Impact of age on the severity, course, and complications of alcohol withdrawal

BACKGROUND: Early identification of alcohol-dependent patients at increased risk for severe or complicated alcohol withdrawal would improve triage and treatment. However, the role of age in predicting alcohol withdrawal outcomes has not been well studied. OBJECTIVE: To assess the impact of age on the severity, course, and complications of alcohol withdrawal. METHODS: We performed a retrospective cohort study of 284 inpatients admitted for alcohol withdrawal between September 1992 and August 1994. Outcomes included alcohol withdrawal severity measured by the revised Clinical Institute Withdrawal Assessment for Alcohol scale, quantity and duration of benzodiazepine therapy, and complications during withdrawal. RESULTS: Initial and maximal withdrawal severity scores, amount of benzodiazepine administered, and duration of benzodiazepine treatment for elevated withdrawal severity scores did not change significantly with age. However, patients aged 60 years and older had increased risk for delirium (adjusted odds ratio [OR], 4.7; 95% confidence interval [CI], 1.5-15.0; P = .008), falls (OR, 3.1; 95% CI, 0.9-11.2; P = .08), and transient dependency in 2 or more activities of daily living (OR, 5.8; 95% CI, 2.9-11.7; P < .001). As age increased, there were significant increases in length of stay (P < .001) and frequency of discharge to an extended care facility (P < .001). CONCLUSIONS: Although alcohol withdrawal severity scores and benzodiazepine requirements were similar across age groups, patients aged 60 years and older were at increased risk for cognitive and functional impairment during withdrawal. These findings support recommendations that older patients with alcohol withdrawal are best treated in closely supervised settings.     

Pseudoabscess of the aortic root caused by ectopic seating of an aortic prosthesis

Twenty-one fetuses with an enlarged fourth ventricle were detected by ultrasound at 14-16 weeks' gestation. No other central nervous system anomalies were observed and a normal size fourth ventricle was noted in all cases on follow-up scans at 22-23 weeks' gestation. Five fetuses had associated structural anomalies: a single umbilical artery in two cases, non-septated cystic hygroma in two cases and ventricular septal defect in one fetus. All fetuses had a normal brain sonogram after delivery. Nineteen newborns who were followed up to the age of one year had no developmental problems. It is concluded that an isolated enlarged fourth ventricle might be a physiological variant in early fetal life.     

Teaching and maintaining behavior management skills with nursing assistants in a nursing home

Since the first report of pancreatic endocrine tumors by Wilder et al. in 1927 and the development of radioimmunoassay of gut hormone by Berson and Yallow in 1961, Japanese clinicians and scientists have contributed significantly in the reporting, investigation, and management of patients with pancreatic endocrine tumors and other multiple endocrine neoplasia. This article summarizes our contribution in this field and contrasts our experiences with those reported in the English literature.     

Developmental neurobiology: notch is tops in the developing brain

Signalling through the cell-surface receptor molecule Notch may regulate oligodendrocyte differentiation, and consequently help determine the timing, and perhaps the pattern, of myelination in the developing vertebrate central nervous system.     

Neonatal stress reactivity and cortisol

Existing data point to the fact that adrenocortical responses are, at least in part, valid representatives of the stress response in term and some preterm infants. At the same time, however, there is conflict regarding the use of cortisol levels as a diagnostic tool in the neonatal intensive care unit. The article reviews the concept of neonatal intensive care unit stress and neonatal stress response development and provides a comprehensive literature review of cortisol production in term and preterm neonates. A neonatal stress response model is presented along with implications for caregiving.     

Biomarkers of fetal exposure to alcohol: identification of at-risk pregnancies

Gnathostomiasis is an important food-borne parasitic zoonosis that is endemic mainly in Asian countries where some people prefer to eat raw freshwater fish. In North America, the first recorded case of gnathostomiasis was in Mexico in 1970, and the numbers of gnathostomiasis patients in Mexico seems to be increasing dramatically with time. However, the epidemiology of this disease in Mexico has never been described in detail. Here we review the current status of gnathostomiasis in Mexico.     

Warfarin-fluconazole. II. A metabolically based drug interaction: in vivo studies

