Dehydrated citrus pulp alters feedlot performance of crossbred heifers during the receiving period and modulates serum metabolite concentrations before and after an endotoxin challenge.

English × Continental heifers ( = 180) were sourced in 2 loads (219.3 ± 16.0 and 221.4 ± 16.4 kg, respectively) from commercial auction barns to study the effects of feeding dehydrated citrus pulp (DCP) on feedlot performance of newly received heifers. A completely randomized block design was used with BW nested within arrival load and blocked by BW into 3 dietary treatments (36 pens, 5 heifers/pen, 12 blocks, 3 pens/block, and 12 pens/treatment). Treatment diets contained 1) 0% DCP (control diet [CON]), 2) 10% DCP, or 3) 20% DCP on a DM basis. Diets containing DCP were exchanged with steam-flaked corn on a 1:1 basis. Cattle were fed a 63, 73, and 83% concentrate diet from d 0 to 28, d 28 to 42, and d 42 to 56, respectively. Over the 56-d trial period, as the amount of dietary DCP increased, DMI decreased ( = 0.01), ADG decreased ( < 0.01), and G:F decreased ( = 0.02). From d 0 to 28, there was no difference in the observed minus the predicted NEg of the diet ( = 0.73); from d 28 to 42, there was a linear increase in NEg favoring DCP treatments ( < 0.01); and from d 42 to 56, there was a linear decrease in NEg against the DCP treatments ( < 0.01). At the conclusion of the trial, a subset of heifers ( = 22; 307.89 ± 3.32 kg on d 63) were used to evaluate blood metabolite concentrations before and after a lipopolysaccharide (LPS) challenge. On d 63, heifers were fitted with jugular catheters and moved into individual stalls. On d 64, heifers were intravenously challenged with LPS (0.5 µg/kg BW), and blood samples were collected every 0.5 h from -2 to 8 h and at 24 h relative to the LPS challenge (0 h). Serum glucose, serum urea nitrogen (SUN), and NEFA concentrations were determined. Cattle lost less weight at both 24 and 72 h after the LPS challenge with increasing DCP percentage ( < 0.01). Glucose ( = 0.12) and NEFA ( = 0.13) concentrations did not differ before the LPS challenge; however, there was a treatment effect for SUN, with elevated concentrations of SUN in CON cattle ( < 0.01). After the LPS challenge, DCP-fed cattle had reduced glucose, elevated NEFA, and reduced SUN concentrations ( ≤ 0.01). Results indicate that dietary DCP modulated metabolite concentrations in heifers following an endotoxin challenge and affected feedlot performance when incorporated in receiving diets in replacement of corn. Future studies will need to address strategies to increase DMI or explore levels of DCP less than 10% in the diet of newly received heifer calves.

Chromium supplementation alters both glucose and lipid metabolism in feedlot cattle during the receiving period.

Crossbred steers (n = 20; 235 ± 4 kg) were fed for 53 d during a receiving period to determine if supplementing chromium (Cr; KemTRACE Chromium Propionate 0.04%, Kemin Industries, Des Moines, IA) would alter glucose or lipid metabolism of newly received cattle. Chromium premixes were supplemented to add 0 (Con) or 0.2 mg/kg of Cr to the total diet on a DM basis. Cattle were fitted with jugular catheters on d 52. A glucose tolerance test (GTT) and an insulin sensitivity test (IST) were conducted on d 53. Blood samples were collected from -60 to 150 min relative to each infusion. Serum was isolated to determine glucose, insulin, and NEFA concentrations. Throughout GTT, no differences were detected in glucose concentrations, glucose clearance rates (k), or preinfusion insulin concentrations (P > 0.50), but insulin concentrations postinfusion tended (P = 0.06) to be greater for the Cr-supplemented steers. This caused an increase in the insulin to glucose ratio (I:G) from 0 to 150 min postinfusion for the Cr-supplemented steers (P = 0.03). In addition, NEFA concentrations during GTT were lower (P ≤ 0.01) for Cr-supplemented steers both preinfusion and postinfusion. During IST, there was no treatment effect on glucose concentrations preinfusion (P = 0.38), but postinfusion glucose concentrations were greater (P< 0.01) in the Cr-supplemented steers. The k of Cr-supplemented steers tended (P = 0.06) to be faster than Con steers from 30 to 45 min postinfusion. During the same test, there was no treatment effect detected for insulin concentrations (P > 0.33). The I:G were not affected by treatment (P > 0.40).Concentrations of NEFA were reduced (P < 0.01) both preinfusion and postinfusion during IST for Cr-supplemented steers. Results of this study indicate that supplementation of Cr can significantly alter lipid metabolism. This suggests that these steers had less dependence on lipid metabolism for energy or sensitivity of adipose tissue to antilipolytic signals was reduced. Results of glucose and insulin metabolism were inconsistently modified after a GTT and an IST.

