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The present study is based on the so-called 1957 Lundby cohort, a geographically defined normal Swedish population of 2612 individuals who were evaluated for mental disorders in 1957 and 1972. The annual age-standardised first incidence of depression, with or without other psychiatric symptoms, all degrees of impairment included, was found to be 4.3 per 1000 person years in men and 7.6 per 1000 person years in women. Up until 70 years of age, the cumulative probability of suffering a first episode of depression was 27% in men and 45% in women. [ABSTRACT FROM AUTHOR]

Fifty-three psychiatric patients who had been receiving treatment with lithium continuously for more than two years were examined to estimate the prevalence of lithium-induced hypothyroidism. It was found to be 20 per cent among women. No men were affected among these patients. In order to study the characteristics of the disorder further cases were drawn from another population. One third of the patients developed hypothyroidism during their first year of treatment, others not until after 9 years. About two thirds of the female patients with hypothyroidism had thyroid antibodies. All cases with lithium-induced hypothyroidism showed elevated levels of serum thyrotropin, which in our experience is the laboratory examination of choice in these as well as other cases of "primary" hypothyroidism. Since the probability of detecting these cases at a given control visit was found to be low, we feel that such visits need not include extensive laboratory investigations. Hypothyroid patients responding well to lithium treatment should continue their medication combined with appropriate thyroxine substitution. [ABSTRACT FROM AUTHOR]

Two methods for detecting the phenolic glycolipid, PGL-1. a Mycobacterium leprae-specific molecule, in the urine of leprosy patients are described. Both methods rely on the l00-fold preconcentration of the urine, which can be accomplished by a single-step ultrafiltration procedure. The equivalent of approximately 2.5μg of PGL-1/ml was detected in the urine of LL patients with an inhibition ILISA. The second method, a direct dot-blot assay on nitrocellulose paper, was much simpler and more sensitive. As little as 3 ng of antigen was detected by the dot-blot technique. PGL-1 was detected in the urine of LL patients. [ABSTRACT FROM AUTHOR]

Myofibrillar myopathies (MFM) are caused by mutations in at least 6 Z-disc associated proteins, including ZASP, myotilin, desmin, BAG3, αβ-crystallin, and filamin C. MFM are characterized by early and prominent disruption of the Z-disc with focal dissolution of myofibrils and ectopic accumulation of myofibrillar proteins. Similar morphological changes in skeletal muscle in MFM suggest a shared cellular and molecular disease mechanism. ZASP interacts with myotilin, and knock down of ZASP in mice results in alterations in the amounts of other MFM gene products. We hypothesize that ZASP associations with other MFM gene products play a role in the disease mechanism in zaspopathy. To examine the effects of ZASP mutations on the other MFM gene products in skeletal muscle, WT and mutant (A147T and A165V) ZASP-GFP proteins were expressed by electroporation in the tibialis anterior muscles of opposite limbs in wild type mice (n =18). Muscle tissues were harvested at 1, 2, and 4weeks after the electroporation. The amount and distribution of MFM gene products, F-actin, and α-actinin-2 were examined in the electroporated mouse muscle fibers and in skeletal muscle fibers of patients with zaspopathy. Wild type and mutant ZASP interactions with other MFM gene products were examined by co-IP and pulldown assays. Preliminary data suggests that wild type and mutant ZASP associate with myotilin, desmin, and BAG3. The effects of ZASP mutations on the other MFM gene products and the effects of the other MFM gene defects on ZASP will provide insight into shared disease mechanisms in this group of degenerative myopathies. [Copyright &y& Elsevier]

Mechanical stress induced by contractions constantly threatens the integrity of muscle Z-disc, a crucial force-bearing structure in striated muscle. The PDZ-LIM proteins have been proposed to function as adaptors in transducing mechanical signals to preserve the Z-disc structure, however the underlying mechanisms remain poorly understood. Here, we show that LDB3, a well-characterized striated muscle PDZ-LIM protein, modulates mechanical stress signaling through interactions with the mechanosensing domain in filamin C, its chaperone HSPA8, and PKCα in the Z-disc of skeletal muscle. Studies of Ldb3 Ala165Val/+ mice indicate that the myopathy-associated LDB3 p.Ala165Val mutation triggers early aggregation of filamin C and its chaperones at muscle Z-disc before aggregation of the mutant protein. The mutation causes protein aggregation and eventually Z-disc myofibrillar disruption by impairing PKCα and TSC2-mTOR, two important signaling pathways regulating protein stability and disposal of damaged cytoskeletal components at a major mechanosensor hub in the Z-disc of skeletal muscle.

