Fracture of lower femoral epiphysis in an infant at birth: a rare obstetrical injury.

We report a case of rare birth injury leading to physeal fracture after a routine cesarean delivery. Because plain radiographics are often normal, therefore these physeal fractures usually present a diagnostic challenge in the newborn. In this case, ultrasonography and magnetic resonance imaging were helpful in making an early accurate diagnosis. The infant received prompt treatment and the physeal fracture healed uneventfully. Physeal fractures should be included in the birth injuries following routine cesarean delivery.

Double-blind, placebo-substitution study of nefazodone in the prevention of relapse during continuation treatment of outpatients with major depression.

The efficacy of nefazodone in prevention of relapse of depression was evaluated in a 36-week double-blind, placebo-substitution, continuation treatment trial. After 16 weeks of acute, single-blind treatment with nefazodone, 131 patients responding to treatment and in stable remission were randomized in a 36-week double-blind trial to either nefazodone (n = 65) or placebo (n = 66). Patients were defined as having relapsed if they had a total score > or = 18 on the 17-item Hamilton Depression Scale on two consecutive visits or if they discontinued treatment for lack of efficacy. Relapse rates were significantly lower for patients randomized to continued nefazodone treatment than for patients switched to placebo. Kaplan-Meier estimates of relapse rates 9 months (36 weeks) after the end of acute treatment were 1.8% for nefazodone versus 18.3% for placebo (P = 0.009) by the Hamilton Depression Scale and 17.3% versus 32.8% (P = 0.028) by discontinuation for lack of efficacy. The mean modal dose of nefazodone was 412 mg/day at study endpoint. These results demonstrate the clinical effectiveness of up to 1 year's treatment (16 weeks acute and 36 weeks continuation) with nefazodone in depressed patients. Long-term efficacy of nefazodone was accompanied by a good safety profile without any weight gain and with minimal symptoms of withdrawal upon abrupt discontinuation of treatment.

Therapeutic trial participants: where do we find them and what does it cost?

Billions of dollars are spent annually in the process of developing and marketing new therapeutic agents. While the methods for testing and assuring safety of these newer agents receive intense scrutiny, the methods by which the patient samples for psychotropic agent studies are recruited has received relatively little attention. It appears that symptomatic volunteers who enter clinical psychopharmacology studies are clinically comparable to treatment-seeking patient samples. There is almost no information regarding the actual proportions of "recruited" to treatment-seeking patients or how many symptomatic volunteers participate in more than one study, and the expense of advertising for symptomatic volunteers has not been investigated. We surveyed 18 experienced investigators around the United States to identify: (1) the relative proportion of clinical trial participants who are symptomatic volunteers versus treatment-seeking patients; (2) the proportion of study volunteers who entered more than one clinical trial; and (3) the cost of recruitment for investigators who conduct these studies. The findings indicate that an average of 87.2 percent of subjects entering trials were recruited via advertising. Most participate in only one study. The expense of identifying and recruiting appropriate symptomatic volunteers is significant, and appears to be increasing. Implications of these findings will be discussed.

Femoral neck fracture following intertrochanteric fracture.

Four patients with femoral neck fracture following healed intertrochanteric fracture were evaluated retrospectively. This situation is a rare occurrence with a current literature review documenting only 15 cases. Patient charts and radiographs were retrospectively reviewed to evaluate the period from initial injury to definitive treatment for the femoral neck fracture. Emphasis was placed on associated risk factors and operative techniques. In case 1, the femoral neck fracture appeared to be clearly a traumatic fracture as it occurred 11 years after the intertrochanteric fracture. In cases 2, 3, and 4, multiple factors were believed to play a role in the generation of the femoral neck fractures, which occurred within 6 months of the original fracture. The etiology of such fractures remains speculative. All four patients were elderly, women with substantial medical comorbidities. Osteoporosis may be the most important single contributing factor to these fractures. Because management of this patient subgroup is notably more complex, surgeons need to be aware of the difficulties and prepared to deal with them.

Geometric analysis of coronal decompensation in idiopathic scoliosis.

