Drug prescribing in hospitals: an international comparison

This paper presents a comparison of prescribing habits for patients hospitalized in medical wards of university hospitals in America and Scotland. American patients received almost twice as many drugs both during and prior to hospitalization than did comparable Scots. The differences between the countries were consistent for symptomatic and for more specific therapies. As compared to Scotland, drug therapy in America costs patients more in terms of financial outlay and adverse drug effects. The data do not permit evaluation of the relative benefits to the patients of the different quantities or types of drug used for similar circumstances in these countries.     

Immobilized metal-ion affinity chromatography: imidazole proton pump and chromatographic sequelae. II. Chromatographic sequelae

Isocratic elution with imidazole of some protein models from a chelating gel, CSFF-IDA-M(II), resulted in their desorption owing to the low pH(6-->4) of the mobile, phase rather than to the imidazole itself (imidazole-generated fall in pH; proton pump). Gradient elution with imidazole was best accomplished when the chelating gel was initially converted into its imidazole complex, CSFF-IDA-M(II)Im. The exploitation of the imidazole-generated proton pump in the IMAC of proteins may enhance the versatility of this type of chromatography.     

Prediction of protein displacement by simplified immobilized metal ion affinity chromatographic model

A simplified theoretical model was developed to predict complex behavior in protein displacement systems of immobilized metal ion affinity chromatography (IMAC). In this paper, experimental techniques for estimating equilibrium parameters were developed. The equilibrium parameters obtained were used to simulate displacement processes and to investigate the effect of mobile phase modifier (MPM) gradients in the IMAC separating systems. In the induced MPM gradient conditions, the solute movement analysis was able to predict the displacement separation well characterized by the intersections of the operation line under the effective displacer concentrations. The theoretical and experimental results demonstrate the utility of the IMAC model in predicting induced mobile phase modifier gradients and complex behavior in metal affinity displacement chromatography. Furthermore, the development of a rapid method for obtaining displacement profiles facilitates methods development and optimization of IMAC displacement separations.     

Gas chromatographic determination of chloramphenicol residues in shrimp: interlaboratory study

An interlaboratory study of a gas chromatographic method for determining chloramphenicol (CAP) residues in shrimp was conducted. An internal standard (Istd), the meta isomer of CAP, was added to the shrimp, and the treated shrimp were homogenized with ethyl acetate. The ethyl acetate extract was defatted with hexane, and the CAP was partitioned into ethyl acetate from an aqueous salt solution. The ethyl acetate was evaporated, and the dried residue was treated with Sylon, a trimethylsilyl derivatizing agent, to yield the trimethylsilyl derivative of CAP. A portion of the solution containing the derivative was injected into a gas chromatograph equipped with an electron capture detector. Levels of fortified and incurred CAP were calculated from the peak area ratio of standard CAP to Istd. Recoveries of CAP from tissue directly fortified at 5 ppb were 102% (within-laboratory relative standard deviation [RSDr] = 5.6%), 104% (RSDr = 5.5%), and 108% (RSDr = 6.3%) from Laboratories 1, 2, and 3, respectively. Incurred-CAP residues at 5 and 10 ppb levels were also determined, with the following results: Laboratory 1: composite A, 4.56 ppb (RSDr = 14.0%); composite B, 8.38 ppb (RSDr = 11.6%); Laboratory 2: composite A, 4.17 ppb (RSDr = 12.5%); composite B, 8.90 ppb (RSDr = 5.60%); Laboratory 3: composite A, 4.66 ppb (RSDr = 14.9%); composite B, 11.0 ppb (RSDr = 11.8%).     

Drug abuse in Nepal: a rapid assessment study

A rapid assessment of drug abuse in Nepal was conducted at different sites, including eight municipalities in the five development regions of the country. To interview various groups of key informants, such methods as semi-structured interviews, in-depth interviews and focus group discussions were used. A snowball sampling strategy for respondents who were drug abusers and a judgemental sampling strategy for the non-drug-using key informants were applied. About one fifth of the sample was recruited from the treatment centres and the rest from the community. Drug abusers in prison were interviewed, and secondary data from treatment centres and prisons analysed. The study revealed that the sample of drug abusers had a mean age of 23.8 years and was overwhelmingly male. Most respondents lived with their families and were either unemployed or students. About 30 per cent of the sample was married. A large majority of the sample had a family member or a close relative outside the immediate family who smoked or drank alcohol and a friend who smoked, drank or used illicit drugs. Apart from tobacco and alcohol, the major drugs of abuse were cannabis, codeine-containing cough syrup, nitrazepam tablets, buprenor-phine injections and heroin (usually smoked, rarely injected). The commonest sources of drugs were other drug-using friends, cross-border supplies from India or medicine shops. The commonest source of drug money was the family. There has been a clear trend towards the injection of buprenorphine by abusers who smoke heroin or drink codeine cough syrup. The reasons cited for switching to injections were the unavailability and rising cost of non-injectable drugs and the easy availability and relative cheapness of injectables. About a half of the injecting drug users (IDUs) commonly reported sharing injecting equipment inadequately cleaned with water. Over a half of IDUs reported visiting needle-exchange programmes at two of the study sites where such programmes were available. Infection by the human immunodeficiency virus (HIV) appears to be low among IDUs, although systematic surveillance is absent. Two thirds of the sample had experienced sexual intercourse. The last sex partners reported by respondents were commercial sex workers, wives or girl friends. Condom use was low with primary partners and relatively high with sex workers. Treatment facilities, mostly located in the central urban areas of the country, are meagre. An overwhelming majority of drug abusers felt the need to stop abusing drugs. Cost-effective drug treatment and HIV prevention programmes for IDUs are urgently needed in all areas of the country.     

