Mitochondria-targeted antioxidant MitoQ ameliorates ischaemia-reperfusion injury in kidney transplantation models.

BACKGROUND: Ischaemia-reperfusion (IR) injury makes a major contribution to graft damage during kidney transplantation. Oxidative damage to mitochondria is an early event in IR injury. Therefore, the uptake, safety, and efficacy of the mitochondria-targeted antioxidant MitoQ were investigated in models of transplant IR injury. METHODS: MitoQ uptake by warm and cooled pairs of pig and declined human kidneys was measured when preserved in cold static storage or by hypothermic machine perfusion. Pairs of pigs' kidneys were exposed to defined periods of warm and cold ischaemia, flushed and stored at 4°C with or without MitoQ (50 nmol/l to 250 µmol/l), followed by reperfusion with oxygenated autologous blood in an ex vivo normothermic perfusion (EVNP). Pairs of declined human kidneys were flushed and stored with or without MitoQ (5-100 µmol/l) at 4°C for 6 h and underwent EVNP with ABO group-matched blood. RESULTS: Stable and concentration-dependent uptake of MitoQ was demonstrated for up to 24 h in pig and human kidneys. Total blood flow and urine output were significantly greater in pig kidneys treated with 50 µmol/l MitoQ compared with controls (P = 0.006 and P = 0.007 respectively). In proof-of-concept experiments, blood flow after 1 h of EVNP was significantly greater in human kidneys treated with 50 µmol/l MitoQ than in controls (P ≤ 0.001). Total urine output was numerically higher in the 50-µmol/l MitoQ group compared with the control, but the difference did not reach statistical significance (P = 0.054). CONCLUSION: Mitochondria-targeted antioxidant MitoQ can be administered to ischaemic kidneys simply and effectively during cold storage, and may improve outcomes after transplantation.

Managing schizophrenia: an update.

Atypical antipsychotic drugs offer hope to schizophrenics and their families. Controversy continues over their cost-effectiveness but patient surveys suggest increased compliance and thus improved mental health. This article reviews schizophrenia management, exploring the consequences of failing to adopt modern therapies in hampering compliance and stigmatizing the mentally ill.

Obsessive-compulsive disorder with delusions.

Obsessive-compulsive (OCD) and delusional disorders (DD) have been recognised with increased frequency in recent years, and the propensity of some OCD subjects to become deluded has become a focus of interest. This study reports illness-specific demography along with measures of symptom severity and tests to assess schizotypal ideation, dysfunctional attitudes, attributional and attention bias in 30 patients with OCD, 29 with DD, 16 with OCD with delusions (OC-DD) and a 30-subject control group (CG). Obsessional features appeared before delusions in the OC-DD group, suggesting that OCD was the primary pathology. Delusions were more likely in subjects obsessional about one rather than multiple themes. There was some support for proposals that depression and schizotypy may bring out delusions in OCD and some evidence for the utility of categorising OCD according to the number of obsessions a subject has.

Delusional disorders: boundaries of a concept.

In 1987, DSM-III introduced the term delusional disorder. In so doing they gave new life to a concept that had predated but was delineated in its modern form by Kraepelin and developed most notably in France in the second and third decades of this century. While the current concept of delusional disorder is defined in a manner that distinguishes it from schizophrenia, a consideration of the evolution of thinking about delusional syndromes in France suggests that current distinctions are based on descriptive convenience rather than any understanding of the mechanisms that might produce phenotypic variations. If the purpose of accurate descriptions is to assist research, this state of affairs would seem unsatisfactory.

Cyclic liquefaction and its evaluation based on the SPT and CPT

Soil liquefaction is a major concern for structures constructed with or on sandy soils. This paper describes the phenomena of soil liquefaction, provides suitable definitions, and provides an update on methods to evaluate cyclic liquefaction using primarily the Standard Penetration. Test and the Cone Penetration Test (CPT). A new method is described to estimate grain characteristics directly from the CPT and to incorporate this into one of the methods for evaluating resistance to cyclic example is also described ffor correcting the results of the CPT in thin layers. A worked example is also provided. This paper is the final submission from the authors to the proceedings of the 1996 NCEER workshop on soil liquefaction; a similar version has been submitted for review to the Canadian Geotechnical Journal. (AU)

Probabilistic reasoning in obsessive-compulsive and delusional disorders.