The core of skeletal muscle Z-discs consists of actin filaments from adjacent sarcomeres that are cross-linked by α-actinin homodimers. Z-disc-associated, alternatively spliced, PDZ motif-containing protein (ZASP)/Cypher interacts with α-actinin, myotilin, and other Z-disc proteins via the PDZ domain. However, these interactions are not sufficient to maintain the Z-disc structure. We show that ZASP directly interacts with skeletal actin filaments. The actin-binding domain is between the modular PDZ and LIM domains. This ZASP region is alternatively spliced so that each isoform has unique actin-binding domains. All ZASP isoforms contain the exon 6-encoded ZASP-like motif that is mutated in zaspopathy, a myofibrillar myopathy (MFM), whereas the exon 8-11 junction-encoded peptide is exclusive to the postnatal long ZASP isoform (ZASP-LΔex10). MFM is characterized by disruption of skeletal muscle Z-discs and accumulation of myofibrillar degradation products. Wild-type and mutant ZASP interact with α-actin, α-actinin, and myotilin. Expression of mutant, but not wild-type, ZASP leads to Z-disc disruption and F-actin accumulation in mouse skeletal muscle, as in MFM. Mutations in the actin-binding domain of ZASP-LΔex10, but not other isoforms, cause disruption of the actin cytoskeleton in muscle cells. These isoform-specific mutation effects highlight the essential role of the ZASP-LΔex10 isoform in F-actin organization. Our results show that MFM-associated ZASP mutations in the actin-binding domain have deleterious effects on the core structure of the Z-discs in skeletal muscle.

Transgenic mice that overexpress PKCalpha in the epidermis (K5-PKCalpha mice) exhibit acute CXCR2-mediated intraepidermal neutrophilic inflammation and a strong epidermal hyperplasia in response to application of 12-O-tetradecanoylphorbol-13-acetate (TPA). We now show that hyperplasia is independent of infiltrating neutrophils. Furthermore, when K5-PKCalpha mice were initiated with 7,12-dimethylbenz(a)anthracene (DMBA) and promoted with a low dose of TPA, 58% of K5-PKCalpha mice developed skin papillomas that progressed to carcinoma, whereas wild-type mice did not develop tumors. We confirmed that CXCR2 is expressed by keratinocytes and showed that transformation by oncogenic ras (a hallmark of DMBA initiation) or TPA exposure induced all CXCR2 ligands. Ras induction of CXCR2 ligands was mediated by autocrine activation of epidermal growth factor receptor and nuclear factor-kappaB, and potentiated by PKCalpha. Oncogenic ras also induced CXCR2 ligands in keratinocytes genetically ablated for CXCR2. However, ras transformed CXCR2 null keratinocytes formed only small skin tumors in orthotopic skin grafts to CXCR2 intact hosts, whereas transformed wild-type keratinocytes produced large tumors. In vitro, CXCR2 was essential for CXCR2 ligand-stimulated migration of ras-transformed keratinocytes and for ligand activation of the extracellular signal-regulated kinase (ERK) and Akt pathways. Both migration and activation of ERK and Akt were restored by CXCR2 reconstitution of CXCR2 null keratinocytes. Thus, activation of CXCR2 on ras-transformed keratinocytes has both promigratory and protumorigenic functions. The up-regulation of CXCR2 ligands after initiation by oncogenic ras and promotion with TPA in the mouse skin model provides a mechanism to stimulate migration by both autocrine and paracrine pathways and contribute to tumor development.