Chromium supplementation alters the performance and health of feedlot cattle during the receiving period and enhances their metabolic response to a lipopolysaccharide challenge.

Crossbred steers (n = 180; 230 ± 6 kg) were fed during a 56-d receiving period to determine if supplementing chromium (Cr; KemTRACE Chromium Propionate 0.04%, Kemin Industries) would improve feedlot performance and health of newly-received cattle. A completely randomized block design (36 pens; 9 pens/treatment; 5 steers/pen) was used. Chromium premixes were supplemented to add 0 (Con), 0.1, 0.2, or 0.3 mg/kg of Cr to the total diet on a DM basis. No differences were detected on d 0 or after the first 14 d on feed. From d 0 to d 28, DMI (P = 0.07) and ADG increased linearly (P = 0.04) as Cr concentrations increased. From d 0 to d 56, BW (P = 0.08) displayed a tendency to increase linearly, and consequently ADG and G:F increased linearly (P ≤ 0.05) as Cr concentrations increased. The number of steers treated at least once for respiratory symptoms tended (P = 0.07) to linearly decrease as Cr concentrations increased. Twenty additional steers (235 ± 4 kg) were fed 56 d to determine if supplementing Cr (Con or 0.2 mg/kg Cr) would alter the metabolic response of newly-received cattle to a lipopolysaccharide (LPS) challenge. Cattle were fitted with jugular catheters on d 52. On d 55, blood samples were collected at 0.5-h intervals from -2 to 8 h, and again at 24 h relative to a LPS challenge (0.5 µg/kg BW) at 0 h. Serum glucose, insulin, and NEFA concentrations were determined from blood samples. Steer BW was also measured at cannulation, and 24 h and 8 d post-LPS. Steer BW did not differ at cannulation (P = 0.37), but 24 h post-LPS, Cr-supplemented steers had lost less BW (P = 0.03). Pre-LPS glucose concentration did not differ (P = 0.97). Post-LPS, there was a time × treatment interaction (P < 0.01) such that glucose concentration peaked earlier (0.5 h) and at a greater concentrations in Cr-supplemented steers (P < 0.01). Insulin concentration did not differ between treatments pre- or post-LPS (P > 0.13). Concentration of NEFA did not differ pre-LPS (P = 0.54); but 0.5 h post-LPS Cr-treated steers produced a greater peak NEFA concentration (P < 0.04). Results of this study indicate that supplementation of Cr to the basal diet can have beneficial effects on the performance and health of newly-received steers. These data also suggest that supplementation of Cr attenuated BW loss and allowed for a quicker recovery after a LPS challenge.

Prevention of venous thromboembolic disease following primary total knee arthroplasty. A randomized, multicenter, open-label, parallel-group comparison of enoxaparin and warfarin.

