REHABILITATION FOR STROKE SURVIVORS—A REVIEW

With the growing advent of rehabilitation units designed particularly for the needs of the stroke patient, a need has arisen for the evaluation of these units. In particular, several questions have to be asked     

A Comparison of the Physicochemical and Biological Properties of Mirtazapine and Mianserin

Although the chemical structures of the antidepressants mirtazapine and mianserin are closely related there are considerable differences in their biological properties. To find an explanation of this, various physicochemical properties of mirtazapine and mianserin were measured or calculated. Isosteric replacement of CH in mianserin by N in mirtazapine has profound effects on physicochemical properties. The charge distributions as indicated by NMR and calculated by semi-empirical quantum mechanics differ, not only for the changed aromatic A-ring (as expected), but also in other regions of the molecule. The N5 atom in particular, which is conjugated to the changed aromatic ring, is less negatively charged in mirtazapine than in mianserin. Consequently the oxidation potential of mirtazapine is significantly higher than that of mianserin. Another result of this difference in charge distribution is that the (calculated) dipole-moment vectors of the compounds are oriented roughly perpendicular to each other. The dipole moment of mirtazapine is, moreover, three times larger than that of mianserin; mirtazapine is, therefore, more polar than mianserin and this is reflected in a lower retention index. Finally, the basicity of mirtazapine, expressed as the pK_a value, is slightly but significantly lower than that of mianserin. The observed differences between the physicochemical properties of mirtazapine and mianserin result in different interactions of these two antidepressants with macromolecules, such as receptors, transporters and metabolizing enzymes; this might explain the differences observed in pharmacological activity and metabolic and kinetic behaviour, that is, the reduced affinity for the α₁-adrenoceptor and negligible noradrenaline reuptake of mirtazapine compared with mianserin.     

Inhibition of 3,3',4,4',5-Pentachlorobiphenyl-Induced Chicken Embryotoxicity by 2,2',4,4',5,5'-Hexachlorobiphenyl

3,3',4,4',5-Pentachlorobiphenyl (pentaCB) caused a dose-dependentinduction of chicken embryolethality, malformations, edema,and liver lesions at doses ranging from 0.5 to 12.0 µg/kg.In contrast, no embryotoxicity was observed after treatmentwith 10, 25, or 50 mg/kg 2,2',4,4',5,5'-hexaCB. In eggs cotreatedwith 2.0 µ/kg, 3,3',4,4',5-pentaCB plus 10, 25, or 50mg/kg 2,2',4,4',5,5'-hexaCB, there was significant protectionfrom 3,3',4,4',5-pentaCB-induced embryo malformations, edema,and liver lesions, whereas no inhibition of embryolethalitywas observed. These results further extend the response-specificnonadditive interactions of binary mixtures of polychlorinatedbiphenyls (PCBs) and should be considered in the developmentof approaches for hazard assessment of PCB mixtures and relatedcompounds.     

Immunotoxicological Profile of Morphine Sulfate in B6C3F1 Female Mice

This study was undertaken to investigate a number of immuneparameters which may be compromised with exposure to morphinesulfate. Mice were implanted subcutaneously with 8-, 25-, or75-mg morphine sulfate pellets. Placebo pellets of identicalmakeup to the 75-mg morphine pellet (without morphine of course)were used as a control. Twenty-four hours after implantationof a 75-mg morphine pellet, blood levels reached a peak of 1610ng/ml. Corticosterone increased in parallel with morphine andreached a peak level of 966 ng/ml 24 hr after implantation.The dose response of morphine to increase corticosterone, however,was fiat. The weight of the lymphoid organs, spleen and thymus,and the liver were significantly reduced in the morphine-treatedgroups. Morphine treatment was associated with an increase inserum albumin, SGPT, BUN, and alkaline phosphatase indicativeof hepatic damage. In contrast to increased serum proteins,the C3 component of complement was reduced in a dose-dependentmanner. Leukocyte number in the peripheral blood was significantlyreduced, while erythro-cyte number and hematocrit were bothincreased. The number of B cells and T cells was decreased inmorphine-treated animals. However, the percentage of T cellsrelative to B cells was increased. The primary IgM antibodyresponse to the T-depen-dent antigen, sheep red blood cells,was decreased. Natural killer cell activity was reduced in responseto morphine, as was the phagocytic capacity of Kupffer cells.Host-resistance models of Listeria monocytogenes or Streptococcuspneumoniae showed an increased resistance following administrationof morphine. This increased host resistance, however, was notdue to an increase in antimicrobial action of sera obtainedfrom mice treated with morphine. The majority of morphine'seffects on the immune system exhibited a flat dose response,suggesting that these effects may be mediated secondarily throughcorticosterone.     

