACL graft was observed to be regionalized and confined to the distal two-thirds of the intraarticular portion of the graft. The portion of the graft exiting the femoral tunnel and within the tibial tunnel retained a normal magnetic resonance signal. The increases in magnetic resonance graft signal were time-dependent, became well established by 3 months, and remained unchanged at 1 year. The clinical outcome could not be predicted based on the magnetic resonance signal of the graft.
This study was designed to analyze how anterior tibial tunnel placement can result in graft impingement by the intercondylar roof. The relationship of the ACL to the intercondylar roof was studied using magnetic resonance scans. An attempt was made to predict the amount of bone that may need to be removed from the intercondylar roof to prevent impingement on a 10 mm thick ACL graft. Magnetic resonance scans of 19 normal ACLs were analyzed. The amount of bone removal required to correct roof impingement was determined for a graft placed either eccentrically or centrally within the ACL insertion, and within the bulk of the normal ACL fibers. An eccentric tibial tunnel placement required approximately 5 to 6 mm and a central placement required 2 to 3 mm of bone removal from the intercondylar roof to prevent impingement. Placing the graft within the bulk of the ACL fibers, just 3 mm posterior to the center of the ACL insertion, required little bone resection to prevent impingement. To prevent ACL graft impingement, roofplasties need to be performed in both acute and chronic ACL reconstructions if the presently accepted locations for positioning the tibial tunnel are used. A more anteriorly placed tibial tunnel requires more bone removal to prevent roof impingement than a more posteriorly positioned tibial tunnel.
In this study we sought both to quantify the forces that result in anterior cruciate ligament graft impingement and the amount of roofplasty necessary to prevent it. The perpendicular force of the intercondylar roof against an anterior cruciate ligament graft was measured in seven fresh-frozen cadaveric knees. Two tibial hole placements were evaluated: an anterior/eccentric hole (26.6% +/- 3.1% of the sagittal depth) and a customized hole aligned 4 to 5 mm posterior and parallel to the slope of the intercondylar roof in the extended knee (42.0% +/- 2.6% of the sagittal depth). A transducer that measured the contact force with the graft was implanted in the roof. An extensive roofplasty was performed so that the sensor would bear all of the roof force. Graft tension was also measured. Extension moments were applied to 20 N-m with a six degree of freedom load application system. Load cycles were repeated with the roof force sensor backed out in 0.8 mm increments. The sensor backout represented a corresponding amount of bone removal in a roofplasty. The flexion angle at roof-graft contact was consistently greater using the anterior tibial hole than the customized one. This held true for all increments of sensor backout. With the anterior hole, the roof sensor (no backout) contacted the graft at 12.8 degrees +/- 6.7 degrees of flexion, whereas the customized hole resulted in contact at 4.1 degrees +/- 4.2 degrees (P = 0.020).(ABSTRACT TRUNCATED AT 250 WORDS)
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The blood supplies of 45 unimpinged, human anterior cruciate ligament grafts were studied during the first 2 years of implantation. Grafts were defined as unimpinged by the low signal intensity of the graft observed on a sagittal proton density magnetic resonance scan. Magnetic resonance imaging with the intravenous contrast agent gadolinium diethylenetriamine pentacetic acid was used to evaluate the blood supply of the hamstring autograft as well as the periligamentous tissues by assessment of enhancement patterns after administration of the agent. The unimpinged anterior cruciate ligament graft acquired no discernible blood supply during the 2 years of implantation. The graft retained the same hypovascular appearance as the normal posterior cruciate ligament. In contrast, the periligamentous soft tissues were richly vascularized and covered the graft by 1 month. The viability of an unimpinged, human anterior cruciate ligament graft may depend more on synovial diffusion than on revascularization.
This study determined that knee extension (range, -30 degrees to 2 degrees) and the slope of the intercondylar roof (range, 26 degrees to 46 degrees) vary widely between knees in both men and women. We found a weak relationship between knee extension and the slope of the intercondylar roof (r2 = 0.207); therefore, roof angle cannot be predicted by clinically measuring knee extension. CLINICAL RELEVANCE; A knee with a given degree of extension can have a variety of different slopes to the intercondylar roof. Knees with the combination of hyperextension and a vertically oriented slope to the intercondylar roof are "unforgiving" because they require a more posterior position for the tibial tunnel to avoid roof impingement and an extensive roofplasty. If the surgical objective is to minimize the extent of the roofplasty and avoid roof impingement, then consideration should be given to customizing the placement of the tibial tunnel to account for variability in knee extension and roof angle when reconstructing the anterior cruciate ligament. Studies have shown that isometric graft placement can be achieved with this surgical approach.