BACKGROUND: Patients treated with total knee arthroplasty are at high risk for the development of venous thromboembolism postoperatively. This study compared the efficacy and safety of two common thromboprophylactic agents, enoxaparin (a low-molecular-weight heparin) and warfarin. METHODS: Three hundred and forty-nine patients were included in a prospective, randomized, multicenter, open-label, parallel-group clinical trial. Treatment with enoxaparin (30 mg, administered subcutaneously twice daily) or warfarin (adjusted to an international normalized ratio of 2 to 3) was initiated during the immediate postoperative period, within eight hours after the surgery, and was continued for four to fourteen days. Venous thromboembolism was defined as deep-vein thrombosis documented by contrast venography, symptomatic deep-vein thrombosis documented by lower-extremity ultrasonography, or symptomatic pulmonary embolism confirmed by a positive lung scan or pulmonary angiography. RESULTS: In the all-treated-patients group, eighty (45%) of the 176 warfarin-treated patients had venous thromboembolism: fifty-nine (34%) had distal deep-vein thrombosis; twenty (11%), proximal deep-vein thrombosis; and one (0.6%), pulmonary embolism. Venous thromboembolism developed in significantly fewer (p = 0.0001) enoxaparin-treated patients (forty-four of 173; 25%): forty-one (24%) had distal deep-vein thrombosis, three (2%) had proximal deep-vein thrombosis, and none had pulmonary embolism. The enoxaparin-treated patients also had a significantly lower prevalence of proximal deep-vein thrombosis (p = 0.002). The estimated odds for the development of venous thromboembolism were 2.52 times greater (95% confidence interval, 2.00 to 3.19) with warfarin than they were with enoxaparin. Major hemorrhage occurred in four warfarin-treated patients and nine enoxaparin-treated patients; with the numbers available, this difference was not significant (p = 0.17). Clinically important operative-site hemorrhage occurred in six (3%) of the warfarin-treated patients and twelve (7%) of the enoxaparin-treated patients (p = 0.15). CONCLUSIONS: A fixed 30-mg subcutaneous dose of enoxaparin, administered twice daily, with the first dose administered within eight hours after the completion of surgery, was significantly more effective than adjusted-dose warfarin in reducing the occurrence of asymptomatic venous thromboembolism, including proximal deep-vein thrombosis, in patients undergoing total knee arthroplasty. With the numbers available, there was no significant difference between groups with regard to the occurrence of major hemorrhagic complications; however, the rate of overall hemorrhagic complications was higher in the enoxaparin group.

Light microscopic and scanning electron microscopic retrieval analyses of implanted biomaterials retrieved from humans and experimental animals.

This paper reports analysis obtained from 200 implant cases retrieved from humans and submitted to the American Academy of Implant Dentistry Research Foundation, Medical College of Georgia implant retrieval center. The samples that were not decalcified were embedded in polymethylmethacrylate and examined with scanning electron microscopy and routine light, polarized, or Nomarski microscopy. Cases included both orthopedic and dental implants, as well as entire mandibles and portions of maxillae obtained at autopsy. A significant number of submitted implants had substantial amounts of adhered bone, which permitted evaluation of human bone remodeling to osseointegrated implants. These implants failed because of implant fracture. As was observed with animal studies, healthy bone supported these implants, with the bone containing an interdigitating canaliculi network that provided communication between interfacial osteocytes and osteocytes deeper within the remodeled osteonal and trabecular bone. Early dental implants containing a coating of beads showed a connective tissue interface, which corresponded to the bead surface of specific orthopedic implants that underwent some degree of micromovement. This is in contrast with the excellent response reported for successful contemporary beaded implants. Significant numbers of osseointegrated fractured hydroxyapatite (HA)-coated dental implants demonstrated the adequate serviceability of these implants before biomaterial fracture. In contrast, the HA coating was dissociated from retrieved orthopedic implants, leading to extensive cup loosening and case failure. This study, therefore, underscores the need for evaluation of failed human dental and orthopedic implants. Correlations can be drawn between human retrieval and experimental animal studies.

Cementless S-ROM femoral component: effect of stem length on stability after extended proximal femoral osteotomy.

The extended proximal femoral osteotomy is becoming increasingly popular in revision total hip replacement. Our study was done to determine the femoral stem length required for stable fixation of a cementless femoral component after an extended proximal femoral osteotomy. Three lengths of the S-ROM femoral stem were implanted in paired cadaver femora and tested under torsional and axial loads. The results indicate that the standard (160 mm) and long (215 mm) stems do not provide adequate torsional stability after a 160 mm extended proximal femoral osteotomy. The extra-long (255 to 315 mm) stems provided significantly greater stability, suggesting that the extended proximal femoral osteotomy may need to be bypassed by more than 2 cortical diameters, especially when a flexible stem such as the S-ROM is used.

Correlative experimental animal and human clinical retrieval evaluations of hydroxyapatite (HA)-coated and non-coated implants in orthopaedics and dentistry.

