Log-linear allometry of fetal craniofacial growth in Down's syndrome

Trisomy 21 develops as a result of nondisjunction of two homologous chromosomes during either the first or second meiotic division. One of the more important consequences of these genetic alterations is the predictable, although variable disturbance in the architecture of the craniofacial region [1]. Postnatal craniofacial morphology has been extensively studied in Down's syndrome (DS). However, little information is available on human prenatal development of the head and face in such patients. The time at which changes in craniofacial phenotype first emerge in Down's syndrome fetuses and at which physical growth begins to diverge from normal is unknown. To explore these questions, we compared prenatal craniofacial growth in 50 Down's syndrome fetuses with that of 555 fetuses judged to be "typical for body weight and age" using the method of log-linear allometry [2].     

Lobectomy combined with volume reduction for patients with lung cancer and advanced emphysema

Methanol-induced conformational transitions of hen egg white lysozyme were investigated with a combined use of far- and near-UV CD and NMR spectroscopies, ANS binding and small-angle X-ray scattering. Addition of methanol induced no global change in the native conformation itself, but induced a transition from the native state to the denatured state which was highly cooperative, as shown by the coincidence of transition curves monitored by the far- and near-UV CD spectroscopy, by isodichroic points in the far- and near-UV CD spectra and by the concomitant disappearance of individual 1H NMR signals of the native state. The ANS binding experiments could detect no intermediate conformer similar to the molten globule state in the process of the methanol denaturation. However, at high concentration of methanol, e.g., 60% (v/v) methanol/water, a highly helical state (H) was realized. The H state had a helical content much higher than the native state, monitored by far-UV CD spectroscopy, and had no specific tertiary structure, monitored both by near-UV CD and NMR spectroscopy. The radius of gyration in the H state, 24.9 angstroms, was significantly larger than that in the native state (15.7 angstroms). The Kratky plot for the H state did not show a clear peak and was quite similar to that for the urea-denatured state, indicating a complete lack of globularity. Thus we conclude that the H state has a considerably expanded, flexible broken rod-like conformation which is clearly distinguishable from the "molten globule" state. The stability of both N and H states depends on pH and methanol concentration. Thus a phase diagram involving N and H was constructed.     

Refining the level for anticipated hepatotoxicity in acetaminophen poisoning

Treatment of an acetaminophen overdose with N-acetyl cysteine usually is based on the position of the 4-h acetaminophen (APAP) level on the Rumack-Matthew nomogram; however, there is disagreement on the level at which clinically relevant hepatotoxicity occurs. A retrospective review of all acute adult formulation APAP exposures reported to our poison center between 1986 and 1993 was performed and cases corresponding to the "possible risk or toxicity" range on the nomogram were identified. Our current poison center protocol for APAP poisoning does not recommend treatment with N-acetylcysteine (NAC) in low-risk patients if the 4-h serum APAP level or the extrapolated equivalent falls within the possible toxicity range on the nomogram. Seventeen cases met the inclusion criteria for the study and received no NAC; six additional patients met inclusion criteria but received one or two doses of NAC before therapy was discontinued. No patients in either group demonstrated clinical evidence of hepatotoxicity. This pilot study suggests that patients with no risk factors and APAP levels in the "possible risk" range may not require NAC therapy.     

Perinuclear antineutrophil cytoplasmic antibodies in patients with Crohn's disease define a clinical subgroup

BACKGROUND & AIMS: Antineutrophil cytoplasmic antibodies (ANCA) have been consistently detected in a subgroup of patients with Crohn's disease (CD). This study was designed to determine whether serum ANCA expression in patients with CD characterizes an identifiable clinical subgroup. METHODS: The study population consisted of 69 consecutive patients with an established diagnosis of CD as determined by a combination of characteristic clinical, radiographic, endoscopic, and histopathologic criteria. Sera from the patients were analyzed for the presence of ANCAs using the fixed neutrophil enzyme-linked immunosorbent assay (ELISA) assay. Perinuclear ANCA (pANCA)-positive and cytoplasmic ANCA (cANCA)-positive results by ELISA were confirmed by indirect immunofluorescence staining. Clinical profiles of the ANCA-positive patients with CD were compared with those of patients with CD not expressing ANCA (ANCA-negative). RESULTS: pANCA-positive patients with CD have endoscopically and/or histopathologically documented left-sided colitis and symptoms of left-sided colonic inflammation, clinically reflected by rectal bleeding and mucus discharge, urgency, and treatment with topical agents. One hundred percent of patients with CD expressing pANCA had "UC-like" features. CONCLUSIONS: In patients with CD, serum pANCA expression characterizes a UC-like clinical phenotype. Stratification of CD by serum pANCA provides evidence of heterogeneity within CD and suggests a common intestinal mucosal inflammatory process among a definable subgroup of patients with CD and UC expressing this marker.     

