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Background context Many studies have documented the efficacy of lateral mass screws, but there are no studies examining the alignment maintenance capability and few large studies examining the complications associated with the use of these devices in cervical spine trauma. Purpose To evaluate complications and alignment maintenance capability associated with lateral mass screw placement for cervical spine trauma by one surgeon at one institution. Study design A retrospective chart and radiograph review of adult patients who underwent lateral mass screw fixation after traumatic injuries to the cervical spine. Patient sample Of 34 consecutive patients with cervical spine injuries who were treated surgically at a level-I regional trauma center, 29 met the inclusion criteria and formed the study group. Outcome measures Sagittal alignment, screw placement, and fusion were assessed on postoperative radiographs. Methods Inclusion criteria included an unstable cervical vertebral fracture or a fracture-dislocation treated with posterior spine fusion and lateral mass instrumentation and a minimum follow-up of 24 months. A review of hospital charts, operative reports, clinic notes, and plain radiographs for the 29 patients was performed, with an emphasis on operative and postoperative complications and alignment maintenance. Results For 28 of the 29 patients, the mean change in sagittal alignment from the immediate postoperative to the most recent follow-up radiographic examination was 2° (range, 0° to 6°). Radiographically, there was one case of instrumentation/fixation failure and loss of sagittal alignment 3 months postoperatively. Other complications included one case of C5 nerve root injury and four wound infections. Conclusions The use of lateral mass screws for traumatic injuries of the cervical spine is associated with excellent maintenance of alignment and minimal complications.

Study Design. Retrospective review of charts and fluoroscopic, radiographic, and computed tomography images for 252 screws (41 patients). Objectives. To describe a fluoroscopically assisted technique of thoracic pedicle screw insertion and to determine the technique’s safety, short-term complications, and accuracy. Summary of Background Data. Pedicle screw instrumentation is safe and effective for lumbar spine stabilization, but evidence of its accuracy and complications in the thoracic spine is lacking. Methods. Between 1997 and 2000, 41 consecutive patients with unstable cervicothoracic, thoracic, and thoracolumbar spine injuries were admitted to a regional, level 1 trauma center. These patients underwent posterior spine arthrodesis and pedicle screw instrumentation placed via intraoperative multiplanar fluoroscopic imaging. Pedicle screw placement accuracy was determined by review of postoperative computed tomography scans. Instrumentation failure prevalence was determined by review of fluoroscopic images, postoperative radiographs, and computed tomography scans. Neurologic, infectious, vascular, and gastrointestinal complications were determined by review of operative reports, hospital records, and clinic notes. Results. Of the 126 (50%) thoracic screws (22 patients) with postoperative computed tomography scans, 16 (12.7%) penetrated the pedicle cortex (4 [2.4%] medially and 13 [10.3%] laterally) and 7 (5.6%) penetrated the vertebral body. There were four surgical complications: one instrumentation failure (broken rod, no loss of correction), one deep infection, and two superficial infections. The infections resolved with irrigation, debridement, and intravenous antibiotics. During the 6- to 24-month follow-up period, there were no neurologic, vascular, or gastrointestinal complications. Conclusions. Cervicothoracic, thoracic, and thoracolumbar spine injuries can be managed safely and effectively with thoracic pedicle screws inserted under multiplanar fluoroscopic imaging.

Although neurologic injury is rarely associated with burst fractures (

Intraoperative proximal femur fractures are a significant concern during noncemented total hip arthroplasty. The current study was performed to investigate the hypothesis that broaching the femur and inserting the stem without using mallet applied impact loads will reduce the risk of intraoperative fracture. Rosette strain gauges were applied to the medial and anteromedial cortex of six human anatomic specimen femurs to compare the strain distribution for broaching and stem insertion. Eight additional femurs were used to compare the strain distribution for stem insertion using impact loading and constant rate stem insertion. For the impact loading stem insertions, the soft tissues surrounding the femur were modeled. Constant rate stem insertions were performed using a mechanical testing machine. The largest strains measured at the medial and anteromedial sites primarily were aligned with the femur hoop axis. The largest strain magnitude, orientation, and sign (tensile or compressive) varied widely among femurs. The stem insertion strains were significantly larger than the broaching strains (two-way analysis of variance with replication). The impact stem insertion strains were not significantly different from the constant rate stem insertion strains. The results indicate that the femur geometry and material properties have a greater influence on the strain distribution than does the implantation technique.

