Testicular leydig cell hyperplasia as a cause of familial sexual precocity.

Testicular Leydig cell hyperplasia was observed in two brothers presenting with progressive sexual precocity at 2 yr of age. Virilization was shown to result from increased secretion rather than decreased clearance of gonadal testosterone. Testosterone hypersecretion appeared to be gonadotropin independent, as basal and gonadotropin-releasing hormone-induced serum LH concentrations were low by both RIA and bioassay. Adrenal steroidogenesis was demonstrated to be normal by ACTH stimulation, dexamethasone suppression, and split adrenal venous function tests. Testicular histology revealed immature reproductive structures in the 2 yr old, but advanced spermatogenesis in the 3 yr-old brother. The etiology of both Leydig cell hyperplasia and reproductive testicular maturation in the absence of significant gonadotropin secretion remains to be established.

Efficacy of behavioral versus triazolam treatment in persistent sleep-onset insomnia.

OBJECTIVE: This study compared differential effects of behavioral therapy and triazolam in a clinical population with sleep-onset insomnia. Triazolam was hypothesized to decrease sleep latency and frequency and duration of awakening, with some effects during the first night's administration. But at follow-up, sleep measures were predicted to return to baseline levels. Behavioral treatment was hypothesized to effect sleep after 2 or more weeks of training which persisted at follow-up. METHOD: Thirty patients with average sleep latencies of 81.48 minutes, who reported chronic insomnia for an average of 2.6 years, were randomly assigned to one of two treatment groups: behavioral stimulus control/relaxation training and triazolam. RESULTS: Both treatments decreased sleep latency but differentially. Triazolam was effective immediately but maintained only some gains at follow-up. Behavioral treatment decreased sleep latency beginning the second week, when subjects expected no improvement, with gains maintained at follow-up. Comparisons showed that triazolam group latencies returned toward baseline, while behavioral group gains were maintained at follow-up. CONCLUSIONS: Triazolam treatment showed superior immediate treatment effects, while behavioral treatment showed superior treatment effects at follow-up, effects that accrued during the training period and differentially persisted at follow-up. One treatment strategy implied by these results would be to combine these two interventions concurrently. This would seem to use the immediate effects produced by the medication until the behavioral skills were learned, at which point medication would be terminated. This strategy could offer immediate relief and sustained effects at drug termination.

Effectiveness of combined triazolam-behavioral therapy for primary insomnia.

The authors examined sleep improvement in subjects with primary insomnia who received triazolam plus behavioral therapy (N = 8) or triazolam plus sleep-related information (N = 7). At follow-up, total sleep and restedness in the morning showed greater improvement with combined triazolam-behavioral therapy and returned toward baseline in the control subjects.

A novel DRB1 allele in DR2-positive American blacks.

Class II D region antigens of the major histocompatibility complex are naturally occurring dimeric proteins found on the surface of lymphoid cells. In most haplotypes at least two of the polymorphic beta chains are associated with a nonpolymorphic alpha chain. The allelic variation of these proteins lies in the first domain of the expressed protein. At present, there are four known DRB genes. DRB1 encodes for the classical DR 1, 3, 4, 5, etc., specificities. DRB3 and DRB4 encode the four supertypic specificities of DRw52 and the single phenotype of DRw53, respectively. Two DRB genes are expressed in human leukocyte antigen DR2-positive individuals. While DRB1 is the more polymorphic gene in most haplotypes, in DR2 haplotypes it appears that DRB5 encodes the polymorphic DR beta chain and the DRB1 encodes a nonpolymorphic beta chain. We attempted to further define the diversity of this region by direct dideoxynucleotide sequencing of polymerase-chain-reaction-amplified genomic DNA. We identified a novel DRB1 allele in DR2-positive individuals that was only observed in the American blacks sampled. This allele may code for a black specific class II antigen.

Sleep disorders in geriatric patients.

The elderly have more organic sleep problems disturbing sleep and contributing to insomnia than younger individuals. The most common disorders afflicting the elderly are obstructive sleep apnea, restless legs syndrome, and nocturnal myoclonus. Poor sleep habits often aggravate or contribute to the ongoing difficulty with sleeping. In the depressed elderly, characteristic EEG changes occur that may help distinguish major depression from pseudodementia; however, it should be considered that pseudodementia may be a harbinger of primary dementia. A careful sleep history and often evaluation by polysomnography are central to the management of sleep problems in the elderly. In conjunction with treatment of any underlying organic sleep disorders, brief administration of short-acting benzodiazepine sedatives for sleep onset insomnia or rapid-acting intermediate half-life benzodiazepines for sleep maintenance insomnia can be quite helpful in the elderly, especially if behavioral techniques also are employed. Elimination of medications, alcohol, and caffeine, which disturb sleep, is also an important part of the treatment approach.

Effects of thallium ion on cellular components of the skin.

Thallium salts have been employed by dermatologists to cause depilation, and dermatologic features are prominent in thallium overdose. These features include alopecia and follicular hyperkeratosis. Administration of thallium to pregnant animals results in limb deformities, similar to those seen after thalidomide embryopathy. These findings suggest that thallium may act on keratinocytes, melanocytes, and endothelial cells. We show that thallium exerts pleiotropic effects on proliferation, cell shape and motility of multiple cell types. These findings may help explain the clinical findings of thallotoxicosis.

Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease.