STUDY DESIGN: Frontal plane geometry of postoperative curves was analyzed using a geometric model to investigate the relationship between coronal decompensation and postoperative apical shifts from the center sacral line for various thoracic and lumbar Cobb angles. OBJECTIVE: To determine if a balanced spinal configuration is possible when the postoperative lumbar curve is larger than the thoracic curve, and to determine the limits on the postoperative magnitude of the lumbar curve relative to the thoracic curve beyond which a spinal configuration with acceptable balance cannot be achieved. SUMMARY OF BACKGROUND DATA: Previous studies have suggested that overcorrection of the primary thoracic curve may be the principal cause of coronal decompensation after selective thoracic correction and fusion in King Type II curves. Also, other causative factors, such as inappropriate selection of fusion levels and hook patterns, have been implicated as possible reasons for decompensation after Cotrel-Dubousset instrumentation for idiopathic scoliosis. METHODS: Postoperative thoracic curves of 20 degrees, 25 degrees, and 30 degrees were simulated on a model spine. For each thoracic Cobb angle, three left lumbar curves were simulated with the lumbar curve larger than thoracic by 5 degrees, 10 degrees, and 15 degrees. For each combination of thoracic and lumbar Cobb angles, spinal configurations corresponding to different lateral shifts of the thoracic and lumbar apical vertebrae from the center sacral line were obtained. RESULTS: For a given combination of postoperative thoracic and lumbar Cobb angles, there is an optimal range of postoperative lateral distance between the thoracic and lumbar apices (relative apical distance) that will maintain acceptable balance (decompensation < or = 10 mm). Smaller values of the relative apical distance will decompensate the spine. For a constant postoperative thoracic Cobb angle, the postoperative distance between the thoracic and lumbar apices needed to maintain a balanced spine increases with increasing postoperative lumbar Cobb angle. Similarly, for a constant difference between the postoperative thoracic and lumbar Cobb angles, the postoperative distance between the thoracic and lumbar apices needed to maintain a balance spine increases with increasing postoperative thoracic Cobb angle. For postoperative thoracic curves of 20 degrees-30 degrees, acceptable balance can be achieved when the magnitude of the postoperative lumbar curve is up to twice the thoracic curve as long as adequate postoperative relative apical distance can be maintained. CONCLUSIONS: Decompensation does not appear to be caused by the relative magnitudes of the postoperative thoracic and lumbar curves, but is a result of inadequate relative distance between the thoracic and lumbar apical vertebrae in the postoperative geometry.

Longitudinal tibial stress fracture.

Fatigue-type stress fractures occur following repetitive loading of normal bone. These occur frequently in the tibia, although vertical orientation to the fracture is much less common than transverse orientation. Without a convincing history of new or accelerated muscular activity, imaging can be difficult to interpret and evaluation may require more than one imaging modality to exclude other diagnostic considerations, including neoplasm and osteomyelitis.

Effect of light therapy on salivary melatonin in seasonal affective disorder.

To investigate the role of a light-induced advance in the timing of the melatonin rhythm in seasonal affective disorder, 11 depressed patients underwent 2 weeks of light therapy with full spectrum or cool white light. Evening saliva samples were collected before and after each week of treatment and assayed for melatonin to determine the time of onset of nocturnal secretion. Both treatments reduced depression scores, advanced the timing of the melatonin rhythm, and increased melatonin concentrations. Time of onset of the nocturnal increase in melatonin did not differ between clinical responders and nonresponders, suggesting that a phase advance in the onset of nocturnal melatonin secretion is not sufficient to induce clinical remission in seasonal affective disorder.

Intraosseous infusions: effects on the immature physis--an experimental model in rabbits.

Intraosseous infusions are becoming more popular in critical care and emergency room settings in pediatric patients. Spinal needles are introduced in metaphyseal bone to establish intravenous (i.v.) access when standard i.v. routes are not accessible. An experimental rabbit model was constructed to simulate intraosseous infusion in human infants to determine effects on the physis and growth rate of the infused bone. Twenty immature rabbits were infused with saline, bicarbonate, or dopamine solutions. Rabbits were killed and tibias harvested at 24 h and 3 weeks, and gross and histologic sections were examined. No growth disturbance occurred in any of the infused tibias. Gross and microscopic changes were confined to metaphyseal bone and had completely resolved after 3 weeks. There was no evidence of physeal injury.

