A 53-year-old patient suffering from delusional disorder developed an anticholinergic syndrome 19 days after initiation of paroxetine in addition to a steady dose of clozapine. The clozapine plasma concentration had doubled and was in the toxic range. On re-exposition with a lower clozapine dosage the increase was significantly lower. The importance of a dose-dependent interaction of both drugs is emphasized and a possible pharmacological explanation described. With regard to interactions of SSRIs and clozapine, fluvoxamine, a potent inhibitor of cytochrome P450 1A2, gives rise to higher clozapine levels at an earlier time, compared to other SSRIs (paroxetine, fluoxetine and sertraline), which are potent cytochrome P450 2D6 inhibitors.
Various diseases with a noticeable autoimmune component and frequent occurrence within one family show a statistically significant correlation with specific human leukocyte antigens (HLA). This correlation was also shown in studies of HLA in psychiatric disorders. However, results have been contradictory. The phenotype frequencies of HLA specificities were investigated in 100 schizophrenic patients and 472 controls from the same geographic area in Germany. The frequency of HLA B27 was significantly increased in the patient group as a whole (P=0.017) and in the subgroups of paranoid patients (P=0.005), chronic schizophrenics (P less than 0.001), patients with poor prognosis (P less than 0.001), and in patients with onset of the disease before the age of 20 years (P=0.004). In the latter three groups an elevated incidence of HLA A9 was also found. The combination A9-B27 was detected in 0.63% of our control group and in 7% of the patients (P less than 0.001). Of these patients 85.7% were chronic paranoid patients with poor prognostic features. This study gives support to the possibility of using HLA typing in genetic studies of schizophrenia, as well as in the differential diagnosis and prognosis.
The influence of prospective HLA-DR matching on the graft survival rate was investigated in a multicenter analysis of 85 transplants. Simultaneously in a retrospective analysis of graft outcome the importance of matching for MT-antigens MT1, MT2 and MT3 as a newly defined B-cell alloantigen system was evaluated. HLA-DR antigens and MT-specificities were determined on B-cells enriched by nylon-wool filtration using locally well characterised HLA-DR antisera and the antiserum set of the 8th International Histocompatibility Workshop ("disease set") which allowed the definition of the HLA-DR specificities HLA-DR 1-9 and of the MT-antigens MT1-3. HLA-DR matching showed a significantly improved graft outcome only in HLA-DR identical donor-recipient combinations. In 11 of 60 patients with one HLA-DR compatibility additional matching for two MT-antigens, however, improved the two year graft survival rate from 60% to 91%. Altogether 17 patients were matched for two MT-specificities with their kidney donor and showed a superior prognosis of 94% at two years compared to 53% or 17% of recipients with one or zero MT compatibility. Graft outcome in this patient group was also superior to that of HLA-DR identical or HLA-AB identical grafts. These data suggested that the MT-system rather than the HLA-DR antigens may be of critical importance in cadaver kidney transplantation. In addition a favorable influence of pretransplant blood transfusions on less HLA-DR matched grafts was confirmed.
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