Drug resistant tuberculosis in prisons in Azerbaijan: case study

Tuberculosis is a significant health problem in Azerbaijan. In prisons, this problem is compounded by overcrowding, poor general health, a high representation of risk groups, late case finding, and incomplete treatments. The present study investigated the extent of drug resistance at the Central Penitentiary Hospital in Baku--the country's only treatment center for prisoners with tuberculosis. This International Committee of the Red Cross program, established in 1995, uses the directly observed treatment, short course (DOTS) strategy. Sputum samples were collected from two groups of prisoners: 1) 28 patients who failed to respond, clinically or bacteriologically, after a minimum of 8 weeks to the treatment regimen recommended by the World Health Organization and 2) 38 patients consecutively enrolled over a 4-week period from whom sputum was taken before the start of treatment. Mycobacterium tuberculosis was isolated from all 66 sputum specimens. In the first group, 25 strains (98%) were multidrug resistant (to rifampicin and isoniazid). Such resistance occurred in all new cases and 14 (82%) of the 17 failure or relapse cases. In the second group, 9 strains (24%) were multidrug resistant and only 12 (32%) were fully susceptible. This resistance was found in 3 strains (15%) among the 20 new cases and in 6 strains (33%) among the 18 cases of treatment failure or relapse. These findings suggest that prisoners may have an important future role in the transmission of tuberculosis, especially multidrug resistant forms, in the former Soviet Union.     

Paramagnetic metal scavenging by melanin: MR imaging

To evaluate the potential application of high performance liquid chromatography or HPLC in performing hemoglobin typing, comparison between this technique and routine methods was carried out. Blood specimens from Pediatric Hematology Unit, Research Center, Faculty of Medicine, Ramathibodi Hospital were examined by these methods. The level of Hb A2, Hb E and Hb F were compared. Hb A2 level determined by HPLC and electrophoresis was statistically significantly different but correlated well. Good correlation was found between Hb A2 level from HPLC compared with microcolumn chromatography although there was a statistical difference. No difference but very good correlation was found between the level of Hb E from HPLC compared with electrophoresis. Statistical difference was encountered when Hb F level determined by HPLC was compared to that determined by Betke alkaline denaturation test. However, good correlation was observed when the level of Hb F was greater than 2.0%. In conclusion, HPLC could be an alternative way of performing hemoglobin typing provided that Hb F is 10% or more, by calculating from the equation: Alk F = (0.83 x Hb F by HPLC) - 0.98.     

Evaluation of several affinity chromatographic supports for the purification of maltose-binding protein from Escherichia coli

To obtain affinity adsorbents with good mechanical resistance, suitable for the purification of maltose-binding protein (MBP) from Escherichia coli and genetically engineered proteins fused to MBP, a series of supports were prepared by grafting amylose on to agarose by different chemistries. Their capacities for MBP and their abilities to be used at relatively high flow-rates were examined. Efficient supports were most conveniently prepared by coupling amylose to epoxy-activated agarose in an aqueous-organic mixture.     

In vitro affinity of piribedil for dopamine D3 receptor subtypes, an autoradiographic study

Receptor binding autoradiography, using the selective ligand [3H]7-OH-(R)DPAT (R(+)-2-dipropylamino-7-hydroxy 1,2,3,4-tetrahydronaphthalene), showed that piribedil is a potent inhibitor at dopamine D3 receptors in limbic regions (island of Calleja), with affinity (IC50) between 30 and 60 nM. The in vitro IC50 of piribedil for inhibition of [3H]spiperone binding to receptors of the dopamine D2-like family (D2, D3 and D4), ranged between 10(-7) and 10(-6) M in different brain regions (medial and lateral caudate putamen, olfactory tubercles, and nucleus accumbens). At the highest concentration tested (10(-5 M) piribedil inhibited dopamine D1 receptor binding by < 50%. It is concluded that piribedil has 20 times higher affinity for dopamine D3 than for dopamine D2-like receptors, and very low affinity for the dopamine D1 receptor subtype in rat brain. How this pattern of receptor affinity is related to the pharmacological profile of piribedil deserves further investigation.     