Phototherapy with broad spectrum white fluorescent light: a comparative study.

The principles of photobiology suggest that the antidepressant effect of phototherapy depends on the dose and spectrum of light. We investigated the effect of spectrum by comparing two broad spectrum fluorescent light sources with different spectral distributions. In a crossover design, 11 patients with seasonal affective disorder (SAD) were treated with broad spectrum fluorescent and cool white light for 7 days. Scores on the Hamilton Rating Scale for Depression were reduced from 22.5 to 8.1 with broad spectrum fluorescent light and from 23.5 to 8.8 with cool white light. The results suggest that both light sources are effective treatments.

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.

Urinary MHPG excretion and treatment with desipramine or amitriptyline: prediction of response, effect of treatment, and methodological hazards.

Urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion was measured in 49 unipolar depressed outpatients to examine the relationship between pretreatment MHPG levels and therapeutic response to desipramine and amitriptyline and to determine the effects of these agents on MHPG excretion. Pretreatment MHPG excretion was greater in amitriptyline responders than amitriptyline nonresponders, but no different in desipramine responders compared to desipramine nonresponders. Pretreatment MHPG excretion did not differentiate desipramine from amitriptyline responders. Treatment for 3 weeks was associated with a decrement in MHPG excretion, particularly in the desipramine responders and combined desipramine and amitriptyline responders. Among patients within the postulated optimal desipramine plasma level range and patients with plasma amitriptyline plus nortriptyline levels greater than 70 ng/ml, high pretreatment MHPG excretion predicted therapeutic response and response was accompanied by a reduction in MHPG excretion. The interpretation of these findings is possibly confounded by the demonstration of a poor correlation (r = 0.61) between duplicate MHPG samples analyzed by a widely employed gas chromatography method and a gas chromatography/mass spectrometry technique. The methodological pitfalls encountered in the course of this investigation and their possible implications for similar studies are discussed.

ECG effects of comparable plasma concentrations of desipramine and amitriptyline.

To compare the electrocardiographic effects of therapeutic doses of desipramine and amitriptyline, weekly electrocardiograms (ECGs) were obtained from 46 depressed outpatients treated blindly for 3 weeks to a maximum of 200 mg/day. There was no difference in mean weekly plasma tricyclic antidepressant levels achieved for the two drugs. Compared to baseline measures, treatment with both drugs was associated with an increase in heart rate and a reduction in T wave amplitude, whereas prolongation of the QRS and QTc intervals was significant only for desipramine patients. Comparisons between drugs revealed a greater prolongation of QRS interval duration with desipramine treatment. Changes in ECG measures were not correlated with plasma tricyclic antidepressant levels. The absence of QRS interval prolongation among amitriptyline patients is additional evidence for the importance of distinguishing between the ECG effects of therapeutic and toxic doses of the tricyclic antidepressant.

Electrocardiogram changes and plasma desipramine levels during treatment of depression.

Twenty-six symptomatic subjects who met research diagnostic criteria for major affective disorder and were free of cardiovascular disease were treated for 3 wk with a fixed dosage schedule of desipramine (DMI) to a maximum of 200 mg/day. An electrocardiogram (ECG) and DMI plasma level determinations were obtained before treatment and weekly thereafter. DMI levels during the trial ranged from 13.4 to 882.2 ng/ml. DMI treatment was associated with increase in heart rate (p less than 0.001), prolongation of the PR (p less than 0.001), QRS (p less than 0.001), and QTc intervals (p less than 0.001), and increase in T wave amplitude (p less than 0.001). Significant (p less than 0.001) but relatively weak correlations were noted between DMI plasma levels and heart rate (r = 0.405), QRS interval (r = 0.346), QTc interval (r = 0.534), and T wave amplitude (r = -0.386). PR interval prolongation was independent of DMI levels (r = 0.171). DMI treatment induced no clinically significant ECG alterations or cardiovascular adverse effects. The relevance of DMI plasma level and the possible roles of other contributing factors in the production of these ECG changes are discussed.