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Background & Aims: The etiology of acute liver failure (ALF) remains elusive in almost half of affected children. We hypothesized that inherited mitochondrial and fatty acid oxidation disorders were occult etiological factors in patients with idiopathic ALF and impaired energy metabolism., Methods: Twelve patients with elevated blood molar lactate/pyruvate ratio and indeterminate etiology were selected from a retrospective cohort of 74 subjects with ALF because their fixed and frozen liver samples were available for histological, ultrastructural, molecular and biochemical analysis., Results: A customized next-generation sequencing panel for 26 genes associated with mitochondrial and fatty acid oxidation defects revealed mutations and sequence variants in five subjects. Variants involved the genes ACAD9, POLG, POLG2, DGUOK, and RRM2B; the latter not previously reported in subjects with ALF. The explanted livers of the patients with heterozygous, truncating insertion mutations in RRM2B showed patchy micro- and macrovesicular steatosis, decreased mitochondrial DNA (mtDNA) content <30% of controls, and reduced respiratory chain complex activity; both patients had good post-transplant outcome. One infant with severe lactic acidosis was found to carry two heterozygous variants in ACAD9, which was associated with isolated complex I deficiency and diffuse hypergranular hepatocytes. The two subjects with heterozygous variants of unknown clinical significance in POLG and DGUOK developed ALF following drug exposure. Their hepatocytes displayed abnormal mitochondria by electron microscopy., Conclusion: Targeted next generation sequencing and correlation with histological, ultrastructural and functional studies on liver tissue in children with elevated lactate/pyruvate ratio expand the spectrum of genes associated with pediatric ALF.

Atrial myxomatous embolization into the coronary arteries is a rare event. Management of large myxomas is usually via surgical resection involving a median sternotomy. Echocardiography is not a routine part of non-ST-elevation myocardial infarction (NSTEMI) management. Here, we present the case of a 70-year-old Caucasian man with a history of hypertension and hyperlipidemia who presented to the emergency department with an NSTEMI. Transthoracic echocardiogram and transesophageal echocardiogram revealed a large and highly mobile atrial mass, traversing through the mitral valve orifice during diastole. Coronary angiography revealed a focal 60% lesion in the right coronary artery and no other significant obstructive coronary artery disease, suggesting that the cause of his presentation was tumor embolization into the coronary circulation. The patient underwent robot-assisted endoscopic resection of his atrial mass and was discharged in stable condition on postoperative day 2. Pathology revealed atrial myxoma. To our knowledge, this is the first reported case of an atrial myxoma presenting with an NSTEMI and managed with a robot-assisted endoscopic approach. This case also highlights the importance of routine early echocardiography in patients presenting with NSTEMI.

Motivated to explore the ultimate limits of surface-enhanced nonlinear spectroscopies, we report on the first observation of molecular second hyper-Raman scattering with the aid of surface enhancement and provide a new theoretical framework for first-principles calculations of the second hyper-Raman effect. Second hyper-Raman enhancement factors, determined to be a minimum of 10(5) times stronger than those in Raman scattering, demonstrate a clear trend toward larger enhancements for nonlinear phenomena, and the nearly quantitative agreement between simulation and experiment provides a unique spectroscopic window into higher-order molecular responses.

Quiescent CD4+ T cells restrict human immunodeficiency virus type 1 (HIV-1) infection at early steps of virus replication. Low levels of both deoxyribonucleotide triphosphates (dNTPs) and the biosynthetic enzymes required for their de novo synthesis provide one barrier to infection. CD4+ T cell activation induces metabolic reprogramming that reverses this block and facilitates HIV-1 replication. Here, we show that phospholipase D1 (PLD1) links T cell activation signals to increased HIV-1 permissivity by triggering a c-Myc-dependent transcriptional program that coordinates glucose uptake and nucleotide biosynthesis. Decreasing PLD1 activity pharmacologically or by RNA interference diminished c-Myc-dependent expression during T cell activation at the RNA and protein levels. PLD1 inhibition of HIV-1 infection was partially rescued by adding exogenous deoxyribonucleosides that bypass the need for de novo dNTP synthesis. Moreover, the data indicate that low dNTP levels that impact HIV-1 restriction involve decreased synthesis, and not only increased catabolism of these nucleotides. These findings uncover a unique mechanism of action for PLD1 inhibitors and support their further development as part of a therapeutic combination for HIV-1 and other viral infections dependent on host nucleotide biosynthesis.

Colonoscopy is a common procedure used for screening, diagnosis, and treatment of gastrointestinal disease. Life-threatening complications are uncommon (28/10 000 procedures) but include perforation, hemorrhage, diverticulitis, and postpolypectomy syndrome. Although previously reported, the association between appendicitis and colonoscopy is not widely known. This case report highlights the underlying pathophysiology, clinical presentation, and diagnosis of postcolonoscopy appendicitis. A 52-year-old man presented to the emergency department with abdominal pain 8 hours after an uncomplicated routine screening colonoscopy. He initially reported mild generalized abdominal discomfort which 3 hours after the procedure intensified and localized to the periumbilical region. Computed tomography of the abdomen with oral and intravenous contrast revealed appendicitis as the cause of his abdominal pain. He underwent laparoscopic appendectomy and recovered uneventfully. Colonoscopy is a common procedure that rarely has life-threatening complications. Although establishing causality is difficult, there is an association between colonoscopy and appendicitis, which may be underreported with literature-based estimates as high as 3.8 appendicitis cases per 10 000 procedures. Timely diagnosis of postcolonoscopy appendicitis may prove challenging given limited knowledge of this association between colonoscopy and appendicitis and similarity of presentation with other more well-known complications. This case report demonstrates that a recent history of colonoscopy should not preclude consideration of a traditionally broad differential diagnosis for abdominal pain, including appendicitis.

