The effect of site of application on the transcutaneous absorption of 17-beta estradiol from a transdermal delivery system (Climara).

OBJECTIVE: The effect of site of application on 17-beta estradiol bioavailability was assessed in an open-label, randomized, crossover study of a once-weekly transdermal estradiol patch (Climara). DESIGN: After placement of a transdermal patch delivering 0.1 mg/day of estradiol on either the buttocks or abdomen, serial plasma samples were obtained over 7 days and for the immediate 24 h after patch removal. Plasma estradiol concentrations were used to estimate pharmacokinetic parameters for the rate and extent of absorption between the two sites. RESULTS: Plasma estradiol concentrations were sustained at premenopausal levels over the week in most subjects. After application on the buttock, mean peak plasma concentration (Cmax) was 125.1% and mean relative bioavailability (AUC(0-168)) was 117.2% of that from the abdomen site. CONCLUSIONS: In summary, the buttocks seem to be an acceptable site for the application for this once-weekly 17-beta estradiol transdermal delivery system. Because the extent of absorption was significantly more for buttock than for abdomen application, this application site may provide an advantage in women who experience menopausal symptoms at the end of the week.

A randomized controlled trial of four doses of transdermal estradiol for preventing postmenopausal bone loss. Transdermal Estradiol Investigator Group.

OBJECTIVE: To determine the effects of four doses of a 7-day transdermal 17beta-estradiol (E2) delivery system, including 0.025 mg/day, on bone loss in postmenopausal women. METHODS: This was a multicenter, double-masked, randomized, placebo-controlled study of the effects of transdermal E2 at doses of 0.025, 0.05, 0.06, and 0.1 mg/day for the prevention of postmenopausal osteoporosis. Efficacy was evaluated from bone mineral density of lumbar vertebrae L2-L4, radius, proximal femur, and total hip measured with dual-energy x-ray absorptiometry. Serum osteocalcin and urinary pyridinoline and deoxypyridinoline concentrations were measured. RESULTS: At 24 months, E2 doses of 0.025, 0.05, 0.06, and 0.1 mg/day resulted in mean increases in bone mineral density of the lumbar spine of 2.37%, 4.09%, 3.28%, and 4.70%, respectively, and increased bone mineral density of the total hip by 0.26%, 2.85%, 3.05%, and 2.03%, respectively. All increases were statistically significantly greater than placebo, which decreased bone mineral density by 2.49% at the spine and 2.04% at the hip. Consistent and significant improvements in biochemical markers of bone turnover also were noted at various intervals in all treatment groups. The most frequent adverse events were local reactions from the transdermal drug-delivery system, effects of estrogen, and menopausal symptoms. CONCLUSION: Transdermal E2 at doses of 0.025, 0.05, 0.06, and 0.1 mg/day effectively prevented bone loss in postmenopausal women.

Arthroscopic distal clavicle excision. Technique and early results.

Since 1941, distal clavicle excision has been a reliable technique for alleviating pain caused by acromioclavicular joint arthritis. Disadvantages of the procedure include permanent shoulder weakness, a lengthy recovery time ranging from weeks to months before useful function of the extremity returns, and lack of cosmesis. By modifying the standard portals used to perform arthroscopic subacromial decompression, the authors have successfully excised the distal clavicle of ten consecutive patients. Using this arthroscopic technique, the surgical time averaged approximately one hour 40 minutes, blood loss was negligible, and there were no complications. Operations were performed in an outpatient setting. Five of ten patients missed work only on the day of surgery, and seven of ten patients required no formal physical therapy. All ten patients achieved a good or excellent result on the UCLA. Shoulder Scale for short-term follow-up evaluation. Postoperative radiographs documented adequate bone resection in all cases. In experienced hands, arthroscopic distal clavicle excision is an excellent substitute for the "open" procedure.

Arthroscopic treatment of full-thickness rotator cuff tears: 2- to 7-year follow-up study.

