Evaluation of ability of biochemical markers of bone turnover to predict a response to increased doses of HRT.

Antiresorptive therapy is usually given in a fixed dose, and we hypothesized that some patients receiving standard doses of hormone replacement therapy (HRT) might benefit from a higher dose, particularly if their bone turnover decreases after increasing the dose of HRT. Eighty-eight women who had been receiving standard-dose (0.625 mg/day) conjugated equine estrogens (CEE) for at least one year were randomized to take either standard-dose (0.625 mg/day, n = 36) or high-dose (1.25 mg/day, n = 52) therapy. Subjects with a uterus were allowed to take either 10 mg of medroxyprogesterone cyclically or 5 mg daily, according to personal preference. Bone Mineral Density (BMD) and biochemical markers of bone turnover were followed for 2 years. Mean bone turnover decreased significantly (-4.1% to -19.1%) after 6 months of high-dose CEE. Decreases in serum BSAP (bone-specific alkaline phosphatase) and serum or urine NTX ( N-terminal telopeptide crosslink of type I collagen) on high-dose therapy were not predictive of an improvement in BMD, but a decrease in serum CrossLaps did predict an improvement in BMD. Mean change in BMD in subjects with a significant decrease in serum CrossLaps at the anteroposterior spine was 3.1% +/- 3.9% versus 1.2% +/- 2.9% for subjects with no significant change in CrossLaps, P < 0.02. There was, however, a wide range of changes in BMD in patients with or without a significant change in CTX on high-dose HRT, making it impossible to predict an improvement in BMD based on an individual's changes in turnover. Measuring of bone density and bone turnover with better precision might be more successful in guiding individual dosing of antiresorptive therapy.

Neuroleptic malignant syndrome in children and adolescents.

OBJECTIVE: Neuroleptic malignant syndrome (NMS) is a serious iatrogenic condition. This report reviews the world literature to characterize the syndrome and evaluate factors that promote early detection and effective intervention. METHOD: The review identified 77 NMS cases (49 males, 27 females, 1 gender unknown); ages ranged from 0.9 to 18 years (mean 14.8 +/- 3.96). Univariate and multiple regression analyses were applied to 38 variables to identify early signs of the disorder, to identify correlates of outcome, and to evaluate treatments. RESULTS: The duration of NMS spanned from 1 to 119 days. Nine percent of patients died and 20% resolved with serious sequelae. Patients receiving low-potency neuroleptics had a poorer outcome (p = .01). Fever was related to longer duration of illness (p = .03). Anticholinergics and bromocriptine were effective and without fatalities, but dantrolene was not useful in this sample of children and adolescents. CONCLUSIONS: Early detection and appropriate interventions appear important in moderating the course and outcome of NMS.

Childhood schizophrenia: theoretical and treatment issues.

Michael is an 8.5-year-old Caucasian male inpatient who presented at admission with severe agitation, suicidal impulses, and aggression toward his 18-month-old sister. He had been treated with stimulant medications before admission. Past history revealed bilateral genetic loading with two primary family members having a history of hallucinations and hospitalization, and two paternal aunts who were hospitalized since early childhood. Michael was raised in a chaotic, violent family environment where there was emotional, physical, and perhaps sexual abuse. Medical history included frequent staring spells. During residential treatment, more extensive interviews revealed a year's history of auditory hallucinations, inappropriate and labile affect, and a fixed delusional system. The patient was switched to neuroleptics and showed a slow response despite high doses.

Fungal infection of the brain: an increasing threat.

A 79-year-old, diabetic man with an ear infection had a temporal lobe abscess from which Aspergillus fumigatus was cultured. He died despite treatment with amphotericin and rifampin, removal of the abscesss, and left mastoidectomy. Because of the ever-increasing number of elderly debilitated patients, the frequency of mild diabetes in the aged, the prevalent use of steroids, antibiotics, cytotoxics and immunosuppressives, and the ubiquity of the organism, Aspergillus infections of the brain have and will become more frequent.