Wilson's disease

An anxious, paranoid, disoriented patient usually requires psychiatric referral. Occasionally, such features are the first noticeable indication of an inherited copper-storage disorder. The authors describe accompanying hepatic and neurologic findings that characterize Wilson's disease and describe their recent experience in diagnosing and treating a patient with this uncommon disease.     

Positive parenting during childhood moderates the impact of recent negative events on cortisol activity in parentally bereaved youth

Rationale  

Early parental loss has been associated with neuroendocrine dysregulation in youth; however, the form of cortisol dysregulation varies widely. Identifying risk and protective factors that influence physiological regulation has important implications for understanding the development of mental health problems in parentally bereaved youth.     

SB-649915-B, a novel 5-HT1A/B autoreceptor antagonist and serotonin reuptake inhibitor, is anxiolytic and displays fast onset activity in the rat high light social interaction test.

Preclinically, the combination of an SSRI and 5-HT autoreceptor antagonist has been shown to reduce the time to onset of anxiolytic activity compared to an SSRI alone. In accordance with this, clinical data suggest the coadministration of an SSRI and (+/-) pindolol can decrease the time to onset of anxiolytic/antidepressant activity. Thus, the dual-acting novel SSRI and 5-HT(1A/B) receptor antagonist, SB-649915-B, has been assessed in acute and chronic preclinical models of anxiolysis. SB-649915-B (0.1-1.0 mg/kg, i.p.) significantly reduced ultrasonic vocalization in male rat pups separated from their mothers (ED(50) of 0.17 mg/kg). In the marmoset human threat test SB-649915-B (3.0 and 10 mg/kg, s.c.) significantly reduced the number of postures with no effect on locomotion. In the rat high light social interaction (SI), SB-649915-B (1.0-7.5 mg/kg, t.i.d.) and paroxetine (3.0 mg/kg, once daily) were orally administered for 4, 7, and 21 days. Ex vivo inhibition of [(3)H]5-HT uptake was also measured following SI. SB-649915-B and paroxetine had no effect on SI after 4 days. In contrast to paroxetine, SB-649915-B (1.0 and 3.0 mg/kg, p.o., t.i.d.) significantly (p<0.05) increased SI time with no effect on locomotion, indicative of an anxiolytic-like profile on day 7. Anxiolysis was maintained after chronic (21 days) administration by which time paroxetine also increased SI significantly. 5-HT uptake was inhibited by SB-649915-B at all time points to a similar magnitude as that seen with paroxetine. In conclusion, SB-649915-B is acutely anxiolytic and reduces the latency to onset of anxiolytic behavior compared to paroxetine in the SI model.     

Management of pain and pain-related symptoms in hospitalized veterans with cancer

Unrelieved pain continues to be a problem among hospitalized patients with cancer. The purpose of this study was to evaluate pain management outcomes in a group of veterans with cancer receiving inpatient care. The sample consisted of 90 veterans with cancer hospitalized in one of two large veterans medical centers in the southeastern United States. Daily pain was assessed by administering the visual analog scale (VAS) for pain three times in a 24-hour period and averaging these three scores. The Brief Pain Inventory (BPI) and Constipation Assessment Scale (CAS) were administered once. The charts were audited using the Chart Audit for Pain (CAP). The sample was predominantly male (93.3%) and white (82.8%). The length of time since diagnosis ranged from newly diagnosed during this hospitalization to 16 years. Average daily pain was 32.9 on the VAS and 4 on the BPI. However, approximately one-fourth of the patients reported average daily pain above the midpoint (VAS > 50), and some patients reported average daily pain to be as high as 98. Fewer than half of charts (42%) showed evidence that a pain rating scale was used. Other assessment data also were very limited. Patients reported that pain interfered with all activities on the BPI, with highest interference scores for walking and sleep (mean, 5.5). Although 80% of the patients reported some problem with constipation, the chart audit indicated that this was recorded in only 11 patient records. No patient records indicated a problem with sedation. The findings indicate that limited attempts were made to manage pain using nonpharmacologic methods. In addition, only one of the nine charts reporting these attempts showed evidence that results from the attempt were evaluated. It may be concluded that pain management continues to be less than ideal in these veterans hospitals. Study results indicate that nurses are not documenting careful assessment of pain, not documenting evaluation of approaches to pain management, and not attending to the constipation that is inevitable when opioids are administered. Continued emphasis on nursing education related to pain management is needed. Future research should be undertaken to evaluate these outcomes.     

