Disposition of loratadine in healthy volunteers.

The absorption, metabolism and excretion of carbon-14-labeled loratadine (LOR, SCH 29851, Claritin) administered orally to healthy male volunteers were evaluated. Following a single oral 10-mg dose of [(14)C]LOR ( approximately 102 microCi), concentrations of LOR and desloratadine (DL; a pharmacologically active descarboethoxy metabolite of LOR) were determined in plasma. Metabolites in plasma, urine and feces were characterized using a liquid chromatography-mass spectrometry system (LC-MS) connected in line with a flow scintillation analyzer (FSA). Maximum plasma LOR and DL concentrations were achieved at 1.5 h and 1.6 h, respectively; thus, LOR was rapidly absorbed but also rapidly metabolized as indicated by these similar t(max) values. Metabolite profiles of plasma showed that LOR was extensively metabolized via descarboethoxylation, oxidation and glucuronidation. Major circulating metabolites included 3-hydroxy-desloratadine glucuonide (3-OH-DL-Glu), dihydroxy-DL-glucuronides, and several metabolites resulting from descarboethoxylation and oxidation of the piperidine ring. LOR was completely metabolized by 6 h post-dose. LOR-derived radiocarbon was excreted almost equally in the urine (41%) and feces (43%). About 13% of the dose was eliminated in the urine as 3-OH-DL-Glu. DL accounted for less than 2% of the dose recovered in the urine and only trace amounts of LOR were detected. 3-OH-DL was the major fecal metabolite ( approximately 17% of the dose). The combined amount of 5- and 6-hydroxy-DL contributed to an additional 10.7% of the dose in feces. Approximately 5.4% and 2.7% of the dose were excreted in the feces as unchanged drug and DL, respectively.

Disposition of desloratadine in healthy volunteers.

The absorption, metabolism and excretion of desloratadine (DL, Clarinex) were characterized in six healthy male volunteers. Subjects received a single oral 10-mg dose of [(14)C]DL ( approximately 104 microCi). Blood, urine and feces were collected over 240 h. DL was well absorbed; drug-derived radioactivity was excreted in both urine (41%) and feces (47%). With the exception of a single subject, DL was extensively metabolized; the major biotransformation pathway consisted of hydroxylation at the 3 position of the pyridine ring and subsequent glucuronidation (3-OH-DL-glucuronide or M13). In five of the six subjects, DL was slowly eliminated (mean t((1/2)) = 19.5 h) and persisted in the plasma for 48-120 h post-dose. This is in contrast to a t((1/2)) of approximately 110 h and quantifiable plasma DL concentrations for the entire 240-h sampling period in one subject, who was identified phenotypically as a poor metabolizer of DL. This subject also exhibited correspondingly lower amounts of M13 in urine and 3-OH-DL (M40) in feces. Disposition of DL in this subject was characterized by slow absorption, slow metabolism and prolonged elimination. Further clinical studies confirmed the lack of safety issues associated with polymorphism of DL metabolism (Prenner et al. 2006, Expert Opinion on Drug Safety, 5: 211-223).

Sternoclavicular joint swelling after surgery of the head and neck region: a case report and differential diagnostic review.

BACKGROUND: Very few published reports in the otolaryngologic literature discuss sternoclavicular joint swelling encountered in the postoperative setting. METHODS: The authors document a case of sternoclavicular joint swelling after medialization laryngoplasty. This report is supplemented with a review of the medical literature related to pertinent conditions affecting the sternoclavicular joint. CONCLUSIONS: In our patient, swelling was thought to be related to joint trauma experienced during surgery secondary to standard shoulder roll extension in a patient with preexisting postmenopausal arthritis. This case stands in contrast to the body of documented cases of postoperative sternoclavicular swelling in which the surgical procedure itself was responsible for such findings.

Shoulder arthrodesis.

Current indications for shoulder arthrodesis include posttraumatic brachial plexus injuries, paralysis of the deltoid muscle and rotator cuff, chronic infection, failed revision arthroplasty, severe refractory instability, and bone deficiency following resection of a tumor in the proximal aspect of the humerus. The trapezius, levator scapulae, serratus anterior, and rhomboid muscles must be functional to optimize the functional result following shoulder arthrodesis. A consensus has not been reached concerning the ideal position of the shoulder arthrodesis, although excessive abduction or flexion has been associated with chronic postoperative pain. Decortication of both the acromiohumeral and the glenohumeral surfaces to increase the surface area available for arthrodesis is the most common means for obtaining successful fusion. Although there are numerous methods for stabilization of a shoulder arthrodesis, the most popular method today is probably the AO technique with either a single plate or double plates.