Background: The study was carried out to quantify the excretion of the selective serotonin reuptake inhibitor paroxetine in breast milk., Method: In 6 lactating women, the concentrations of paroxetine in breast milk and serum were studied at the times for assumed minimum (24 hours after dose intake) and maximum (4-7 hours after dose intake) drug levels in milk. Moreover, a seventh subject was studied with frequent and regular sampling throughout a dose interval of 24 hours at 2 different dose levels., Results: The mean milk/serum concentration ratios in the first 6 subjects ranged from 0.39 to 1.11 (overall mean +/- SD = 0.69 +/- 0.29), and the mean estimated dose to the infants ranged from 0.7% to 2.9% (overall mean +/- SD = 1.4% +/- 0.79%) of the weight-adjusted maternal dose. Based on area-under-the-curve data from the seventh subject, the milk/serum concentration ratio was 0.69 at a dose of 20 mg/day and 0.72 at a dose of 40 mg/day; the estimated relative doses to the infant were 1.0% and 2.0%, respectively. The mean increase in milk paroxetine concentrations from assumed minimum to assumed maximum was 61% (range, 4%-172%; p < .01). The mean paroxetine concentration in hindmilk was 78% higher than in foremilk (range, 16%-169%; p < .01), an increase that was parallel to the increase in milk triglyceride levels (r = 0.83, p = .005). No adverse drug reactions or unusual behaviors were reported in the infants., Conclusion: The study indicates that the relative dose to a suckling infant for paroxetine is lower than that reported for fluoxetine and citalopram and higher than that reported for sertraline and fluvoxamine.

Hippocampal pyramidal neuron size was determined in all Cornu Ammonis subregions - CA1-CA4 - in five chronic schizophrenic men and compared with eight controls matched with respect to age and sex. Four out of five probands and the same eight controls had been examined in a previous study showing a significantly lower cell count and disorientation of pyramidal cells in the CA1- CA3 subregions of the schizophrenics. There was also a negative correlation between the total number of cells and the number of disoriented cells. In this study it was shown that the schizophrenic probands also had significantly smaller neurons in all subregions. There was a significant negative correlation between pyramidal neuron size and the number of disarrayed neurons in each subregion, and there was a significant positive correlation between neuron size and the total number of pyramidal cells in CA1 and CA2, but not in CA3 and CA4. The consistency of hippocampal anomalies in these schizophrenics is, thus, demonstrated by the statistical relations between the different parameters examined.

Aims: The objective of this study was to measure to secretion of the selective serotonin uptake inhibitor citalopram in breast milk., Methods: The excretion of citalopram in breast milk was studied at steady-state conditions in two patients with depression and in one healthy volunteer after ingestion of a single dose citalopram., Results: Milk/serum concentration ratios based on single pairs of samples from the two patients ranged from 1.16 to 1.88. Based on milk concentration data from the patients, the absolute dose ingested by a suckling infant would be 4.3-17.6 micrograms kg-1 day-1, and the relative dose 0.7-5.9% of the weight-adjusted maternal dose. Based on area-under-the-time-concentration curves from the healthy volunteer, the milk/serum ratio was 1.00, the absolute dose to the infant during steady-state conditions would be 11.2 micrograms kg-1 day-1 and the relative dose 1.8% of the weight-adjusted maternal dose., Conclusion: The study shows that the relative dose to a suckling infant is close to that reported for fluoxetine, and higher than reported for fluvoxamine, paroxetine and sertraline.

Setting: Enzymes from Mycobacterium tuberculosis are potent antigens and might thus be of interest in the serodiagnosis of tuberculosis., Objective: The purpose of the study was to purify and characterize the two enzymes isocitrate dehydrogenase (IDH) and malate dehydrogenase (MDH) from, M. tuberculosis and to evaluate their potential in the serodiagnosis of tuberculosis., Design: The two enzymes were analysed for specificity by electrophoresis and then purified by means of affinity chromatography using reactive dyes and ion exchange chromatography. The two isolated enzyme fractions were analysed by ELISA, using antisera against related organisms. They were then tested as antigens in ELISA together with sera from tuberculous patients and controls., Results: The electrophoretical analyses showed that the two enzymes each differed markedly from the corresponding enzymes of other mycobacteria. The serological analyses, however, could not distinguish between either IDH or MDH from other mycobacteria, but organisms of other genera, such as Nocardia, gave much weaker responses. When IDH and MDH were tested with sera from tuberculous patients and controls the former gave clearly higher optical density values than the latter., Conclusion: The enzymes/antigens IDH and MDH may be of value in developing a serological test for tuberculosis. The latter fraction seemed particularly capable of discriminating patients from controls.