Probenecid has been shown to decrease renal and biliary excretion of organic acids. In a randomized crossover study, the effect of coadministered probenecid on nonrenal excretion of ceftriaxone was studied in six functionally anephric patients in whom ceftriaxone is eliminated exclusively by nonrenal or presumably by biliary excretion. Each patient received 0.5 g IV ceftriaxone without and with probenecid (0.5 g at 10 and 2 hours prior to ceftriaxone and 0.5 g q12h X 3 doses post ceftriaxone). Serial blood samples were collected over 48 hours and plasma analyzed for ceftriaxone by high performance liquid chromatography (HPLC). Pharmacokinetic analysis was based on a model-independent approach. Probenecid did not significantly affect the disposition of ceftriaxone in this study, thus suggesting that nonrenal excretion of ceftriaxone is not inhibited by probenecid.

Traumatic injuries to the cervical spine are often difficult to detect and are associated with substantial morbidity and mortality. Along with standard trauma radiographs, a thorough physical examination and meticulous documentation are of the utmost importance because many neurologic injuries evolve over time. Although many injuries to the cervical spine can be treated nonoperatively, any injuries with neurologic deficits, instability, or ligamentous injury require instrumentation and fusion. It is crucial to recognize injuries to the cervical spine and the different treatment options. Computed tomography can be very helpful in defining the bony injury and evaluating the spinal canal, whereas magnetic resonance imaging can better evaluate the spinal cord and assess ligamentous injury.

Greater trochanteric pain syndrome (GTPS) is a regional syndrome characterized by pain and reproducible tenderness in the region of the greater trochanter, buttock or lateral thigh that may mimic the symptoms of lumbar nerve root compression. Despite these known features, the diagnosis of GTPS is often missed, and documentation of its prevalence in an orthopedic spine specialty practice is lacking.To determine the prevalence of the GTPS in patients referred to a tertiary care orthopedic spine referral center for the evaluation of low back pain, and to describe the demographic and clinical characteristics of patients with this syndrome.Retrospective analysis.A total of 247 consecutive patients referred for low back pain from August 1998 through December 2000.Clinical response to injection, demographic characteristics, physical examination findings, prevalence of GTPS and preexisting diagnostic evaluations.The diagnosis of GTPS was made based on history and physical examination and was confirmed by response to anesthetic corticosteroid injection. Demographic and clinical characteristics of the study group were evaluated. Follow-up data were available at a mean of 8 weeks postinjection (range, 2 to 48 weeks).The prevalence of GTPS was 20.2% (51 of 252). Mean age (54 years) was the same for patients with (range, 25 to 85 years) and without (range, 17 to 85 years) GTPS. Significantly more women than men had GTPS (p.03). Of the 51 patients diagnosed with GTPS at initial presentation, 54.9% (28 of 51) had already obtained a magnetic resonance imaging examination (although only 15.7%, ie, 8 of 51, demonstrated objective neurologic findings) and 62.7% (32 of 51) had previously been evaluated by an orthopedist or neurosurgeon; one patient had undergone two lumbar decompressions without clinical improvement before our evaluation.GTPS accounts for a substantial proportion of patients referred to our center for evaluation of low back pain. Both primary care physicians and specialty surgeons may miss this diagnosis, most common in middle-aged women. Accurate recognition of this problem earlier in the evaluation of patients with low back, buttock or lateral thigh symptoms may dramatically reduce costly patient referrals and diagnostic tests and may prevent unwarranted surgery.

I INTRODUCTION Diffuse idiopathic skeletal hyperostosis (DISH), as its name implies, is a condition characterized by a generalized (diffuse) abundant ossification of ligaments (skeletal hyperostosis) of unknown etiology (idiopathic). The spine is the most commonly affected area of the body. The longitudinal ligaments of the spine, in particular the anterior longitudinal ligament (ALL), are most often affected. Exuberant ossification and bony spurring is also seen at ligament and tendon insertions throughout the body. In particular, DISH patients demonstrate calcifications at ligamentous insertions involving the iliac crests in 66% of patients, and the ischial tuberosities, lesser trochanters, and greater trochanters in 53%, 42%, and 36%, respectively.

A complete review of the literature disclosed that there were 42 reports of 2025 hips treated by either core decompression (1206 hips) or nonoperative management (819 hips), excluding electrical stimulation, for osteonecrosis of the femoral head. The peer-reviewed published reports included general surveys, prospective studies, and multicenter studies, but excluded case reports. Satisfactory clinical results were reported in 63.5% of hips in 24 studies of core decompression and in 22.7% of hips in 21 studies of nonoperative management. When looking at only precollapse hips, there were 71% versus 34.5% good results, respectively. Recalculation excluding reports by the 4 centers that do the most core decompressions (and report the best results) showed a clinical success rate for core decompression of 53% versus 22.7% for the nonoperatively treated group. Investigators of multiple studies have reported that nonoperative management leads to extremely poor results. Core decompression has been reported to have a notable effect on the natural history and clinical progression in early stages of osteonecrosis of the femoral head. In view of the limitations of this data, further clarification of this effect only can be obtained by large prospective randomized studies.

