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1.
JBJS Case Connect ; 14(2)2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38870326

ABSTRACT

CASE: We present a 64-year-old woman with loss of lumbar lordosis with a preoperative computed tomography scan demonstrating the presence of an intrapelvic kidney with aberrant vasculature. A 2-level anterior lumbar interbody fusion with a 2-level oblique interbody fusion was planned. An anterior approach was successfully used to access the anterior spine without damaging the pelvic kidney. CONCLUSION: Anatomic variations, both congenital and acquired, can pose significant challenges to surgeons during their dissection. We present a case where multilevel anterior interbody cage placement can be safely performed, even in a patient whose anatomy is complicated by an intrapelvic kidney.


Subject(s)
Lumbar Vertebrae , Spinal Fusion , Humans , Spinal Fusion/methods , Female , Middle Aged , Lumbar Vertebrae/surgery , Lumbar Vertebrae/diagnostic imaging , Kidney/diagnostic imaging , Kidney/abnormalities , Kidney/surgery , Tomography, X-Ray Computed
2.
Neurogastroenterol Motil ; 35(5): e14548, 2023 05.
Article in English | MEDLINE | ID: mdl-36942766

ABSTRACT

BACKGROUND: Gulf War Illness (GWI) is a chronic, multi-symptom disorder affecting 25%-32% of Gulf War veterans. Veterans with GWI disproportionately suffer from gastrointestinal (GI) disorders. Given the increasing evidence supporting a gut-brain axis, we explore the relationship between post-traumatic stress disorder (PTSD), GWI, and self-reported GI disorders among GW veterans. METHODS: Veterans from the Gulf War Era Cohort and Biorepository responded to a mail-based survey (N = 1058). They were stratified by GWI (Centers for Disease Control definition) and PTSD status. This yielded three groups: GWI-, GWI+/PTSD-, and GWI+/PTSD+. Multivariable logistic regression adjusting for demographic and military characteristics examined associations between GWI/PTSD groups and GI disorders. Results were expressed as adjusted odds ratios (aOR) with 95% confidence intervals (95% CI). KEY RESULTS: The most frequently reported GI disorders were irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), and colon polyps (CP). The GWI+/PTSD+ group had a higher odds of these disorders than the GWI+/PTSD- group (aORIBS  = 3.12, 95% CI: 1.93-5.05; aORGERD  = 2.04, 95% CI: 1.44-2.90; aORCP  = 1.85, 95% CI: 1.23-2.80), which had a higher odds of these disorders than the GWI- group (aORIBS  = 4.38, 95% CI: 1.55-12.36; aORGERD  = 2.51 95% CI: 1.63-3.87; aORCP  = 2.57, 95% CI: 1.53-4.32). CONCLUSIONS & INFERENCES: GW veterans with GWI and PTSD have significantly higher odds of specific self-reported GI disorders than the other groups. Given the known bidirectional influences of the gut and brain, these veterans may benefit from a holistic healthcare approach that considers biopsychosocial contributors to the assessment and management of disease.


Subject(s)
Gastroesophageal Reflux , Gastrointestinal Diseases , Irritable Bowel Syndrome , Persian Gulf Syndrome , Stress Disorders, Post-Traumatic , Veterans , Humans , Veterans/psychology , Self Report , Gulf War
3.
Sci Adv ; 6(31): eabb3379, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32832690

ABSTRACT

The ongoing conservation treatment program of the Ghent Altarpiece by Hubert and Jan Van Eyck, one of the iconic paintings of the west, has revealed that the designs of the paintings were changed several times, first by the original artists, and then during later restorations. The central motif, The Lamb of God, representing Christ, plays an essential iconographic role, and its depiction is important. Because of the prevalence of lead white, it was not possible to visualize the Van Eycks' original underdrawing of the Lamb, their design changes, and the overpaint by later restorers with a single spectral imaging modality. However, by using elemental (x-ray fluorescence) and molecular (infrared reflectance) imaging spectroscopies, followed by analysis of the resulting data cubes, the necessary chemical contrast could be achieved. In this way, the two complementary modalities provided a more complete picture of the development and changes made to the Lamb.