The lens in hereditary hyperferritinaemia cataract syndrome contains crystalline deposits of L-ferritin

BACKGROUND/AIM: Hereditary hyperferritinaemia cataract syndrome (HHCS) is an autosomal dominant disorder characterised by elevated serum L-ferritin and bilateral cataracts. The ocular manifestations of this disorder are poorly studied. This study therefore sought to determine the origin of cataracts in HHCS. METHODS: L-ferritin ELISA, immunohistochemical and ultrastructural analysis of a lens nucleus from an HHCS individual. RESULTS: The HHCS lens L-ferritin content was 147 microg/g dry weight of lens compared with <16 microg/g for a non-HHCS control cataract lens. The cataract comprised discrete crystalline inclusions with positive staining with anti-L-ferritin but not anti-H-ferritin. CONCLUSIONS: This unusual finding of crystalline opacities in the lens may be unique to HHCS and is likely to result from disturbed metabolism of L-ferritin within the lens or an abnormal interaction between L-ferritin and lens proteins.     

Broad spectrum anticonvulsant activity of BW534U87: possible role of an adenosine-dependent mechanism

The novel putative anticonvulsant drug 1-[2,6-difluorophenyl)-methyl]-1H-1,2,3-triazolo[4,5-c]) pyridine-4-amine monohydrochloride (BW534U87) effectively reduced seizures induced in rodents by threshold maximal and supramaximal electroshock, electrical kindling, pentylenetetrazole (PTZ) infusion and by vestibular stimulation in the genetically seizure-prone epilepsy-like (EL) mouse. The range of animal seizure models in which BW534U87 was effective is consistent with a broad spectrum anticonvulsant profile. In the EL mouse, the activity of BW534U87 was partially reversed by predosing with the selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), suggesting that an adenosine-dependent mechanism contributed to the antiseizure activity of the drug. BW534U87 inhibited rat brain homogenate adenosine deaminase activity, thus, raising the possibility that, by blocking the metabolism of endogenous adenosine by this route, BW534U87 limited seizure activity by promoting the inhibitory tone mediated by endogenous adenosine in the brain. The seizure protection conferred by the selective adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) in EL mice and mice infused with PTZ confirms that inhibition of adenosine metabolism by deamination is an effective antiseizure strategy in these models.     

Which common clinical conditions should medical students be able to manage by graduation? A perspective from Australian interns

The objectives of the study were to report the development of a core curriculum that details the clinical conditions medical students should be able to manage upon graduation; and to canvass the opinion of interns (first-year postgraduate doctors) regarding their perceptions of the level of skill required to manage each condition. Literature relating to core curriculum development and training of junior medical officers was reviewed and stakeholders in the education and training of medical students and junior doctors in the state of New South Wales, Australia (intern supervisors, academics, registrars, nurses and interns) were consulted. The final curriculum spanned 106 conditions, 77 'differentiated' and 29 'undifferentiated'. Four levels of skill at which conditions should potentially be managed were also identified: 'Theoretical knowledge only'; 'Recognize symptoms and signs without supervision'; Initiate preliminary investigations, management and/or treatment without supervision'; and 'Total investigation, management and/or treatment without supervision'. The list of conditions in the curriculum was converted to a survey format and a one-in-two random sample of interns (n = 193) practising in New South Wales who graduated from the state's three medical schools were surveyed regarding the level of skill required for managing each clinical condition at graduation. A total of 51.3% of interns responded to the survey. Interns felt they should be able to initiate preliminary investigation, management and/or treatment for most conditions in the curriculum, with more than half acknowledging this level of management for 53 of the differentiated and 28 of the undifferentiated conditions. It is concluded that developing core curricula in medical education can involve multiple stakeholders, including junior doctors as the consumers of educational experiences. The data gathered may be useful to medical schools revising their curricula.