Since the observation of single-molecule surface-enhanced Raman scattering (SMSERS) in 1997, questions regarding the nature of the electromagnetic hot spots responsible for such observations still persist. For the first time, we employ electron-energy-loss spectroscopy (EELS) in a scanning transmission electron microscope (STEM) to obtain maps of the localized surface plasmon modes of SMSERS-active nanostructures, which are resolved in both space and energy. Single-molecule character is confirmed by the bianalyte approach using two isotopologues of Rhodamine 6G. Surprisingly, the STEM/EELS plasmon maps do not show any direct signature of an electromagnetic hot spot in the gaps between the nanoparticles. The origins of this observation are explored using a fully three-dimensional electrodynamics simulation of both the electron-energy-loss probability and the near-electric field enhancements. The calculations suggest that electron beam excitation of the hot spot is possible, but only when the electron beam is located outside of the junction region.

In this longitudinal study, the authors provide support for the validity of the claim that differences in the nature of the reinforcement that adolescent girls expect from eating contribute to the development of different forms of maladaptive eating. The learned expectancy that eating is pleasurable and rewarding predicted higher levels of social/celebratory overeating across the first year of middle school but did not predict higher levels of clinical binge eating. In contrast, the expectancy that eating helps one manage negative affect predicted higher levels of binge eating but not of social/celebratory overeating across the same time period (n = 394). The results also supported a reciprocal model in which binge eating predicted higher levels of the expectancy that eating will manage negative affect but not that eating is pleasurable and rewarding; conversely, social/celebratory overeating predicted higher levels of the expectancy that eating is pleasurable and rewarding but not that eating will manage negative affect.

Ultrasound images of a patient presenting to the emergency department with expressive aphasia who was found to have carotid dissection. The first image is a standard two dimensional image that depicts the internal carotid with a visible flap within the lumen. The second image is a color Doppler image showing turbulent flow within the true lumen and visible flow within the false lumen. The case and the patient's outcome are summarized along with some teaching points about carotid dissection. Also, there is some background and research on using ultrasound to help identify dissection.

The authors applied person-environment transaction theory to test the acquired preparedness model of eating disorder risk. The model holds that (a) middle-school girls high in the trait of ineffectiveness are differentially prepared to acquire high-risk expectancies for reinforcement from dieting or thinness; (b) those expectancies predict subsequent binge eating and purging; and (c) the influence of the disposition of ineffectiveness on binge eating and purging is mediated by dieting or thinness expectancies. In a three-wave longitudinal study of 394 middle-school girls, the authors found support for the model. Seventh-grade girls' scores on ineffectiveness predicted their subsequent endorsement of high-risk dieting or thinness expectancies, which in turn predicted subsequent increases in binge eating and purging. Statistical tests of mediation supported the hypothesis that the prospective relation between ineffectiveness and binge eating was mediated by dieting or thinness expectancies, as was the prospective relation between ineffectiveness and purging. This application of a basic science theory to eating disorder risk appears fruitful, and the findings suggest the importance of early interventions that address both disposition and learning.

Objective: We describe videolaryngoscopy equipment and technique for endotracheal intubation and airway evaluation in the delivery room (DR) and NICU for endotracheal intubation and airway evaluation. We report our first experience of 47 patients., Methods: Forty-seven infants who weighed 530 to 6795 g and required endotracheal intubation or airway evaluation were considered for intubation or assessment by using the modified Kaplan-Berci videolaryngoscope. We report quality-improvement data after initial introduction of newly approved technology., Results: We report results of 48 intubations in 42 patients and videolaryngoscopic inspection without intubation in 5 patients. Five intubation attempts were successful after failed attempts by experienced intubators; 6 attempts by residents were completed with video guidance rather than requiring an additional attempt. Only 3 intubations required more than 2 attempts. Enlarged panoramic view and recording assisted in correct diagnosis of vocal cord paralysis. The features and main advantages are discussed in detail. No complications or difficulties resulting from the technology occurred., Conclusions: This new technique and technology show promise to improve airway management, evaluation, and teaching. Future research to validate improved intubation success in difficult airways and in teaching situations is warranted.

Background: Reflection is a learning tool increasingly being used in medical education. It has not been well studied as a method of communicating resident rotation goals and objectives., Purpose: The purpose was to study the effect of monthly resident reflection on achieving curriculum goals., Methods: During the first half of the 2005-06 academic year, obstetrics/gynecology residents at a community hospital received curriculum goals in a traditional written manner. During the second 6 months, the same trainees underwent 1-hr monthly structured reflection sessions on the rotation goals and objectives., Results: Sixteen residents were studied. Compared to control, residents reported the rotation goals as better defined during reflection months. More trainees rated reflection as more valuable than the didactic time it replaced. All 16 residents documented more cumulative procedures in the Accreditation Council for Graduate Medical Education operative log Web site during reflection months for each of the three major categories; there was a mean increased number of procedures logged in Obstetrics (23.1 +/- 14.0, p < .001), Gynecology (18.3 +/- 10.9, p < .001), and Primary Care (21.1 +/- 23.5, p = .003). Overall, there was a mean of 62.6 +/- 32.1 (p < .001) more procedures entered during the reflection period, which translated to an 18% increase., Conclusions: Structured monthly reflection may lead to a higher success of achieving rotation goals.