Strains of Mycobacterium bovis, M. bovis BCG, and M. tuberculosis, including a so-called Canetti strain, were analyzed by means of two-dimensional immunoelectrophoresis (2D-IE), 2D-IE combined with enzyme staining, and multilocus enzyme electrophoresis (MEE). The results demonstrated a close antigenic and enzymatic resemblance among all the strains tested, even though the BCG strains could be divided into two groups based on the presence of one precipitinogen. Eight of the precipitinogens were shown to correspond to enzymes in M. bovis BCG and 10 in M. tuberculosis. Thus, catalase, isocitrate dehydrogenase, malate dehydrogenase, peroxidase, and several others were identified. By means of MEE the strains of M. tuberculosis, M. bovis, and M. bovis BCG could be differentiated. The analyses further indicated that the M. tuberculosis strain Canetti was more closely related to M. bovis than to M. tuberculosis.

Eleven schizophrenic psychotic and 11 manic psychotic patients have been compared with each other and with a reference group of 34 dentists with respect to their emotional experience of seven complex nonverbal sounds. A rating form was used which measures three factors of emotional perception: tension-relaxation (factor I), gaiety-gloom (factor II), and attraction-repulsion (factor III). Analyses of variance of the factor scores revealed main tendencies between the psychopathological groups in factor I and III, i.e. schizophrenic psychotics rated the sounds generally as more tense and more attractive than manic psychotics. The manic psychotics rated the sounds as generally less tense and very much more attractive than the other groups. In factor II the manic psychotics rated one piece as significantly more gay than the other groups. It is discussed in what ways these differences of complex sound perception may be related to characteristic symptoms of the psychopathological states. No convincing evidence may be drawn from this study supporting the assumption that the two psychopathological groups might differ in a specific way in relation to any elementary structural property of the sounds.

The concept of cycloid psychosis has gained increasing acceptance during recent decades. Using the diagnostic criteria of Perris and Brockington, an intelligible delineation of a group of patients has been obtained. Few epidemiological data on cycloid psychosis have been reported so far. The objective of the present study was to describe the one-year incidence of cycloid psychosis in a clinical sample. The diagnostic registers of all patients hospitalized for a functional or an organic psychosis and discharged in the year 1983, in Lund, Sweden were investigated. 514 patients were identified of whom 83 were admitted to hospital for the first time. 29 of these patients had a functional psychosis and were below the age of 50. In this age group 7 cases (4 women, 3 men) fulfilled the diagnostic criteria of cycloid psychosis and thus constituted almost one fourth of all first admissions of functional psychoses that year. The one-year incidence for first admission in cycloid psychosis was 5.0 per 100,000 inhabitants in women and 3.6 per 100,000 inhabitants in men within the age group 15-50 years in the catchment area of 163,175 persons. We conclude that cycloid psychosis constitutes a considerable proportion of functional psychoses in both sexes.

Cerebrospinal fluid (CSF), urine, platelet and neuroendocrine challenge tests of monoaminergic function give evidence of monoamines, especially serotonin, playing an important role in suicidal behavior. However, additional clinical, social and biochemical factors are necessary to better define suicide-prone psychiatric patients.

Vascular dementia represents a group of diseases of great medical and social impact. Its etiology is largely unknown but is most likely multifactorial. Factors related to the brain circulation are involved. The aim of the present study was to find out if personality and social background factors might have a clear precipitating or protective value. This study comprises a total population of 2,612 individuals from a geographically delimited area, Lundby, in southern Sweden. In 1957, Hagnell personally examined 99% of the population. A follow-up study of the same individuals, irrespective of domicile, was performed 15 years later. No social background factors proved to be relevant in this study. Personality factors, including psychosomatic reactions, did, however, demonstrate a highly predictive influence on the risk of developing vascular dementia.