We examined the effect of prenatal stress exposure on sensitivity to caffeine using behavioral and physiological measures. Pregnant rat were handled 5 minutes daily from the 14th to 21st day of gestation. Male offspring were tested when 60 days of age in a modified open field apparatus 30 and 90 minutes after injection with caffeine (0, 10, 30 mg/kg). Caffeine increased crossover frequency and duration at the 10 mg/kg dose. Rearing frequency and duration were increased by the 10 mg/kg dose while the 30 mg/kg dose was ineffective. Gnawing was increased by caffeine, especially 90 minutes postinjection. Headpoke activity was decreased by caffeine treatment. Caffeine had no effect on defecation and urination. Gnawing activity was increased by caffeine in prenatally nonstressed animals, but was depressed in prenatally stressed animals. Prenatal stress increased sensitivity to caffeine on corner activity and rearing. The other measures were not affected differentially by prenatal stress exposure. Rectal temperature was depressed 0.75°C in both prenatally stressed and nonstressed animals, by the 30 mg/kg dose of caffeine. Thus, our results indicate that prenatal stress affects sensitivity to caffeine in the adult offspring. However, the long-term effects of prenatal stress exposure are dependent on the measures employed.

Labeled medazepam (7-chloro-2,3-dihydro-1-methyl-5-phenyl-1H-1,4-benzo-diazepine-5-14C) and metabolites were identified and measured by two-dimensional thin-layer chromatography. In the dog, 2 mg/kg of medazepam-5-14C HCl given orally or i.v. did not yield measurable blood levels of intact drug. The close agreement of the amount of 14C excreted in the urine after oral and i.v. administration and of the rates of this excretion indicated that the labeled compound was well absorbed. Fractionation of the blood revealed that biotransformation of medazepam was a rapid process. After a higher dose, 20 mg/kg i.v., medazepam disappeared from the blood bi-exponentially with half-lives of 0.16 and 2.7 hr. Pathways of medazepam metabolism, which apparently did not include diazepam as an intermediate, were postulated on the basis of metabolites identified in experiments both in vivo and in vitro. In the rat, highest tissue concentrations of14C were seen 2–4 hr after an oral dose of 14C-medazepam HCl. It was clear from the metabolites identified that the formation of diazepam and phenolic diazepam metabolites represented an important pathway of medazepam metabolism in this species. The labeled compound was rapidly absorbed by two human subjects who received single 30-mg oral doses. The peak blood levels of medazepam (less than 0.2 μg/ml at 1–2 hr) declined rapidly with a half-life of 1–2 hr. A marked difference between the subjects in rates of elimination of metabolites from the blood and in excretion of urinary metabolites appeared related to body weight and the activity of drug-metabolizing enzymes. Preliminary evidence for diazepam formation in man was also obtained.

A correlation between the duration of the anticonvulsant activity of diaze- pam [7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one (Ro 5-2807)] and the physiological disposition of the intact drug and three metabolites—(1) the N -demethylated derivative [7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one (Ro 5-2180)], (2) the hydroxylated derivative [7-chloro-1,3-dihydro-3-hydroxy-1-methyl-5-phenyl-2H-1, 4-benzodiazepin-2-one (Ro 5-5345)], and (3) oxazepam [7-chloro-1 ,3-dihydro-3-hydroxy-5-phenyl-2H-1, 4-benzodiazepin-2-one (Ro 5-6789)]—in mice is presented. Maximal protection for 6 hr against a standard 125 mg/kg s.c. convulsant dose of metrazol was afforded by a single 2.5 mg/kg oral dose of diazepam. Quantitative 3 H distribution after the oral administration of a single 2.5 mg/kg dose of diazepam- 3 H shows rapid absorption and a rapid increase over 1–30 min in the tissue-to-blood 3 H ratios of the brain, muscle, heart, fat and carcass. These ratios thereafter increase gradually or remain constant to 4 hr after drug administration. A 125 mg/kg s.c. injection of metrazol given 30 min after the oral administration of diazepam does not significantly affect the tissue-to-blood 3 H ratios nor does it alter the 3 H disposition, except between 4 and 6 hr, during which time a definite increase in the total 3 H concentration of the blood, brain and muscle is observed. This increase is reflected in an increase in the concentration of the parent compound and of the products of its hydroxylation and desmethylation in blood, brain and muscle. Differential analyses of blood, brain and muscle tissue samples for diazepam and three of its major metabolites (Ro 5-2180, Ro 5-5345 and Ro 5-6789) from 30 min to 24 hr show that, although the concentration of each component at 30 min is similar both in the absence and presence of metrazol, a definite shift in the slope of the fall-off patterns toward a slower rate of disappearance of the parent compound and of its hydroxylated and desmethylated derivatives is evident when the administration of diazepam is followed by a subcutaneous injection of metrazol. The major constituent in all three tissues, both in the absence and presence of metrazol, is the end product of metabolism, namely oxazepam (Ro 5-6789). Besides being present in much higher concentrations, unlike the parent compound and the other metabolites, Ro 5-6789 maintains a fairly constant level in all three tissues from 30 min to 12 hr and then gradually falls to 24 hr. Although the contribution of the parent compound and its hydroxylated derivative to the duration and degree of protection cannot be accurately defined, it appears that the degree of protection to the convulsant action of metrazol is most closely related to the rate of disappearance of the N -desmethyl derivative.