The unimolecular reactions of CF(2)ClCFClCH(2)F and CF(2)ClCF(2)CH(2)Cl molecules formed with 87 and 91 kcal mol(-1), respectively, of vibrational energy from the recombination of CF(2)ClCFCl with CH(2)F and CF(2)ClCF(2) with CH(2)Cl at room temperature have been studied by the chemical activation technique. The 2,3- and 1,2-ClF interchange reactions compete with 2,3-ClH and 2,3-FH elimination reactions. The total unimolecular rate constant for CF(2)ClCF(2)CH(2)Cl is 0.54 +/- 0.15 x 10(4) s(-1) with branching fractions for 1,2-ClF interchange of 0.03 and 0.97 for 2,3-FH elimination. The total rate constant for CF(2)ClCFClCH(2)F is 1.35 +/- 0.39 x 10(4) s(-1) with branching fractions of 0.20 for 2,3-ClF interchange, 0.71 for 2,3-ClH elimination and 0.09 for 2,3-FH elimination; the products from 1,2-ClF interchange could be observed, but the rate constant was too small to be measured. The D(CH(2)F-CFClCF(2)Cl) and D(CH(2)Cl-CF(2)CF(2)Cl) were evaluated by calculations for some isodesmic reactions and isomerization energies of CF(3)CFClCH(2)Cl as 84 and 88 kcal mol(-1), respectively; these values give the average energies of formed molecules at 298 K as noted above. Density functional theory was used to assign vibrational frequencies and moments of inertia for the molecules and their transition states. These results were combined with statistical unimolecular reaction theory to assign threshold energies from the experimental rate constants for ClF interchange, ClH elimination and FH elimination. These assignments are compared with results from previous chemical activation experiments with CF(3)CFClCH(2)Cl, CF(3)CF(2)CH(3,) CF(3)CFClCH(3) and CF(2)ClCF(2)CH(3).

Purpose: To test the hypothesis that radiation dose to key sites in the upper aerodigestive tract is associated with long-term functional outcome after (chemo)radiotherapy for head-and-neck cancers., Methods and Materials: This study examined the outcome for 27 patients treated with intensity-modulated radiotherapy for definitive management of their head-and-neck cancer who were disease free for at least 1 year after treatment. Head-and-neck cancer-specific quality of life (QoL) was assessed before treatment and at 1 year after treatment. Type of diet tolerated, presence of a feeding tube, and degree of weight loss 1 year after treatment were also used as outcome measures. Radiation doses delivered to various points along the upper aerodigestive tract, including base of tongue, lateral pharyngeal walls, and laryngeal structures, were determined from each treatment plan. Radiation doses for each of these points were tested for correlation with outcome measures., Results: Higher doses delivered to the aryepiglottic folds, false vocal cords, and lateral pharyngeal walls near the false cords correlated with a more restrictive diet, and higher doses to the aryepiglottic folds correlated with greater weight loss (p < 0.05) 1 year after therapy. Better posttreatment speech QoL scores were associated with lower doses delivered to structures within and surrounding the larynx., Conclusion: Our data show an inverse relationship between radiation dose delivered to laryngeal structures and speech and diet and QoL outcomes after definitive (chemo)radiation treatment. These findings suggest that efforts to deliver lower doses to laryngeal structures may improve outcomes after definitive (chemo)radiation therapy.

One's expectancies for reinforcement from eating or from thinness are thought to represent summaries of one's eating-related learning history and to thus influence the development of binge-eating and purging behavior. In a 3-year longitudinal study, the authors tested this hypothesis and the hypothesis that binge eating also influences subsequent expectancy development. The authors used trajectory analysis to identify groups of middle school girls who followed different trajectories of binge eating, purging, eating expectancies, and thinness expectancies. Initial eating and thinness reinforcement expectancies identified girls whose binge eating and purging increased during middle school, and expectancies differentiated girls who began these problem behaviors from girls who did not. Initial binge-eating scores differentiated among eating expectancy developmental trajectories. The onset of most behaviors can be understood in terms of learned expectancies for reinforcement from these behaviors. The same model can be applied to the risk for eating disorders., ((c) 2007 APA, all rights reserved.)