This study analyzes the midterm follow-up results of 40 full-thickness rotator cuff tears treated by arthroscopic subacromial decompression and debridement. Patients were selected for this prospective study based on a variety of factors, including physiologic age, handedness, activity level in occupation or avocation, and preoperative estimate of repairability. Patients were divided into three groups based on the size of the tear as measured during surgery; results were evaluated on the UCLA shoulder rating scale. This study emphasizes the importance of patient selection when applying arthroscopic treatment for full-thickness rotator cuff tears. Small (0-2 cm) tears (n = 10) in older individuals not involved in strenuous activities did well (90% satisfactory). Patients with larger (2-4 cm) repairable tears (n = 8) did poorly (50% satisfactory) in comparison with our previous study of the results of open repair (84% satisfactory). Arthroscopic treatment in patients with massive, irreparable tears (n = 22) did not restore lost strength or range of motion, but there was significant pain relief, and 86% were satisfied with the results on a limited-goals basis. The study concludes that with proper patient selection, arthroscopic treatment has a valuable, but limited, role in the treatment of full-thickness rotator cuff tears.

Early degenerative joint disease simulating impingement syndrome: arthroscopic findings.

Eighteen patients who underwent shoulder arthroscopy for impingement syndrome were shown at operation to have coexisting glenohumeral degenerative joint disease (DJD) which was not apparent during preoperative clinical and radiographic evaluation. Because traditional ("open") techniques of anterior acromioplasty do not allow inspection of the glenohumeral joint, it is almost certain that this pathology would have been missed at operation if open acromioplasty had been performed. We conclude that arthroscopic subacromial decompression (ASD), by allowing easy inspection of the glenohumeral joint, offers a distinct advantage over traditional acromioplasty. Furthermore, arthroscopic evaluation of some of these patients' glenohumeral joints provided us with evidence supporting the existence of subluxation arthropathy. We have also developed a new clinical test, the "compression-rotation" test, which has been helpful in distinguishing patients with both impingement syndrome and early DJD syndrome from those with isolated impingement syndrome. Although patients in this study appeared to be doing well at short-term follow-up status post-ASD and glenohumeral debridement, no long-term results are yet available.

Arthroscopic subacromial decompression for chronic impingement. Two- to five-year results.

Subacromial decompression was performed arthroscopically on 65 patients who were evaluated two to five years after the procedure. None had full thickness rotator cuff tears. Patients with partial thickness cuff tears were included in this study in order to allow comparison of arthroscopic acromioplasty with open acromioplasty for stage II impingement. On the UCLA shoulder rating scale, 89% of the cases in this study achieved a satisfactory result. These results compare favourably with those reported following open acromioplasty. The arthroscopic procedure is technically demanding. When properly performed in patients with appropriate indications, hospitalisation is brief, return to activities is rapid, there is little risk of deltoid muscle complications, and the results are lasting.

Diagnosis and treatment of incomplete rotator cuff tears.

The histopathologic changes leading to rotator cuff rupture are gradual and progressive. Incomplete tears can be observed in the articular or bursal surface. These partial lesions are infrequently demonstrated with arthrography or bursography. Although structural variations in cuff integrity can be demonstrated with ultrasound or magnetic resonance imaging, precise definition of partial tears is difficult. The exact location and extent of incomplete tears can be documented with shoulder arthroscopy. Anterior acromioplasty, either open or arthroscopic, is indicated for the treatment of chronic mechanical impingement refractory to conservative management. When a sizable partial defect is identified at open surgery, the degenerated tissue is excised and the tendon is reattached to bone or repaired with side-to-side suture. Arthroscopic treatment consists of debridement of the torn cuff margins, followed by arthroscopic subacromial decompression (ASD). When the incomplete tear in an active individual involves more than one-half the cuff thickness, arthroscopic and open techniques can be combined. Twenty partial-thickness tears were encountered among 130 patients who had ASD for chronic impingement. Fifteen had a satisfactory result, but five required additional surgery. A system of grading partial-thickness tears based on location, depth, and area is presented in an effort to standardize the observations of various investigators and to permit comparison of the results of arthroscopic treatment.

Arthroscopic treatment of impingement of the shoulder.

Arthroscopic subacromial decompression is an alternative to open anterior acromioplasty in patients who have advanced stage II and selected stage III impingement syndromes. This procedure can be performed in an outpatient setting and postoperative morbidity is minimal; however, the procedure is technically demanding. Because the deltoid is not detached, immediate full range of active motion is possible, allowing an early return to activities of daily living. Substantial pain relief can be anticipated in a large majority of patients.

