HETEROGENEITY OF SYSTEMIC LUPUS ERYTHEMATOSUS ELUCIDATED BY CLUSTER ANALYSIS

For 75 patients with systemic lupus erythematosus (SLE), 39 laboratory and clinical characteristics, including HLA-A, B, C and DR typing, were analysed using a cluster analysis technique. Three groups were identified. Group I (46 patients) was characterized by infrequently severe disease, good response to therapy and infrequent multisystem involvement. Group I1 (24 patients) was characterized by a severe course of disease (although the tendency to remit after therapy was not unusual), and, frequently, renal involvement and pericarditis. Group 111 (5 patients) was characterized by more severe renal disease. Of the 75 patients studied, 38.7% possessed HLA-DR3, compared to 17.4% of controls. Group I patients did not differ from controls but 80% of Group II patients and 4/5 Group III patients had DR3. Cluster analysis identifies subsets of SLE patients who show marked differences in disease course and severity, correlated with possession of the HLA B8, DR3 phenotype.     

Triggering of respiratory burst by phagocytosis in monocytes of patients with systemic lupus erythematosus.

The triggering of the respiratory burst by phagocytosis via different receptors in monocytes of patients with systemic lupus erythematosus (SLE) was investigated. The superoxide anion synthesis was assayed by reduction of ferricytochrome C that was inhibited by superoxide dismutase. The mononuclear cell suspensions were triggered by IgG-coated latex, C3 complement fragment-coated and uncoated yeast (Saccharomyces cerevisiae). Superoxide generation induced by phagocytosis via Fc gamma R was decreased in monocytes of patients with SLE. On the other hand, MoAbs against Fc gamma RI, Fc gamma RII and especially CR3 could also induce superoxide anion synthesis. At the same time, superoxide generation induced by anti-CR3 could be inhibited with C3-coated yeast.     

Differentiating moderate and severe depression using the Montgomery-Asberg depression rating scale (MADRS)

BACKGROUND: MADRS cut-off scores for moderate and severe depression were estimated in relation to the Hamilton Depression Rating Scale (HAMD(17)) and the Clinical Global Impressions Scale (CGI). METHOD: HAMD(17), MADRS, and CGI ratings from patients with major depression (DSM-IV) were analyzed (N=85). Receiver operating characteristics (ROC) curves were applied. RESULTS: Mean age was 51.4+/-14.5 years, 69% were female. Mean MADRS scores were 23.4+/-13.2, HAMD(17), MADRS, and CGI scores were highly correlated (r>0.85; P<0.0001). Best separation between moderate and severe depression according to CGI criteria was achieved with a MADRS score of 31 (sensitivity 93.5%, specificity 83.3%). LIMITATIONS: Studies to validate severity gradations including DSM-IV or ICD-10 diagnostic severity categories are recommended. CONCLUSIONS: Empirically based MADRS cut-off scores to separate moderate from severe depression on the basis of HAMD(17) and CGI severity ratings in patients with major depression were yielded.     

Twenty-four hour leukocyte adherence inhibition test in thyroid cancer patients

The effect of TG cell depletion taking place during 24 hour incubation on the leukocyte adherence inhibition phenomenon was investigated in patients suffering from cancer of the thyroid and healthy volunteers. The depletion coincided with the increase of the adherence inhibition if PPD was used as antigen in both groups, but the reaction to the tumour associated antigen could not be brought into relation with the depletion of TG cells.     

Seroquel (ICI 204 636), a putative “atypical” antipsychotic,in schizophrenia with positive symptomatology: results of an open clinical trial and changes of neuroendocrinological and EEG parameters

Preclinical data indicated that seroquel (ICI 204 636), a dibenzothiazepine with 5-HT₂ and D₂-like receptor antagonistic properties, might be an effective antipsychotic agent, causing fewer extrapyramidal side effects than typical neuroleptics. In the present study, 12 patients suffering from schizophrenia or schizophreniform disorder with predominantly positive symptomatology were treated in an open clinical trial for 4 weeks with seroquel at a maximum dosage of 750 mg/day. The drug was generally well tolerated, and virtually no adverse extrapyramidal side effects such as acute dystonia, parkinsonism or akathisia were observed. Total scores for BPRS (item score 0–6; baseline: 42.0±2.3; mean±SeM), SAPS (64.5±4.8) and SANS (55.0±4.3) showed a moderate decrease at the end of treatment (BPRS: 30.0±3.5; SAPS: 36.1±6.7; SANS: 42.5±5.9), when intention-to-treat analysis was applied. There were considerable interindividual differences in treatment response, with some subjects showing almost full remission of positive symptoms, in contrast to about half of the patients who showed no satisfactory clinical improvement. Interestingly, patients showing good antipsychotic response reported slight initial side effects like mild sedation. Prolactin and TSH levels were not altered during seroquel administration. As to pharmaco-EEG investigations, seroquel caused a moderate increase of the absolute power in the alpha, theta, and beta frequency bands, paralleled by a decrease of delta activity. There were no signs of paroxysmal EEG activity under seroquel. Our results suggest that seroquel may be a well tolerated drug with some antipsychotic properties, exhibiting no extrapyramidal side effects that could be of use in the treatment of schizophrenic patients with positive symptomatology. Further double-blind studies with higher doses, in order to test presumably better efficacy, and with monitoring of plasma levels, are needed to extend the present results.     