BACKGROUND: Delusional disorder (DD) and obsessive-compulsive disorder (OCD) have been investigated in previous studies using probabilistic reasoning paradigms and abnormalities in each group have been reported. No study to date has compared results between these groups. This study compares patients with these disorders with those who have both phenomena. METHODS: Thirty subjects with DD, 29 with OCD and 16 with obsessive and delusional features were compared with 30 normal controls in a study of probabilistic reasoning using two different computer-based tasks involving a Bayesian paradigm. RESULTS: Deluded subjects showed a 'jump to conclusions' reasoning style, but on a test that added a consequence to their choices did not differ from normals. OCD subjects deviated from Bayesian and control norms to a greater degree than did DD subjects. In subjects with mixed psychopathology, the presence of both phenomena appeared to 'normalize' these probability estimates. CONCLUSIONS: Our findings extend those of others but require cautious interpretation as to the role of probabilistic reasoning in the genesis of delusions or obsessions. Obsessionals in both the OCD and Mixed groups, showed substantial deviation from Bayesian norms, suggesting that obsessionality leads to a reasoning style that is less 'normal' than that of delusionals. Further work is required to investigate clinical correlates of these findings which provide modest support for the proposal that the combination of obsessions and delusions confers greater functional advantages than simply having delusions or obsessions.

Partial trisomy of 15q due to inserted inverted duplication.

A de novo abnormal chromosome 15, with an inverted duplication of the segment (15q13.3 --> 15q21.3) at 15q24.3, was found in a boy with mild developmental delay, facial dysmorphism, Marfan-like appearance and severe language delay. There is an unusual disparity between the severe lack of speech and the presence of reasonable skills in other areas.

Attributional style and delusions: an investigation based on delusional content.

Individuals with persecutory delusions have been reported to make external and stable attributions for negative events and to have a tendency towards internal attributions for positive events. It remains unclear whether this abnormality is present in individuals with non-persecutory delusions. Using the Attributional Style Questionnaire, we assessed the attributional style of 19 individuals with persecutory or grandiose delusions (PG), 12 individuals whose delusional beliefs were non-persecutory and non-grandiose (NPG) and 24 controls. The PG group displayed externality in their causal attributions for bad events but those in the NPG group did not differ from controls. Both deluded groups were significantly more stable in their attributions for bad events in comparison to controls. Such findings argue against a primary role for attributional biases in the genesis of delusions, although a role in shaping delusional content and maintaining the disorder and a role for external attributions in defending against reductions in self-esteem cannot be excluded.

Two sibs with anophthalmia and pulmonary hypoplasia (the Matthew-Wood syndrome).

We describe two sibs with pulmonary hypoplasia and anophthalmia; one also had a number of other malformations. Only one other broadly similar case could be found in the literature, and it was an isolated occurrence. The condition is named the Matthew-Wood syndrome.

Delusional phenomenology--dimensions of change.

Although the application of cognitive techniques to both the measurement and modification of delusional beliefs has recently been developed in more theoretical detail (e.g. Chadwick & Lowe, 1994, Behaviour Research and Therapy, 32, 355-367) there has not been an effort to examine the variability of delusional phenomenology across time. In the present study we report on the treatment of 6 individuals who fulfilled DSM-III-R (American Psychiatric Association, 1987) criteria for Delusional Disorder and who received cognitive therapy targeted specifically on the single symptom of their delusional belief(s). Single-case time-series methodology was used to examine the associations between different aspects of delusional phenomenology through baseline and intervention study phases. Belief maintenance factors were found to be significantly associated with conviction in all 3 individuals who responded to the intervention. Negative behaviours, affect associated with the belief, preparedness to talk to others about the belief and insight were associated with conviction in some individuals but not others. Preoccupation and acting on the belief were aspects of delusional phenomenology that were found to systematically vary independent of belief conviction. The results support a multidimensional view of delusional phenomenology and the process of change during cognitive intervention.

Cognitive processes in delusional disorders.