4.
Child Abuse Negl ; 101: 104306, 2020 03.
Article in English | MEDLINE | ID: mdl-32004822

ABSTRACT

BACKGROUND: Parental criminal justice system (CJS) involvement is a marker for child protective services (CPS) involvement. OBJECTIVE: To document how parental criminal case processing affects children's CPS involvement. PARTICIPANTS AND SETTING: Participants included mothers and fathers with a serious criminal charge (mothers = 78,882; fathers = 165,070) and without any criminal charge (mothers = 962,963; fathers = 743,604) between 2008-2012. Statewide North Carolina records on court proceedings, births, CPS assessments/investigations, and foster care placements were used. METHODS: The observational unit was an individual's first charge date of a year. Outcomes were CPS assessment/investigation and foster care entry within six months and alternatively three years following the charge. Key explanatory variables were whether the charges resulted in prosecution, conviction following prosecution, and an active sentence conditional on conviction. An instrumental variables approach was used. RESULTS: Parents charged with a criminal offense had higher rates of having a CPS assessment/investigation during the three years preceding the charge than parents who were not charged. Among mothers who were convicted, CPS assessment/investigation increased 8.1 percent (95 % CI: 2.2, 13.9) and 9.5 percent (95 % CI: 1.3, 17.6) 6 months and 3 years following the charge. An active sentence increased CPS assessment/investigations by 21.6 percent (95 % CI: 6.4, 36.7) within 6 months. For fathers, active sentence increased foster care placement by 1.6 percent (95 % CI: 0.24, 2.9) within 6 months of the criminal charge. CONCLUSIONS: Changing parental incarceration rates would change CPS caseloads substantially. The criminal justice and CPS systems work with overlapping populations, data and services sharing should be considered a high priority.


Subject(s)
Child Protective Services/statistics & numerical data , Criminal Law/statistics & numerical data , Fathers/legislation & jurisprudence , Mothers/legislation & jurisprudence , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , North Carolina
5.
Aliment Pharmacol Ther ; 47(2): 268-278, 2018 01.
Article in English | MEDLINE | ID: mdl-29115682

ABSTRACT

BACKGROUND: With its increasing incidence, nonalcoholic fatty liver disease (NAFLD) is of particular concern in the Veterans Health Administration (VHA). AIMS: To evaluate risk factors for advanced fibrosis in biopsy-proven NAFLD in the VHA, to identify patients at risk for adverse outcomes. METHODS: In randomly selected cases from VHA databases (2005-2015), we performed a retrospective case-control study in adults with biopsy-defined NAFLD or normal liver. RESULTS: Of 2091 patients reviewed, 399 met inclusion criteria. Normal controls (n = 65) had normal liver function. The four NAFLD cohorts included: NAFL steatosis (n = 76), nonalcoholic steatohepatitis (NASH) without fibrosis (n = 68), NAFLD/NASH stage 1-3 fibrosis (n = 82), and NAFLD/NASH cirrhosis (n = 70). NAFLD with hepatocellular carcinoma (HCC) was separately identified (n = 38). Most patients were older White men. NAFLD patients with any fibrosis were on average severely obese (BMI>35 kg/m2 ). Diabetes (54.4%-79.6%) and hypertension (85.8%-100%) were more common in NAFLD with fibrosis or HCC. Across NAFLD, 12.3%-19.5% were enrolled in diet/exercise programs and 0%-2.6% had bariatric surgery. Hispanics exhibited higher rates of NASH (20.6%), while Blacks had low NAFLD rates (1.4%-11.8%), particularly NAFLD cirrhosis and HCC (1.4%-2.6%). Diabetes (OR 11.8, P < .001) and BMI (OR 1.4, P < .001) were the most significant predictors of advanced fibrosis. CONCLUSIONS: In the VHA, diabetes and severe obesity increased risk for advanced fibrosis in NAFLD. Of these patients, only a small proportion (~20%) had enrolled in diet/exercise programs or had bariatric surgery (~2%). These results suggest that providers should focus/tailor interventions to improve outcomes, particularly in those with diabetes and severe obesity.