Radiologic, mechanical, and histologic evaluation of 2 glenoid prosthesis designs in a canine model.

Aseptic loosening of glenoid components is a common problem associated with total shoulder arthroplasty. A new glenoid design aimed at improving fixation outcomes was compared with conventional keeled glenoids in weight-bearing canine shoulders. Radiographic, histologic, and mechanical tests were performed at 3 postoperative intervals (0, 3, and 6 months). The uncemented pegged glenoid achieved bone ingrowth around the peg flanges in each case. This result was confirmed histologically and radiographically. Mechanical results indicated that mean fixation strength increases significantly between 0 and 3 months after surgery and remains strong through 6 months. In contrast, conventional keeled glenoids were found to have partial or complete radiolucent lines around the keel in each instance, and mechanical testing demonstrated that mean fixation strength weakens significantly between 0 and 3 months after surgery and remains weak through 6 months. These results show that stem design changes can improve implant fixation. A cementless fluted peg stem was superior to a conventional cemented keel design in achieving osseous integration and fixation in a weight-bearing animal model.

Complications of metallic suture anchors in shoulder surgery: A report of 8 cases.

PURPOSE: Metallic suture anchors are widely used in open and arthroscopic operations about the shoulder. We report the cases of 8 patients who were referred to our institution with complications following shoulder surgery in which metallic suture anchors were used. TYPE OF STUDY: Retrospective case series. METHODS: There were 7 male patients and 1 female patient with an average age of 36 years (range, 18 to 76 years). The initial operation was open anterior reconstruction for anterior instability of the glenohumeral joint in 5 patients, open rotator cuff tear repair in 2 patients, and an open posterior capsular reconstruction for posterior instability in 1 patient. All patients were referred for evaluation after a failed index reconstructive procedure. RESULTS: On average, 5.5 suture anchors (range, 3 to 8) per shoulder were used. Of 4 patients undergoing reconstruction with glenoid anchors only, 3 patients had an extraosseously positioned device. In this subset of glenoid-sided reconstructions, when more than 3 anchors were used, at least 1 anchor was inserted in an extraosseous position. In 2 of 3 patients with isolated humeral anchors, there was evidence of migration over time (1 intra-articular, 2 bursal). Three patients (38%) developed severe articular damage that was directly caused by a loose or intra-articular metal suture anchor. One patient developed a wound infection after reconstructive surgery. In all 8 patients, the index procedure failed and required subsequent surgery. CONCLUSIONS: The use of metallic suture anchors about the shoulder is commonplace and useful, but, as with other hardware used about the shoulder, there are significant risks if the anchors are improperly placed or if the index procedure fails.

The often overlooked posterior dislocation of the shoulder.

Unlike most shoulder dislocations, the posterior dislocation is truly a diagnostic challenge to the treating physician because it may be missed more often than it is recognized. In fact, more than 60% of posterior dislocations are misdiagnosed initially by the treating orthopedic surgeon, and the correct diagnosis is often delayed for months or years. A history of seizures, electroshock, or a fall onto a flexed, adducted arm should alert the physician to the possibility of posterior dislocation. A careful physical examination with comparison to the unaffected arm must be performed with particular attention given to subtle posterior fullness and anterior flatness of the shoulder, along with a lack of external rotation and abduction. A radiographic trauma series made in the scapular plane must always be obtained in cases of shoulder trauma to rule out posterior dislocation. A computed tomographic scan may also be necessary. The correct diagnosis of this injury will facilitate proper orthopedic evaluation and treatment and will reduce the incidence of missed posterior shoulder dislocation and its associated morbidity.

Knot security in simple sliding knots and its relationship to rotator cuff repair: how secure must the knot be?

