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.

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.

Subtypes of depression--diagnosis and medical management.

Depression is both a common and a greatly undertreated illness in the United States today. The focus of this review is a definition of the characteristics of four subtypes of depression which appear to be differentially sensitive to four different classes of medications. The tricyclic antidepressants should be used for patients with unipolar depression and vegetative symptoms. Lithium appears to be most effective for bipolar depressives. The monoamine oxidase (MAO) inhibitors are best used for patients with atypical depression. Antipsychotic medications appear to be useful for depressed patients with psychotic symptoms or agitation. Recent pharmacokinetic and biochemical data, including serum lithium levels, plasma tricyclic levels, and the predictive ability of pretreatment urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) levels are also reviewed.

Prediction of tricyclic antidepressant response: a critical review.

This article reviews all the prospective, double-blind controlled studies that have evaluated the prediction of response to imipramine hydrochloride and amitriptyline hydrochloride in depressed patients. Despite widely divergent methodologies, an attempt is made to extract clinically useful conclusions from these data. Critiques of each study and the criteria used in their evaluation are presented, with suggestions for future research included. The predictors of positive response to imipramine and amitriptyline are as follows: upper socioeconomic class, insidious onset, anorexia, weight loss, middle and late insomnia, and psychomotor disturbance. The predictors of poor response are the following: neurotic, hypochondriacal, and hysterical traits, multiple prior episodes, and delusions. Pretreatment urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) levels may some day be useful in predicting to which of these two tricyclic antidepressants a patient will respond.