Retrieval analyses disclosed in vivo dissociation of HA in orthopaedic acetabular components, but excellent bone ingrowth into intact HA coatings on dental retrievals. Initial healing and the bone interface between HA-coated and non-coated implants in the posterior maxilla (Mx) and mandible (Md) was assessed in an animal model using light microscopy (LM), including confocal (CM) and Nomarski (NM) microscopy. Seventy-two implants (36 HA-coated; 36 non-coated) were placed into jaws of six dogs; half after extraction, half after 3 months healing. Animals were euthanized 3 months postimplantation. All implants osseointegrated; however, preliminary morphometry showed higher BCL for HA-coated (51%) than non-coated implants (44%) in the Mx (p < 0.05). BCL for HA-coated Md implants was not significantly higher (64%) than non-coated implants (62%). Bone closely apposed both implant types; however, LM suggested a more intimate association with HA coatings. Serial sections disclosed a reddish coating on the HA, possibly analogous to oral tissue proteoglycans, which was not visible with non-coated implants. This material was continuous with similar material coating endosteum, osteoid regions, and osteocyte (Os) lacunae close to the implant. An interdigitating canaliculi network allowed communication between interfacial Os and Os deeper within the bone. Data suggest HA offers enhanced initial bone fixation in the Mx, and that adequate bone exists for non-coated implant stability in the Md. No HA dissociation was seen with implants in the animal study, which was consistent with retrieved human HA dental implants.

Complications in total knee arthroplasty with and without surgical drainage.

The standard practice in total joint arthroplasty has included the use of postsurgical drains to minimize perioperative wound complications, particularly infection. This practice is not without cost and potential morbidity. Our recent cemented and cementless total knee arthroplasties (TKAs) have been done without the use of postoperative surgical drains and without any appreciable increase in wound complications. To confirm this, we retrospectively reviewed 227 consecutive TKAs, specifically evaluating perioperative wound complications. No statistical increase in perioperative complications in TKAs without drains was found. A lower percentage of complications was seen in the cementless population when compared with cemented or drained knees. We suggest that surgical drainage is not required in TKA, even when cementless fixation is used.

Retrieval analyses of implanted biomaterials: light microscopic and scanning electron microscopic analyses of implants retrieved from humans.

We report analyses obtained from 135 implant cases retrieved from humans and submitted to the American Academy of Implant Dentistry Research Foundation--Medical College of Georgia Implant Retrieval Center. The undecalcified samples were embedded in polymethyl-methacrylate and examined with scanning electron microscopy and with routine light via polarized or Nomarski microscopy. Cases included both orthopedic and dental implants as well as entire mandibles obtained at autopsy. Significant numbers of submitted implants had substantial amounts of adhered bone, which permitted evaluation of human bone remodeling to osseointegrated implants. These implants failed because of implant fracture. As has been observed in animal studies, an interdigitating canaliculi network provided communication between interfacial osteocytes and osteocytes deeper within the remodeled osteonal and trabecular bone. Significant numbers of osseointegrated fractured hydroxyapatite-coated dental implants demonstrated the adequate serviceability of these implants prior to biomaterial fracture. In contrast, the hydroxyapatite coating was dissociated from retrieved orthopedic implants, leading to extensive cup loosening and case failure. Caution is advised for the use of hydroxyapatite-coated acetabular implants. This study therefore underscores the need for evaluation of failed human dental and orthopedic implants. Correlations can be drawn between human retrieval and experimental animal studies.

The biologic tissue responses to uncoated and coated implanted biomaterials.

Ultrastructural examination of the morphology and morphometry of the bone supporting uncoated titanium and ceramic implants was assessed in an experimental animal model involving 120 implants placed into the mandibles of 30 adult mongrel dogs. Further, preliminary morphologic and morphometric observations of the bone supporting uncoated and hydroxylapatite-coated endosteal titanium implants was evaluated in a second investigation involving 72 implants placed into the mandibles and maxillae of 6 additional dogs. A densely mineralized collagen fiber matrix was observed directly interfacing with uncoated implants. The only material interposed between the implant and bone matrix was a 20- to 50-nm electron-dense material suggestive of a proteoglycan. Also seen in these same osseointegrated implants were narrow unmineralized zones interposed between the implant and bone matrix. In these zones of remodeling bone, numerous osteoblasts were observed interacting with the collagen fiber matrix. It was shown that a normal homeostasis of anabolic osteoblastic activity and catabolic osteoclastic activity resulted in bone remodeling and the resultant osseointegration of the implants. Hydroxylapatite-coated implants intimately interfaced with healthy bone. The mineralized matrix extended into the microporosity of the HA coating. This matrix contained viable osteocytes.