The rate and extent of levodopa absorption and excretion following intravenous and oral administration of 2− 14 Clevodopa to acute and chronically treated dogs were investigated. Plasma levels of intact levodopa following the intravenous administration declined rapidly during the first 4-6 hr. The elimination-rate constant of intact levodopa from the plasma ranged between 0.73 and 0.99 hr. −1 , which corresponds to a half-life of approximately 40-60 min. The elimination-rate constant of total plasma 14 C ranged between 0.007 and 0.085 hr. −1 , which corresponds to a half-life of 8-9 hr., indicating that the total 14 C was eliminated at one-tenth the rate of intact levodopa. Peak plasma levels of intact levodopa and of total plasma 14 C following oral administration were attained 25-30 min. after dosing. Approximately 70-75% of the intravenous and 57-70% of the oral radioactive doses were excreted in urine over a 72-hr. period. Levodopa and dopamine accounted for a very small percentage of the radioactivity in the urine. Approximately 3.0-7.0% of the intravenous or oral radioactive dose was excreted in the feces. The efficiency of absorption of total radioactivity was calculated to range between 83.0 and 92.0%. Analysis of the ratio of intact levodopa levels to total 14 C levels indicated that only 22.0-30.0% of the administered dose reached the general circulation as intact levodopa, suggesting that the remainder of the absorbed dose, approximately 60.0%, is biotransformed in the gastrointestinal tract prior to absorption and/or in the liver during its "first passage" to the general circulation.

Clonazepam (CZP) was measured in the plasma of eight subjects for 48 hr after a 0.03-mg/kg oral dose. After pretreatment for 19 days with phenytoin (DPH, 4.3 mg/kg/day), plasma CZP concentrations were determined in the same subjects after another 0.03-mg/kg oral dose of CZP. The same protocol was followed in eight additional subjects using phenobarbital (PB, 1.4 mg/kg/day) instead of DPH. DPH pretreatment lowered mean plasma CZP concentration in 8 of the 12 time points. DPH pretreatment increased CZP clearance by 46% to 58% and decreased CZP half-life (t½) by 31%. Both changes were statistically significant. After PB pretreatment the mean plasma CZP concentration was lowered by an average of 11%, but the decrease was statistically significant for only 1 of the 12 time points. PB decreased mean CZP t½ by 11% and increased CZP clearance by 19% to 24%, but only the increase in clearance was statistically significant. Both DPH and PB increased CZP clearances and decreased the areas under the plasma concentration-time curves without altering the volumes of distribution. This observation is consistent with induction of CZP metabolism. The overall effect of DPH (4.3 mg/kg/day) was greater than the effect of PB (1.4 mg/kg/day). Neither the DPH or PB had a significant effect on the extent of CZP protein binding. Clinical Pharmacology and Therapeutics (1980) 28, 368–375; doi:10.1038/clpt.1980.175