We sought to determine which simple sliding knot configurations would have adequate strength for rotator cuff repair. Four knot configurations were tied with both No. 1 polydioxanone suture and No. 2 Ethibond suture (Ethicon, Somerville, NJ) using 3 different tying techniques: hand-tie, standard knot pusher, and cannulated double-diameter knot pusher. The knots were then tested to failure on a materials testing system. The weakest standard knot configuration was S=S=S=S. The other 3 knot configurations (S//S//S//S, SxSxSxS, and S//xS//xS//xS) generally failed in the 35 to 50 N range. Ultimate strength in this range can be shown to be adequate to withstand, without suture failure, a maximal contraction of a repaired rotator cuff tear within the rotator crescent, assuming certain conditions are met (suture anchors placed 1 cm apart, 2 sutures per anchor). More complex knots are not necessary for adequate knot security. However, the same configuration with only 1 suture per anchor will not be strong enough because the suture will fail under maximum physiological load. This study shows that we can predict the adequacy of a given knot configuration under maximum physiological loading conditions.

Isolation and characterization of polyethylene wear debris associated with osteolysis following total shoulder arthroplasty.

We evaluated the interface membranes surrounding three total shoulder prostheses that had been removed because of progressive aseptic loosening associated with osteolysis. The mean time between the uncomplicated initial arthroplasty and the revision procedure was twelve years (10.5, 10.5, and 16.0 years). Membranes from around both the humeral and the glenoid component were obtained from all three shoulders and were studied histologically to determine the biological response involved in the development of aseptic loosening. For the purpose of comparison, periprosthetic tissue was also obtained from the sites of four failed total hip prostheses that were associated with osteolysis. Polyethylene particles were retrieved with an enzymatic digestion technique that involved the use of papain. Raman vibrational spectroscopy verified that the particles were ultra-high molecular weight polyethylene. The particles were isolated from the tissue, and a computerized image-analysis system characterized 582 of them in terms of size and morphology. Each particle was defined with the use of six shape descriptors: equivalent circle diameter, roundness, form factor, aspect ratio, elongation, and outline fractal dimension. The particles from the hips had a mean equivalent circle diameter (and standard error of the mean) of 0.62 +/- 0.03 micrometer, were predominantly globular in shape, and had low mean values for aspect ratio (1.46 +/- 0.02) and elongation (1.85 +/- 0.03) and relatively high values for roundness (0.74 +/- 0.01) and form factor (0.87 +/- 0.01). In contrast, the particles from the shoulders had a mean equivalent circle diameter of 1.04 +/- 0.03 micrometers. In addition, they had relatively high values for aspect ratio (2.36 +/- 0.07) and elongation (4.96 +/- 0.23) and correspondingly low values for roundness (0.54 +/- 0.01) and form factor (0.67 +/- 0.01), indicating that they were more fibrillar in shape. The particles from the shoulders and those from the hips were significantly different (p < 0.0001) with respect to all of the descriptors except outline fractal dimension. The particles from the shoulders, in general, were larger and more fibrillar than the particles from the hips.

Capsulorrhaphy through an anterior approach for the treatment of atraumatic posterior glenohumeral instability with multidirectional laxity of the shoulder.

Between June 1983 and March 1992, we performed a capsular reconstruction procedure through an anterior approach in ten patients (ten shoulders) who had multidirectional laxity of the shoulder and symptomatic atraumatic posterior glenohumeral instability. The procedure included closure of the capsule in the rotator interval and imbrication of the anterior, inferior, and posteroinferior aspects of the capsule by a double-breasting technique that decreases the overall capsular volume. The mean duration of follow-up was sixty months (range, twenty-four to 103 months). According to the system of Rowe and Zarins, the result was graded as excellent for five shoulders, good for four, and poor for one. On the basis of our results, we recommend capsular reconstruction through an anterior approach only in patients who have persistent multidirectional laxity and symptomatic atraumatic posterior instability of the shoulder despite participation in an intensive rehabilitation program.

Neuropathic arthropathy of the shoulder.

We retrospectively reviewed the records of six men (seven shoulders) with neuropathic arthropathy of the shoulder who were referred to our shoulder service during a twenty-eight-year period (from 1969 through 1997). The etiology of the neuropathic condition was syringomyelia in five patients (six shoulders) and chronic alcoholism in one patient. Five patients (six shoulders) were initially misdiagnosed, and seven operative procedures that were unrelated to the etiology of the neuropathic condition were performed in four of these patients. Radiographs revealed destruction of the shoulder joint and marked resorption of the humeral head in all patients. Magnetic resonance images revealed a syrinx of the central cord in all of the patients except for the one who had chronic alcoholism.

Loop security as a determinant of tissue fixation security.