Elevated sympathetic outflow contributes to the maintenance of blood pressure in water-deprived rats. The neural circuitry underlying this response may involve activation of a pathway from the hypothalamic paraventricular nucleus (PVH) to the rostral ventrolateral medulla (RVLM). We sought to determine whether the PVH-RVLM projection activated by water deprivation is glutamatergic and/or contains vasopressin- or oxytocin-neurophysins. Vesicular glutamate transporter 2 (VGLUT2) mRNA was detected by in situ hybridization in the majority of PVH neurons retrogradely labeled from the ipsilateral RVLM with cholera toxin subunit B (CTB; 85% on average, with regional differences). Very few RVLM-projecting PVH neurons were immunoreactive for oxytocin- or vasopressin-associated neurophysin. Injection of biotinylated dextran amine (BDA) into the PVH produced clusters of BDA-positive nerve terminals within the ipsilateral RVLM that were immunoreactive (ir) for the VGLUT2 protein. Some of these terminals made close appositions with tyrosine-hydroxylase-ir dendrites (presumptive C1 cells). In water-deprived rats (n=4), numerous VGLUT2 mRNA-positive PVH neurons retrogradely labeled from the ipsilateral RVLM with CTB were c-Fos-ir (16-40%, depending on PVH region). In marked contrast, few glutamatergic, RVLM-projecting PVH neurons were c-Fos-ir in control rats (n=3; 0-3%, depending on PVH region). Most (94% +/- 4%) RVLM-projecting PVH neurons activated by water deprivation contained VGLUT2 mRNA. In summary, most PVH neurons that innervate the RVLM are glutamatergic, and this population includes the neurons that are activated by water deprivation. One mechanism by which water deprivation may increase the sympathetic outflow is activation of a glutamatergic pathway from the PVH to the RVLM., (J. Comp. Neurol. 494:673-685, 2006. (c) 2005 Wiley-Liss, Inc.)

Preparing for and recovering from disasters Planning is the most important thing a medical practice can do to prepare for a disaster. Learn from the experiences of a medical group in Florida that weathered four hurricanes in 2004. Its trials provide insights for other groups that might suffer calamities such as blizzards, floods, tornadoes, earthquakes, blackouts and even acts of terrorism.

Markers of serotonergic, gamma-aminobutyric acid (GABA)-ergic (glutamic acid decarboxylase, 67 kDa isoform; GAD-67), and glutamatergic transmission (vesicular glutamate transporter 3; VGLUT3) have been detected in presumed sympathetic premotor neurons of the medullary raphe, a region that controls sympathetic tone to brown fat, skin blood vessels, and heart. In this study, the degree of coexpression of these markers was examined in raphe neurons by simultaneous histological detection of tryptophan hydroxylase (TrpOH) immunoreactivity with GAD-67 mRNA and VGLUT3 mRNA. Over half (52%) of the VGLUT3 mRNA-positive neurons expressed one or both of the other markers. The proportion of VGLUT3 neurons containing at least one of the other two markers was even higher (89%) for VGLUT3 spinally projecting neurons. VGLUT3 neurons containing markers for both serotonin and GABA were especially numerous (50-72%, depending on rostrocaudal level) within the marginal layer of raphe pallidus and the parapyramidal region. The dual GABAergic and glutamatergic nature of some bulbospinal raphe neurons was suggested by the presence of nerve terminals immunoreactive (ir) for both VGLUT3 and GABA in the intermediolateral cell column (IML) as detected by electron microscopy. VGLUT3-ir terminals formed approximately equal numbers of symmetric and asymmetric synapses onto presumed preganglionic neurons (nitric oxide synthase-ir profiles) or GABA-ir dendrites in IML, and terminals immunoreactive for both VGLUT3 and GABA always formed symmetric synapses. These data suggest that medullary raphe VGLUT3 neurons could inhibit sympathetic outflow and that their spinal targets include both preganglionic neurons and GABAergic interneurons., (Copyright 2005 Wiley-Liss, Inc.)

A long-standing theory posits that central chemoreception, the CNS mechanism for CO(2) detection and regulation of breathing, involves neurons located at the ventral surface of the medulla oblongata (VMS). Using in vivo and in vitro electrophysiological recordings, we identify VMS neurons within the rat retrotrapezoid nucleus (RTN) that have characteristics befitting these elusive chemoreceptors. These glutamatergic neurons are vigorously activated by CO(2) in vivo, whereas serotonergic neurons are not. Their CO(2) sensitivity is unaffected by pharmacological blockade of the respiratory pattern generator and persists without carotid body input. RTN CO(2)-sensitive neurons have extensive dendrites along the VMS and they innervate key pontomedullary respiratory centers. In brainstem slices, a subset of RTN neurons with markedly similar morphology is robustly activated by acidification and CO(2). Their pH sensitivity is intrinsic and involves a background K(+) current. In short, the CO(2)-sensitive neurons of the RTN are good candidates for the long sought-after VMS chemoreceptors.

Most of the CNS neurons that regulate circulation and respiration reside in regions of the brain characterized by extreme cellular heterogeneity (nucleus of the solitary tract, reticular formation, parabrachial nuclei, periaqueductal gray matter, hypothalamus, etc.). The chemical neuroanatomy of these regions is correspondingly complex and teasing out specific circuits in their midst remains a problem that is usually very difficult if not impossible to solve by conventional tract-tracing methods, Fos methodology or electrophysiology in slices. In addition, identifying the type of amino acid or peptide transmitter used by electrophysiologically recorded neurons has been until recently an especially difficult task either for lack of a specific marker or because such markers (many peptides for example) are exported to synaptic terminals and thus undetectable in neuronal cell bodies. In this review, we describe a general purpose method that solves many of these problems. The approach combines juxtacellular labeling in vivo with the histological identification of mRNAs that provide definitive neurochemical phenotypic identification (e.g. vesicular glutamate transporter 1 or 2, glutamic acid decarboxylase). The results obtained with this method are discussed in the general context of amino acid transmission in brainstem cardiorespiratory pathways. The presence of markers of amino acid transmission in specific aminergic pre-sympathetic neurons is especially emphasized as is the extensive co-localization of markers of GABAergic and glycinergic transmission in the brainstem reticular formation.