Ultrastructural analyses of the attachment (bonding) zone between bone and implanted biomaterials.

This report presents transmission electron and high voltage transmission electron microscopic observations of bone and associated remodeling tissues directly interfacing with endosteal dental implants. Undecalcified interfacial tissues were serially sectioned from mandibular samples encasing 60 implants placed into 30 dogs. Two-dimensional ultrastructural analyses and three-dimensional stereology showed that osteogenesis adjacent to dental implants is a dynamic interaction of osseous cells and a collagenous fiber matrix. This study showed that the interfacial bone consists of a mineralized collagen fiber matrix associated with an inorganic (hydroxylapatite) matrix. This study suggested that an unmineralized collagen fiber matrix initially is laid down directly at the implant surface, and that this matrix then is mineralized. Osteoblasts interacted with this matrix, eventually becoming encased within developing lacunae during the remodeling process. This process formed the cellular (osteocyte) aspects of the developed bone. Osteocyte processes extended through canaliculi directly to the implant surface. Apparently, these processes also were entrapped within canaliculi during the mineralization events. At times, these processes paralleled the implant surface. The bone-implant interfacial zone was primarily fibrillar (both mineralized and unmineralized) in morphology, with an electron-dense, ruthenium positive deposition. This electron-dense material was approximately 20 to 50 nanometers in thickness, and only this thin layer separated the remodeled mineralized bone from the implant.

In vivo evaluation of the biocompatibility of implanted biomaterials: morphology of the implant-tissue interactions.

Electron microscopic observations were made from tissues apposing titanium and ceramic root form and blade implants. The tissue was serially sectioned from the most coronal epithelium, through the gingival connective tissue, to the osseous support tissues, and directly to the most apical tissue support. Of the thousands of sections analyzed for each implant, 500 micrographs were routinely viewed for each of the implants analyzed by this study. Of the 120 total implants placed in 30 adult dogs, 60 were used for electron microscopy. Osseointegrated implants were often apposed by a mineralized matrix of collagenous fibers. The dense mineralized collagen matrix was often separated from the implant by only a ruthenium positive electron dense deposit 20 to 50 nanometers thick. Areas of the same implant were also apposed by an unmineralized collagen fiber stroma, which ranged in thickness, that contained osteoblasts. Interaction of the osteoblasts and the unmineralized collagen fibers resulted in the mineralization events of osteogenesis. Also apposing other areas of the same integrated implants were lacunar areas containing osteoclasts and vessels. These zones were similar to Howship's Lacunae. These results demonstrated that a normal homeostasis of catabolic osteoclastic activity and metabolic osteoblastic activity resulted in a dynamic implant-tissue interface. This biocompatible and dynamic support complex provides a construct for the long-term clinical serviceability of osseointegrated implants.

Determination of accuracy of preoperative templating of noncemented femoral prostheses.

The purpose of this study was to determine the accuracy of preoperative templating of primary, noncemented femoral components. A retrospective review of charts and radiographs was performed on 74 hips in 64 patients who had undergone either noncemented total hip arthroplasty (THA) or placement of an endoprosthesis (including bipolar). Preoperative radiographs were templated by a total joint arthroplasty attending surgeon, a senior orthopaedic resident, and a junior resident. The templated size corresponded to the actual femoral implant used in approximately 50% of cases. When femoral prostheses within one size above or below the templated size were included, the accuracy of preoperative templating rose to 88-95%. When implants within two sizes of the templated size were included, the accuracy approached 100%. Factors associated with discrepancies in the size of femoral stem used included placement of an undersized implant, presence of metal hardware that obscured the ability to template accurately, proximal bone deformity, sclerotic bone, acute femoral neck fracture, and inadequate preoperative radiographs. The accuracy of templating increased gradually with the level of training. The most experienced investigator was able to template within one size of the actual implant used in 95% of cases, compared with 88% and 82% for the less experienced investigators. Acute femoral neck fractures and proximal bone deformity were associated with the largest discrepancies in templated sizes.

Avascular necrosis of the medial femoral condyle in HIV-infected patients.

Avascular necrosis (AVN) of the femoral head has been described in the literature in patients infected with the human immunodeficiency virus. It has been associated with either a hypertriglyceridemic state or the presence of antiphospholipid antibodies. We describe a case of AVN of the medial femoral condyle in an HIV-infected patient associated with a hypertriglyceridemic state.

