A randomised, double-blind, placebo-controlled study of topiramate in the treatment of Tourette syndrome.

OBJECTIVE: To investigate the effects of topiramate on Tourette syndrome (TS). BACKGROUND: Dopamine-receptor-blocking drugs have been traditionally used to control tics in patients with TS, but these neuroleptics are associated with potentially limiting side effects. METHODS: This is a randomised, double-blind, placebo-controlled, parallel group study. To be included in the study, subjects required a DSM-IV diagnosis of TS, were 7-65 years of age, had moderate to severe symptoms (Yale Global Tic Severity Scale (YGTSS) > or =19), were markedly impaired as determined by the Clinical Global Impression (CGI) scale severity score of > or =4 and were taking no more than one drug each for tics or TS comorbidities. RESULTS: There were 29 patients (26 males), mean age 16.5 (SD 9.89) years, randomised, and 20 (69%) completed the double-blind phase of the study. The primary endpoint was Total Tic Score, which improved by 14.29 (10.47) points from baseline to visit 5 (day 70) with topiramate (mean dose 118 mg) compared with a 5.00 (9.88) point change in the placebo group (p = 0.0259). There were statistically significant improvements also in the other components of the YGTSS as well as improvements in various secondary measures, including the CGI and premonitory urge CGI. No differences were observed in the frequency of adverse events between the two treatment groups. CONCLUSION: This double-blind, placebo-controlled trial provides evidence that topiramate may have utility in the treatment of moderately severe TS.

Periodic limb movement in sleep in children with Williams syndrome.

OBJECTIVE: Williams syndrome (WS) is associated with neurobehavioral abnormalities that include irritability and attention-deficit/hyperactivity disorder. Parents often report children having difficulties initiating and maintaining sleep because of restlessness and arousals. Therefore we evaluated a group of children with WS for the presence of a movement arousal sleep disorder. METHODS: Twenty-eight families of children with WS participated in a telephone survey aimed to screen for a movement arousal disorder. Of the 16 children identified as having such a disorder, 7 (mean age, 3.9 +/- 2.2 years) underwent polysomnography. Their studies were compared with those of 10 matched control subjects (mean age, 5.3 +/- 2.0 years). RESULTS: The 7 subjects with WS who were screened by the survey had sleep latency, total sleep time, arousals, and awakenings that were similar to those of control subjects. However, they presented with a disorder of periodic limb movement in sleep (PLMS). The PLMS index in the subjects with WS was 14.9 +/- 6.2 versus 2.8 +/- 1.9 in control subjects (P < .0001). In addition, arousal and awakening in subjects with WS were strongly associated with PLMS. Moreover, children with WS spend more time awake during sleep periods than control subjects (10.0% +/- 7.0% vs 4.4% +/- 4.7%; P < .05). Five children were treated with clonazepam, and in 4 a significant clinical response was noted. CONCLUSION: We report an association between WS and PLMS. Clonazepam may reduce the clinical symptoms of PLMS in some of these children.

Simultaneous quantification of ephedrines in urine by high-performance liquid chromatography.

A high-performance liquid chromatographic method for the simultaneous determination of ephedrine, pseudoephedrine, phenylpropanolamine, norpseudoephedrine and methylephedrine in urine is described. Samples were extracted at basic pH into diethyl ether and then back extracted into a small volume of acetic acid. These extracts were chromatographed on a Phase Sep Spherisorb ODS 1 column with tetraethylammoniumphosphate-methanol mobile phase and the analytes were detected by UV absorbance at 214nm. Calibration curves were linear over the range 0.5-100 microgram/ml for each analyte. The selectivity of the method was demonstrated for several drugs found with the ephedrines in pharmaceutical formulations. This method has an excellent accuracy, precision and recovery for all the ephedrine at the cut-off concentrations as set by the IOC for a positive doping case and can thus be used to quantify these ephedrines when present in the urine obtained from sportspersons.

Pediatricians and sleep disorders: training and practice.