Subject(s)
Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/pathology , Veterans/statistics & numerical data , Adult , Aged , Biopsy/methods , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/epidemiology , Case-Control Studies , Disease Progression , Female , Humans , Liver Cirrhosis/epidemiology , Liver Cirrhosis/etiology , Liver Cirrhosis/pathology , Liver Neoplasms/complications , Liver Neoplasms/epidemiology , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/complications , Retrospective Studies , Risk Factors , Severity of Illness Index , United States/epidemiology , United States Department of Veterans Affairs , Veterans Health
6.
AJNR Am J Neuroradiol ; 31(8): 1541-8, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20538827

ABSTRACT

BACKGROUND AND PURPOSE: PTA effectively treats vasospasm and arterial disease in peripheral, coronary, and large proximal cerebral vessels but rarely reaches small vessels like the distal MCA beyond the bifurcation. Our purpose was to evaluate the safety and efficacy of PTA for distal MCA occlusions in acute ischemic stroke. MATERIALS AND METHODS: Seven patients had strokes in branches of their MCAs. Following diagnostic angiography, all received microballoon angioplasty and various combinations of IA alteplase (rtPA), abciximab, and/or nitroglycerin. Two also underwent stent placement. Comprehensive retrospective review of the patients' records was performed. Patients' NIHSS scores were reassessed before discharge. Recanalization was evaluated by angiography after treatment and at follow-up. RESULTS: PTA was successfully performed in 7 patients without treatment-associated intracerebral hemorrhage. Two patients received distal MCA angioplasty as a secondary intervention: 1 following failed treatment with a Merci retriever and the other after successful removal of proximal clot with a Merci retriever. One patient did not recover from the initial ischemic event despite an excellent angiographic result. Complete recanalization (modified TIMI grade 4) was achieved in 4 patients and near-complete recanalization with mild flow deficit (modified TIMI grade 3), in 3 patients. CONCLUSIONS: PTA of the distal MCA with a microballoon is safe and effective for acute ischemic stroke. This case series demonstrates that endovascular treatment beyond the MCA bifurcation can dramatically reverse neurologic deficits.


Subject(s)
Angioplasty, Balloon/methods , Brain Ischemia/therapy , Cerebral Revascularization/methods , Infarction, Middle Cerebral Artery/therapy , Acute Disease , Adult , Aged , Aged, 80 and over , Brain Ischemia/diagnostic imaging , Cerebral Angiography , Female , Follow-Up Studies , Humans , Infarction, Middle Cerebral Artery/diagnostic imaging , Male , Middle Aged , Retrospective Studies , Stents
7.
Hum Mol Genet ; 14(16): 2323-33, 2005 Aug 15.
Article in English | MEDLINE | ID: mdl-16000322

ABSTRACT

Mutations in the human ALMS1 gene cause Alström syndrome (AS), a progressive disease characterized by neurosensory deficits and by metabolic defects including childhood obesity, hyperinsulinemia and Type 2 diabetes. Other features that are more variable in expressivity include dilated cardiomyopathy, hypertriglyceridemia, hypercholesterolemia, scoliosis, developmental delay and pulmonary and urological dysfunctions. ALMS1 encodes a ubiquitously expressed protein of unknown function. To obtain an animal model in which the etiology of the observed pathologies could be further studied, we generated a mouse model using an Alms1 gene-trapped ES cell line. Alms1-/- mice develop features similar to patients with AS, including obesity, hypogonadism, hyperinsulinemia, retinal dysfunction and late-onset hearing loss. Insulin resistance and increased body weight are apparent between 8 and 12 weeks of age, with hyperglycemia manifesting at approximately 16 weeks of age. In addition, Alms1-/- mice have normal hearing until 8 months of age, after which they display abnormal auditory brainstem responses. Diminished cone ERG b-wave response is observed early, followed by the degeneration of photoreceptor cells. Electron microscopy revealed accumulation of intracellular vesicles in the inner segments of photoreceptors, whereas immunohistochemical analysis showed mislocalization of rhodopsin to the outer nuclear layer. These findings suggest that ALMS1 has a role in intracellular trafficking.


Subject(s)
Diabetes Mellitus, Type 2/genetics , Disease Models, Animal , Nerve Degeneration/genetics , Obesity/genetics , Proteins/physiology , Retinal Degeneration/genetics , Animals , Cell Cycle Proteins , Electroretinography , Female , Hearing Loss/genetics , Humans , Hyperinsulinism/genetics , Insulin Resistance/genetics , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Protein Transport/genetics , Proteins/genetics , Sequence Homology, Amino Acid , Syndrome
9.
Comput Chem ; 24(3-4): 421-7, 2000 May.
Article in English | MEDLINE | ID: mdl-10816012

ABSTRACT

In our continuing efforts to provide a predictive toxicology capability, we seek to improve QSARs (quantitative structure-activity relationships) for chemicals of interest. Currently, although semi-empirical molecular orbital methods are hardly the state of the art for studying small molecules, AM1 calculations appear to be the method of choice when calculating quantum-chemical descriptors. However, with the advent of modern computational capabilities and the development of fast algorithms, ab initio molecular orbital and first principles density functional methods can be expeditiously applied in current QSAR studies. We present a study on halogenated alkanes to assess whether more accurate quantum methods result in QSARs that correlate better with experimental data. Furthermore, improved QSARs can also be obtained through development of new descriptors with explicit physical interpretations that should lead to better understanding of the mechanisms involved in the toxic response. We show that descriptors calculated from chemical intermediates may be useful in future QSARs.