We studied 100 patients in whom symptomatic pseudarthrosis had been established at more than 9 months after lumbar spine fusion. All patients were treated with a pulsed electromagnetic field device worn consistently 2 hours a day for at least 90 days. Solid fusion was achieved in 67% of patients. Effectiveness was not statistically significantly different for patients with risk factors such as smoking, use of allograft, absence of fixation, or multilevel fusions. Treatment was equally effective for posterolateral fusions (66%) as with interbody fusions (69%). For patients with symptomatic pseudarthrosis after lumbar spine fusion, pulsed electromagnetic field stimulation is an effective nonoperative salvage approach to achieving fusion.

The Eating Disorder Inventory-2 (EDI-2) and Bulimia Test-Revised (BULIT-R) have demonstrated strong reliability and validity in college students and adults. Although used in adolescent samples, little is known about the psychometric properties of these measures for adolescents. The reliability, factor structure, and mean levels of five EDI-2 scales and the BULIT-R were evaluated over 3 years. Data were collected yearly from two samples of adolescent females, one recruited from three public middle schools (n = 239, mean baseline age = 12.8) and one from two public high schools (n = 119, mean baseline age = 15.9). Results provide strong evidence for the reliability and stability of these measures. Mean levels of both measures appeared remarkably consistent over the 3 years. These results provide evidence of good psychometric performance for these scales in adolescence. The lack of change in these measures raises questions about the developmental trajectory of these variables through adolescence.

Objective: To demonstrate the validity of two measures of eating and dieting expectancies (The Eating Expectancy Inventory [EEI] and the Thinness and Restricting Expectancy Inventory, [TREI]) for use with adolescents., Method: Seventh (N = 392) and tenth graders (N = 300) completed the Bulimia Test-Revised (BULIT-R), the Eating Disorder Inventory (EDI-II), and two factors of the Three-Factor Eating Questionnaire (TFEQ)., Results: Findings replicated for the two adolescent samples. The expectancy that thinness leads to overgeneralized life improvement correlated with measures of "successful" dieting, dieting plus disinhibition, and bulimic symptomatology. Expectancies for negative reinforcement from eating (e.g., eating helps manage negative affect and alleviate boredom) correlated with dieting plus disinhibition and bulimic symptoms, but not with successful dieting. Negative reinforcement from eating and reinforcement from thinness expectancies accounted for different bulimic symptom variance than that accounted for by the personality factors of perfectionism, interpersonal distrust, and ineffectiveness., Discussion: Results were consistent with prior work on college and clinical samples, thus supporting use of the expectancy measures with adolescents., (Copyright 2002 by Wiley Periodicals, Inc.)

Humoral hypercalcemia is rarely associated with colon carcinoma; cutaneous metastases from colon carcinoma are also infrequent. To the authors' knowledge, no cases of colon carcinoma presenting with both hypercalcemia and cutaneous metastases have been reported to date. A case of advanced poorly differentiated colon carcinoma with neuroendocrine features with both humoral hypercalcemia of malignancy (HHM) and cutaneous metastases is presented. A poorly differentiated colon carcinoma with neuroendocrine features occurred in a 42-year-old patient with metastases to the liver, both femurs, left orbit, and scalp. The hypercalcemia was caused by the expression of a parathyroid hormone related peptide by both the primary and cutaneous metastatic tumors. Bisphosphonate treatment helped normalize serum calcium in a few days, but hypercalcemia recurred approximately 3 weeks later. Chemotherapy only mildly reduced the size of the cutaneous metastases. The patient died 8 months after initial diagnosis. To the authors' knowledge, the case presented in the current study is the first to be reported with both HHM and cutaneous metastases. Hypercalcemia and cutaneous metastases are separately associated with a poor prognosis and indicate advanced and widely metastatic disease. Although still unclear, the mechanism by which colon cancer causes cutaneous metastases and hypercalcemia, in light of current theories presented in the literature, is discussed.

Background: Mental retardation and other disabilities (including ectopia lentis, osteoporosis, and thromboembolism) in patients who have homocystinuria as a result of a deficiency of cystathionine beta-synthase can be prevented by the screening of newborns with measurement of blood methionine, followed by the early treatment of affected infants. Many infants with this disorder, however, are not identified by screening and have irreversible brain damage., Methods: We reviewed the results of neonatal screening for homocystinuria over a period of 32 years in New England. Additional specimens were requested for repeated analysis when blood methionine measurements were at or above the established cutoff level. Homocystinuria due to cystathionine beta-synthase deficiency was confirmed by quantitative amino acid analyses., Results: For the first 23.5 years of the review period, the blood methionine cutoff value was 2 mg per deciliter (134 micromol per liter). Among the 2.2 million infants screened during that period, 8 with homocystinuria were identified (1:275,000). In 1990, the cutoff value was reduced to 1 mg per deciliter (67 micromol per liter). Among the 1.1 million infants screened in the subsequent 8.5 years, 7 with the disorder were identified (1:157,000). During the latter period, the specimens were collected from six of the seven infants when they were two days of age or less; five of the six had blood methionine concentrations below 2 mg per deciliter. Use of the reduced cutoff level increased the false positive rate from 0.006 percent to 0.03 percent., Conclusions: A cutoff level for blood methionine of 1 mg per deciliter in neonatal screening tests for homocystinuria should identify affected infants who have only slightly elevated concentrations of methionine and reduce the frequency of false negative results.