Shoulder impingement syndrome: MR findings in 53 shoulders.

The shoulder impingement syndrome refers to a condition in which the supraspinatus tendon and subacromial bursa are chronically entrapped between the humeral head inferiorly and either the anterior acromion itself, spurs of the anterior acromion or acromioclavicular joint, or the coracoacromial ligament superiorly. As a result, the space for the bursa and tendon is reduced, and repeated trauma to these structures leads to bursitis and rotator cuff injury. Although pain and limitation of motion are common early findings, the diagnosis is often delayed until a complete tear of the rotator cuff has occurred. In an attempt to determine if MR can be used to depict the abnormalities associated with impingement syndrome (subacromial bursitis, supraspinatus tendinitis, and rotator cuff tear), we reviewed 107 MR scans of painful shoulders. Changes consistent with impingement syndrome were found in 53 patients (50%), 32 of whom underwent subsequent arthrography or surgery. MR was found capable of depicting several soft-tissue and bony abnormalities that have been clinically described in impingement syndrome. In regions of inflammation, we found that the supraspinatus tendon and/or the subacromial bursa were compressed by spurs (25 shoulders), capsular hypertrophy of the acromioclavicular joint (six shoulders), and/or low-lying acromion (14 shoulders). While T1-weighted MR imaging was highly sensitive to abnormalities of the supraspinatus tendon, tendinitis could be differentiated from a small tear of the supraspinatus tendon only with T2-weighted imaging. Large, full-thickness tears, especially if chronic, produced characteristic MR findings on both T1- and T2-weighted images. We conclude that MR can be used to detect several abnormalities associated with the shoulder impingement syndrome.

Shoulder arthroscopy: current indications and techniques.

The role of arthroscopy in the diagnosis and treatment of shoulder disorders is evolving. Arthroscopic subacromial decompression is an alternative to open anterior acromioplasty in the treatment of chronic stage II impingement syndromes prior to the development of full thickness rotator cuff tear. Patients with massive and otherwise unrepairable cuff tears have achieved significant pain relief from arthroscopic decompression and debridement of the floppy and irregular cuff margins. Routine repairable full thickness cuff tears are best treated by open reconstruction. The arthroscope is an adjunct in confirming the diagnosis and direction of shoulder instability. Arthroscopic stabilization is most feasible when the anterior glenohumeral ligament/labral complex is detached. The introduction of a metal staple is controversial, however, reported complications are diminishing with experience. Alternate methods of stabilization are being investigated. Effective arthroscopic techniques have been established for the removal of loose bodies, the treatment of calcific tendinitis, septic arthritis, and other disorders. Shoulder arthroscopy will undoubtedly achieve an appropriate place in the armamentarium of the orthopedic surgeon.

Arthroscopic subacromial decompression: analysis of one- to three-year results.

Arthroscopic subacromial decompression (ASD) is a method of performing anterior acromioplasty utilizing basic arthroscopic techniques. The procedure is indicated in cases of chronic impingement syndrome that have failed to respond to prolonged conservative management. The purpose of this study is to present an analysis of the 1- to 3-year follow-up results of the initial 50 consecutive cases of ASD that I have performed. Forty (80%) of the cases had advanced stage II impingement without rotator cuff tear. Ten (20%) had full-thickness tears of the rotator cuff. Patients were evaluated pre and postoperatively on the UCLA Shoulder Rating Scale, which includes an assessment of pain, function, range of motion (ROM), strength, and patient satisfaction. Eighty-eight percent of the cases were rated "satisfactory" (excellent or good), and 12% were rated "unsatisfactory" (fair or poor). The procedure is technically demanding, and to achieve a satisfactory result the criteria of open anterior acromioplasty must be met. Arthroscopic subacromial decompression is presented as an alternative to open anterior acromioplasty in advanced stage II and selected cases of stage III impingement syndrome.

Repair of the rotator cuff. End-result study of factors influencing reconstruction.