Consistent with expectations based on human in vitro microsomal experiments, administration of fluconazole (400 mg/day) for 6 days to six human volunteers significantly reduced the cytochrome P450 (P450)-dependent metabolic clearance of the warfarin enantiomers. In particular, P4502C9 catalyzed 6- and 7-hydroxylation of (S)-warfarin, the pathway primarily responsible for termination of warfarin's anticoagulant effect, was inhibited by approximately 70%. The change in (S)-warfarin pharmacokinetics caused by fluconazole dramatically increased the magnitude and duration of warfarin's hypoprothrombinemic effect. These observations indicate that co-administration of fluconazole and warfarin will result in a clinically significant metabolically based interaction The major P450-dependent, in vivo pathways of (R)-warfarin clearance were also strongly inhibited by fluconazole. 10-Hydroxylation, a metabolic pathway catalyzed exclusively by P4503A4, was inhibited by 45% whereas 6-, 7-, and 8-hydroxylations were inhibited by 61, 73, and 88%, respectively. The potent inhibition of the phenolic metabolites suggests that enzymes other than P4501A2 (weakly inhibited by fluconazole in vitro) are primarily responsible for the formation of these metabolites in vivo as predicted from in vitro kinetic studies. These data suggest that fluconazole can be expected to interact with any drug whose clearance is dominated by P450s 2C9, 3A4, and other as yet undefined isoforms. Overall, the results strongly support the hypothesis that metabolically based in vivo drug interactions may be predicted from human in vitro microsomal data.     

Neoplastic transformation and DNA-binding of 4,4''-methylenebis(2-chloroaniline) in SV40-immortalized human uroepithelial cell lines

1. The effects of cyclopiazonic acid (CPA) and thapsigargin (TG), both of which are known to inhibit sarcoplasmic reticular Ca(2+)-ATPase, on the mechanical activities, intracellular Ca2+ level and electrical activities of smooth muscle of the carotid artery of stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY) were compared. 2. Both CPA and TG induced elevation of tension of the smooth muscle, which was composed of a phasic and a tonic component. The level of tension attained, especially the tonic component, was greater in the preparation from SHRSP. 3. The elevation of tension was associated with an increased intracellular Ca2+ level. Both the elevation of tension and the increase in intracellular Ca2+ were diminished by the removal of extracellular Ca2+ or by the application of verapamil. 4. The resting membrane potential of the preparations from SHRSP were depolarized to a greater extent than those from WKY.CPA depolarized the smooth muscle from both SHRSP and WKY, and the final level was also more depolarized in the preparation from SHRSP. 5. These results indicate that the elevation of tension induced by these drugs is mainly due to increased Ca2+ influx through voltage-dependent Ca2+ channels, and the difference in the action between the preparation from SHRSP and that from WKY can be explained mainly by the changes in the channels. 6. Thus, differences in the action of these drugs on the tension of smooth muscle between preparations from WKY and SHRSP can mainly be explained by the difference in the membrane potential which is related to the difference in voltage-dependent Ca2+ influx.     

Determination of disulfide structure in agouti-related protein (AGRP) by stepwise reduction and alkylation

The agouti-related protein gene (Agrp) plays an important role in body weight regulation. The mature human protein is a single polypeptide chain of 112 amino acid residues, consisting of an N-terminal acidic region and a unique C-terminal cysteine-rich domain. The disulfide structure of recombinant human AGRP was determined by chemical methods using partial reduction with tris(2-carboxyethyl)phosphine under acidic conditions, followed by direct alkylation with N-ethylmaleimide or fluorescein-5-maleimide. Partial reduction and alkylation provided several forms of AGRP that were modified in a stepwise fashion. The resulting proteins were characterized by peptide mapping, sequence analysis, and mass spectrometry, showing that AGRP contained a highly reducible disulfide bond, C85-C109, followed by less reactive ones, C90-C97, C74-C88, C67-C82, and C81-C99, respectively. The chemically defined disulfide connectivity of the recombinant human AGRP was homologous to that of omega-agatoxin IVB except for an additional disulfide bond, C85-C109.     

Functional correction of Fanconi anemia group A hematopoietic cells by retroviral gene transfer

Fanconi anemia (FA) is an autosomal recessive genetic disorder characterized by a variety of physical anomalies, bone marrow failure, and an increased risk for malignancy. FA cells exhibit chromosomal instability and are hypersensitive to DNA cross-linking agents such as mitomycin C (MMC). FA is a clinically heterogeneous disorder and can be functionally divided into at least five different complementation groups (A-E). We previously described the use of a retroviral vector expressing the FAC cDNA in the complementation of mutant hematopoietic cells from FA-C patients. This vector is currently being tested in a clinical trial of ex vivo hematopoietic progenitor cell transduction. The FA-A group accounts for over 65% of all FA cases, and the FAA cDNA was recently identified by both expression and positional cloning techniques. We report here the transduction and phenotypic correction of lymphoblastoid cell lines from four unrelated FA-A patients, using two amphotropic FAA retroviral vectors. Expression of the FAA transgene was adequate to normalize cell growth, cell-cycle kinetics, and chromosomal breakage in the presence of MMC. We then analyzed the effect of retroviral vector transduction on hematopoietic progenitor cell growth. After FAA transduction of mutant progenitor cells, either colony number or colony size increased in the presence of MMC. In addition, FAA but not FAC retroviral transduction markedly improved colony growth of progenitor cells derived from an unclassified FA patient. FAA retroviral vectors should be useful for both complementation studies and clinical trials of gene transduction.