OBJECTIVE: A series of studies were conducted to investigate pediatricians' training, knowledge, and practices regarding sleep and sleep disorders in children and adolescents. METHOD AND RESULTS: Study 1, a national survey of 156 pediatric residency programs, found that pediatricians receive a mean of 4.8 hours of instruction on sleep and sleep disorders, although the mode and median hours of instruction is 0 hours. In study 2, 88 pediatricians completing a questionnaire concerning general knowledge about sleep disorders in children and adolescents received a mean score of 71.8% (range, 40% to 93%). Pediatricians appear to know the most about developmental issues and sleep hygiene and the least about specific disorders such as narcolepsy and parasomnias. In the third study, 183 pediatricians were surveyed about their actual beliefs and practices regarding young children's sleep problems. Together, those surveyed reported that approximately 25% of their patients experience some type of sleep problem. Most pediatricians recommend behavioral interventions, although 14.8% of pediatricians report prescribing pharmacological treatments, and 48.9% inform parents that their child is likely to outgrow the problem. CONCLUSIONS: The results of these studies support the need for more education in sleep and sleep disorders in children and adolescents within medical schools, pediatric residency programs, and the practicing pediatric community.

Culturally sensitive breast cancer screening programs for older black women.

Breast cancer is the leading cause of cancer mortality among black women. Elderly black women are particularly vulnerable and suffer the "double jeopardy" effect of older age and minority status. Older black women are not benefiting from the early detection provided through breast cancer screening. Factors that prevent this population from using breast cancer screening include cost, accessibility, availability, lack of knowledge, health care provider variables, and lack of community involvement. Breast cancer screening programs are needed that address cultural diversity to screen women who presently are not seen according to established guidelines. This article focuses on the need for primary care providers to offer culturally sensitive breast cancer screening programs designed for the older black woman. A model is presented based on Leininger's Culture Care Theory and the Health Belief Model. Specific strategies to increase the older black woman's participation in breast cancer screening practices are described.

Bacterial meningitis: fluid balance and therapy.

Fluid administration in children with meningitis should be conservative in an attempt to minimize cerebral edema and electrolyte disturbances that frequently complicate the course of meningitis. Since these complications have been shown to correlate with poor neurologic outcome, it is believed that appropriate fluid management will minimize the morbidity and mortality associated with bacterial meningitis in children.

Automated high-performance liquid chromatographic method for the determination of mianserin in plasma using electrochemical detection.

An automated high-performance liquid chromatographic method for the determination of mianserin in plasma is described. Extraction and injection of the samples were automatically done by the Gilson ASPEC system using C8, 100-mg Supelclean solid-phase extraction columns. The extracts were chromatographed on a reversed-phase C18 column (150 mm x 3.9 mm I.D.) with a phosphate buffer-acetonitrile-methanol mobile phase and the analytes detected electrochemically. Calibration curves were linear to at least 53.7 ng/ml at which the between-day relative standard deviation was 5% and the recovery 101%. The limit of quantification was 1.67 ng/ml at which the between-day relative standard deviation was 9% and the recovery 92% using a sample volume of 0.5 ml. The method was applied to the determination of mianserin in the plasma of normal human volunteers participating in a comparative bioavailability study.

Wooden transnasal intracranial penetration: an unusual presentation.

A 2 1/2-year-old child presented to the emergency department with a wooden stick lodged firmly in her right nares. No nasal discharge or neurological abnormalities were noted at presentation. After plain radiographs failed to demonstrate any evidence of a foreign body, computed tomography (CT scan) was obtained that revealed a hypodense region in the right frontal lobe corresponding to the projected tract of the branch. The patient underwent a right frontal craniotomy with debridement of her contused right frontal lobe. She was discharged 8 days postoperatively without evidence of neurologic sequelae. This case illustrates an unusual presentation of intracranial penetration, with only six similar cases found in the literature. It also highlights the need for the emergency physician to be concerned about intracranial penetration when treating intranasal foreign bodies, particularly those of the nonmetallic type. The literature is reviewed regarding transnasal intracranial penetration by wooden foreign bodies.

Hypoxemia and hemodynamic changes during the hypercarbia stimulation test.