Subject(s)
Hydrocarbons, Halogenated/chemistry , Hydrocarbons, Halogenated/toxicity , Computer Simulation , Models, Molecular , Predictive Value of Tests , Structure-Activity Relationship
11.
Hematol J ; 1(4): 235-42, 2000.
Article in English | MEDLINE | ID: mdl-11920196

ABSTRACT

INTRODUCTION: Spectrin, a heterodimer of alpha- and beta-subunits, is the major protein component of the red blood cell membrane skeleton. The mouse mutation, sph, causes an alpha-spectrin-deficient hereditary spherocytosis with the severe phenotype typical of recessive hereditary spherocytosis in humans. The sph mutation maps to the erythroid alpha-spectrin locus, Spna1, on Chromosome 1. MATERIALS AND METHODS: Scanning electron microscopy, osmotic gradient ektacytometry, cDNA cloning, RT-PCR, nucleic acid sequencing, and Northern blot analyses were used to characterize the wild type and sph alleles of the Spna1 locus. RESULTS: Our results confirm the spherocytic nature of sph/sph red blood cells and document a mild spherocytic transition in the +/sph heterozygotes. Sequencing of the full length coding region of the Spna1 wild type allele from the C57BL/6J strain of mice reveals a 2414 residue deduced amino acid sequence that shows the typical 106-amino-acid repeat structure previously described for other members of the spectrin protein family. Sequence analysis of RT-PCR clones from sph/sph alpha-spectrin mRNA identified a single base deletion in repeat 5 that would cause a frame shift and premature termination of the protein. This deletion was confirmed in sph/sph genomic DNA. Northern blot analyses of the distribution of Spna1 mRNA in non-erythroid tissues detects the expression of 8, 2.5 and 2.0 kb transcripts in adult heart. CONCLUSION: These results predict the heart as an additional site where alpha-spectrin mutations may produce a phenotype and raise the possibility that a novel functional class of small alpha-spectrin isoforms may exist.


Subject(s)
Frameshift Mutation , Spectrin/genetics , Spherocytosis, Hereditary/genetics , Alleles , Amino Acid Sequence , Animals , Base Sequence , DNA, Complementary/genetics , Genotype , Mice , Mice, Inbred C57BL , Mice, Mutant Strains , Molecular Sequence Data , Myocardium/chemistry , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction , Sequence Deletion , Spectrin/chemistry , Spectrin/deficiency , Spectrin/physiology , Structure-Activity Relationship
12.
Ostomy Wound Manage ; 45(10): 41, 44-6, 48-49, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10687651

ABSTRACT

Stage II and III pressure ulcers present product development and product choice challenges to manufacturers and professional wound care clinicians respectively. We evaluated the clinical performance and cost of use associated with a new synthetic polymer dressing for the management of these wounds. A total of 10 home healthcare patients, each with a Stage II or III pressure ulcer, were enrolled and randomized for wound treatment using either the new polymer hydrogel wound dressing or the leading market hydrocolloid dressing. Dressings were changed on an as needed basis only. The wounds were assessed weekly and parameters recorded using the Bates-Jensen Pressure Sore Status Tool. In addition, the clinical performance of the dressing and treatment costs were evaluated. The overall healing rate for the two groups was similar. However the new polymer hydrogel dressing was found to have a more favorable overall clinical performance evaluation based largely on its more favorable support of autolytic debridement. The new polymeric dressing also had a more favorable cost of use based on the evaluation. We conclude that the new polymer dressing may be a favorable alternative to the leading market hydrocolloid dressing for the treatment of Stage II and III pressure ulcers due to a better clinical performance and the substantially lower treatment costs associated with its use.