Objective: Children learn about alcohol and about how to drink through modeling experience, in part. Modeling is typically studied by asking parents to describe their drinking behavior. However, children's perception of parents' drinking may differ from the way parents describe it. This study examined the degree to which children's perceptions and parents' reports agreed., Method: A sample of 177 grade-school children and their parents was drawn from a public school in Kentucky. Children completed questionnaires inquiring about their perceptions of the quantity, frequency and the positive and negative consequences of their parents' drinking. Their parents completed similar questionnaires describing their own drinking and its consequences., Results: As hypothesized, first and second grade children's perceptions of parents' drinking were unrelated to parents' self-reports: Most of these children perceived their parents as nondrinkers even though parents reported drinking. Also as hypothesized, children's perceptions and parents' reports were significantly correlated for third through sixth grade students. However, there was a great deal of reliable, but unshared variance between these older children's perceptions and parents' reports. Children's perceptions and parents' reports were consistently quite different, even when both child and parent described the parent as a drinker., Conclusions: Studies of modeling influences on children regarding drinking should assess children's perceptions of their parents' behavior rather than parents' self-reports.

Objective: To determine how the loop electrosurgical excision procedure (LEEP) compares to cold knife conization in providing an adequate diagnostic specimen., Study Design: Between 1991 and 1995, 95 patients underwent either diagnostic LEEP or cold knife conization at Allegheny University Hospitals. The indications for the procedure were a cytologic/histologic discrepancy, unsatisfactory colposcopic evaluation, positive endocervical curettage or exclusion of invasion., Results: Severe thermal artifact rendered the LEEP specimens uninterpretable in 4.4% of cases. A median number of two passes were required for LEEP excision of the transformation zone. The number of passes correlated with the amount of thermal artifact detected (P = .034). Regarding recurrence patterns, normal follow-up cervical cytology was similar for both groups: 96.7% in the LEEP group vs. 100% in the cold knife conization group., Conclusion: We conclude that LEEP is an acceptable diagnostic alternative to traditional cold knife conization. Thermal artifact remains a disadvantage that can be minimized by limiting the number of passes required to obtain a complete specimen.

The rationale of anterior versus posterior, or combined fusion is discussed with regards to different clinical diagnoses and situations. Factors involved in the decision-making process include stability, magnitude of deformity, rigidity of deformity, neurologic considerations, bone quality, and medical/metabolic factors. Careful preoperative assessment and planning are required as well as consideration for the patient's overall well being.

This article examines cervical deformities and their treatments, such as iatrogenic deformities, posttraumatic deformities, ankylosing spondylitis, rheumatoid arthritis, degenerative subaxial spondylolisthesis, myopathy, infectious spondylitis, and tumors. Congenital scoliosis and kyphosis and torticollis and rotatory atlanto-axial subluxation also are discussed.

Study Design: This was a human cadaver study of the accuracy of biplanar roentgenography in determining pedicle screw position., Objective: To determine the independent accuracy of radiologic evaluation of screw placement and to determine if there are any particular screw malpositions that are more likely to produce a false sense of acceptable screw position., Summary of Background Data: Other investigators have reported the correlation between radiologic evaluation and anatomic dissection. However, in those studies the radiologic evaluation was not independent of the surgeons placing the screws. There has been no comment in the literature regarding particular screw malpositions that would lead the surgeon into a false sense of successful screw placement., Methods: Pedicle screws were placed in cadaver spines, and biplanar roentgenograms of the specimens were evaluated by independent observers. The results of the roantgenogram evaluation then were compared to those of the anatomic dissection., Results: The accuracy of roentgenogram evaluation varied from 73% to 83%, depending on the experience of the surgeon grading the roentgenograms. Screws misplaced medially into the spinal canal are more likely to give the surgeon a false sense of successful screw placement., Conclusions: The surgeon must not rely solely on the roentgenograms, but instead continue to use tactile sensory skills, anatomic knowledge, and additional modalities such as electromyography monitoring.

Study Design: This case-control study was undertaken to determine if relatives of patients who had been admitted for surgery for degenerative disc disease-related problems were at increased risk for lower back pain or sciatica., Objectives: To determine if familial factors play a role in placing a person at risk for development of degenerative disc disease of the lumbar spine., Summary of Background Data: It is known that smoking and various occupational factors can place a person at risk for degenerative disc disease problems. It is not known if a familial predisposition may also exist., Methods: The family members and relatives of 65 patients who had undergone surgery for lumbar degenerative disc disease were interviewed with a standardized questionnaire and compared with a control group of 67 patients who had been admitted to hospital for non-spine-related orthopedic procedures. The same interview and standardized questionnaire was used for both groups by a single observer., Results: In the study group of 65 patients who had undergone surgery for degenerative disc disease, 44.6% were noted to have a positive family history, whereas 25.4% of the patients in the control group had a positive family history. Eighteen and one-half percent of relatives in the study group had a history of having spinal surgery, compared with only 4.5% of the control group., Conclusions: The results indicate that a familial predisposition to degenerative disc disease can exist along with other risk factors.

