Treatment of ventricular arrhythmias

Within the past 20 years, our knowledge concerning the epidemiology, natural history, and treatment of VT has expanded greatly. A variety of effective pharmacologic, surgical and electrical therapies for VT are now available to the clinician. Patients who present with ventricular, tachyarrhythmias should undergo a comprehensive medical evaluation directed at identifying and treating such factors as ischemia, congestive heart failure, valvular heart disease, sensitivity to cardioactive drugs, and metabolic derangements. Many patients who present with asymptomatic ventricular arrhythmias do not require specific antiarrhythmic drug therapy. However, certain patients who have already suffered a life-threatening arrhythmia or who are at high risk for such arrhythmia should be vigorously treated with specific antiarrhythmic therapy guided for that individual patient. The efficacy of any antiarrhythmic treatment should be assessed by ECG monitoring, exercise testing, and/or electrophysiologic study. In the near future, potentially revolutionary new electrical therapies for ventricular tachyarrhythmias will be evaluated. It is to be hoped that these devices used in combination with pharmacologic and surgical therapies may dramatically reduce the incidence of sudden cardiac death in high-risk patients.     

Variability of the pattern electroretinogram

Conflicting results have been obtained concerning the parametric properties of the pattern electroretinogram. These discrepancies may be due to the large amount of variability inherent in recording amplitudes. We have found the variability within a single stimulus condition to be so large (ranging from 30% to 67% of the mean value) that it could mask any underlying spatial frequency tuning. Changing the stimulus conditions failed to significantly reduce the observed variability, although changing recording conditions produced some reduction. The use of a narrower rejection band, a greater number of sweeps, and placement of the reference electrode on the ipsilateral ear (as opposed to the ipsilateral temple) combined to decrease variability of the pattern electroretinogram within a single recording session; however, intersession variability remained high. Therefore one must be careful in evaluating data from this technique, and caution is advised in its clinical use.     

Oral and maxillofacial surgery in patients with chronic orofacial pain.

PURPOSE: In this investigation, we evaluated a population of patients with chronic orofacial pain who sought treatment at a pain center in an academic institution. These patients were evaluated with respect to 1) the frequency and types of previous oral and maxillofacial surgery procedures, 2) the frequency of previous significant misdiagnoses, and 3) the number of patients who subsequently required surgical treatment as recommended by an interdisciplinary orofacial pain team. The major goal of this investigation was to determine the role of oral and maxillofacial surgery in patients with chronic orofacial pain. Patients and Methods: The study population included patients seen at the Center for Oral, Facial and Head Pain at New York Presbyterian Hospital from January 1999 through April 2001. (120 patients; female-to-male ratio, 3:1; mean age, 49 years; average pain duration, 81 months; average number of previous specialists, 6). The patient population was evaluated by an interdisciplinary orofacial pain team and the following characteristics of this population were profiled: 1) the frequency and types of previous surgical procedures, 2) diagnoses, 3) the frequency of previous misdiagnoses, and 4) treatment recommendations made by the center team. RESULTS: There was a history of previous oral and maxillofacial surgical procedures in 38 of 120 patients (32%). Procedures performed before our evaluation included endodontics (30%), extractions (27%), apicoectomies (12%), temporomandibular joint (TMJ) surgery (6%), neurolysis (5%), orthognathic surgery (3%), and debridement of bone cavities (2%). Surgical intervention clearly exacerbated pain in 21 of 38 patients (55%) who had undergone surgery. Diagnoses included myofascial pain (50%), atypical facial neuralgia (40%), depression (30%), TMJ synovitis (14%), TMJ osteoarthritis (12%), trigeminal neuralgia (10%), and TMJ fibrosis (2%). Treatment recommendations included medications (91%), physical therapy (36%), psychiatric management (30%), trigger injections (15%), oral appliances (13%), biofeedback (13%), acupuncture (8%), surgery (4%), and Botox injections (1%) (Allergan Inc, Irvine, CA). Gross misdiagnosis leading to serious sequelae, with delay of necessary treatment, occurred in 6 of 120 patients (5%). CONCLUSIONS: Misdiagnosis and multiple failed treatments were common in these patients with chronic orofacial pain. These patients often have multiple diagnoses, requiring management by multiple disciplines. Surgery, when indicated, must be based on a specific diagnosis that is amenable to surgical therapy. However, surgical treatment was rarely indicated as a treatment for pain relief in these patients with chronic orofacial pain, and it exacerbated and perpetuated pain symptoms in some of them.     

Kinetic characteristics of ICI D1694: a quinazoline antifolate which inhibits thymidylate synthase.

The thymidylate synthase (TS) inhibitor ICI D1694 (N-(5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N -methylamino]-2 - thenoyl)-S-glutamic acid) is a structural analogue of the substrate N5,N10-methylenetetrahydrofolate (5,10-CH2FH4) and is currently under clinical evaluation as a treatment for cancer. The compound is shown here to be a mixed non-competitive inhibitor of TS from murine leukemia (L1210) cells when 5,10-CH2FH4 is varied. This result suggests formation of an inactive complex between TS, 5,10-CH2FH4 and the inhibitor. Thus, binding to only one of the two active sites on the TS homodimer may be sufficient to prevent catalysis fully. Treatment of L1210 cells with ICI D1694 is known to cause intracellular accumulation of the tetraglutamate derivative which is shown here to have a 60-fold higher affinity for TS. The IC50 for inhibition of L1210 cell growth is below the Ki value of ICI D1694 for L1210 TS but above that of the tetraglutamate. The formation of polyglutamates and concentration of drug inside cells, therefore, seem to be responsible for biological activity.     

Compression plating for child and adolescent femur fractures.

Twenty-five children ranging in age from 6-16 years underwent AO compression plate fixation for treatment of a femur fracture. Generally, the most common reason for plate fixation was to simplify nursing care and rehabilitation of children with an associated severe head injury or polytrauma. Twenty-three fractures healed in 11 weeks on the average, most by periosteal bone formation. Leg length discrepancy was not a clinical problem. Nursing care and polytrauma rehabilitation were simplified in all children. We believe that plate fixation is a reasonable treatment option for femoral fracture care in children aged less than 11 years with severe head injury or associated polytrauma.