BACKGROUND: Studies of schizophrenics with persecutory delusions have shown cognitive biases in subjects who are deluded. It has been suggested that their delusions defend against depression. This study challenges the assumption that delusional disorder (DD) patients are covertly depressed. METHOD: Clinical and demographic data, and responses to questionnaires designed to assess schizotypy, depression, dysfunctional attitudes, attributional and attention biases were collected from 29 patients satisfying DSM-III-R criteria for DD. These were compared with 20 matched normal controls and results from published studies of schizophrenics. RESULTS: DD subjects did not show abnormal levels of overt or covert depression or schizotypy. They showed high levels of dysfunctional attitudes (P < 0.0001), a distinctive attributional style (P = 0.01), and increased attention to threat-related stimuli (P = 0.01). CONCLUSIONS: DD is a distinct disorder predicated upon sensitivity to threat and biases of attention and attribution. These findings may have implications for the cognitive therapy of these disorders.

Trypsin inhibition: a potential cause of cobalamin deficiency common to the pathogenesis of Alzheimer-type dementia and AIDS dementia complex?

There is increasing evidence for an association between Alzheimer-type dementia (AD) and nutritionally independent cobalamin deficiency. Furthermore, low serum cobalamin values occur in a kindred with familial Alzheimer's disease (FAD) and histopathological confirmation of AD neuropathology. The Cobalamin deficiency could be either a consequence or cause of amyloidogenesis. Cobalamin deficiency is also associated with the acquired immunodeficiency syndrome (AIDS). A common pathogenic mechanism may exist for AIDS dementia complex (ADC) and AD, but there is no explanation at present for these associations. This paper presents the hypothesis that protease inhibition is a common factor in AD and ADC resulting in protein-bound cobalamin malabsorption and disrupted cobalamin metabolism.

Propofol anaesthesia in electroconvulsive therapy. Reduced seizure duration may not be relevant.

BACKGROUND: The induction agent propofol is known to reduce electroconvulsive therapy (ECT) seizure duration. It is assumed that outcome from depression is adversely affected by this agent. This study compares propofol and methohexitone as induction agents for ECT. METHOD: In a prospective, randomised, double-blind study 20 subjects with major depressive disorder (DSM-III-R criteria) received propofol or methohexitone anaesthesia. The Hamilton Depression Rating Scale and Beck Depression Inventory were used to assess depression before therapy, at every third treatment, and at the end of therapy. Seizure duration was measured using the cuff technique. RESULTS: Mean seizure durations (P < 0.01) and mean total seizure duration (P < 0.01) were shorter in the propofol group. There was no difference in outcome. CONCLUSIONS: Use of propofol may not adversely affect outcome from depression and it is not necessarily contraindicated as an induction agent for ECT. Our results should be interpreted cautiously, and larger studies are needed.

Prenatal testosterone levels in XXY and XYY males.

It has been postulated that behavioural differences between normal males and those with an additional X or Y chromosome may be related to pre- or postnatal hormonal variations. The prenatal hormone status was investigated using amniotic fluid obtained at antenatal diagnosis between 16 and 20 weeks gestation from fetuses with sex chromosome abnormalities and from controls of the same gestational age. After log transformation, the (geometric) mean testosterone levels were XY 439.4 pmol/l, range 165-1,027 (n = 29), XYY 490.7 pmol/l, range 224-1,092 (n = 20); and XXY 419 pmol/l, range 87-1,021 (n = 20). There were no significant differences between the three male groups and all three were significantly higher than the XX fetuses at 147.0 pmol/l, range 41-474 (p < 0.001). These findings give no support to the hypothesis that prenatal testosterone levels contribute to later behavioural characteristics.

Two cases of interstitial deletion 1p.

We report two cases of interstitial deletion of the short arm of chromosome 1. The first was a 10 year old boy whose karyotype was 46,XY,del(1) (p22.1p31.2); the second was a 6 month old boy with a chromosome complement of 46,XY,del(1) (p22.3p31.3). A number of the malformations observed were common to both cases. There has been one previously reported case with the same breakpoints as our case 1 and a phenotype that was strikingly similar.

A 45,X/69,XXY fetus.

Post-mortem examination of a 20-week fetus showed incompletely masculinised external genitalia, hypoplastic adrenal glands and minor physical stigmata suggestive of a chromosome abnormality. Gonad and skin were karyotyped and both were found to contain two cell lines, 45,X and 69,XXY. It appears this fetus is a true 45,X/69,XXY mosaic.