We have examined factors that alter the effect of diazepam (DZ) on plasma corticosterone (CS) in rats. DZ had a biphasic effect on plasma CS levels: CS decreased with doses below 5 mg/kg and increased with higher doses. Peak response occurred 90 minutes post injection in both sexes. Plasma DZ levels were significantly higher in females than in males and peak at 10 and 30 minutes post injection in males and females, respectively. There was also a sex difference in the pattern of DZ metabolites. An acute stressor (30 minutes of immobilization) did not affect plasma CS levels in rats injected with a 5 mg/kg dose of DZ. Prenatally stressed animals did not differ in basal CS levels or in their response to 5 mg/kg of DZ compared to prenatally non-stressed animals. These two groups of animals also did not differ in plasma levels of DZ or of its metabolites. By contrast, the 5 mg/kg dose of DZ had no effect on plasma testosterone levels in control animals, but increased it in prenatally stressed animals. Furthermore, compared to non-stressed controls, prenatally stressed animals had lower baseline plasma testosterone levels. These results indicate that the effect of DZ on plasma CS is influenced by endogenous as well as exogenous factors and that these effects vary with the particular biochemical parameter under examination.

1. Blood levels and tissue distribution of chlordiazepoxide and its major metabolites have been correlated with observed changes in ‘aggression” and ‘activity” following oral administration of the compound to cynomolgus (Macaca fascicularis) primates.2. Distribution of 14C after a single oral dose of [2-14C] chlordiazepoxide (5 mg/kg) is indicative of rapid absorption, approximately 30% and 80% dose being absorbed by 0.25 h and 2 h respectively. Highest blood concentrations are observed 2-6 h after dosing. The relatively high content of 14C in the tissues and the corresponding low content in urine and faeces at 2-12 h after dosing are suggestive of tissue storage and/or enterohepatic recirculation.3. Analysis of blood, brain and muscle for chlordiazepoxide and its major metabolites indicate that these are present 0.25 h after dosing. Chlordiazepoxide and its N-desmethylated derivative reach peak concentrations in all three tissues 2 h after dosing while the peak for ‘lactam” is attained at 6 h. In all 3 t...

The duration of the anticonvulsant (antimetrazol) activity of chlordiazepoxide in mice in relation to blood levels and tissue distribution patterns of the parent drug and its major metabolites is presented. Quantitation of the effect of a 125 mg/kg s.c. injection of metrazol and the degree of protection by a single 20 mg/kg oral dose of chlordiazepoxide, based on measuring the incidence of defined seizure reactions, indicated maximal protection for 4 hr after chlordiazepoxide administration. The quantitative 14C distribution after the oral administration of a single 20 mg/kg dose of chlordiazepoxide-2-14C is indicative of a rapid absorption onset as well as of a gradual increase in the tissue-to-blood 14C ratios from 0.5 to 6 hr after administration. In contrast, a 125 mg/kg subcutaneous injection of metrazol given 30 min after the oral administration of chlordiazepoxide appears both to reduce markedly the rate of absorption and to alter the disposition of chlordiazepoxide. This alteration includes a reduction in the blood 14C and tissue 14C levels immediately after metrazol injection to 4 hr after chlordiazepoxide administration. Although the initial tissue-to-blood 14C ratios are similar to those seen in the absence of metrazol, they do not show the marked increment with time. Differential spectrofluorometric analyses of blood, brain and muscle tissue samples for chlordiazepoxide and its major metabolites show that N-desmethylchlordiazepoxide is the major constituent in all three tissues both in the absence and in the presence of metrazol. Besides being present in much higher concentrations, unlike the parent compound and other metabolites, the N-desmethyl derivative maintains a maximum level from 30 min to 4 hr in the brain and from 30 min to 6 hr in blood and muscle. Correlation of the levels of chlordiazepoxide and its metabolites in these tissues to its anticonvulsant (antimetrazol) activity indicates that it is the concentration of the N-desmethyl metabolite that most closely parallels the pattern of this anticonvulsant activity.

1. Changes in ‘aggression’ and ‘activity’ observed in cynomolgus primates (Macaca fascicularis) following administration of a single 2·5 mg/kg oral dose of diazepam have been related to blood levels and tissue distribution of the parent compound and its major metabolites.2. Distribution of 14C after a single oral dose of [2-14C]diazepam shows rapid absorption, 75% of the dose being absorbed by 2 h at which time highest blood concn. are observed. With the exception of muscle and carcass, tissue-to-blood ratios exceed 1·0 throughout 24 h. High 14C content in excreta between 2 and 12 h after dosing suggests hepatic recycling and/or tissue storage.3. Analyses of blood, brain and muscle from 0·25 to 24 h after dosing show the presence of diazepam and its major metabolites as early as 0·25 h after dosing, the N-desmethyl derivative predominating throughout the 24 h period. The concn. of diazepam in all three tissues falls relatively faster than its metabolites.4. Max. reduction in ‘aggression’ (79%) and...