Clinical and technical factors in endoscopic skull base surgery associated with reconstructive success.

BACKGROUND: In this study, we identified key discrete clinical and technical factors that may correlate with primary reconstructive success in endoscopic skull base surgery (ESBS). METHODS: ESBS cases with intraoperative cerebrospinal fluid (CSF) leaks at four tertiary academic rhinology programs were retrospectively reviewed. Logistic regression identified factors associated with surgical outcomes by defect subsite (anterior cranial fossa [ACF], suprasellar [SS], purely sellar, posterior cranial fossa [PCF]). RESULTS: Of 706 patients (50.4% female), 61.9% had pituitary adenomas, 73.4% had sellar or SS defects, and 20.5% had high-flow intraoperative CSF leaks. The postoperative CSF leak rate was 7.8%. Larger defect size predicted ACF postoperative leaks; use of rigid reconstruction and older age protected against sellar postoperative leaks; and use of dural sealants compared to fibrin glue protected against PCF postoperative leaks. SS postoperative leaks occurred less frequently with the use of dural onlay. Body-mass index, intraoperative CSF leak flow rate, and the use of lumbar drain were not significantly associated with postoperative CSF leak. Meningitis was associated with larger tumors in ACF defects, nondissolvable nasal packing in SS defects, and high-flow intraoperative leaks in PCF defects. Sinus infections were more common in sellar defects with synthetic grafts and nondissolvable nasal packing. CONCLUSIONS: Depending on defect subsite, reconstructive success following ESBS may be influenced by factors, such as age, defect size, and the use of rigid reconstruction, dural onlay, and tissue sealants.

Review and action plan for oral health improvement in Sheffield special schools.

A description of the process of a review of oral health improvement in special schools in Sheffield and the implementation of an action plan for these activities. Public health competencies encompassed: assessing the evidence on oral health and dental interventions, programmes and services; strategic leadership and collaborative working for health; oral health improvement.

Craniocerebral magnetic resonance imaging measurement and findings in Lesch-Nyhan syndrome.

OBJECTIVE: To provide the first comprehensive magnetic resonance imaging (MRI) assessment of brain in a series of patients with Lesch-Nyhan syndrome (LNS), with emphasis on basal ganglia measurements. DESIGN: Routine readings of MRI studies, repeated reading in random order blinded to subject diagnosis, and 3-dimensional volumetric measures of basal ganglia regions. SETTING: The Johns Hopkins Hospital, Baltimore, Md. PATIENTS: Seven patients with LNS who have hypoxanthine guanine phosphoribosyltransferase levels less than 1.6% and characteristic clinical features of the disorder, which include hyperuricemia, cognitive impairment, and dystonic movement disorder, were compared with 7 age-matched control subjects. Five of the 7 patients demonstrated self-injurious behavior. MRI studies were performed using general anesthesia because of the severity of the movement disorder. MAIN OUTCOME MEASURES: Measurement of brain regions from MRI-obtained images. RESULTS: Routine readings described mild cerebral atrophy in 2 of 7 patients, but no caudate or putamen abnormalities were reported. However, on the directed blinded rereading, small caudates were suspected in 5 of 7 cases, and abnormalities in cerebral size and cranium were identified. Volumetric studies of the patients with LNS confirmed a 34% decrease in caudate volume (P<.001), a 17% decrease in total cerebral volume (P<.03), and a 12% decrease in putamen volume (P=.19). CONCLUSIONS: To our knowledge, this is the first demonstration of consistent neuroanatomic abnormalities in LNS. The findings of reduced basal ganglia volume are consistent with the dystonic movement disorder.

Critical overview: adverse cutaneous reactions to psychotropic medications.