OBJECTIVE: Glial cell line-derived neurotrophic factor (GDNF) exerts potent trophic influence on midbrain dopaminergic neurons. This randomized controlled clinical trial was designed to confirm initial clinical benefits observed in a small, open-label trial using intraputamenal (Ipu) infusion of recombinant human GDNF (liatermin). METHODS: Thirty-four PD patients were randomized 1 to 1 to receive bilateral continuous Ipu infusion of liatermin 15 microg/putamen/day or placebo. The primary end point was the change in Unified Parkinson Disease Rating Scale (UPDRS) motor score in the practically defined off condition at 6 months. Secondary end points included other UPDRS scores, motor tests, dyskinesia ratings, patient diaries, and (18)F-dopa uptake. RESULTS: At 6 months, mean percentage changes in "off" UPDRS motor score were -10.0% and -4.5% in the liatermin and placebo groups, respectively. This treatment difference was not significant (95% confidence interval, -23.0 to 12.0, p = 0.53). Secondary end point results were similar between the groups. A 32.5% treatment difference favoring liatermin in mean (18)F-dopa influx constant (p = 0.019) was observed. Serious, device-related adverse events required surgical repositioning of catheters in two patients and removal of devices in another. Neutralizing antiliatermin antibodies were detected in three patients (one on-study and two in the open-label extension). INTERPRETATION: Liatermin did not confer the predetermined level of clinical benefit to patients with PD despite increased (18)F-dopa uptake. It is uncertain whether technical differences between this trial and positive open-label studies contributed in any way this negative outcome.

Effectiveness of yohimbine in treating narcolepsy.

Yohimbine was used in four men and four women ranging in age from 21 to 64 years with nocturnal polysomnography and multiple sleep latency test-verified narcolepsy. All achieved a stimulant response in doses ranging from 2.7 to 16.2 mg/day. The effective dose was defined as the amount of medication required to maintain subjective wakefulness for 8 consecutive working hours. The average effective dose was approximately 8 mg/day. While one subject became immediately tolerant, others maintained a response for several weeks. The first subject continued to have good control of sleepiness for 17 months. Mild and transient side effects were insomnia, diarrhea, dyspepsia, flushing, and tremor. Alpha-2 adrenergic receptor abnormalities are suspected in narcolepsy, which could explain the improvement in sleepiness for these patients.

Hemochromatosis and iron therapy of Restless Legs Syndrome.

Restless legs syndrome (RLS) occurs in some persons with iron deficiency, and some persons with RLS benefit from oral iron therapy. Approximately one in 200 persons of northern European ancestry have hemochromatosis attributable to inheritance of two common mutations of the hemochromatosis-associated HFE gene on chromosome 6. We evaluated and treated a 46-year-old man with RLS who was diagnosed as having hemochromatosis after he developed new symptoms associated with taking iron therapy for RLS. He had transferrin saturation 88%, serum ferritin 658 ng/ml, and C282Y homozygosity. Therapeutic phlebotomy of one unit of blood (450-500 ml) weekly (total 24 units) relieved his non-RLS symptoms, caused RLS symptoms to occur more frequently, and was associated with transient fatigue and mild dependent edema. His sister, who also has RLS, was subsequently diagnosed as having hemochromatosis. We conclude that serum transferrin saturation and ferritin levels should be measured before initiation of iron therapy of RLS. Patients with a history of iron deficiency or low serum iron parameters should undergo evaluation for iron deficiency; patients who have histories suggestive of hemochromatosis or iron overload or elevated pre-treatment transferrin saturation or serum ferritin levels should undergo evaluation to determine the cause of these abnormalities before they are treated with iron. In all persons with RLS treated with oral iron, serum iron parameters should be re-measured once or twice yearly during therapy.

[Treatment of obstructive sleep apnea with methods of orthognathic surgery]. / Die Behandlung der obstruktiven Schlafapnoe mit Methoden der Dysgnathiechirurgie.

The only surgical means available up to now for treating obstructive sleep apnea syndrome (OSAS) consisted in uvulopalatopharyngoplasty (UPPP), which failed to produce satisfactory results. The ultima ratio frequently resorted to was tracheotomy with all its medical and social drawbacks. Complete advancement of the maxillomandibular complex opens up new avenues for the treatment of upper airways obstruction. The present report is on 13 patients operated for polysomnographically established OSA. The maxillomandibular complex was brought as far forward as possible and esthetically justifiable. This operation was occasionally combined with other procedures to enhance upper airways function, such as conchotomy, palatopharyngoplasty, chin graft and reduction of tongue size. In 85% of the cases the apnea and hypopnea index (RDI) could be lowered to below 10 per hour sleep, i.e. these patients were cured.

Maxillomandibular advancement surgery in 23 patients with obstructive sleep apnea syndrome.

Twenty-three patients with obstructive sleep apnea syndrome (OSAS) documented by polysomnography underwent maxillomandibular advancement via Le Fort I, and sagittal ramus split osteotomies followed by rigid fixation with miniplates and bicortical screws. Partial turbinectomies and septal reconstruction were simultaneously performed. Pre- and post-operative cephalometric radiographs were analyzed by computer. Hyoid position and posterior airway space changes did not correlate with clinical success. The surgical success (respiratory disturbance index less than 10) with maxillomandibular advancement was 65%. The total desaturations below 90% greatly decreased. Ninety-six percent of patients were subjectively and objectively improved.

Sleep apnea and the Arnold-Chiari malformation.

We present a polysomnogram-documented report of central sleep apnea (427 events) and moderately severe decreases in arterial oxygen saturation (to 81%) associated with the Arnold-Chiari malformation (ACM). Daytime hypersomnolence and other symptoms had significantly impaired our patient's work performance. After surgical correction of the ACM, there was marked improvement in symptomatology. A post-surgery polysomnogram revealed marked improvement in the number of central apneas (74 events) and only mild decreases in oxygen saturation (to 94%).