Subject(s)
Bandages/economics , Bandages/standards , Hydrogel, Polyethylene Glycol Dimethacrylate/economics , Hydrogel, Polyethylene Glycol Dimethacrylate/therapeutic use , Polymers/economics , Polymers/therapeutic use , Pressure Ulcer/nursing , Adult , Aged , Autolysis , Cost-Benefit Analysis , Debridement/methods , Exudates and Transudates , Female , Humans , Humidity , Male , Middle Aged , Pilot Projects , Pressure Ulcer/classification , Pressure Ulcer/physiopathology , Severity of Illness Index , Treatment Outcome , Wound Healing
13.
Genomics ; 50(1): 79-88, 1998 May 15.
Article in English | MEDLINE | ID: mdl-9628825

ABSTRACT

Mouse erythroid ankyrin is encoded by the Ank1 gene on Chromosome 8. The best studied isoform is 210 kDa and contains three large functional domains. We have recently reported a small Ank1 isoform (relative mobility 25 kDa) that localizes to the M and Z lines in skeletal muscle. Analyses of cDNA and genomic clones show that three transcripts of 3.5, 2.0, and 1.6 kb code for this protein. The different transcript sizes are due to their 3'-untranslated regions. They are encoded by a new first exon located in intron 39 of the Ank1 gene and three previously described Ank1 exons (40, 41, and 42). The 5'-flanking region contains a putative muscle-specific promoter. The sequence of the first 72 amino acids is novel and is predicted to form a transmembrane helix at the NH2-terminus. Functional testing of the putative transmembrane segment indicates that it acts as a membrane anchor, suggesting that the new Ank1 isoform may play an important role in organizing the contractile apparatus within the cell.


Subject(s)
Alternative Splicing/genetics , Ankyrins/genetics , Erythrocyte Membrane/chemistry , Exons/genetics , Peptide Fragments/genetics , Alleles , Amino Acid Sequence , Animals , Ankyrins/biosynthesis , Ankyrins/physiology , Base Sequence , Cloning, Molecular , DNA, Complementary/isolation & purification , Immunoblotting , Mice , Mice, Inbred C57BL , Molecular Sequence Data , Muscle, Skeletal/chemistry , Organ Specificity/genetics , Peptide Fragments/biosynthesis , Peptide Fragments/physiology , Promoter Regions, Genetic/genetics , Protein Isoforms/biosynthesis , Protein Isoforms/genetics , Protein Isoforms/physiology , Transcription, Genetic
14.
Behav Anal ; 21(2): 253-79, 1998.
Article in English | MEDLINE | ID: mdl-22478311

ABSTRACT

The present paper examines the relationship between the development of moral behavior and the development of verbal regulatory processes. Relational frame theory and the distinctions among pliance, tracking, and augmenting forms of rule governance are applied to the domain of moral behavior and its development, in order to identify the specific social and verbal contingencies that are responsible for an evolving moral repertoire. It is argued that moral behavior is controlled by relational and rule-following repertoires, and that these can be arranged into a rough progression: pliance, tracking, augmenting, social concern for pliance, social concern for tracking, and social concern for augmenting. Congruence with data derived from other research traditions is examined, and applied implications are explored.

15.
J Behav Ther Exp Psychiatry ; 28(1): 53-63, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9110239

ABSTRACT

The issue of cognition has often been divisive among behavior therapists. Typically the debate has centered around the causal status of cognition. Cognitive psychologists have argued for the causal efficacy of cognition, while behavior analysts have argued against it. These disputes are not entirely empirical matters. In part, they reflect irreconcilable differences at the level of theory and philosophy. Such differences may make theoretical integration impossible. However, in this paper we examine the potential for reconciliation of the cognitive and behavioral wings of behavior therapy when the issue of cognition is approached as a shared content area, rather than at the level of theory and philosophy. Behavior therapy has always been comprised of very diverse theoretical positions. Historically they found common ground around a set of shared values centered on an empirical science of clinical work. We will argue that this core of shared values still exists, and that even controversial topics can provide an arena for reconciliation when we focus on the core values that initially brought us together.