Corticotropin-releasing hormone (CRH), somatostatin (SOM), delta-sleep-inducing peptide (DSIP), neuropeptide Y (NPY), beta-endorphin (beta-END), and vasopressin (AVP), which are regarded as being involved in the HPA-regulation were investigated in lumbar CSF of 44 suicide attempters. The patients were diagnosed according to the DSM-III-R, and rated with the MADRS. The neuropeptides were compared with the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in CSF and with post-dexamethasone plasma cortisol. We found strong correlations between CRH and the peptides SOM and beta-END. The latter also correlated positively with SOM. There were no differences between men and women. Patients with major depressive disorders had significantly lower SOM, CRH, and DSIP than other patients. Both SOM and beta-END correlated negatively with post dexamethasone plasma cortisol in all patients. We found no significant relationships between neuropeptides and CSF 5-HIAA. Patients who had made previous suicide attempts had significantly lower CRH than those who had not. No other significant associations between neuropeptides and suicidal subgroups of patients appeared, and there was no indication of specific neuropeptide patterns in patients who later completed suicide. Intercorrelations of some neuropeptides and low SOM and DSIP in major depressed patients are findings in line with those by others.

Biochemical studies related with suicidal behavior have mainly dealt with monoaminergic and corticosteroidal measures. We used some of these measures in a study of 61 suicide attempters who, except for occasional doses of benzodiazepines, had been medication free for a mean of 16 days. The monoamine metabolites 5-hydroxyindoleacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenylglycol were measured in lumbar cerebrospinal fluid (CSF). We found that violent suicide attempters (N = 18) had 5-hydroxyindoleacetic acid concentrations below the median of all patients, whereas the concentrations of 3-methoxy-4-hydroxyphenylglycol were mainly above the median. We found no significant differences between violent and nonviolent (N = 43) attempters concerning CSF homovanillic acid, 24-hour urinary norepinephrine-epinephrine and cortisol, activity of monoamine oxidase in platelets, or post-dexamethasone plasma cortisol. Four patients completed suicide, and 3 of them had CSF 5-hydroxyindoleacetic acid concentrations at or below the median. All completed suicides had CSF 3-methoxy-4-hydroxyphenylglycol concentrations above the median. Urinary measures and platelet monoamine oxidase activity of completed suicides were in the higher concentration ranges. Patients who repeated suicidal behavior after the index investigation had low 24-hour urinary cortisol levels more often than those who did not repeat. Because our subgroups of patients are small, we cannot draw any firm conclusions about the value of our CSF and urinary biochemical findings predicting suicidal behavior. However, our CSF findings in violent suicide attempters are similar to those observed in other studies.

In recent years research on senile dementia of the Alzheimer type (SDAT) has made progress within the field of pathology and to a certain extent in that of heredity. Within epidemiology, the search for risk factors is intensifying but the findings are still inconclusive. The present study of possible risk factors concentrates on environmental and personality factors. The total population of 2612 persons from a geographically delimited area, Lundby, two neighbouring parishes in southern Sweden, was examined in 1957 by one psychiatrist (Hagnell). A follow-up study of the same population, irrespective of domicile, was performed 15 years later, in 1972. Various precipitating as well as protective personality background factors were found to be significant for the outcome of SDAT, but no environmental factors appeared to be statistically significant in this cohort.

In this study, a total population, the 1957 Lundby cohort, was investigated with regard to the incidence of vascular dementia over a 15-year period, and to provide a succeeding study with basic data concerning the background factors for vascular dementia. The 1957 cohort comprises 2,612 persons who were registered in the geographically delimited Lundby area on July 1, 1957. The lifetime risk of developing vascular dementia was found to be 34.5% in men and 19.4% in women when all degrees of impairment were taken into account, the preponderance for the male sex being very obvious.

Peripheral serotonergic parameters were studied in 17 patients with a history of suicidal behavior and in 17 age- and sex-matched healthy controls. Serotonin2 receptor function in platelets, measured as serotonin-induced [32P]phosphatidylinositol 4,5-bisphosphate hydrolysis, was significantly higher in patients than in age- and sex-matched controls. Increased serotonin2 receptor transduction was not correlated to psychiatric diagnosis, drug treatment or a history of violent suicide attempt. Monoamine oxidase activity was lower in platelets from patients with a history of suicidal behavior than in controls. In addition, whole blood serotonin was analyzed but no significant alterations were found in blood from patients.

