DOES LIVER DYSFUNCTION EXPLAIN NEUROPSYCHOLOGICAL STATUS IN RECENTLY DETOXIFIED ALCOHOL-DEPENDENT CLIENTS?

In the search for explanation of persistent cognitive impairmentassociated with alcohol dependence, the possible role of liverdisease has aroused considerable interest. However, review ofthe relevant literature provides only ambiguous support forany general relationship between neuropsycho-logical statusand laboratory tests of liver function. We tested the generalhypothesis, and also two specific hypotheses relating particularliver function parameters (     

Delta opioid receptor selective ligands; DPLPE-deltorphin chimeric peptide analogues†

Further efforts to correlate the topography of the bioactive structures of DPDPE and the deltorphins, two δ-opioid receptor active peptide families, are reported. A number of DPLPE-deltorphin chimeric peptides have been synthesized in which the C-terminal dipeptide δ-address of the deltorphins (-Val-GlyNH₂, -Nle-GlyNH₂) have been linked to the highly δ-opioid selective cyclic peptides DPDPE or DPLPE. These studies demonstrate that a major structural feature determining high potency of hybrid analogues is the chirality of the amino acid residue in position 5. The radioligand binding assays have revealed a decrease in potency (compared to DPDPE) at §-receptors when the C-terminal dipeptides were added to DPDPE. On the other hand, chimeric peptides of DPLPE with these same C-terminal dipeptides retained high δ-selectivity and affinity. Similar results were obtained using the mouse vas deferens (MVD) and guinea pig ileum (GPI) bioassays. The importance of the hydrophilicity of amino acids in positions 2 and 5 for δ-selectivity is consistent with the previous finding for DPLPE and DPDPE. On the other hand, the replacement of phenylalanine-4 with p-chlorophenylalanine-4 did not increase δ-selectivity as in DPDPE. These findings suggest that the δ-receptor interacts with hybridized enkephalins and deltorphins somewhat differently than with DPDPE.     

Covalent Binding of Inhaled Formaldehyde to DNA in the Nasal Mucosa of Fischer 344 Rats: Analysis of Formaldehyde and DNA by High-Performance Liquid Chromatography and Provisional Pharmacokinetic Interpretation

Covalent Binding of Inhaled Formaldehyde to DNA in the NasalMucosa of Fischer 344 Rats: Analysis of Formaldehyde and DNAby High-Performance Liquid Chromatography and Provisional PharmacokineticInterpretation. CASANOVA, M., DEYO, D. F., AND HECK, H. D'A.(1989). Fundam Appl. Toxicol. 12, 397–417. Inhalationof ³HCHO and H¹⁴CHO(6 ppm, 6 hr) resulted in the formation ofDNA-protein crosslinks in the rat nasal respiratory mucosa.The DNA was extracted and was fractionated into aqueous (AQ)and interfacial (IF) portions. AQ DNA and IF DNA were enzymaticallyhydrolyzed to deoxyribonucleosides in Tris buffer and analyzedby HPLC with liquid scintillation counting (LSC). HCHO was boundexclusively to the IF DNA, indicating that the HCHO was boundas DNA-protein crosslinks. Hydrolysis of the DNA quantitativelyreleased the HCHO; no evidence was obtained for the formationof hydroxymethyl adducts. An adduct detected previously followingincubation of mammalian cells with HCHO, N⁶-hydroxymethyldeoxyadenosine(hm6dA)[Beland F. A., Fullerton, N. F., and Heflich, R. H. (1984) J.Chromartogr. 308 121–131], was shown to be produced byreaction of HCHO with deoxyadenosine (dA) in bis-Tris bufferunder conditions similar to those used for hydrolysis of theDNA. This reaction does not occur in Tris buffer. Evidence wasobtained that most or all of the hm6dA observed can be explainedby this reaction. Based on these results, an improved methodto determine the amount of H¹⁴CHO bound to DNA was developed:the DNA is hydrolyzed in Tris buffer and analyzed by HPLC, andthe released H¹⁴CHO is derivatized with dimedone and quantitatedby LSC. Rats were exposed to a wide range of H¹⁴CHO concentrations(0.3, 0.7, 2, 6, or 10 ppm; 6 hr). DNA-protein crosslinkingoccurred at all concentrations. The formation of crosslinkswas interpreted in terms of a nonlinear pharmacokinetic modelincorporating oxidation of inhaled HCHO as a defense mechanism.The slope of the fitted concentration-response curve at 10 ppmis 7.3-fold greater than at 0.3 ppm, and the fitted detoxicationpathway is half-saturated at an airborne concentration of 2.6ppm.     

