The effect of inhibition of 5-lipoxygenase by zileuton in mild-to-moderate asthma.

OBJECTIVE: To evaluate the effectiveness of inhibiting the formation of the 5-lipoxygenase products of arachidonic acid by the 5-lipoxygenase inhibitor zileuton in the treatment of mild-to-moderate asthma. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: University hospitals and private allergy and pulmonary practices. PATIENTS: A total of 139 persons with asthma who had a forced expiratory volume in 1 second (FEV1) of 40% to 75% of the predicted value and who were not being treated with inhaled or oral steroids. INTERVENTION: Zileuton, 2.4 g/d or 1.6 g/d, or placebo for 4 weeks. MEASUREMENTS: Airway function, beta-agonist use, and symptoms; inhibition of 5-lipoxygenase assessed by measurement of urinary leukotriene E4 (LTE4). RESULTS: Zileuton produced a 0.35-L (95% CI, 0.25 to 0.45 L) increase in the FEV1 within 1 hour of administration (P < 0.001 compared with placebo), equivalent to a 14.6% increase from baseline. After 4 weeks of zileuton therapy, airway function and symptoms improved, with the greatest improvements occurring in the 2.4 g/d group: This group's FEV1 increased by 0.32 L (CI, 0.16 to 0.48 L), a 13.4% increase, compared with a 0.05-L (CI, -0.10 to 0.20 L) increase in patients taking placebo (P = 0.02). Symptoms and frequency of beta-agonist use also decreased with zileuton, 2.4 g/d. The mean urinary LTE4 level decreased by 39.2 pg/mg creatinine (CI, 18.1 to 60.4 pg/mg creatinine) and 26.5 pg/mg creatinine (CI, 6.6 to 46.5 pg/mg creatinine) in the 2.4 g/d and 1.6 g/d groups, respectively, compared with a slight increase in the placebo group (P = 0.007 and P = 0.05). No difference was noted in the number of adverse events among treatment groups. CONCLUSIONS: Inhibition of 5-lipoxygenase can improve airway function and decrease symptoms and medication use in patients with asthma, suggesting that this inhibition can be useful therapy for asthma. Also, 5-lipoxygenase products may mediate part of the baseline airway obstruction in patients with mild-to-moderate asthma.

A miniature piezoelectric polymer transducer for in vitro measurement of the dynamic contact stress distribution.

Previous studies of contact pressure measurement between articular surfaces have been mostly limited to static techniques. The purpose of our study was to develop a new dynamic technique for a direct measurement of the local contact stresses, and to apply the new method to an in vitro cadaver study of the patellofemoral joint pressures. The miniature transducer consists of a 2 mm diameter and 28 microns thick piece of piezoelectric polymer film sandwiched between two stainless steel electrodes of similar diameter. A water-resistant capsule consisting of Teflon film and Hysol epoxy was applied around the transducer. The transducer was 3 mm in diameter and 0.7 mm in thickness. A 3 mm well was made at six locations in the patella, corresponding to superior, middle, and inferior regions of both facets. Six transducers were cemented within each well, flush with the articular cartilage. The transducers were calibrated in situ before and after the experiment. The femur was rigidly fixed to the loading apparatus and the tibia was allowed to flex and extend through a 90 degrees range of motion using an Instron and a pulley system connected to the quadriceps tendon. Q angles of 0, 5, 10 and 15 degrees were established by adjusting the direction of the quadriceps tendon. Stresses ranging from 0.1-1.3 MPa were recorded at various locations. These values varied in flexion and extension. An overall decrease in these stresses was noted after tuberosity elevation up to 1.5 cm, following which increased values up to 1.8 MPa were recorded mostly in the superior section.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of propranolol on bone metabolism in the rat.

Propranolol, a nonspecific beta-blocker has many physiologic effects. Its effects on bone in vivo are unknown, although beta receptor sites have been found on osteoblasts. In this study, the hypothesis tested was that low doses of propranolol could alter bone properties and enhance orthotopic endochondral bone formation. In a group of nonsurgical rats, propranolol treatment increased femoral torsional strength on biomechanical testing. In the rat surgical model used, right femora were fixed to a polyethylene plate and then defects were created mid-diaphysis and subsequently filled with demineralized bone matrix. These rats (defect rats) were randomly divided into groups that were given propranolol or a saline carrier for 19 consecutive days. In the defect rats, increased trabecular femoral metaphyseal mineral apposition rates were observed in propranolol-treated groups. Densitometry and roentgenographic scoring of callus formation after 12 weeks in propranolol-treated rats revealed increased callus and bone union. The results of this study indicate that propranolol treatment can significantly affect bone properties.

Estazolam treatment of insomnia in generalized anxiety disorder: a placebo-controlled study.