In spite of the great impact of senile dementia of the Alzheimer type (SDAT) on society, far too little is known about its epidemiology. In this study of a total, normal population from a geographically delimited area in Sweden, Lundby, 2612 persons were examined in 1957 by one psychiatrist (Hagnell). In 1972 the same population was reexamined irrespective of domicile. The incidence and risk of contracting SDAT during the 15 years were calculated. No cases of SDAT were diagnosed before the age of 60 years. The lifetime risk was for men 25.7% and for women 26.2%. When only the very severely impaired were taken into account, the figures were 14.5% in men and 14.6% in women.

The incidence and risk of cycloid psychosis were investigated in the 1947 cohort of the Lundby Study. No male cases were found. For women the incidence rate (per 100 observation years) was 0.016%. The cumulative probability, i.e. risk up to 60 years of age, was 0.7%. These figures are about half of those for schizophrenia in women in the same population. It is concluded that cycloid psychosis constitutes a substantial part of psychotic disorders among women.

The attitudes of patients were measured after 4 days and at discharge during two 4-month periods. The attitudes were related to ratings of symptoms, patient background, and type of treatment contract used (cooperation or staff-directed). The patients were generally satisfied with their treatment. A mere 7% disapproved of the general ward structure. The attitude data were subjected to a factor analysis and a 7-factor solution explaining 70% of the variance was found to be suitable. The factors were labelled Ward Structure, Key Worker, Nursing Care, Group Treatment, Psychopharmacological Treatment, Social Network, and Other Patients. A high level of satisfaction in the Ward Structure, Nursing Care, Psychopharmacological Treatment, and Other Patients factors was found to be related to a lower incidence of symptoms at discharge. The staff-contract group showed more favourable attitudes in the Nursing Care factor (both initially and at discharge) and the Psychopharmacological Treatment factor (only initially), while the cooperation-contract group did so in the Social Network factor. It is suggested that the two contract procedures resulted in the development of different kinds of interpersonal relationships during treatment, the cooperation group relying more on the social network, whereas the staff-contract group was more apt to rely on psychopharmacological treatment and on the nursing staff.

A medium frequency flicker stimulus of 10 Hz is evaluated in routine clinical ERG recording in detecting cone disorders. Tested on a number of normal eyes and on eyes with confirmed or suspected retinal disease it appears to be very useful as a complement to the standard program with the Krakau-Ohman apparatus. It yields an easily recordable and quantified response.

In 1957 all inhabitants (2,612) in a delimited geographical area, Lundby, were examined by a psychiatrist. Personality traits were scored for each individual. During the following 15 years 58 men became alcoholics (44 who had been 15 years or over in 1957). Among the men who in 1957 were scored 'subsolid in combination with symptom neurosis' the risk of becoming an alcoholic was increased 13.5 to 15.8 times. Protective against alcoholism was 'subvalidity in combination with psychosomatic symptoms'. The men with this combination had their risk decreased 12 times. The prediction of alcoholism depended on which factors and which combinations were used. With a sensitivity of 50% a specificity of almost 90% was reached; with a sensitivity of 60% specificities between 70% and 80% were reached.

The general trend of avoiding and shortening in-patient treatment raises the question of the stability of treatment gains made during hospitalization. A 6-month follow-up was made for patients treated on a short-term psychiatric ward. The origin was a controlled study of two models of patient involvement in treatment planning. Patients benefiting most from a cooperation procedure during hospitalization were those with socio-psychological treatment objectives and those treated in a Basic Activation Group on the ward. The superior outcome for these patients was not stable during the period of follow-up, resulting in an incongruence between in-hospital and post-hospital adjustment. Furthermore, these patients at time of follow-up showed an increased confidence in the staff of the ward and a decrease in the rated importance of their social network. It is suggested that this is the result of dependency reactions and a separation process from the therapeutic milieu of the ward which were not resolved at time of discharge. Greater concern should be invested in formulating the treatment contract in an out-patient context in order to place the emphasis on the real life situation of the patient.