Modification of the Phe3 aromatic moiety in delta receptor-selective dermorphin/deltorphin-related tetrapeptides Effects on opioid receptor binding

The previously described cyclic delta opioid receptor-selective tetrapeptide H-Tyr-d -Cys-Phe-d -Pen-OH (JOM-13) was modified at residue 3 by incorporation of both natural and unnatural amino acids with varying steric, electronic, and lipophilic properties. Effects on mu and delta opioid receptor binding affinities were evaluated by testing the compounds for displacement of radiolabeled receptor-selective ligands in a guinea pig brain receptor binding assay. Results obtained with the bulky aromatic 1-Nal³ and 2-Nal³ substitutions suggest that the shape of the receptor subsite with which the side chain of the internal aromatic residue interacts differs for delta and mu receptors. This subsite of either receptor can accommodate the transverse steric bulk of the 1-Nal³ side chain but only the delta receptor can readily accept the more elongated 2-Nal³ side chain. Several analogs with pi-excessive heteroaromatic side chains in residue 3 were examined. In general, these analogs display diminished binding to mu and delta receptors, consistent with previous findings for analogs with residue 3 substitutions of modified electronic character. Several analogs with alkyl side chains in residue 3 were also examined. While delta receptor binding affinity is severely diminished with Val³, Ile³, and Leu³ substitutions, Cha³ substitution is very well tolerated, indicating that, contrary to the widely held belief, an aromatic side chain in this portion of the ligand is not required for delta receptor binding. Where possible, comparison of results in this delta-selective tetrapeptide series with those reported for analogous modification in the cyclic delta-selective pentapeptide [d -Pen², d -Pen⁵]enkephalin (DPDPE) and linear pentapeptide enkephalins reveals similar trends.     

Radiofrequency Catheter Ablation of an Atriofascicular Pathway During Atrial Fibrillation:

Atriofascicular Ablation During Fibrillation. Introduction: A male patient with an atriofascicular pathway underwent catheter ablation of the atriofascicular pathway during atrial fibrillation.
Methods and Results: The patient had preexcited atrial fibrillation both clinically and repeatedly during electrophysioiogic study. A preexcited tachycardia with a 1:1 AV relationship and regular RR intervals was also induced. Catheter ablation of the atriofascicular pathway could only be performed during persistent atrial fibrillation, based on mapping of the pathway's insertion into the right bundle branch. Following successful ablation and cardioversion to sinus rhythm, a regular QRS tachycardia (atrioventricular [AV] nodal reentry) having (he same rate, atrial activation sequence, and His-atrial time as the regular preexcited tachycardia noted preablation was initiated. An AV nodal slow pathway modification eliminated this tachycardia. Neither atrial fibrillation nor AV nodal reentry has recurred on follow-up.
Conclusion: This is the first report of atriofascicular mapping and ablation performed exclusively during atrial fibrillation and illustrates the utility of mapping the pathway's ventricular insertion. Other unusual features ("bystander" pathway activation during AV nodal reentry, possible role of the pathway in genesis of atrial fibrillation) are discussed.     