Intraoperative arterial occlusion in total joint arthroplasty.

Major arterial occlusion during surgery is an uncommon complication. The authors report on two patients who developed intraoperative arterial occlusion during total joint arthroplasty. Both of the patients were smokers and had significant peripheral vascular disease.

Ipsilateral fractures of the femoral neck and shaft.

The management of ipsilateral fractures of the femoral neck and shaft has proved to be a challenge to the orthopaedist. Most major institutions have treatment protocols that emphasize early rigid stabilization of the femoral-neck fracture to minimize the incidence of avascular necrosis of the femoral head. Since 1985, the authors' protocol has been to reduce and stabilize the femoral-neck fracture anatomically, followed by treatment of the femoral-shaft fracture. In 1990, we began treating this segmental fracture pattern with reconstruction nails. This study reviews the cases of 11 patients treated at the Medical College of Georgia Hospital from November 1985 to March 1992. Nine of the 11 underwent surgery within 12 hours of injury; 4 of these patients were treated with reconstruction nails. The mean follow-up was 2 years. Seven of the 11 had a good functional outcome, whereas 4 had a fair outcome. The results indicate that patients with ipsilateral fractures of the femoral neck and shaft can obtain good results when early (< 12 hours) rigid anatomic stabilization of the femoral neck is performed. The authors recommend utilizing a reconstruction nail for stabilizing this dual fracture whenever possible.

Temporal stability of paraspinal electromyographic recordings in low back pain and non-pain subjects.

This paper presents the results of two studies in which bilateral surface EMG recordings of paraspinal muscle tension were measured in 29 lower back pain and 20 normal subjects in 6 different positions (standing, bending from the waist, rising, sitting with back supported, sitting unsupported, prone) on two occasions, and a comparison of the data from both studies. Measures were highly reliable when examined using analysis of variance procedures. Statistically significant reliability coefficients were obtained when the absolute values of the measures were examined, although in some instances less than 20% of the variance was explained. When examined as relative [percent change from baseline (prone) condition] values, differences between the two groups were observed: the normals were statistically more reliable than lower back pain subjects during every condition. Implications for clinical work and both basic and applied research are discussed.

Chronic beta-carotene supplementation does not alter the gastric mucosal response to acute aspirin ingestion.

Carotenoids and retinoids have been reported to reduce gastrointestinal mucosa damage from a variety of irritants. We performed double-blind, placebo-controlled endoscopic trial to evaluate the effect of chronic beta-carotene supplementation upon the gastric mucosal response to acute aspirin injury. Six subjects taking chronic beta-carotene and six taking placebo each ingested 650 mg of aspirin after an endoscopy confirmed normal gastric mucosa. Three hours later, mucosal lesions were counted at repeat endoscopy. beta-Carotene did not prevent acute mucosal injury better than placebo.

Assessment of cefazolin and cefuroxime tissue penetration by using a continuous intravenous infusion.

A continuous intravenous infusion was used to assess the tissue penetration of cefazolin (14 subjects) and cefuroxime (15 subjects) in orthopedic surgery patients. Subjects were randomly assigned to receive a continuous intravenous infusion of cefazolin (mean, 178.6 mg/h) or cefuroxime (mean, 330.0 mg/h) at a rate estimated to achieve a target steady-state total concentration of 50 micrograms/ml in serum. The infusion was initiated 12 to 14 h before surgery, and blood and muscle tissue samples were collected intraoperatively at the times of incision and wound closure. Although there was a significant difference between the free concentrations of cefazolin (at incision, 9.3 micrograms/ml; at closure, 9.2 micrograms/ml) and cefuroxime in serum (at incision, 26.9 micrograms/ml; at closure, 31.8 micrograms/ml), there was no difference in the total concentrations in muscle at either surgical incision (cefazolin, 6.1 micrograms/g; cefuroxime, 5.6 micrograms/g) or wound closure (cefazolin, 7.7 micrograms/g; cefuroxime, 7.4 micrograms/g). There was a significant correlation between the pooled free serum and total muscle concentrations for cefazolin (P = 0.001); however, there was no correlation between these variables with the pooled cefuroxime data (P = 0.403). These findings indicate that the free drug concentration in serum alone is not consistently predictive of the total concentration of cephalosporin in muscle.