Study Design: This study evaluates and compares the stiffness of two cervical spine fixation techniques., Objectives: This biomechanical study was carried out to compare the interspinous and Dewar cervical spine fixation techniques., Summary of Background Data: Interspinous wiring is a commonly used method of fixation in the cervical spine. The Dewar technique is less commonly known and practiced, and clinical experience has suggested that it may be a more stable technique., Methods: Cervical spine specimens stabilized with the interspinous and "Dewar" techniques were biomechanically tested in flexion and in torsion. Stiffness and energy absorption under moderate loads were compared. The Dewar technique uses contoured double corticocancellous iliac grafts as internal grafts/splints fixed to the spine with threaded pins and wire. The interspinous technique is a single interspinous wire loop. Eleven fresh human cervical spines were harvested from cadavers. The spines were destabilized at C4-C5 by sectioning all tissue except the anterior longitudinal ligament. Each fixation technique was applied alternatively and tested on each spine., Results: In torsion testing (n = 5), the Dewar fusion was 61% stiffer than the interspinous technique (P < 0.02). Dewar: 11.3 N/mm (s.d. 4.9 N/mm) and interspinous: 8.4 N/mm (SD 3.3 N/mm). In flexion testing (n = 6), the Dewar technique was 35% stiffer than the interspinous technique (P < 0.10). Dewar: 655.4 Nmm/degree (SD 293 Nmm/degree) and interspinous: 406.8 Nmm/degree (SD 113.0 Nmm/degree). Energy absorption with the interspinous technique was greater in flexion (P < 0.10) and in torsion (P < 0.005), indicating more deformation with the interspinous technique. There was no statistically significant difference between the means of specimens tested first and those tested second independently of the fixation technique., Conclusions: These tests indicate that the Dewar cervical spine fixation is stiffer than the single interspinous wire in both flexion and particularly torsion. This project is the only biomechanical study of the Dewar technique that we are aware of, and the results support the clinical findings regarding the effectiveness of this technique.

Guidelines for radiographs of the lumbar spine are established. In general, radiographs are not believed to be necessary for a first episode of low back pain present for less than 7 weeks. Exceptions to this include various medical or physical findings, which are listed. In general, anteroposterior and lateral views only should be done initially. Indications for other views are discussed.

With the current emphasis on cost containment, it is important to order the single best diagnostic test when clinical uncertainties must be resolved. Magnetic resonance imaging is currently the optimal imaging modality to provide the maximum amount of information when evaluating patients with suspected spinal disorders. A comprehensive magnetic resonance imaging study is needed along with a subspecialty interpretation to provide the greatest amount of useful clinical information.

Perennially ice-covered lakes are found in the McMurdo Dry Valleys of southern Victoria Land, Antarctica. In contrast to temperate lakes that have diurnal photic periods, antarctic (and arctic) lakes have a yearly photic period. An unusual feature of the antarctic lakes is the occurrence of O2 at supersaturated levels in certain portions of the water column. Here we report the first sediment O2 profiles obtained using a microelectrode from a perennially ice-covered antarctic lake. Sediment cores collected in January and October 1987 from Lake Hoare in Taylor Valley show oxygenation down to 15, and in some cases, 25 cm. The oxygenation of sediments several centimeters below the sediment-water interface is atypical for lake sediments and may be characteristic of perennially ice-covered lakes. There is a significant difference between the observed January and October sediment O2 profiles. Several explanations may account for the difference, including seasonality. A time-dependent model is presented which tests the feasibility of a seasonal cycle resulting from the long photoperiod and benthic primary production in sediments overlain by a highly oxygenated water column.

When the dorsal root ganglion is irritated by any of a variety of mechanisms, pain is referred to the various structures innervated by that root. In many circumstances, this pain is specific and may be used as a diagnostic aid. Unfortunately, emphasis is placed on defining a dermatomal distribution; the existence of a myotomal or sclerotomal origin of referred pain is often overlooked. This review presents the embryologic, anatomic, and neurophysiologic etiology of referred pain from the lumbar spine.

This study was done to define and characterize those adult patients with scoliosis who will have problems of pain and/or progression leading to a surgical procedure and to review the results of these surgical procedures. The authors reviewed the cases of 49 adult patients who had undergone surgical treatment for scoliosis (average follow-up, 34 months; range, 24-140 months). The patients were categorized according to age, which allowed analysis of the data comparing age and the incidence and level of pain, age versus the degree of curvature, and age versus the incidence of progression. The relative incidence of pain and progression as indications for surgery were found to vary with respect to age. In the younger groups, progression was more often the indication for surgery than in the older groups. The younger groups also had larger curves than did the older groups, on average. The degree of pain was not found to correlate with the magnitude of the deformity. Surgical complications occurred in 20 patients; however, 14 of these were minor complications during the perioperative period, which did not result in any sequelae. Surgical treatment can be done with a relatively low serious complication rate and good results in terms of pain relief and reasonable correction of the deformity.

We evaluated the long-term results of 202 capitellocondylar total elbow replacements that had been performed, from July 1974 through June 1987, in 172 patients. The duration of follow-up averaged sixty-nine months (range, twenty-four to 178 months). At the most recent follow-up examination, use of a 100-point rating score demonstrated an improvement from an average preoperative score of 26 points (range, 2 to 50 points) to an average postoperative score of 91 points (range, 45 to 100 points). The most improvement occurred in the categories of relief of pain, functional status, and range of motion in all planes except extension. The improvements in these categories and in the roentgenographic appearance that were seen in the early postoperative period did not deteriorate with time. The average preoperative arc of motion at the elbow ranged from -37 degrees of extension to 118 degrees of flexion. The average postoperative arc of motion at the elbow ranged from -30 degrees of extension to 135 degrees of flexion. Supination improved from 45 degrees preoperatively to 64 degrees postoperatively; pronation improved from 56 degrees preoperatively to 72 degrees postoperatively. The roentgenograms showed a radiolucent line adjacent to eight humeral and nineteen ulnar components; most of the lines were incomplete and one millimeter wide or less. Revision of the prosthesis was necessary in three elbows (1.5 per cent) because of loosening without infection, and in three additional elbows because of dislocation of the prosthesis. Complications included deep infection in three elbows (1.5 per cent); problems related to the wound in fifteen (7 per cent); permanent, partial sensory ulnar-nerve palsy in five (2.5 per cent); permanent, partial motor ulnar-nerve palsy in one (0.5 per cent); and dislocation in seven (3.5 per cent).