BACKGROUND: Adverse cutaneous reactions (ACRs) are common, potentially life-threatening or symptomatically and cosmetically unappealing side effects of psychotropic drugs. DATA SOURCES: A MEDLINE search of the literature was employed to cite the association of various psychotropic drugs with specific cutaneous reactions. DATA SYNTHESIS: In addition to the common exanthematous eruption, we explore several serious reactions including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria, angioedema, anaphylaxis, hypersensitivity syndrome, hypersensitivity vasculitis, erythroderma, and drug-induced lupus erythematosus. Other side effects such as alopecia, pigmentary disorders, photosensitivity, lichenoid lesions, fixed drug eruptions, and psoriasiform, acneiform, and seborrheic eruptions are discussed. Attention is paid to the morphology and distribution, systemic findings, diagnosis, and treatment of these conditions. CONCLUSION: Awareness of ACRs will allow psychiatrists to deter their continuation or recurrence, educate patients who have them, and diagnose serious instances of them.

Ontogeny of noradrenergic effects on ultrasonic vocalizations in rat pups.

The ontogeny of noradrenergic effects and the interaction of opioid and noradrenergic systems on vocalizations in rat pups from Day 10 to Day 18 were evaluated. Day 10 pups given clonidine (0.05 or 0.5 mg/kg) ip showed a sustained high level of calling throughout a 25-min isolation period that was reversed with yohimbine (0.1 mg/kg). Day 15 pups showed identical profiles with a lower baseline rate. Day 17 pups' calls were differentially affected according to dose; Day 18 pups reduced vocalizing with clonidine. In addition, it was found that at all ages when clonidine increased calling during isolation, the pups vocalized in the nest as well. Naltrexone, an opioid antagonist, lost its effectiveness to increase vocalizations after Day 15 unless it was given subsequent to clonidine. These results suggest that pups' vocalizations are differentially affected by noradrenergic and opioid stimulation or inhibition with developmental changes.

Is excessive daytime sleepiness characteristic of Prader-Willi syndrome? The effects of weight change.

OBJECTIVES: To assess nighttime and daytime sleep patterns in patients with Prader-Willi syndrome and to examine the effects of weight change on excessive daytime sleepiness in patients with this disorder. DESIGN: Case series (within-subject design). SETTING: A university sleep disorders center. PATIENTS: Eight patients (5 males and 3 females), ranging in age from 5.5 to 21 years, who met the diagnostic criteria for Prader-Willi syndrome. INTERVENTIONS: Overnight sleep polysomnographic recording and daytime Multiple Sleep Latency Test. Four of the 8 patients were restudied after their weight had changed. MAIN OUTCOME MEASURES: Changes in the sleep disordered breathing rate and Multiple Sleep Latency Test measures. RESULTS: Sleep-disordered breathing occurred in all patients and was principally characterized by obstructive hypoventilation or episodes of apnea that occurred primarily during rapid eye movement sleep. After weight reduction, 3 patients had respiratory values that were within the broad normal range (disordered breathing rate, < 15 breaths per hour). Statistically significant (P < .05) weight loss effects occurred during nonrapid eye movement sleep (decrease with weight loss, F = 6.243). Excessive daytime sleepiness was documented in 6 of 7 patients who completed the Multiple Sleep Latency Test. Excessive daytime sleepiness was not consistently correlated with body weight or any of the nocturnal sleep variables. CONCLUSIONS: A sleep-related breathing disorder occurred during rapid eye movement and nonrapid eye movement sleep and improved with weight change in patients with Prader-Willi syndrome, emphasizing the importance of weight reduction in clinical management. However, excessive daytime sleepiness persisted despite a reduction in sleep-disordered breathing after weight loss, suggesting a primary disturbance of sleep. Our findings provide additional support for the view that primary hypersomnia is a characteristic feature of the Prader-Willi syndrome.

Mediation of separation distress by alpha 2-adrenergic mechanisms in a non-human primate.

This study provides the first behavioral evidence in support of an alpha-adrenergic mechanism underlying imipramine's amelioration of separation distress. The rate of separation-induced vocalization by adult squirrel monkeys was decreased by imipramine and the alpha 2-adrenergic agonist clonidine, and increased by the alpha 2-adrenergic antagonist yohimbine. Yohimbine, but not the alpha 1-antagonist prazosin, reversed the clonidine effect suggesting that drugs acting directly on alpha 2-receptors may have a role in management of separation anxiety.

