Verapamil-digoxin interaction in chronic hemodialysis patients

Verapamil increases the serum-digoxin concentration (SDC) in digoxin treated normals due to a compromised renal and extrarenal clearance. In chronic hemodialysis patients (CHD-patients) treated with digoxin where the renal elimination is diminished, verapamil has been shown to cause substantial increases of SDC with risk of digoxin intoxication. The effect of verapamil treatment on SDC in 8 nearly anephric (Uvol less than 1 l/d) CHD-patients on digoxin treatment was assessed. The patients were continuously treated with verapamil for two periods of two weeks at two dosage levels, 120 mg/d and 240 mg/d, whereafter verapamil was withdrawn. SDC and serum-verapamil were measured weekly. The SDC increased from 1.1 mmol/l to 1.7 mmol/l (p less than 0.05, N = 7) during the first two weeks. Increasing the dose of verapamil to 240 mg/d did not cause a further increment in SDC; on the contrary, the mean SDC decreased. The SDC increments varied between 0 and 200% of baseline values. We conclude that verapamil treatment decreases digoxin clearance in CHD-patients and that the influence of verapamil on SDC in CHD-patients shows great interindividual variation with no close dose dependency and decreases to pretreatment level in 2-3 weeks.     

Effect of ethanol on ascorbate release in the nucleus accumbens and striatum of freely moving rats.

An in vivo voltammetry technique was used to monitor the extracellular ascorbate (AA) concentration in the nucleus accumbens and striatum of unanesthetized, freely moving rats. A single injection of ethanol, 1.0 g/kg intraperitoneally (IP), induced a significant increase in extracellular AA concentration in both the nucleus accumbens and striatum. This effect was dose dependent within a dose range from 0.5-2.0 g/kg. 4-Methylpyrazole (50 mg/kg, IP), which inhibits alcoholdehydrogenase, could not prevent the increase in AA concentration, evoked by ethanol. Furthermore, systemic administration of acetaldehyde (20 mg/kg, IP), the main metabolite of ethanol, did not have any effect on the level of AA in the nucleus accumbens or striatum. These results show that ethanol can alter the brain extracellular AA levels and that this effect seems to be attributed to ethanol itself and not to acetaldehyde. Consequently, these results indicate that a role for AA in the action of ethanol in the brain should be considered.     

Subtypes of schizophrenia: a cluster analytic approach.

OBJECTIVES: To identify empirical subtypes of schizophrenia, based upon the symptoms recorded over the duration of the illness, and to validate the resulting clusters against other systems that are used for subtyping schizophrenia. METHOD: Data for 55 symptoms of schizophrenia over the history of the illness from 107 chronic schizophrenia patients were analyzed using hierarchical cluster analysis with Euclidean distance and Ward's method. Except for 1 patient, all met DSM-III criteria. There were 40 men and 67 women, average (SD) age of 38.2 (9.91) years, with a mean (SD) hospitalization of 27.9 (27.35) months. RESULTS: No clear and unambiguous solution for the number of clusters was evident. Examination of the clusters led to further analysis of 2- and 6-cluster solutions. These were contrasted with DSM-III, DSM-III-R, and DSM-IV criteria and with the subtypes taken from the literature. There was limited support for any of these types, with none replicating, including the paranoid-nonparanoid distinction. CONCLUSIONS: Empirical clusters derived from lifetime symptom data failed to agree with either the established DSM or other empirically derived subtypes. Subtypes may have little utility when the variability of symptoms over the longitudinal course of the illness is considered.     

Longitudinal relationship between incisal tooth wear and periodontal condition

The purpose of the study was to examine the relationship between the longitudinal development of incisal tooth wear and periodontal conditions in 51 persons. Stone casts obtained at the ages of 15 and 27 yr were used to assess incisal wear according to a graded scale, the Incisal wear Index (Iwl). The wear increase after 12 yr, ΔIwI, was related to the various health index scores at the age of 15 yr, including the Plaque Index (PII) and Gingival Index (GI) systems. The chi-square tests showed a statistically significant association between AIwI and periodontal condition in 15-yr-olds. Thus, relatively low P1I and GI values were accompanied by relatively high AIwI values. It was concluded that in 15-yr-olds, P1I and GI levels are clinical predictors of future wear (ΔIwI) of maxillary and mandibular central incisors. Pocket depth (PD) was a less valuable clinical predictor of such wear.     

Influence of aminoglutethimide on plasma oestrogen levels in breast cancer patients on 4-hydroxyandrostenedione treatment

Summary The clinical and biochemical effects of combined treatment with the two aromatase inhibitors aminoglutethimide and 4-hydroxyandrostenedione were evaluated in 10 patients suffering from advanced breast cancer. All patients had become resistant to treatment with one of the drugs before having combined treatment. Seven patients progressing on 4-hydroxyandrostenedione who had aminoglutethimide added to their treatment and achieved a further suppression of plasma oestradiol by a mean of 40.0% (p<0.05). Plasma oestrone was suppressed by a mean of 40.6% (p<0.025) and plasma oestrone sulphate was suppressed by a mean of 63.6% (p<0.025). Two of the patients, neither of whom had responded to 4-hydroxyandrostenedione alone, experienced objective tumour regression when aminoglutethimide was given in concert. Three patients progressing on aminoglutethimide who had 4-hydroxyandrostenedione added showed no further suppression of their plasma oestrogen levels, and no tumour regression was observed. These findings suggest a dose-response relationship between plasma oestrogen suppression at low postmenopausal levels and objective tumour response in breast cancer.     

Effects of cyclophosphamide on the in vivo response of outbred athymic (nude) mice to a thymus-independent antigen (DNP-AGG-Ficoll).

Both nude mice (nu/nu) and their heterozygous littermates (nu/+) were injected with a single IP dose of 300 mg cyclophosphamide (CY)/kg. CY is a known immunosuppressive agent, which affects primarily B lymphocytes. Immunization with the thymus independent antigen DNP-AGG59-Ficoll after CY treatment disclosed that restoration of the primary direct PFC response occurred more rapidly in nude mice than in nu/+ mice. However in these same experiments, the primary indirect PFC response, recovered earlier in nu/+ mice than in nude mice. After CY treatment, secondary indirect PFC responses were delayed in both nude and nu/+ mice, but the greatest effect was seen in nude mice. The data suggest that the presence of T cells has little if any influence on the recovery capacity of those B cells which are destined to become direct PFC. However the recovery of B cells which are destined to produce indirect PFC responses is facilitated by the presence of T cells.