Cross-linked filamentous phage as an affinity matrix

A strategy for the prevention and control of candidiasis, pneumocystosis, and tuberculosis, based on the idiotypic network of the yeast killer effect has been envisaged. Anti-idiotypic antibodies representing the internal image of a candidacidal, pneumocysticidal, and mycobactericidal killer toxin from Pichia anomala and idiotypes of killer toxin-neutralizing monoclonal antibodies mimicking the specific cell wall receptor of sensitive microorganisms might provide a unique approach for engineering innovative antibiotics and vaccines active against taxonomically unrelated pathogenic microorganisms. The rationale of the strategy relies on a phenomenon of microbial competition which has been mutated by the immune system in the response to natural infections.     

Improved method for the on-line metal chelate affinity chromatography-high-performance liquid chromatographic determination of tetracycline antibiotics in animal products

An improved on-line metal chelate affinity chromatography-high-performance liquid chromatography (MCAC-HPLC) method for the determination of tetracycline antibiotics in animal tissues and egg has been developed. Extraction was carried out with ethyl acetate. The extract was then evaporated to dryness and reconstituted in methanol prior to on-line MCAC clean-up and HPLC-UV determination. Recoveries of tetracycline, oxytetracycline, demeclocycline and chlortetracycline in the range 42% to 101% were obtained from egg, poultry, fish and venison tissues spiked at 25 micrograms kg-1. Limits of detection less than 10 microgram kg-1 were estimated for all four analytes. This method has higher throughput, higher recovery and lower limits of detection than a previously reported on-line MCAC-HPLC method which involved aqueous extraction and solid-phase extraction clean-up.     

On-line metal chelate affinity chromatography clean-up for the high-performance liquid chromatographic determination of tetracycline antibiotics in animal tissues

An on-line high-performance liquid chromatographic (HPLC) method for the determination of tetracycline, oxytetracycline, chlortetracycline and demeclocycline using metal chelate affinity chromatography-reversed-phase HPLC has been developed. The drugs were extracted with succinate buffer and the extract diluted with EDTA-pentanesulphonate buffer. Diluted extract was then absorbed onto a C8 or XAD-2 solid-phase extraction (SPE) cartridge and eluted with methanol. The eluate was then injected onto a TSKgel chelate column which had been preloaded with copper(II). The tetracyclines were eluted from this column onto the analytical column (Polymer Labs. PLRP-S) with an EDTA-containing buffer. Elution of the analytical column was via a methanol-acetonitrile gradient and detection was by UV at 350 nm. Average recoveries at the 10, 20, 50 and 300 micrograms kg-1 levels were 50-80%. The limit of detection (LOD) was 10 micrograms kg-1 for oxytetracycline and tetracycline and 20 micrograms kg-1 for chlortetracycline and demeclocycline. The method was validated for sheep liver and cattle kidney.     

Drug eruptions in Bangkok: a 1-year study at Ramathibodi Hospital

Concentration of camphorquinone initiator, exposure time of the light source and particle size of a radiopaque glass filler have been varied for an indigenously developed light-curing dental composite and the changes in the microhardness, compressive strength and diametral tensile strength studied. Higher initiator concentration and exposure times are found to improve the microhardness values while a concentration above 0.25% does not signify any drastic improvement in compressive and diametral strength. Changes in properties are found to be statistically significant at low initiator concentrations. A filler particle size around 1 microm is found to give better properties compared with larger sizes.     

Drug and alcohol use in orthopedic trauma patients: a prospective study

Six groups of 16 rats each were fed a standard diet for 8 weeks. Aluminium (Al) complexed with organic anions (citrate, lactate, malate, or tartrate) was added to the diet of four of the groups and aluminium hydroxide to the diet of one group (control 'Al +'). Aluminium concentrations in the diets were 1500-2000 mg/kg. The sixth group (control 'Al -') served as control. Plasma, bone (femur), kidneys, cerebral cortex and cerebellum levels of aluminium were determined at 4 and 8 weeks. All the complexing agents increased tissue accumulations, compared with values in the two control groups, especially citrate in bone and kidneys and lactate in cerebral cortex. There were no significant differences (P < 0.05) in aluminium levels in the tissues considered between the 'Al +' and 'Al -' control groups. Our results show the ability of dietary organic acids to increase aluminium absorption and tissue accumulation and indicate that concurrent intake of aluminium and dietary organic acids is not appropriate.     