Estazolam, a triazolobenzodiazepine with an intermediate elimination half-life, has been shown previously to be an effective and safe hypnotic in insomniacs without concomitant psychiatric illness. Our study of the efficacy of estazolam in patients with insomnia associated with generalized anxiety disorder began when 108 patients meeting criteria for generalized anxiety disorder (mean total score of Hamilton Rating Scale for Anxiety [HAM-A] = 22.0 +/- 3.1 [SD]) and insomnia were given single-blind placebo for 7 nights. Nine patients whose anxiety and/or insomnia improved were dropped as placebo responders. The remaining 99 patients were randomly allocated (1:1) to double-blind treatment with either estazolam 2.0 mg or matching placebo for 7 nights. Hypnotic efficacy, as determined by patient-completed sleep questionnaires, was statistically significant for estazolam 2.0 mg versus placebo for all sleep indices (p less than 0.01). Patients treated with estazolam 2.0 mg showed significantly greater improvement in anxiety than those receiving placebo on the mean total score of HAM-A ([placebo, -3.4; estazolam, -7.1; p less than 0.001] and without the insomnia item [placebo, -2.7; estazolam, -5.5; p less than 0.001]). Anxiety scores on the State-Trait Anxiety Inventory showed greater improvement in the estazolam group, but without statistical significance (p = 0.237). Estazolam 2.0 mg is an effective hypnotic in patients with generalized anxiety disorder and appears to have a favorable anxiolytic action.

Fractures of the sesamoid bones of the thumb.

Sesamoid fractures of the metacarpophalangeal joint of the thumb may be classified into two types: (1) with palmar plate intact, and (2) with palmar plate ruptured. In type 1, the patient maintains a normal flexion posture of the metacarpophalangeal joint as well as the ability to flex the metacarpophalangeal joint and interphalangeal joint. In type 2, the metacarpophalangeal joint assumes a hyperextension posture and the patient is unable to flex the metacarpophalangeal joint. Three cases are described to illustrate the two types of the injury. An open fracture of a thumb sesamoid associated with laceration of the palmar plate in a child was treated by reapproximating the palmar plate and the fracture fragments with sutures. Two additional closed fractures of the thumb sesamoid were treated by splinting the metacarpophalangeal joint in comfortable flexion for 2 to 3 weeks. Normal hand function was restored in all the three patients.

Clicking at the wrist due to fibroma in an anomalous lumbrical muscle: a case report and review of literature.

A 33-year-old man had clicking at the wrist and symptoms that were characteristic of carpal tunnel syndrome, which were secondary to a fibroma arising from an anomalous lumbrical muscle in the carpal tunnel. Carpal tunnel release and excision of the fibroma relieved both of the conditions.

Medical castration produced by the GnRH analogue leuprolide to treat metastatic breast cancer.

Leuprolide (Lupron, TAP Pharmaceuticals, North Chicago), a gonadotropin-releasing hormone analogue, was administered to 26 premenopausal women with metastatic breast cancer. Of 25 evaluable patients, 11 (44%) had a partial response with a median duration of 39 weeks and five (20%) remained stable. Six patients showed early rapid progression of their disease. Toxicity was mild and included hot flashes, nausea, vomiting, and headache. Leuprolide induced amenorrhea in all patients who received treatment for ten weeks or longer. We conclude that this GnRH analogue provides a safe and effective means of producing medical castration in premenopausal patients with metastatic breast carcinoma.

Lipofibroma of the median nerve in the palm and digits of the hand.

Lipofibroma of the median nerve or its cutaneous branches is a rare benign tumor. The diagnosis is usually made at surgical exploration of a mass in the distal part of the forearm, the wrist, the palm, or the digits of the hand, which may be asymptomatic or associated with symptoms of carpal-tunnel syndrome. The diagnosis should be made when exploration reveals fusiform enlargement of a segment of the median nerve or its cutaneous branches without hypertrophy of the regional tissues. The tumor is limited to within the epineurial sheath, which is intact, shiny, orange-yellow, firm, thick, and non-resilient to dissection. The nerve tumor does not infiltrate the surrounding tissues nor do the surrounding tissues infiltrate the nerve. If the epineurium is opened, the nerve fibers are found to be inseparably infiltrated by fibrous and fatty tissues. Histologically, these are of epineurial, perineurial, and endoneurial origin. A forzen-section biopsy of a palmar cutaneous branch is suggested to confirm the diagnosis. Once the diagnosis is confirmed, the treatment should be limited to release of the fascia over the involved nerve. The tumorous part of the median nerve was partly or completely excised in seven of twenty-six cases reviewed in the literature and this report. It is to emphasize a conservative approach when such a tumor of the median nerve is encountered at surgery that we describe two more cases.

Transverse bayonet dislocation of the proximal interphalangeal joint.

Complete dislocation of the proximal interphalangeal joint with complete rupture of both the collateral ligaments and volar plate was seen in 8 patients. We call this, "transverse bayonet dislocation of the proximal interphalangeal joint." When treated early, closed manipulation resulted in stable reduction. After a brief period of immobilization of 3 to 5 days with a dorsal aluminum splint, sustained active range of motion exercises were begun by strapping the injured finger to the adjacent finger obtaining good end results in all cases. An untreated dislocation of 5 weeks duration needed operative reduction. This was achieved with good result by release of all the retaining ligaments around the proximal interphalangeal joint including both the collateral ligaments, the volar plate, the transverse retinacular ligaments, and extensor tenolysis.

Fracture of the capitulum humeri.

Fourteen patients with fracture of the capitulum of the humerus were treated, ten by excision of a large fragment or multiple small fragments. Their results were superior to those in patients treated either by closed reduction or by open reduction and fixation. Nine had good to excellent retention of elbow motion, six had no pain, and three had minimum pain. None of the ten had valgus deformity or instability.