Experimental animal modeling of depression and anxiety.

Experimental animal models have been introduced to study aspects of psychiatric symptoms of depression and anxiety; however, there is no comprehensive animal model for these conditions. The models introduced may simulate certain symptoms (despair), be used to evaluate behavioral theories (cognitive theory of learned helplessness), allow study of underlying neurochemical mechanisms (CSF metabolites, genetic, neurotransmitter model), be used to evaluate developmental issues, and lead to finding new treatments through preclinical pharmacologic trials. A variety of models are needed, as each one attempts to deal with a particular aspect of a syndrome. Pharmacologic models, the model of uncontrollability, separation models, and genetic approaches have been summarized. Depression is viewed as a complex, multifactorial illness. Anxiety models have focused on pharmacologic treatment of motivational conflict and the elicitation of fear and panic through environmental and drug manipulations. The most recent investigations in this area address separation calls and alarm calls in primates as potential models for separation distress and panic symptomatology, arguing that the behavioral context as well as the specific behavior be considered. Animal models have emphasized adult psychopathology in the past. However, with increased recognition of psychiatric disorders in children and adolescents, animal modeling of disorders that begin in the development period assumes importance. Studies in the animal modeling of depression and anxiety involving genetic models, psychosocial models, and stress-induction models are the focus of continuing investigations and may be pertinent to child and adolescent psychopathology. They offer hope for learning more about the neurobiologic mechanisms involved in these conditions and for testing new treatment approaches.

The effect of nitrofen [4-(2,4-dichlorophenoxy)nitrobenzene] on the reproductive performance of male rats.

Technical grade nitrofen was fed to 4 groups (25/group) of male Sprague-Dawley rats for 13 weeks at dietary concentrations of 0, 100, 500, or 2500 ppm. Untreated female rats of the same age and strain were mated with treated males and fertility, gestation, and lactation indices were monitored. After mating, males were bled for clinical chemistry and hematology analyses, killed, and necropsied; organ weights were recorded, and liver, testes, and kidneys evaluated histopathologically. Offspring were observed for 35 days to determine general health and viability. At 2500 ppm, body weights of paternal animals were reduced throughout the dosing period. No hematologic abnormalities were seen. Statistically significant changes noted in clinical chemistry parameters included increased total protein, albumin, globulin, and cholesterol and decreased glucose. Testes, kidneys, and liver weights were increased at 500 and 2500 ppm, but histologic changes were limited to the liver with hypertrophy and cytoplasmic basophilia of centrilobular hepatocytes occurring at 500 and 2500 ppm. There were no effects on fertility, gestation, litter size, weight, or sex ratio in any group. Offspring health and survival to day 35 was unaffected. Based on the parameters examined, the no-observed effect level (NOEL) for male rats fed nitrofen for 13 weeks was 100 ppm. Male reproductive performance was not affected at dietary concentrations up to and including 2500 ppm.

Hyperlexia in infantile autism.

Twenty boys meeting the current DSM III criteria for infantile autism at the time of diagnosis were found to be hyperlexic in childhood and have been followed up for 7-17 years. The most striking feature of the group was the compulsion to decode written material without comprehension of its meaning, and this constituted a behavioral phenotype for this population. On word recognition tests such as the WRAT, they scored significantly higher than would be predicted on the basis of intelligence but demonstrated severe reading retardation on tests of reading comprehension such as the Gates-McGinitie. Major differences in intelligence were detected, ranging from severe mental retardation to very superior intelligence. Major differences in verbal and nonverbal abilities were also noted. Many were found to have unusually good memory, both visual and auditory, and the majority possessed an excellent stored vocabulary that could be used with written words despite the poverty of their expressive language. It is suggested that the presence of hyperlexia may identify a subgroup of autistic children.

The spectrum of inherited mutations causing HPRT deficiency: 75 new cases and a review of 196 previously reported cases.