Nineteen patients with roof impingement of an anterior cruciate ligament graft had their grafts inspected during second-look arthroscopy. The diagnosis of roof impingement was suspected from the clinical findings of an effusion, extension deficit, recurrent instability, or anterior knee pain. The diagnosis was confirmed when a portion of the tibial tunnel was anterior to the tibial intersection of the slope of the intercondylar roof on a lateral roentgenogram of the fully extended knee. During second-look arthroscopy the impinged anterior cruciate ligament graft had one or more of the following features: fractured bundles, guillotined remnants at the tibial insertion, parallel fragmentation of an uninterrupted graft, fibrous nodule, or an extrusion of graft material at the outlet of the notch. We hypothesize that these changes in the integrity of the anterior cruciate ligament graft are caused by mechanical injury from roof impingement. CLINICAL RELEVANCE. One should suspect that a patient with an effusion, extension deficit, recurrent instability, or anterior knee pain after an anterior cruciate ligament reconstruction may have roof impingement. A lateral roentgenogram in full extension is diagnostic if the tibial tunnel is anterior to the intercondylar roof. The surgeon should be aware that impinged grafts can have a variety of arthroscopic appearances in addition to the previously reported fibrous nodule or Cyclops lesion.
This study compared the stiffness (K), yield load (YL), and slippage (SL) of six tibial fixation methods. These properties were determined from load-to-failure and cyclic tests of double-looped tendon grafts fixed to both animal and young human tissue. Tandem washers (K = 259 N/mm, YL = 1159 N, SL = 0.5 mm) and the Washerloc (K = 248 N/mm, YL = 905 N, SL = 2.0 mm) were the two best fixations. At 500 N of load, which is the estimated daily tension of an anterior cruciate ligament graft during intensive rehabilitation, slippage was significantly greater in either of the other two methods for sutures tied to a post (4.9 mm), double staples (3.3 mm), and a 20-mm spiked metal washer (3.5 mm). Interference screw fixation performed well in animal tissue (YL = 776 N), but was significantly worse in young human tissue (YL = 350 N), with 57% of the fixations failing before 500 N of load. Animal tissue should not be used to estimate the performance of interference screw fixation in human tissue. Because 57% of the interference screw fixations using human tissue failed at loads below 500 N, their ability to provide adequate fixation during intensive rehabilitation should be questioned. However, both the Washerloc and tandem washers and screws provide fixation structural properties in young human tibia that should be appropriate for intensive rehabilitation.
The tension in an anterior cruciate ligament graft may not be normal when the femoral tunnel is placed using the single-incision arthroscopic technique because the femoral tunnel is drilled through the tibial tunnel. We hypothesized that the in vivo tensile behavior of the double-looped semitendinosus and gracilis tendon graft can be normal or abnormal compared with the native anterior cruciate ligament, that the placement and angle of the tibial tunnel can predict the tensile behavior of the graft, that the graft with abnormal tensile behavior is associated with a nonanatomically placed tibial tunnel, and that the tensile behavior of the graft determines the stability of the reconstructed knee at 1 year. Total tension in the graft and knee flexion angle were measured in 14 subjects as the knee was flexed from 0 degree to 90 degrees. A graft force greater than 40 N at 80 degrees of flexion was considered abnormal. One year after surgery, the angle and position of the tibial tunnel were determined from roentgenograms, and knee stability was measured with a KT-1000 arthrometer. The criteria for anatomic tibial tunnel placement in the sagittal and coronal planes were derived from magnetic resonance images of uninjured knees. The tensile graft behavior was either normal (4 of 14) or abnormal (10 of 14) with the single-incision arthroscopic technique. The angle of the tibial tunnel in the coronal plane was predictive of abnormal tensile behavior. Abnormal tensile behavior occurred in anatomically placed tibial tunnels and was compatible with a stable and functional reconstructed knee at 1 year.
We evaluated three methods for fixing a medial meniscal autograft to determine which method restored tibial contact mechanics closest to normal. The contact mechanics (maximum pressure, mean pressure, contact area, and location of the center of maximum pressure) of the medial tibial articular surface were determined using pressure-sensitive film while knee specimens were loaded in compression to 1000 N at 0 degree, 15 degrees, 30 degrees, and 45 degrees of flexion. Pressure was measured for the intact knee, the knee after meniscectomy, and the knee with the original meniscus removed and reimplanted as an autograft using three different fixation methods. The contact mechanics of the autograft reinserted with bone plug fixation were closest to normal; however, the maximum pressure was significantly greater than in the intact knee. Adding peripheral sutures neither improved nor worsened the contact mechanics. Fixation with sutures only did not restore normal contact mechanics. We concluded that medial meniscal transplantation requires anatomic fixation of bone plugs attached to the anterior and posterior horns to restore contact mechanics closest to normal. Fixation of the meniscal horns with sutures alone cannot be recommended.