Neuromelanin of the human substantia nigra: a mixed-type melanin

Model melanins, synthesized with different cysteinyldopamine/dopamine ratios in the incubates, were oxidized with KMnO4 and the resulting compounds were analyzed by HPLC. The ratios between a phaeomelanin-derived compound, thiazole-4,5-dicarboxylic acid (TDCA), and a compound derived from eumelanin, pyrrole-2,3,5-tricarboxylic acid (PTCA), reflected the composition of the model melanins. The neuromelanin of the human substantia nigra was isolated, and the pigment, as well as intact brain tissue from human substantia nigra was oxidized with KMnO4 and the TDCA/PTCA ratios were determined. Analysis of the isolated neuromelanin showed it to contain 2.3% sulfur and 8.1% nitrogen. The sulfur content indicates the pigment is a mixed-type melanin, and the TDCA/PTCA ratio indicates that it consists of units derived from benzothiazines and from indoles in about equal amounts.     

Drug use and street crime in Miami: an (almost) twenty-year retrospective

Researchers at the University of Delaware have been conducting field studies of drug use and crime in Miami, Florida, since 1977. This paper reviews this research and its contributions to understanding drugs-crime relationships. Early studies tested mechanisms for accessing street populations of heroin users and assessing the nature and extent of their drug use and criminality. Subsequent studies targeted a variety of crime-involved heroin and cocaine users, including women as well as men, serious delinquents, adolescent and adult crack users, and cocaine users in treatment as well as on the street. Major findings include the low risk of arrest for income-generating crimes committed by heroin users, and the prevalence of HIV-risk behaviors among both serious delinquents and women crack users. Analyses consistently show the critical importance of sample characteristics in research on drug use, including age, cohort, and street-versus-treatment status.     

Studies on an affinity label for the sulfuryl acceptor binding site in an aryl sulfotransferase

Active site-directed affinity labeling was utilized to elucidate peptide sequences at the binding site for sulfuryl acceptors in rat hepatic aryl sulfotransferase (AST) IV (also known as tyrosine-ester sulfotransferase, EC 2.8.2.9). The affinity labeling reagent, N-bromoacetyl-4-hydroxyphenylamine, was designed on the basis of substrate specificity studies with para-substituted phenols, utilization of a bromoacetamido group for reactivity with active site amino acid residues and its similarity to acetaminophen, a known substrate for aryl (phenol) sulfotransferases. AST IV utilized N-bromoacetyl-4-hydroxyphenylamine as a substrate with kinetic constants that compared favorably to those obtained with acetaminophen. Incubation of AST IV with N-bromoacetyl-4-hydroxyphenylamine at pH 7.0 in the absence of PAPS and other substrates resulted in an irreversible inactivation of the enzyme that was both time- and concentration-dependent. [14C]-N-bromoacetyl-4-hydroxyphenylamine was synthesized and used to analyze the regions of protein sequence that were involved in the binding of the affinity label. AST IV was incubated with [14C]-N-bromoacetyl-4-hydroxyphenylamine, hydrolyzed with endoproteinase Lys-C and the labeled peptides were purified by HPLC. Control incubations of AST IV with the affinity label in the presence of 4-propylphenol and PAP were utilized to ascertain the specificity of the interaction. Sequence analysis of the labeled peptides, carried out by automated Edman degradation, revealed labeling sites on cysteine (Cys-232, Cys-283 and Cys-289) and lysine (Lys-286) residues near the C-terminus of the protein. The locations of these labeling sites were further evaluated both by sequence-alignment with other sulfotransferases and by theoretical calculations on predicted secondary structure.     

Rolandic epilepsy: an incidence study in Iceland

PURPOSE: We wished to determine incidence, clinical features, and prognosis of benign rolandic seizures (BRS) and benign rolandic epilepsy (BRE) in a total population. METHODS: Cases were ascertained through review of all EEG records, and diagnosis was verified by review of medical records. Follow-up information regarding seizures and treatment was obtained from parents and treating physicians. RESULTS: In the Icelandic population aged 3-15 years, the incidence of BRS is 6.2 and BRE 4.7 in 100,000. Five years after onset 95% were seizure-free. At last follow-up, all were seizure free and had not been treated with antiepileptic drugs (AEDs) for at least 1 year. CONCLUSIONS: Our study demonstrates that BRS is a common entity in children. The prognosis is excellent and treatment is not necessary in all cases. It is important to identify BRE/BRS correctly and distinguish it from other types of epilepsy.     

Astrocyte-regulated synaptogenesis: an in vitro ultrastructural study

Striatal neurons from E15 rat embryos were dissociated, plated at low cell density on polyornithine or on astrocyte monolayers derived from the striatum (homotopic) or mesencephalon (heterotopic), and cultured in a chemically defined medium. Dendrites developing in homotopic co-cultures could reach a state of maturation allowing the establishment of synapses with axons from mesencephalic explants. This culture system thus partially reproduces the in vivo conditions in which striatal neurons developing in an homotopic glial environment can serve as synaptic targets for afferent mesencephalic axons.