In humans, mutations in the gene encoding the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) are associated with a spectrum of disease that ranges from hyperuricemia alone to hyperuricemia with profound neurological and behavioral dysfunction. Previous attempts to correlate different types or locations of mutations with different elements of the disease phenotype have been limited by the relatively small numbers of available cases. The current article describes the molecular genetic basis for 75 new cases of HPRT deficiency, reviews 196 previously reported cases, and summarizes four main conclusions that may be derived from the entire database of 271 mutations. First, the mutations associated with human disease appear dispersed throughout the hprt gene, with some sites appearing to represent relative mutational hot spots. Second, genotype-phenotype correlations provide no indication that specific disease features associate with specific mutation locations. Third, cases with less severe clinical manifestations typically have mutations that are predicted to permit some degree of residual enzyme function. Fourth, the nature of the mutation provides only a rough guide for predicting phenotypic severity. Though mutation analysis does not provide precise information for predicting disease severity, it continues to provide a valuable tool for genetic counseling in terms of confirmation of diagnoses, for identifying potential carriers, and for prenatal diagnosis.

Combined opiate/adrenergic receptor blockade enhances squirrel monkey vocalization.

This study provides evidence for the interaction between opiate and noradrenergic neuronal systems on primate vocal behavior. The rate of twitters produced by adult squirrel monkeys was increased in an additive or synergistic manner by the combined administration of the alpha 2 adrenergic antagonist yohimbine and the opiate antagonist naloxone. Similar effects were not demonstrated on the isolation call. In addition, the drug combination led to an increase of autonomic symptoms. The anatomical localization of these findings and mechanism for the production of increased twitters requires further investigation.

Ocular motor dysfunction in Lesch-Nyhan disease.

Eye movements were assessed in 22 patients with varying degrees of hypoxanthine-guanine phosphoribosyltransferase deficiency. Ocular motility was clinically normal in seven patients with moderate enzyme deficiency but grossly abnormal in 15 patients with severe enzyme deficiency. In patients with severe deficiency, fixation was interrupted by frequent unwanted saccades toward minor visual distractions. Voluntary saccades were associated with an initial head movement and/or eyeblink in all of these patients. When head motion was prevented, voluntary saccades were often delayed and sometimes absent. In contrast, saccade speed, reflexive saccades, and other reflexive eye movements appeared clinically normal. Four patients with severe enzyme deficiency also experienced mild blepharospasm, and two had ocular tics. These disturbances of ocular motility are consistent with dysfunction of the basal ganglia or its connections with ocular motor centers in the prefrontal cortex or midbrain.

A combined behavioral/pharmacological treatment of sleep-wake schedule disorder in Angelman syndrome.

Angelman syndrome (AS) is a genetic disorder associated with a deletion on chromosome 15. Behavior problems among children with AS include sleep difficulties. Data are presented on the successful treatment of a sleep-wake schedule disorder (SWSD) in a 9-year-old boy with AS. The treatment program included behavioral and pharmacological components. During baseline, the child slept a mean of 1.9 hours per night and 1.3 hours during the day; night sleep was increased to a mean of 8.3 hours and day sleep was reduced to a mean of .08 hours after introduction of the full-treatment program. Medication was discontinued subsequently, and the child slept a mean of 7.8 hours during the night and .07 hours during the day. At 45-day follow-up, night sleep was maintained at 7.1 hours and day sleep remained stable at .29 hours. This is the first known report of an effective treatment of a SWSD in a child with AS.

The spectrum of mutations causing HPRT deficiency: an update.

Mutations in the gene encoding hypoxanthine-guanine phosphoribosyltransferase (HPRT) cause Lesch-Nyhan disease, which is characterized by hyperuricemia, severe motor disability, and self-injurious behavior. Mutations in the same gene also cause less severe clinical phenotypes with only some portions of the full syndrome. A large database of 271 mutations associated with both full and partial clinical phenotypes was recently compiled. Since the original database was assembled, 31 additional mutations have been identified, bringing the new total to 302. The results demonstrate a very heterogeneous collection of mutations for both LND and its partial syndromes. The differences between LND and the partial phenotypes cannot be explained by differences in the locations of mutations, but the partial phenotypes are more likely to have mutations predicted to allow some residual enzyme function. The reasons for some apparent exceptions to this proposal are addressed.