Adult onset Still disease: comment on two cases

The adult onset Still disease is a systemic disease of an unknown etiology. As a separate entity, it was described firstly in 1971. The diagnosis is problematic and based upon special criteria. In this study, we present the cases of two patients with adult onset Still's disease, causing several serious differential-diagnostic problems. In the beginning of the disease a high, remittent-intermittent fever was present which reacted well to salycilates. Almost simultaneously, a characteristic, confluent, no itching rash appeared on the trunk and limbs. Pain of little joints of the hands was an early symptom of the disease in both of the cases. Before the final diagnosis, the possibility of any infectious diseases, haematologic malignancies or other autoimmune disease had to be excluded. The aim of this work was to show an overall, up-to-date picture of the disease based on two typical cases.     

The HTR1B 861G>C receptor polymorphism among patients suffering from alcoholism, major depression, anxiety disorders and narcolepsy

The HTR1B receptor gene has been linked to antisocial alcoholism in a Finnish population and an American Indian tribe [Lappalainen et al. , Arch. Gen. Psychiatry, 55 (1998) 989]. Using a candidate gene approach, we genotyped 209 patients with alcoholism, 108 patients with major depression, 32 patients with panic disorder, 50 patients with generalized anxiety disorder, 58 patients with narcolepsy and 74 healthy volunteers for the HTR1B 861G>C polymorphism. There was a higher frequency of the HTR1B 861G alleles among the alcohol-dependent patients as compared to the control subjects (chi(2)=4.02, d.f.=2, P=0.04). However, the association resulted from higher frequencies of the opposite alleles (HTR1B 861G), as originally reported by Lappalainen et al. (1998). Although the association in our study might be due to a type I error, the higher degree of HTR1B allele sharing within both populations could also argue for another alcoholism-relevant gene within the proximity of the HTR1B gene on human chromosome 6.     

No Association Between the Dopamine D2 Receptor Taq I A1 Allele and Earlier Age of Onset of Alcohol Dependence According to Different Specified Criteria

BACKGROUND: The presence of the A1 allele of the dopamine D2 receptor TaqI restriction fragment length polymorphism has been reported to be associated with an earlier age of onset of alcohol dependence as a marker for severity. METHODS: We tested this hypothesis with special regard to the definition of the age of onset of alcoholism in 243 patients with alcohol dependence, according to DSM-IV criteria assessed by the standardized interview Münchner Composite International Diagnostic Interview (M-CIDI), consecutively admitted for detoxification. Additionally, the Addiction Severity Index (ASI) was performed. The TaqIA polymorphism was amplified by polymerase chain reaction (PCR), and the PCR product was digested by the restriction enzyme TaqI. Patients were subsequently divided into an A1 (presence of at least one A1 allele, n = 88) and an A2 group (absence of an A1 allele, n = 155). The following criteria for different definitions of age of onset were used: (1) age of onset of the first occurring symptom necessary for the diagnosis of alcohol dependence according to M-CIDI; (2) age of onset of the last symptom of alcohol dependence according to M-CIDI; (3) age of onset of more than 3 drinking days per week on a regular basis according to ASI; (4) age of onset of more than 3 drinking days-of more than five drinks per drinking day-or at least one binge drinking episode per week on a regular basis according to ASI. RESULTS: The frequency of the A1 allele in our patient sample was 0.208. No statistically significant association between the A1 allele and the age of onset of alcoholism was found. The mean age of onset according to criterion 1 was 30.4 +/- 10.8 years for the A1 group and 30.2 +/- 10.2 years for the A2 group (p = 0.89); for criterion 2, it was 33.3 +/- 10.0 years for the A1 group and 33.9 +/- 10.2 years for the A2 group (p = 0.77); for criterion 3, it was 18.0 +/- 7.5 years for the A1 group and 18.1 +/- 6.1 years for the A2 group (p = 0.92); and for criterion 4, it was 22.3 +/- 9.7 years for the A1 group and 21.8 +/- 8.5 years for the A2 group (p = 0.76). CONCLUSIONS: No association was found between the A1 polymorphism and age at onset of alcohol dependence according to different specified criteria.