Secure arthroscopic repair of rotator cuff tears and Bankart lesions requires tight knots (knot security). Equally important, but usually overlooked, is the tightness of the suture loop (loop security). This study compared loop security in knots tied with No. 1 PDS suture using three different methods: (1) hand-tied, (2) single-hole standard knot pusher, and (3) cannulated double-diameter knot pusher. The results of this study show that the double-diameter knot pusher maintained tight suture loops that were equivalent in circumference to hand-tied loops and were significantly tighter than suture loops tied with a standard single-hole knot pusher. This study highlights the fact that loop security is equally important to knot security in tissue fixation.

Reconstruction of chronic and complete dislocations of the acromioclavicular joint.

The authors report on a technique for the treatment of symptomatic, chronic complete dislocations of the acromioclavicular joint. The coracoacromial ligament is substituted for the coracoclavicular ligaments, and a special temporary coracoclavicular lag screw is used to stabilize the clavicle to the coracoid during ligament healing. The technique has been used on 23 patients who were observed for an average of 5.2 years. Good to excellent results were obtained in 19 of 23 patients. The four patients with fair or poor results had one or more resections of the distal clavicle before the reconstruction. Subjectively, 22 of 23 patients reported improvement in their shoulder.

Repair of soft tissue to bone using a biodegradable suture anchor.

The medial collateral ligaments of 18 New Zealand rabbits were surgically detached from bone. In one knee, the ligament was repaired using a biodegradable suture anchor composed of a co-polymer of lactic and glycolic acid. The contralateral medial collateral ligament was not repaired. Animals were sacrificed at 4, 8, and 12 weeks after the operation, and the knee that had the ligament repair was compared with the contralateral control knee. All knees were tested manually tested for stability to valgus stress and then prepared for histologic examination. Medial collateral ligaments repaired using the biodegradable suture anchor demonstrated stability to valgus stress and anatomic healing at the bone-tendon junction. Resorption of the implant was virtually complete by 12 weeks. All specimens demonstrated less inflammatory reaction to the suture anchor than to the attached Vicryl suture. This contrasts with the control group, which was grossly unstable and demonstrated scarring in this nonanatomic position. These results demonstrate efficacy of this particular material of biodegradable implant and justify further investigative efforts.

Morphology of the axillary nerve in an anteroinferior shoulder arthroscopy portal.

An anteroinferior portal can be safely used in arthroscopic shoulder surgery but requires an in-depth knowledge of axillary nerve anatomy. The purpose of this report is to present the qualitative and spatial anatomy of the axillary nerve and to describe patterns of arborization that may affect safe anteroinferior arthroscopic portal placement. Measurements were taken in 42 embalmed cadaveric shoulders (20 male, 22 female). The distance from the acromioclavicular (AC) joint to the axillary nerve averaged 7.90 cm (range, 7.2 to 9.1 cm) in males and 6.37 cm (range, 5.2 to 8.1 cm) in females. We describe the axillary nerve index (distance of nerve from the AC joint/length of deltoid from AC joint) which can be used to predict the location of the axillary nerve along the anterior clavicular line (ACL). The axillary nerve index averaged 0.48 (range, 0.42 to 0.57) in males and 0.41 (range, 0.31 to 0.57) in females. Four types of morphology were noted in the axillary nerve: (1) main trunk with superior and inferior branches, (2) main trunk with superior branches, (3) main trunk with inferior branches, and (4) main trunk only. Our work supports the traditional operable safe zone for the axillary nerve.

Operative treatment of irreparable rupture of the subscapularis.

Between 1980 and 1994, 221 shoulders with recurrent anterior glenohumeral subluxation or dislocation were reconstructed at our institution. At the time of the operation, thirteen shoulders were found to have an irreparable injury of the subscapularis muscle, which we believed to be a contributing factor to the ongoing instability. All but three of the thirteen patients had had two to six previous reconstructions. Operative treatment of the irreparable rupture included a dynamic muscle transfer using the pectoralis major in seven shoulders, the pectoralis minor in five, and both of these muscles in one. According to a modification of the grading system of Neer and Foster, the result was satisfactory for ten shoulders and unsatisfactory for three at a mean of five years after the operation. All shoulders with a satisfactory result demonstrated active contraction of the transferred pectoralis muscle and diminished anterior glenohumeral translation. On the basis of our analysis, we concluded that transfer of the pectoralis muscle is effective for reconstruction of the shoulder in patients who have loss of the subscapularis muscle.