Laparoscopic vs. open wedge biopsy of the liver

The number of people smoking free-base cocaine, or "crack," has increased dramatically in recent years. Concomitantly, the literature describing complications of such use has grown as well. Adverse pulmonary effects are being increasingly noted, such as respiratory symptoms, pulmonary hemorrhage, pulmonary edema, asthma, and pulmonary barotrauma. These and other pulmonary effects are reviewed.     

After-hours telephone coverage: the application of an area-wide telephone triage and advice system for pediatric practices

BACKGROUND: After-hours telephone calls are a stressful and frustrating aspect of pediatric practice. At the request of private practice pediatricians in Denver, a metropolitan area-wide system was created to manage after-hours pediatric telephone calls and after-hours patient care. This system, the After-Hours Program (AHP), uses specially trained pediatric nurses with standardized protocols to provide after-hours telephone triage and advice for the patients of 92 Denver pediatricians, representing 56 practices. OBJECTIVES: This report describes the AHP, presents data from 4 years' experience with the program, and describes results of our evaluation of the following aspects of the program: subscribing physician satisfaction, parent satisfaction, the accuracy and appropriateness of telephone triage, and program costs. METHODS: After-Hours Program records (including quality assurance data) for all 4 years of operation were retrospectively reviewed, tabulated, and analyzed. The results of two subscribing physician surveys and one parent caller satisfaction survey are presented. A retrospective review of after-hours patient care encounter forms assessed the necessity for after-hours visits triaged by the AHP. An analysis of the total cost of this program to 10 randomly selected subscribing physicians was conducted using current AHP data and a survey of the 10 physicians. RESULTS: In 4 years, 107,938 calls have been successfully managed without an adverse clinical outcome. Minor errors in using protocols occurred in one call out of 1450 after-hours calls. After-hours phoen calls necessitated an after-hours patient visit 20% of the time and generated one after-hours hospital admission out of every 88 calls. Just over half of the patients were managed with home care advice only, and 28% were given home care advice after-hours and seen the next day in the primary physician's office. Of all patients directed by the telephone triage nurses to be seen after hours, 78% were determined to have a condition necessitating after-hours care. Data are presented regarding call volumes by time of day, day of week, patient age, and patient's initial complaint. The 6 most common complaints accounted for more than one half of the calls, and 38 complaints accounted for more than 95% of all after-hours calls. Utilization by subscribing physicians is described. Satisfaction among subscribing pediatricians was 100%, and among parents was 96% to 99% on a variety of issues. The total cost to participating Denver pediatricians (which includes revenues "given up" as a result of not seeing patients after hours) ranged from 1% to 12% of their annual net income, depending on a variety of factors. CONCLUSIONS: Large-scale after-hours telephone coverage systems can be effective and well-received by patients, parents, and primary physicians. Data presented in this report can assist in planning the training of personnel who provide after-hours telephone advice and triage. Controversies associated with this type of program are discussed. Suggestions are made regarding the direction of future programs and research.     

Choroidal neovascular membrane in Best's vitelliform macular dystrophy

The right eye of a 9-year-old white boy with Best's vitelliform macular dystrophy had an intact egg-yolk lesion and a retinal pigment epithelial defect superiorly, suggesting an early pseudohypopyon stage. The disruptive phase of the left eye showed subretinal hemorrhages, a "signet ring," and a subretinal neovascular membrane.     