The hypercarbia stimulation test is a valuable technique to document the absence of brainstem responsiveness to elevated levels of carbon dioxide (PCO2); however, its application has been limited by concern that hypoxemia may induce cardiovascular instability. We investigated hemodynamic and oxygen (PO2) changes in 19 patients: group 1 (17 patients) had no spontaneous ventilations at PCO2 values ranging from 37-129 torr; group 2 (2 patients) had spontaneous ventilations at less than 38 torr. Group 1 was separated into 2 subgroups: A (10 patients) with PO2 greater than 153 torr and B (7 patients) with PO2 less than 80 torr. Hemodynamic changes (less than 10% variation in baseline pulse and blood pressure) occurred in 9 of 10 patients in group 1A and all patients in Group 1B. Mean differences in pulse and blood pressure changes between these groups were not significant; therefore, pulse and blood pressure changes are not predictive of hypoxemia and hypercarbia is not necessary to induce spontaneous ventilation in patients with intact medullary function.

Computed tomography in global cerebral cortical ischemia of the neonate and young infant.

The authors have encountered three unique neonates with global cerebral cortical ischemia. The pathogenesis and computed tomography scans of these patients who sustained profound hypoxemia is described. Follow-up computed tomography scans in each case demonstrated generalized loss of cortical substance.

Clinical, laboratory, and environmental features of infant botulism in Southeastern Pennsylvania.

Forty-four cases of botulism occurred in infants in Southeastern Pennsylvania between 1976 and 1983. Forty-three were caused by Clostridium botulinum type B. Progressive weakness necessitated ventilatory support in 39 infants. Complications during hospitalization included otitis media in 13 patients and aspiration pneumonia in 11. Eight infants developed the syndrome of inappropriate secretion of antidiuretic hormone and two developed adult respiratory distress syndrome. One infant died of progressive bradycardia despite adequate control of ventilation. Manifestations of autonomic nervous system dysfunction recognized on admission to the hospital were constipation, distention of the urinary bladder, and decreased salivation and tearing. During hospitalization, some infants had unexpected fluctuations of skin color, blood pressure, and heart rate. Infants' strength improved despite persistent intestinal elaboration of toxin. C botulinum was isolated from seven of nine home or work environments sampled. All 44 infants were white and were receiving breast milk at the time of onset of symptoms. The majority had first feedings of nonhuman food substances within 4 weeks prior to onset of symptoms. Delineation of fecal flora in seven infants revealed predominance of enterobacteriaceae. Perturbations of intestinal flora during infancy, especially at weaning, may cause transient permissiveness to colonization by C botulinum.

Case 4. The first fatal Baylisascaris infection in humans: an infant with eosinophilic meningoencephalitis.

Baylisascaris procyonis, the ascarid of raccoons, causes a characteristic, rapidly fatal eosinophilic meningoencephalitis with ocular involvement in many naturally and experimentally infected aberrant hosts, including monkeys. Warnings that humans are potentially susceptible to the devastating infection have been issued, but an instance in humans has not been recognized. This report describes a boy who died from an eosinophilic meningoencephalitis, which mimicked B. procyonis infection in monkeys. The causative agent was not identified during life. Autopsy showed a systemic larval ascarid infection with massive involvement of the brain. The size and anatomy of the larvae in histologic sections were identical to those recorded for B. procyonis. The larvae were indistinguishable from the B. procyonis larvae observed in histologic sections of experimentally infected monkeys. An indirect immunofluorescence test was positive for B. procyonis. Exposure to raccoon feces was highly likely. The evidence suggests that this is the first recognized B. procyonis infection in humans. Prudent avoidance of exposure to raccoon feces is indicated.

The hemostatic system in children undergoing intensive plasma exchange.

We report the effects on the hemostatic system of intensive plasma exchange therapy using replacement fluids devoid of plasma coagulation proteins. Five children were studied during ten exchanges. There were no hemorrhagic episodes clearly attributable to the plasma exchange, but one patient developed recurrent thrombosis of the vascular access used for the procedure. Plasma values of the various coagulation factors (II to XII) were decreased by 35 to 67% immediately following the plasmapheresis. The mean decrease in levels of antithrombin III antigen and activity and of plasminogen were 58, 60, and 66%, respectively. The recurrent thrombosis of the vascular access in one of the patients, and the decrease in antithrombin III and plasminogen values in plasma following plasmapheresis in all patients, suggest that there is increased potential for thrombosis in patients undergoing intensive plasmapheresis, despite the depletion of coagulation factors. At 24 hours following plasmapheresis the values for all factors were within normal limits, attesting to the ability of the synthetic mechanisms in children to replenish hemostatic factors rapidly.