Subject(s)
Behavior Therapy , Behaviorism , Cognitive Science , Behavior Therapy/methods , Behavior Therapy/standards , Causality , Cognitive Behavioral Therapy/methods , Cognitive Behavioral Therapy/standards , Humans , Treatment Outcome , Verbal Behavior
16.
J Consult Clin Psychol ; 64(6): 1152-68, 1996 Dec.
Article in English | MEDLINE | ID: mdl-8991302

ABSTRACT

Syndromal classification is a well-developed diagnostic system but has failed to deliver on its promise of the identification of functional pathological processes. Functional analysis is tightly connected to treatment but has failed to develop testable, replicable classification systems. Functional diagnostic dimensions are suggested as a way to develop the functional classification approach, and experiential avoidance is described as 1 such dimension. A wide range of research is reviewed showing that many forms of psychopathology can be conceptualized as unhealthy efforts to escape and avoid emotions, thoughts, memories, and other private experiences. It is argued that experiential avoidance, as a functional diagnostic dimension, has the potential to integrate the efforts and findings of researchers from a wide variety of theoretical paradigms, research interests, and clinical domains and to lead to testable new approaches to the analysis and treatment of behavioral disorders.


Subject(s)
Mental Disorders/diagnosis , Mental Disorders/therapy , Adaptation, Psychological , Agoraphobia/complications , Agoraphobia/psychology , Child , Child Abuse, Sexual/psychology , Child, Preschool , Cognitive Behavioral Therapy , Humans , Panic Disorder/complications , Panic Disorder/prevention & control , Psychiatric Status Rating Scales , Substance-Related Disorders , Suicide
17.
Xenobiotica ; 25(8): 825-46, 1995 Aug.
Article in English | MEDLINE | ID: mdl-8779224

ABSTRACT

Over a broad range of tertiary N-methyl amines, whenever alkyl-nitrogen bond cleavage was observed, N-demethylation was also observed. Alkyl-nitrogen bond cleavage in rings, alkyl-nitrogen bond cleavage if the carbon of the N-dealkylation reaction-site is in a ring and the nitrogen atom of the reaction-site is not in a ring, and dedimethylamination are not likely to occur relative to N-demethylation. Structure-reactivity relationships for other N-dealkylations, such as N-debenzylation, N-dethiophenation, and N-dedimethylaminoethylation of tertiary amines were evident from a visual inspection of the structure-reactivity map. Structure-reactivity maps proved to be a useful tool for ascertaining structural environments influencing the relative occurrence of alkyl-nitrogen bond cleavage in tertiary N-methyl amines.


Subject(s)
Methylamines/chemistry , Methylamines/metabolism , Models, Chemical , Biotransformation , Molecular Structure , Structure-Activity Relationship
18.
IEEE Trans Image Process ; 4(8): 1061-9, 1995.
Article in English | MEDLINE | ID: mdl-18292000

ABSTRACT

A predictive image coder having minimal decoder complexity is presented. The image coder utilizes recursive interpolative DPCM in conjunction with adaptive classification, entropy-constrained trellis coded quantization, and optimal rate allocation to obtain signal-to-noise ratios (SNRs) in the range of those provided by the most advanced transform coders.

19.
SAR QSAR Environ Res ; 2(1-2): 105-27, 1994.
Article in English | MEDLINE | ID: mdl-8790642

ABSTRACT

The relative occurrence of N-demethylation and N-oxidation in a structurally diverse set of N-methyl tertiary amines was examined using structure-reactivity maps. A structure-reactivity map of the data indicated important structural features useful for predicting the relative occurrence of these reactions. A steric index which describes the degree of steric hinderance at the N-methyl reaction site is defined. A QSAR between the relative occurrence of N-demethylation and N-oxidation of N-methyl tertiary amines and the steric index was developed.


Subject(s)
Xenobiotics/metabolism , Animals , Biotransformation , Humans , Linear Models , Methylation , Microsomes/metabolism , Models, Chemical , Models, Molecular , Oxidation-Reduction , Rats , Structure-Activity Relationship , Xenobiotics/chemistry
20.
J Chem Inf Comput Sci ; 32(6): 591-9, 1992.
Article in English | MEDLINE | ID: mdl-1474108

ABSTRACT

Structure maps are presented as an efficient means of indicating structure-reactivity relationships in metabolic pathway databases. The relative occurrence of N-demethylation and N-oxidation of N-methyl tertiary amines was examined using the structure map methodology. A new family of reaction site representations, the n-level representations, was developed to describe the N-methyl reaction sites of the compounds in the data set. It was possible to differentiate N-demethylation and N-oxidation reaction sites using a structure map constructed from a 3-level representation of the reaction sites.


Subject(s)
Xenobiotics/pharmacokinetics , Binding Sites , Biotransformation , Computers , Databases, Factual , Structure-Activity Relationship , Xenobiotics/chemistry , Xenobiotics/metabolism
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