Laparoscopic adrenalectomy for nonmalignant disease: improved safety, morbidity, and cost-effectiveness

The genetic diversity displayed by Plasmodiumfalciparum field isolates, the occurrence of variant forms of the parasite at different frequencies in different geographic areas, and the complexity of the infections represent major obstacles for the development of effective malaria control measures. However, since most of the existing studies have been performed in regions where P. falciparum transmission is high, little is known about the diversity and complexity of parasite populations circulating in areas of low malaria endemicity. We investigated the extent of genetic polymorphism in P. falciparum field isolates from Honduras, a region where its transmission is low and seasonal. Allelic diversity was analyzed in the highly polymorphic parasite genes encoding the merozoite surface proteins- (MSP-1) and -2 (MSP-2) and the glutamate-rich protein (GLURP) by the polymerase chain reaction. Gene polymorphism was also assessed in the EB200 region derived from the highly size polymorphic Pf332 gene. Limited size polymorphism was detected in all genes analyzed, with four and three variants for the MSP-1 and MSP-2 alleles, respectively, and two size variants for the GLURP and Pf332 genes. Moreover, based on the studied genetic markers, most infections consisted of only a few genetically distinct parasite clones. These results suggest that the P. falciparum parasite populations circulating in this region are genetically homogeneous and point to an association between the extent of parasite genetic diversity and the intensity of malaria transmission.     

Localization and dynamic regulation of biogenic amine transporters in the mammalian central nervous system

The monoamines, serotonin, dopamine, norepinephrine, epinephrine and histamine, play a critical role in the function of the hypothalamic-pituitary-adrenal axis and in the integration of information in sensory, limbic, and motor systems. The primary mechanism for termination of monoaminergic neurotransmission is through reuptake of released neurotransmitter by Na+, CI-dependent plasma membrane transporters. A second family of transporters packages monoamines into synaptic and secretory vesicles by exchange of protons. Identification of those cells which express these two families of neurotransmitter transporters is an initial step in understanding what adaptive strategies cells expressing monoamine transporters use to establish the appropriate level of transport activity and thus attain the appropriate efficiency of monoamine storage and clearance. The most recent advances in this field have yielded several surprises about their function, cellular and subcellular localization, and regulation, suggesting that these molecules are not static and most likely are the most important determinants of extracellular levels of monoamines. Here, information on the localization of mRNAs for these transporters in rodent and human brain is summarized along with immunohistochemical information at the light and electron microscopic levels. Regulation of transporters at the mRNA level by manipulation in rodents and differences in transporter site densities by tomographic techniques as an index of regulation in human disease and addictive states are also reviewed. These studies have highlighted the presence of monoamine neurotransmitter transporters in neurons but not in glia in situ. The norepinephrine transporter is present in all cells which are both tyrosine hydroxylase (TH)- and dopamine beta-hydroxylase-positive but not in those cells which are TH- and phenyl-N-methyltransferase-positive, suggesting that epinephrine cells may have their own, unique transporter. In most dopaminergic cells, dopamine transporter mRNA completely overlaps with TH mRNA-positive neurons. However, there are areas in which there is a lack of one to one correspondence. The serotonin transporter (5-HTT) mRNA is found in all raphe nuclei and in the hypothalamic dorsomedial nucleus where the 5-HTT mRNA is dramatically reduced following immobilization stress. The vesicular monoamine transporter 2 (VMAT2) is present in all monoaminergic neurons including epinephrine- and histamine-synthesizing cells. Immunohistochemistry demonstrates that the plasma membrane transporters are present along axons, soma, and dendrites. Subcellular localization of DAT by electron microscopy suggests that these transporters are not at the synaptic density but are confined to perisynaptic areas, implying that dopamine diffuses away from the synapse and that contribution of diffusion to dopamine signalling may vary between brain regions. Interestingly, the presence of VMAT2 in vesicles underlying dendrites, axons, and soma suggests that monoamines may be released at these cellular domains. An understanding of the regulation of transporter function may have important therapeutic consequences for neuroendocrine function in stress and psychiatric disorders.     

Common pediatric esophageal disorders

Esophageal disorders in children can result in significant morbidity. The most common esophageal disorder seen in children is gastroesophageal reflux. Other common disorders affecting the esophagus include peptic esophageal strictures, esophageal atresia with or without tracheoesophageal fistula, caustic and foreign body ingestions, achalasia, and cricopharyngeal achalasia. We discuss what is currently known about these common pediatric esophageal disorders with regard to pathophysiology, clinical presentation, and diagnostic and treatment strategies.