Nucleotide degradation products in cerebrospinal fluid (CSF) in inherited and acquired pathologies.

CSF purines were grossly elevated compared with controls only in adenylosuccinate lyase (ADSL) deficiency and TB meningitis. The former representing low permeability, the latter severe damage to the normal blood/brain barrier. By contrast, the similarity to controls, with no difference between Lesch-Nyhan disease (LND) or LND variants, would exclude hypoxia as a factor in the severe neurological deficits in LND. Similar findings in purine nucleoside phosphorylase (PNP) deficiency (although nucleosides replace the normal bases) likewise exclude hypoxia in the aetiology of the albeit milder neurological deficits.

Western equine encephalomyelitis in horses in the Northern Red River Valley, 1975.

In mid-July, 1975, western equine encephalomyelitis (WEE) virus was isolated from mosquitoes collected in flooded areas of eastern North Dakota and western Minnesota. Inasmuch as clinical manifestations of WEE are usually observed in horses before human cases of encephalitis are recognized, surveillance of equine disease was initiated. Sixty-one practicing veterinarians from the are under surveillance reported 281 cases of WEE in horses from June through September, with peak incidence in late July. The high percentage of sero-positive, clinically normal, unvaccinated horses in one region suggested that many horses had developed non-clinical infections. The efficacy of vaccines used by the practitioners appears to have been execllent, as none of the horses vaccinated before the epizootic became ill during the period of surveillance. It was concluded that data collected from routine surveillance of encephalomyelitis in horses could be used to predict epidemics of WEE.

Dental disease and caries related microflora in children with dystrophic epidermolysis bullosa.

PURPOSE: The purpose of this study was to investigate dental caries, bacterial dental plaque, gingivitis and caries related oral microflora in children with predominantly autosomal recessive Dystrophic Epidermolysis Bullosa (DEB). METHODS: Thirty children with DEB from The Great Ormond Street Hospital for Children and 31 control children matched for age, gender and ethnicity were included in the study. RESULTS: The main findings were: 1. A significantly greater mean dmft in the DEB children (p < 0.05). 2. A significantly greater mean plaque score for the DEB children for both the primary (p < 0.001) and permanent teeth (p < 0.02) compared with the control children. 3. A significantly greater mean gingivitis score for the DEB children for both the primary (p < 0.002) and permanent teeth (p < 0.0001) compared with the control children. 4. A significantly greater salivary total anaerobic count for the control children compared with the DEB children (p < 0.001). CONCLUSIONS: The results reflect the difficulties that children with DEB have with basic oral hygiene procedures combined with slow oral clearance.

Breast cancer: cured or not?

Survival following treatment of breast cancer may be estimated through the recognition of various prognostic factors. The Case Study presented here calls attention to several of these factors. The reliability and relative value of these prognosticators are discussed. Recommendations are offered for the practical application of prognostic information in the determination of expected mortality.

T wave lability: a clue for separating the good from the bad, when ugly.

Non-specific T wave abnormalities have challenged both the clinician and the insurance medical director for decades. Distinction between pathologic and physiologic T wave changes often requires costly and time-consuming diagnostic studies. The literature is reviewed on the subject of T wave manipulation by the oral administration of both potassium and glucose, introducing the concept of T wave lability. Based on this concept, a simple technique is suggested which, in many cases, can safely, expeditiously and inexpensively distinguish between organic and functional T wave changes. When employed in the investigation of asymptomatic insurance applicants with unexplained T wave abnormalities but no known cardiovascular or renal disease, this technique appears to be sufficiently reliable to classify the risk posed by non-specific T wave changes without resorting to a sophisticated, lengthy and costly cardiovascular investigation.