The aqueous flare (AF) of an intact rabbit eye was measured by a photoelectric instrument. Local application of prostaglandin E2 (PGE2) and its precursor arachidonic acid (AA) gave an almost identical increase of the AF. The response to AA but not to PGE2 was inhibited by pretreating the eye locally with a solution of indomethacin. The ability of indomethacin to inhibit the aqueous flare response (AFR) to an agent is assumed to indicate that a kind of prostaglandin is the effector of the AF. Indomethacin blocked the AFR to infrared irradiation of the iris and to intravenous administration of endotoxin but not to subcutaneous administration of alpha-melanocyte-stimulating hormone (alpha-MSH).

The differentiating power of two individually related measures of outcome, target complaints and psychiatrists' evaluation of individually defined treatment objectives, were studied in two models of treatment planning, one with and one without active patient participation. Target complaints were measured at admission, after 5 days and at discharge. Treatment objectives were initially defined in written treatment contracts and evaluated at discharge. These measures were compared with patients' self-reported symptoms as well as with independently rated clinical symptoms at admission and discharge. Both target complaints and psychiatrists' evaluations measured improvement during treatment. The differentiating power between the two experimental conditions was, however, much weaker than that of the symptom rating scales. The psychiatrists' evaluations were strongly influenced by state at discharge and only to a minor extent by changes during treatment. It is concluded that symptom rating scales are superior to individualized measures of outcome in studies on a general psychiatric ward, possibly because the patients are fairly homogenous concerning anxiety.

Selective staining procedures for four different enzymes (malate dehydrogenase, glutamic oxaloacetic transaminase, leucine aminopeptidase and glucose phosphate isomerase) in combination with two-dimensional immunoelectrophoresis were successfully applied to the analysis of antigen preparations from mycobacteria. Thus, a precipitate corresponding to malate dehydrogenase could e.g. be demonstrated in multi-linear precipitation patterns of Mycobacterium avium, Mycobacterium bovis BCG, Mycobacterium intracellulare, Mycobacterium kansasii, Mycobacterium marinum and Mycobacterium phlei. The analytical approach described can be advantageously used for identification of mycobacterial precipitinogens of enzyme character.

Fifty-three patients with acute psychotic disorders (diagnosed according to DSM-III) were treated with thioridazine alone and observed during periods of up to 2 months. The amelioration of paranoid ideas and hallucinations (target symptoms) and of concentration difficulties, disorientation, reduced appetite, and reduced sleep (additional symptoms) was studied by repeated psychopathology ratings (CPRS). The patients were classified as "fast, slow or partial responders" according to the therapeutic effect registered on each target symptom. Paranoid ideas disappeared completely after less than 3 weeks of treatment in 28% of the patients (fast responders) and after more than 3 weeks in 32% (slow responders). Hallucinations disappeared significantly faster than paranoid ideas; 47% of the patients were completely free from hallucinations after less than 2 weeks of treatment (fast responders) and 38% after more than 2 weeks (slow responders). The following factors were significantly correlated to positive treatment effects of thioridazine: 1) diagnosis involving a brief history of psychotic symptoms before admission; 2) a low CPRS score for paranoid ideas on admission; 3) presence of disorientation on admission; 4) normal appetite on admission, and 5) rapidly reached optimal serum concentration of the drug.

Twenty-one serum samples from 11 schizophrenic patients receiving long-term haloperidol therapy were analyzed for haloperidol concentrations by two different radioimmunoassays (RIAs) and gas chromatography (GC). There was a good correspondence between the RIA and GC values over a wide range of drug concentrations. However, compared with the specific GC technique, both RIA methods overestimated haloperidol concentrations, reflecting differences in the specificities of the two RIA antibodies. One of the RIA methods had the requisite specificity for application to patients treated with long-term haloperidol therapy, although further methodological refinement will be required for its general clinical application. Haloperidol values determined by GC and RIA analyses correlated highly with prolactin concentrations in the same samples, suggesting that the usefulness of prolactin measurement as an "in vivo bioassay" for circulating levels of haloperidol should be further explored.