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Objective : Subtypologies of schizophrenia based on cross-sectional criteria, such as the nomenclature of the DSMs, have not been successful in identifying valid diagnostic subgroups among patients with schizophrenia. A subtypology that uses criteria to classify individuals on the basis of longitudinal deficits in self-care may identify a more valid subgroup of schizophrenic patients. Method : This study describes the clinical characteristics ofa group of schizophrenic patients identified on the basis ofa longitudinal criterion : at least 5 years of continuous and complete dependence on others for obtaining and maintaining the basic necessities of life, including food, clothing, and shelter. Results : Sixty-one Kraepelinian schizophrenic inpatients, when compared to 80 non-Kraepelinian schizophrenic inpatients who were similar in years of illness, age, and education, demonstrated more severe negative symptoms and more severe formal thought disorder ; yet the severity of their delusions, hallucinations, and bizarre behavior did not differ significantly. None of the Kraepelinian patients and eight non-Kraepelinian patients met DSM-III-R criteria for schizoaffective disorder. Conclusions : Data from this replication study suggest that Kraepelinian schizophrenic patients, identified on the basis of a longitudinal course characterized by severe dysfunctions in self-care, may represent an alternative, and possibly more valid, method of subtyping schizophrenia.

The recently discovered apelin family of peptides mediate their actions by a single G-protein coupled receptor, APJ. We have previously shown that apelins have three major actions in the human cardiovascular system: endothelium-dependent vasodilatation; direct vasoconstriction by interacting with smooth muscle APJ receptor and increased cardiac contractility by action on cardiac myocytes. Our aim was to discover shorter sequences of (Pyr1)apelin-13 retaining agonist activity and use a computational ligand-based strategy to design cyclic peptide agonists and antagonists. Over 50 compounds were synthesised and tested in a competition binding assay. Functional assays for agonists measured vasoconstrictor action in endothelium-denuded human saphenous veins. Antagonist activity was measured in cyclic AMP assays against (Pyr1)apelin-13. Data are expressed as mean±SE, pD2=−log10EC50, Emax=maximum response. The predicted cleavage product of the angiotensin converting enzyme 2 (ACE-2), apelin-13(1–12), inhibited radiolabelled apelin binding and was identified as the shortest sequence potently constricting endothelium-denuded saphenous vein (pD2 9.07%±0.40, Emax 29.30%±9.43% KCl, n=5). The most potent cyclic analogue identified, MM07, inhibited binding with a KD=86%±30 nM, (n=3) and pD2 10.53%±0.24, Emax 21.80%±5.72% KCl, n=3) with a comparable potency and efficacy to (Pyr1)apelin-13 (pD2=8.8%±0.3, Emax 26%±4%, n=15). MM54 inhibited binding, KD=3.42%±0.45 μmol/l, (n=3) and was identified as an antagonist with a pA2 value of 5.9 in a cyclase inhibition assay. The novel cyclic peptide MM07 retains potency and we have identified the first apelin receptor antagonist, MM54 as a pharmacological tool to characterise the apelin system and in the design of small molecule drugs.

Kraepelinian schizophrenics are defined as a subgroup of schizophrenic patients who display at least five continuous years of complete dependence on others for food, shelter, and clothing. These patients have been empirically distinguished from nonkmepelinian schizophrenics in several areas of diagnostic validation. Kraepelinians demonstrate an absence of treatment response, greater CT vencicular abnormalities, more severe formal thought disorder and negative symptoms, less severe symptoms of mood disorder, and greater morbid risk for schizophrenia spectrum disorders in their first degree relatives. The deficit syndrome, as described by Carpenter et al (1987), is defined as the presence of enduring negative symptoms considered to be primary (ie., not secondary to such factors as depression, medication, etc.) and stable (i.e., present both during and between exacerbations of positive symptomatology for at least one year), it was the aim of the present study to assess the relationship between Kraepelinian status and the deficit syndrome, two longitudinal subtypologies of schizophrenia. The Schedule for the Deficit Syndrome was completed by 16 Kraepelinian and 31 nonkmepelinian schizophrenic patients, similar in terms of age, education, and duration of illness. Kraepelinian patients were significantly more likely to present with the deficit syndrome than were nonkraepelinian patients (chi-square 18.0, dfi, p -.0001). Every Kraepelinian patient met criteria for the deficit syndrome while only 35% of the nonkraepelinian patients (I I out of 31) exhibited the deficit syndrome. Of 27 total deficit patients, only 16 were Kraepelinian. Thus, there is substantial overlap between the Kraepelinian and the deficit syndrome subtypes, with the Kraepelinian subtype identifying a more restricted group of patients. 290. EMPIRICAL EVALUATION OF THE FACTORIAL STRUCTURE OF CLINICAL SYMPTOMS IN SCHIZOPHRENIA: IS THE PANSS A VALID SCALE?

The authors found that growth hormone (GH) response to edrophonium was no different in 12 Alzheimer's disease patients than in eight healthy elderly subjects. Previously reported differences could be due to differences in gender or baseline GH concentrations between patients and control subjects.