Advances in pharmacotherapy: depression in the elderly– issues and advances in treatment

Depression continues to be a major cause of morbidity and mortality in the elderly. It is estimated that 1–5% of elderly persons who live in the community and 5–43% of nursing–home patients have major depression. Symptoms of depression in the elderly do not differ substantially from younger patients. Tricyclic antidepressants continue to be the drugs of choice in the elderly because of their long record of use with proven efficacy, known adverse effect profile and availability of less expensive generic formulations. The newer secondgeneration antidepressants, including serotonin reuptake inhibitors, appear to offer a major advantage of fewer serious adverse effects in the elderly. This review will highlight recent developments regarding the prevalence and treatment of depression in the elderly.     

The Perceived Influence of Clinical Pharmacy Services on Physician Prescribing Behavior: A Matched-Pair Comparison of Pharmacists and Physicians

In contrast with cross-sectional designs used in previous studies, this exploratory study compared survey data from 127 matched pairs of clinical pharmacists and physicians working together. Physicians' perceptions of the importance of clinical pharmacy activities for patient care and the competence of pharmacists performing the activities were examined for their influence on prescribing behavior in an institutional setting. Data from a national survey showed that physicians rated pharmacists higher regarding recommendations based on drug use evaluations (p = 0.004) and competency to provide all clinical pharmacy services. Scores for pharmacokinetics ratings were similar between pharmacists and physicians (p = 0.168). Pharmacists rated the importance of recommendations based on cost-effectiveness higher than physicians (p = 0.012). Overall, physicians' perceptions of activity importance for patient care and pharmacist competency appear to dictate pharmacists' influence on physician prescribing behavior (R = 0.723).     

Monitoring Anti-HPA-1a Platelet Antibody Levels during Pregnancy Using the MAIPA Test

Anti-HPA-1a platelet antibody levels in pregnant women with a history of fetomaternal alloimmune thrombocytopenia (FMAIT) were monitored longitudinally using the monoclonal antibody immobilisation of platelet antigens (MAIPA) assay, in order to examine any variation in optical density (OD) readings obtained over the course of pregnancy and after delivery. Seven women were selected; 4 were studied retrospectively and 3 prospectively (the latter being treated with intravenous gammaglobulin; IVGG). Levels of anti-HPA-1a were measured at various intervals after delivery of the first affected infant, to post delivery of the following affected infant. A decrease in MAIPA OD was demonstrated in all patients during the course of these pregnancies. This assay is a useful tool for monitoring anti-HPA-1a in women with a history of infants affected with FMAIT. A maternal antibody 'resting' level prior to, or early in the first trimester, must be established for comparison.     

A multicentre assessment of the specificity of ten anti-HBc screening tests

SUMMARY. Samples from 1828 donations were screened for anti-HBc at seven sites in the UK using kits supplied by 10 manufacturers. Only 10 (0.55%) donations were considered to have true anti-HBc reactivity and these were detected by all 10 kits. Additional markers of HBV infection were found in nine of these 10 donations. Additional reactives were found by all kits, the number ranging from 1 to 43.
In the four more specific kits, the 10 true reactives were clearly distinguished from the 'false reactives' by the strength of the reaction. It is concluded that the reliance on a single ELISA test for anti-HBc diagnosis is unwise. The use of a second test known to be more specific than the screening ELISA is recommended.     

Effects of physiological and pathological levels of glucocorticoids on skeletal muscle glutamine metabolism in the rat

The effects of physiological and pathological concentrations of glucocorticoids were investigated using the glucocorticoid antagonist RU486 and the synthetic glucocorticoid dexamethasone, respectively. The effects of these treatments on the concentrations of glutamine and other amino acids in skeletal muscle and plasma and on the rates of release of glutamine and alanine from incubated preparations of skeletal muscle of the rat were investigated. Dexamethasone treatment increased the concentration of glutamine and the rate of release of this amino acid from incubated soleus muscle preparations. This treatment decreased the concentration of glutamine in both gastrocnemius and EDL muscles, but was without effect on the rate of glutamine release from EDL muscles. In contrast, administration of the glucocorticoid antagonist RU486 decreased the rate of glutamine release from muscle. It is concluded that glucocorticoids have marked effects on the metabolism of glutamine by skeletal muscle per se and that these hormones may be important in the control of the rate of glutamine release from muscle in both physiological and pathological conditions.     

Fetal antigen retained by mature neurons and ependyma studied with a monoclonal antibody (6B9)

A mouse monoclonal antibody (MAb 6B9, isotype IgM) was raised against autopsy tissue samples from the central nervous system (CNS) of multiple sclerosis (MS) patients. By immunofluorescence microscopy, MAb 6B9 intensely stains most or all cells in fetal rats. However, MAb 6B9 differentially stains various cell types in adult rats. Neurons, ependymal cells, and adrenal chromaffin cells are stained intensely, whereas astrocytes and oligodendrocytes are not stained. The 6B9-reactive antigen (6B9 antigen) is sensitive to periodic acid, but insensitive to treatment with protease, RNase, or hyaluronidase. Results from immunofluorescence microscopy on semithin sections and cultured neuroblastoma cells indicate that 6B9 antigen is intracellular. This is supported by immunoelectron microscopy, where labeling for 6B9 antigen appears in the cytoplasm distinct from any identifiable organelle. Further studies on 6B9 antigen should reveal its chemical nature as well as the significance of developmental changes in its distribution.     

Facilitated uptake of zinc into human erythrocytes. Relevance to the treatment of sickle-cell anaemia

The ability of a number of heterocyclic metal chelators to deliver zinc into red cells, to release the liganded zinc to haemoglobin and thereby cause a left shift in the oxygen dissociation curve of intact red cells has been investigated. Incubation of neutrally charged zinc-pyrone and zinc-pyridin-2-one complexes with red cells led to the rapid accumulation of zinc within cells, whereas unliganded zinc in the form of zinc acetate, zinc chloride or zinc sulphate accumulated only slowly. The rate at which zinc was delivered to red cells by pyrone and pyridin-2-one ligands increased with increasing lipid solubility of the ligands. The uptake of zinc into both normal adult and sickle red cells was associated with a dose-dependent increase in the oxygen affinity of haemoglobin. The degree of left shift in the oxygen dissociation curve following the incubation of red cells with zinc-pyrone and -pyridin-2-one complexes suggests that these complexes may find application as agents to increase the oxygen affinity of haemoglobin in sickle cell disease and thereby decrease the probability of intravascular sickling at low tissue oxygen tensions. Ethylmaltol appears to be a particularly useful agent due to its known low toxicity.     

Comparison of two analytical procedures for the determination of free urinary catecholamines under the demands of shiftwork experiments

Summary A typical shiftwork experiment was chosen to prove the validity of an automated procedure for the analysis of free noradrenaline and adrenaline in urine. The method consists of a column switching technique with an adsorption/elution clean-up and a reversed phase high performance liquid chromatography followed by chemical reaction detection based on the trihydroxyindole method. The analysis of variance was performed using a second data set obtained by a semi-automated procedure for which the accuracy had already been confirmed. The analysis of covariance showed that for field studies, as well as for laboratory experiments in which the variances contributed by the experiments themselves are greater than 10% rel., the data sets of the two methods provide the same information.Dedicated to Prof. H. Hartkamp, University of Wuppertal, on the occasion of his 60th birthday