Interethnic variation of drug metabolism

There are many examples of differences between ethnically defined populations with regard to drug-metabolizing enzymes i.e. enzymes that serve as defences against exogenous chemicals. The prevalence of variants of enzymes such as monooxygenases, dehydrogenases, esterases and some transferases is not uniform, and this leads to differences in metabolism of drugs such as aspirin and diazepam, among others. Werner Kalow explains why the mere counting of a genetic variant may not be sufficient to uncover more major problems such as may be posed by multiple allelism or heterozygosity, and why it may be predicted that a large number of drugs will display interethnic differences in function.     

Homogeneous, micelle quenching fluoroimmunoassay for detecting amphetamines in urine

We developed a homogeneous fluoroimmunoassay for detecting amphetamines in urine. Only fluorescence intensity need be measured because the emission of non-protein-bound fluorescein-labeled amphetamine is preferentially quenched by detergent micelles. In a previous reported prototype assay system for measuring gentamicin in serum we used fluorescein and dodecyl sulfate (Anal Chem 1985; 57:1928-30). We have found that favorable hydrophobic and (or) ionic character of the analyte and unfavorable polar and (or) ionic character of the fluor are important determinants of the desired interactions. An anionic detergent and fluorescein, therefore, should be appropriate for apolar of cationic analytes, such as gentamicin and amphetamines. A greater [H+] at the anionic micelle surface is important for quenching emission from the fluor moiety. Millimolar concentrations of dodecyl sulfate rapidly denature immunoglobulin unless hapten is bound with sufficiently high affinity. Affinity was sufficiently high for the antibody used in the prototype gentamicin assay but not for the amphetamine antibody. Thus for the amphetamine assay, we used a non-denaturing detergent, dodecyl(oxyethylene)12 sulfate. The assay requires 30 microL of specimen in 2 mL of total assay volume. Amphetamine(d-,dl-, and meth-), at a concentration of 1 mg per liter of urine, is readily detected.     

Screening for psychosis in the general population with a self-report interview

This analysis applies methods of screening to the problem of psychosis. A probability sample of 810 individuals from the Eastern Baltimore Mental Health Survey was interviewed in the self-report modality with the Diagnostic Interview Schedule and shortly thereafter by a psychiatrist. It is shown that a configuration of responses in the self-report modality can screen moderately well for psychosis, as measured by psychiatrists in the clinical modality.     

Cardiovascular intervention for high-risk families: the Heart Smart Program

The Heart Smart Family Health Promotion Program is a multidisciplinary, school-based program for cardiovascular risk reduction among high-risk children and their families. As a program that includes young adults at high risk, it is adaptable to a clinical practice. Nineteen fourth and fifth graders were selected as probands for elevated risk factors after a general screening to identify families for an intervention program. Twenty-three parents participated in a 12-week program focused on eating, exercise, and smoking behavior changes enhanced by behavicral support strategies. Weekly sessions were held in the auditorium/cafeteria of the elementary school and consisted of orientation and presentations, cardiovascular (CV) screening with medical feedback, activities, self-monitoring, counseling, and contingency contracting. Information gathered before and after the program included medical history, CV health knowledge and relevant behavior, blood pressure, serum lipid and lipoprotein values, anthropometric measurements, and urine electrolyte excretion. Both children and parents showed positive changes in eating habits and physical activity and significant changes in knowledge and blood pressure levels, while the children halted their weight gain. We believe this multidisciplinary, behavior-oriented, school-based program can be an effective cardiovascular risk intervention adaptable for a clinical office practice.     

Computed tomography in CNS tuberculosis

Computed tomography (CT) was performed in 14 cases of tuberculous meningitis (TBM), 12 of which were examined during the acute phase of the disease. CT findings in these cases included internal hydrocephalus (6/12), internal combined with external hydrocephalus (2/12), focal lesions consistent with localized encephalitis (3/12), diffuse brain edema (1/12), and middle cerebral artery infarction (1/12). In comparison to 32 cases of nonspecific bacterial meningitis, internal hydrocephalus was found significantly more often in TBM than in nonspecific meningitis (p less than 0.01) making CT an additional tool for the differentiation of these conditions in doubtful cases. In addition, CT features of 2 cases of cerebral tuberculoma are presented.     

Hypoxic ischemic encephalopathy (asphyxia)

This article concerns itself with the effects of HIE on the brain of the full-term infant. Several treatment options are available, with phenobarbital being the drug of choice, but the course remains observation and careful monitoring of the at-risk infant.     

Chronic exposure of rats to cognition enhancing drugs produces a neuroplastic response identical to that obtained by complex environment rearing.

Recent data suggest that Alzheimer's patients who discontinue treatment with cholinesterase inhibitors have a significantly delayed cognitive decline as compared to patients receiving placebo. Such observations suggest cholinesterase inhibitors to provide a disease-modifying effect as well as symptomatic relief and, moreover, that this benefit remains after drug withdrawal. Consistent with this suggestion, we now demonstrate that chronic administration of tacrine, nefiracetam, and deprenyl, drugs that augment cholinergic function, increases the basal frequency of dentate polysialylated neurons in a manner similar to the enhanced neuroplasticity achieved through complex environment rearing. While both drug-treated and complex environment reared animals continue to exhibit memory-associated activation of hippocampal polysialylated neurons, the magnitude is significantly reduced suggesting that such interventions induce a more robust memory pathway that can acquire and consolidate new information more efficiently. This hypothesis is supported by our findings of improved learning behavior and enhanced resistance to cholinergic deficits seen following either intervention. Furthermore, the level of enhancement of basal neuroplastic status achieved by either drug or environmental intervention correlates directly with improved spatial learning ability. As a combination of both interventions failed to further increase basal polysialylated cell frequency, complex environment rearing and chronic drug regimens most likely enhanced cognitive performance by the same mechanism(s). These findings suggest that improved memory-associated synaptic plasticity may be the fundamental mechanism underlying the disease modifying action of drugs such as cholinesterase inhibitors. Moreover, the molecular and cellular events underpinning neuroplastic responses are identified as novel targets in the search for interventive drug strategies for the treatment of neurodegenerative and neuropsychiatric disorders.     

工作作为药物及酒精滥用者有效的干预策略和治疗方法

1Introduction Substanceabusecontinuestobeamongthemostsevereso cialandcostlyhealthproblemsdevastatingindividualsandtheir familiesintheUnitedStates.Initssimplestdefinition,sub stanceabuseisthecontinueduseofalcoholorotherdrugsde spiteknowledgeofhavingapersistentsocial,vocational,psy chologicalorphysicalproblemthatiscausedorexacerbatedby theuseofalcoholorotherdrugs(DSMIV TR,1994).All drugsofabuse,includingalcohol,aretoxicandcannegatively impacteverysysteminthehumanorganism.Protractedsub stance…