A retrospective review was carried out on 40 patients who met the criteria of 1) having a significant lumbar scoliosis associated with spinal stenosis, with symptoms of neurogenic claudication; and 2) having been treated with posterior decompression and pedicular screw fixation techniques. The average age of the patients was 61.5 years (range, 38-77 years), and 25 of the 40 patients were female. Eighty-eight percent of the patients had significant back pain in addition to lower extremity pain. All patients had pedicular screw fixation at all levels. Zielke instrumentation was used in 24 patients, Cotrel-Dubousset instrumentation in 8 patients, and Texas Scottish Rite Hospital instrumentation in the remaining 8 patients. After surgery, there was marked improvement in regard to pain status: 34 patients (83%) had severe pain before surgery, with 38 patients (93%) reporting mild or no pain at follow-up. Average length of follow-up was 44 months (range, 24-61 months). There were no deaths and no instrument-related failures or pseudarthroses noted in this series. A mean correction of the deformity of 19 degrees was obtained. Average scoliosis was 37 degrees before surgery and 18 degrees at follow-up.

We report results from 10 years of ice thickness measurements at perennially ice-covered Lake Hoare in southern Victoria Land, Antarctica. The ice cover of this lake had been thinning steadily at a rate exceeding 20 cm yr-1 during the last decade but seems to have recently stabilized at a thickness of 3.3 m. Data concerning lake level and degree-days above freezing are presented to show the relationship between peak summer temperatures and the volume of glacier-derived meltwater entering Lake Hoare each summer. From these latter data we infer that peak summer temperatures have been above 0 degrees C for a progressively longer period of time each year since 1972. We also consider possible explanations for the thinning of the lake ice. The thickness of the ice cover is determined by the balance between freezing during the winter and ablation that occurs all year but maximizes in summer. We suggest that the term most likely responsible for the change in the ice cover thickness at Lake Hoare is the extent of summer melting, consistent with the rising lake levels.

Fifteen knees were treated with a surgical technique designed for recurrent patellar dislocations when associated with patella alta. The average number of patellar dislocations preoperatively was 12, and the determination of patella alta was made using the technique described by Insall and Salvati, which is a ratio of the length of the patellar tendon to the longest diagonal length of the patella. The normal value for this ratio is 1.02 plus or minus 20%. The average preoperative ratio in this study was 1.58 (range, 1.2-2.1), which changed to 1.08 (range, 0.99-1.14) by the time of follow-up examination. The surgical technique used involves transposing the patellar tendon insertion distally without any medialization or recessing and allows for good bone contact for healing, secure fixation, and immediate postoperative motion. There were no recurrences of patellar dislocation postoperatively and few complications. Only one patient complained of anterior knee pain in the follow-up period. This technique is thought to give good results when it is used specifically for recurrent patellar dislocations associated with patella alta.

Between 1983 and 1985, 170 consecutive patients received doxorubicin-containing adjuvant chemotherapy through central venous catheters, and four via a long indwelling catheter in the antecubital fossa. The objective of this retrospective study is to determine the acute and chronic complications associated with indwelling catheters. Ninety-four (56%) patients did not experience any complications. The incidence of acute complications was 2%, which included three pneumothorax. Twenty-nine (17%) patients experienced chronic complications. Of those, 20 (12%) developed infectious complications, and 9 (19%) developed thrombus. In addition, 12 (7%) developed multiple complications, and 32 (19%) patients had other local complications at the catheter site, which included allergic reactions and catheter breakage. Each of these complications was resolved with appropriate treatment. None of the patients died from complications of the indwelling catheter.

Bone undergoes structural changes with aging, but the nature of qualitative changes remains to be established. Blocks of midshaft femur were taken at autopsy from men of four different age groups: 20-25 years, 40-45 years, 60-65 years, and 80-85 years. Each femoral specimen was analyzed by density fractionation, a technique that allows the separation of bone by extent of mineralization and maturity. In the 20-25 group, lower density bone predominates. The 40-45 group is characterized by more highly mineralized bone with an increase in the 2.1-2.2 g/cc fraction. At 60-65 years, an increase in the lower density fraction was found, indicating an increase in new bone formation. At 80-85 years, there is an increase in the highest density bone (2.2-2.3 g/cc), which may represent regions of interstitial bone not properly removed through remodeling processes. Chemical studies did not reveal any change in Ca, P, Ca + PO4, or Ca/P molar ratio with respect to age. X-ray diffraction studies show no changes in apatite crystal size with respect to age or degree of mineralization. Morphological studies documented increased remodeling activity and endosteal trabecularization in the older age groups, as well as increased intracortical porosity. An increase in the highest density fraction with aging may represent a pool of bone mineral that is less accessible to remodeling, which may be the interstitial bone.