In fifty patients who had fifty tears of the rotator cuff that had been repaired, we correlated the preoperative findings by history, physical examination, and radiography with the operative findings, the difficulty of the repair, and the results after an average follow-up of 3.5 years. The results, which were rated on the basis of pain, function, range of motion, strength, and satisfaction of the patient, were satisfactory in 84 per cent and unsatisfactory in 16 per cent. The correlations of the preoperative findings with the results showed that pain and functional impairment, the primary indications for repair, were significantly relieved. The longer the duration of pain was preoperatively, the larger the cuff tear and the more difficult the repair were. The strength of abduction and of external rotation before repair was of prognostic value: the greater the weakness, the poorer the result. The poorest results were in patients with strength ratings of grade 3 or less. Limitation of active motion preoperatively was also of prognostic value: in patients who were unable to abduct the shoulder beyond 100 degrees preoperatively, there was an increased risk of a poor result. An acromiohumeral distance of seven millimeters or less (measured on the anteroposterior radiograph) suggested a larger tear and the likelihood that after repair there would be less strength in flexion, less active motion, and lower scores. Single or double-contrast arthrography was not consistently accurate in estimating the size of the tear. After so-called watertight repair and anterior acromioplasty, successful results can be anticipated in a high percentage of patients.

The rarity of shortening of the Q-T interval in patients with hypercalcemia.

Shortening of the Q-T interval on the 12-lead ECG is often attributed to hypercalcemia and is sought in critically ill patients to confirm suspected hypercalcemia. In our experience, hypercalcemia of greater than 13 mg/dl (3.25 mM/L) was unaccompanied by ECG changes. The records of the Brooklyn VA Medical Center for a 3-year period were reviewed and yielded 125 patients with hypercalcemia. Of these, 48 (38%) had a serum calcium of greater than 13 mg/dl. Of these 48, 10 (21%) had an ECG recorded at the same time. The mean serum calcium in these patients was 13.6 mg/dl (3.40 mM/L). None had an abnormally short Q-T interval when the interval was corrected for heart rate (Q-Tc). The ionized calcium was estimated and yielded a mean of 2.26 mM/L (normal range = 0.94-1.33 mM/L). No cause for overestimation of ionized calcium was apparent. It is concluded that the Q-T interval is not a useful clue to the presence of hypercalcemia.

Human ciliary beat frequency at three levels of the tracheobronchial tree.

The intrinsic beating frequency of human ciliated respiratory epithelium at 3 different levels of the respiratory tree was examined. Ciliated epithelium was collected from the trachea, mainstem, and basal segment of 30 patients during fiberoptic bronchoscopy, and ciliary beat frequency was measured in vitro using a photoelectric technique. Specimens from the first group of 15 patients were measured at room temperature (23 to 25 degrees C) and those of the second group of 15 were measured at 37 degrees C. For group I the over-all mean beat frequencies at the trachea, right mainstem, and basal segment were 11.3, 11.1, and 11.4 beats/s, respectively, and for group II the over-all mean beat frequencies were 14.7, 14.7, and 14.8 beats/s, respectively. Within each group there were no significant differences (P greater than 0.05) in the over-all means recorded at the 3 sample sites. Although for a given subject, ciliary beat frequency was not significantly different for specimens taken from the trachea, mainstem, and basal segment, the pool mean beat frequency varied from 1 patient to another. Variations in beat frequency among patients could not be related to age, smoking habits, alcohol consumption, or disease history.

Pulmonary function in scleroderma.

Pulmonary function tests were performed in 45 patients with scleroderma. Thirteen patients (29%) were found to have restrictive disease, 12 patients (27%) were found to have obstructive disease, and 19 patients (42%) had small airway disease (SAD). Smoking did not seem to be a factor underlying either obstructive or small airway disease in these patients. A low diffusing capacity was most common in patients with restrictive disease and rarely the only abnormality in pulmonary function. SAD was usually found in patients who had normal chest radiographs and no pulmonary symptoms and was often the only abnormality. SAD is therefore an early and sensitive indicator of pulmonary involvement in scleroderma.

Anterior angulation deformity of the radial head. An unusual lesion occurring in juvenile baseball players.

Four cases of an unusual angulation deformity of the radial head were seen in juvenile baseball players, with or without associated lesions of osteochondritis in the contiguous capitellum of the humerus and loose-body formation. The established deformity did not show a tendency toward anatomical restitution. In each case, symptoms produced by this deformity were noted to appear in association with athletic activity.