NOTES ON AN ENDEMIC CENTRE OF KALA-AZAR IN THE PROVINCE OF HUPEH, CENTRAL CHINA

While the larger and more important endemic areas of kala-azar are fairly well defined, the actual extent of these areas westwards''and southwards appears to be extremely vague. In a recent article Hoeppli* states "that although kala-azar may exist in West, Central and South China, the important endemic centres so far have all been ~ound north of the Yangtze Valley." The uncertainty of our knowledge of the ex- tent,rbf the fringes of the endemic areas should constitute a challenge to all working in those places to make a determined effort to prove the presence or, if possible, the absence of the disease. In these notes I propose to record experiences gained dunng 1936-37 in the small city of Anlu (old name: Teian-fu) in Hupeh which indicate that in that district the disease occurs with sufficient frequency to constitute an endemic focus of kala-azar in Central China and only a few miles north of the Yangtze Valley. .     

Breastfeedilzg Support Services in the Neonutd Intensive-Care Unit

Objective: To describe a model for providing breastfeeding support in the neonatal intensive-care unit (NICU).
Design: Naturalistic, participant observation.
Setting: Suburban Level III NICU.
Patients: One hundred thirty-two mother-infant pairs over 1 year. Infants were hospitalized In the NICU, and mothers had initiated lactation efforts.
Interventions: Investigators provided breastfeeding interventions for the mother-infant pairs, based on identified problems, the research literature, or both.
Main Outcome Measures: Percentage of mothers who were breastfeeding at the time of discharge from the NICU.
Results: Interventions were classified into jive categories: expression and collection of mothers' milk, gavage feeding of expressed mothers' milk, in-hospital breastfeeding sessions, postdischarge breastfeeding management, and additional consultation.
Conclusions: This model was effective In preventing breastfeeding failure for this population. The model can provide the basis for NICU breastfeeding standards of care, protocols, and chart records, or for reimbursement purposes. The model also provides a framework for studying a specific category or breastfeeding intervention.     

A computerized analysis of intrinsic forces in the skin

The skin of the volar forearm is a site selected for many biometrological studies. We studied the influence of forearm position when evaluating the surface topography and mechanical properties of the skin in normal young adults. Optical profilometry of skin replicas and the suction biomechanical method (Cutometer ®, 2 and 8 mm probes) were used in combination with evaluation of the thickness and sliding mobility of the dermis and dermohypodermal tissues. The dermal and dermohypodermal thicknesses did not correlate with the various profilometric and biomechanical measurements. The surface topography and the axial sliding mobility of the skin were markedly influenced by forearm position, while the only mechanical property of the skin to be affected was skin stretchability assessed with the 2 mm probe. It is concluded that limb position mostly influences biometrological measurements made in the plane of the skin surface, while it has little effect on most of the Cutometer measurements.     

Cross system agreement for substance use disorders: DSM-III-R, DSM-IV and ICD-10

This report presents results of a field trial of Substance Use Disorders as defined by DSM-III-R, DSM-IV (proposed) and ICD-10. Diagnoses based on the three systems were derived from interviews using the Composite International Diagnostic Interview (CIDI) in a heterogeneous sample of 521 adults drawn from clinical and community settings. Two issues are addressed: (1) cross system agreement; and (2) syndrome coherence of proposed criterion sets for Substance Dependence in each of the three systems. Findings were as follows: (1) Cross system agreement for Dependence was generally high, especially between DSM-III-R and DSM-IV. (2) Cross system agreement was lower for DSM-III-R and DSM-IV Abuse and very low for DSM-IV Abuse and ICD-10 Harmful Use. (3) Agreement varied across drug categories with lowest DSM-III-R/DSM-IV agreement for alcohol abuse and DSM-IV/ICD-10 agreement for marijuana use disorders. (4) Overall prevalence differed for the three systems with DSM-IV yielding highest rates followed by DSM-III-R and ICD-10 in that order. (5) Factor analysis of Dependence criteria showed high loadings of all items on a single factor across the three diagnostic systems and for all categories of drugs. Implications for validity of the dependence syndrome construct and for revisions in DSM-IV are discussed.