Vital exhaustion, extent of atherosclerosis, and the clinical course after successful percutaneous transluminal coronary angioplasty

It has been observed that vital exhaustion, a state characterizedby unusual tiredness, increased irritability and feelings ofdemoralization not uncommonly precedes myocardial infarctionin apparently healthy individuals. This observation raised thequestion as to whether vital exhaustion is a marker of subclinicalcoronary disease. To answer that question the condition wasassessed in 105 male patients (mean age 54·8 year) beforeand 2 weeks after successful percutaneous transluminal coronaryangioplasty (PTCA) by the Maastricht questionnaire. Vital exhaustionwas found to be significantly correlated with the number ofdiseased vessels before PTCA and to decrease significantly afterPTCA. However, the association was rather modest (R²=0·08)and most patients remained exhausted after PTCA. During a follow-upperiod of 1·5 years, 32 patients (30%) experienced anew cardiac event (cardiac death, myocardial infarction, coronaryartery bypass grafting, repeat PTCA, a new coronary lesion orrecurrent angina with documented ischaemia). Univariate andmultivariate analyses showed that the number of diseased vessels,hypercholesterolaemia, and vital exhaustion were independentlyassociated with future events. The odds ratios were 3·74(P=0·02), 3·08 (P=0·08) and 3·07(P=0·04), respectively. It is concluded that the tirednesspreceding a cardiac event is only modestly associated with theextent of coronary artery disease and that a state of exhaustionafter PTCA increases the risk for a new cardiac event.     

An Electron Microscopic Study of the Bone Marrow of the Rat in an Experimental Myelogenous Leukemia

Alterations in the vascular sinus and hematopoietic compartment of rat bonemarrow were observed with electronmicroscopy during the pathogenesis of anacute myelogenous leukemia. As the disease progresses, the sinus wall becomesdamaged and disintegrates; normal hemicelements disappear, and the marrow compartment becomes packed with leukemicmyeloblasts. Viruslike particles are present in intercellular spaces and appear tobud from leukemic cells.

Submitted on December 14, 1970 Revised on April 29, 1971 Accepted on July 16, 1971     

Steroid Hormone Metabolism in Chronic Myelogenous Leukemia

Individual metabolites of steroid hormones were isolated and measuredfrom the urine of patients with chronic myelogenous leukemia. The resultswere compared with earlier studies of patients with chronic lymphatic leukemia, men with prostatic cancer, women with breast cancer and normalmen and women. The metabolites of hydrocortisone were in the normal rangefor the patients with chronic myelogenous leukemia but the amount of tetrahydrocortisol was generally greater than that of tetrahydrocortisone. Therewas no evidence for a sex difference in the production of these metabolites.The tentative conclusion was drawn that metabolites of the "adrenal androgens" were also in the normal range in chronic myelogenous leukemia. Theseresults contrast with those in chronic lymphatic leukemia patients where asex difference in production of hydrocortisone was evident and the metabolitesof "adrenal androgens" were at low levels in both sexes.

Submitted on August 13, 1964 Accepted on September 20, 1964