ROLE OF MACROPHAGES IN ACETAMINOPHEN (PARACETAMOL)-INDUCED HEPATOTOXICITY

Research into the pathogenesis of acetaminophen (paracetamol)-induced hepatotoxicity has concentrated on the generation of toxic metabolites by the hepatocytes. It has, however, recently been shown that human macrophages cultured with acetaminophen secrete increased quantities of tumour necrosis factor (TNF). This study examines whether macrophages have a direct role in acetaminophen toxicity, using a mouse model in which it is possible to eliminate more that 99 per cent of hepatic macrophages by previously injecting liposomes containing dichloromethylene disphosphonate (DMDP). Acetaminophen-induced liver damage was assessed biochemically and histologically. It was shown that the liver damage occurring 0·5, 1, and 2 h after an intraperitoneal injection of acetaminophen was significantly less in mice previously injected with liposomes containing DMDP than in previously untreated mice, or mice previously injected with empty liposomes. By 4 h there was no difference between the groups. We conclude that macrophages play an early and probably a direct role in mediating the liver damage due to acetaminophen. This is consistent with the role that macrophages have been shown to play in the pathogenesis of alcohol-induced liver damage.     

THE ROLE OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN A MURINE CHRONIC GRANULOMATOUS TISSUE AIR POUCH MODEL OF ANGIOGENESIS

Chronic granulomatous inflammation may be considered an angiogenic-dependent process. Recently it has been demonstrated that vascular endothelial growth factor (VEGF) or vascular permeability factor is essential for tumour angiogenesis. Its role in inflammation-mediated angiogenesis has yet to be determined. In this study, the murine chronic granulomatous air pouch model was used to investigate the role of VEGF in angiogenesis. Animals were treated twice weekly with 10 μ g per animal of neutralizing antibody to rh VEGF and the vascularity and granuloma dry weight were assessed after 7 days. This resulted in significant suppression of both angiogenesis and granuloma dry weight. Western blot analysis demonstrated the presence of VEGF; the levels of protein paralleled the angiogenic response. These results demonstrate for the first time that VEGF may be an important regulator of angiogenesis in inflammation.     

LATE ONSET HUNTINGTON'S DISEASE AS A CAUSE OF DEMENTIA: WHERE SHOULD THE CLINICIAN'S INDEX OF SUSPICION LIE?

Our experience with two genetically confirmed cases of late onset Huntington's disease (HD) in a longitudinal dementia research study suggested that clinical misdiagnosis can easily occur. We therefore undertook genetic testing for HD in a further 84 elderly subjects, 81 of whom had come to postmortem; 75 subjects had dementia and nine were normal controls. A quarter of the demented group had demonstrated extrapyramidal symptoms in life but in none had HD formed part of the differential diagnosis. Although no genetically confirmed cases were found in this second group, the original cases serve as a reminder that late onset HD is a cause of dementia. Genetic confirmation should be sought when the condition forms part of the final differential diagnosis. Further studies conducted in the routine clinical setting are now required since it is in this environment that late onset HD is likely to be misdiagnosed in favour of other forms of dementia.     

WHAT BECOMES OF PEOPLE WITH DEMENTIA REFERRED TO COMMUNITY PSYCHOGERIATRIC TEAMS?

Objective: To monitor key processes and outcomes in joint health and social services community psychogeriatric teams. Design: Six month follow-up of new referrals to 4 teams in Cambridge. Data collected from structured clinical assessment forms at baseline and interviews with keyworkers at follow-up. Data for groups with and without dementia were compared. Setting: Two rural and two urban teams in area with relatively large long stay inpatient facility but low independent sector provision. All were routine service teams, rather than run for research purposes. Main outcome measures: The main outcome measures were survival, institutionalisation, key worker assessments of avoidable admissions, appropriateness of placement, unmet needs, carer stress and global outcome for patient and carers. Results: Rates of referral to urban teams were double rural rates. Around forty percent of the dementia group had a social worker as assessor and keyworker. The dementia group was significantly more dependent and received more informal and formal care. After six months, only 54% of the dementia group were alive and living outside institutional care, compared to 79% in the functionally ill group. Unplanned admissions to hospitals or homes were rarely judged avoidable by keyworkers. Outcomes for carers were judged poor in 15% of both groups, and 13% and 11% of carers respectively were judged to be under severe stress. Unmet needs were more common in the dementia group, and related principally to residential care and carer respite. A number of measures, including evidence of geographical inequity and identification of unmet needs, provided an important contribution to local policy development. Further work is needed on the validity of keyworker assessments of carer stress, given the findings of the carer interview sub-study.     

Factor deficiencies in venom‐induced consumption coagulopathy resulting from Australian elapid envenomation: Australian Snakebite Project (ASP‐10)

Summary. Background: Limited information exists on the dynamics of hemostasis in patients with venom‐induced consumption coagulopathy (VICC) from snake envenomation. Objective: The aim of the present study was to investigate specific factor deficiencies and their time course in Australasian elapid envenomation. Methods: We measured coagulation parameters and factor concentrations in patients recruited to the Australian Snakebite Project, an observational cohort study. There were 112 patients with complete VICC, defined as an international normalized ratio (INR) > 3, and 18 with partial VICC. Serial citrated plasma samples were collected from 0.5 to 60 h post‐bite. INR, activated partial thromboplastin time (aPTT), coagulation factors (F)I, II, V, VII, VIII, IX, X, von Willebrand factor antigen (VWF:Ag) and D‐dimer concentrations were measured. Results: Complete VICC was characterized by near/total depletion of fibrinogen, FV and FVIII, with an INR and aPTT that exceeded the upper limits of detection, within 2 h of snakebite. Prothrombin levels never fell below 60% of normal, suggesting that the toxins were rapidly eliminated or inactivated and re‐synthesis of clotting factors occurred irrespective of antivenom. Partial VICC caused limited depletion of fibrinogen and FV, and almost complete consumption of FVIII. Onset of VICC was more rapid with brown snake (Pseudonaja spp.) venom, which contains a group C prothrombin activator toxin, compared with the tiger snake group, which contains a group D prothrombin activator toxin and requires human FVa formation. Resolution of VICC occurred within 24–36 h irrespective of snake type. Conclusions: These results suggest that Australasian elapid prothrombin activators have a potent but short duration of action. Antivenom is unlikely to be administered in time to prevent VICC.     

Stereotypic movement disorder: easily missed

Aim To expand the understanding of stereotypic movement disorder (SMD) and its differentiation from tics and autistic stereotypies. Method Forty‐two children (31 males, mean age 6y 3mo, SD 2y 8mo; 11 females, mean age 6y 7mo, SD 1y 9mo) consecutively diagnosed with SMD, without‐self‐injurious behavior, intellectual disability, sensory impairment, or an autistic spectrum disorder (ASD), were assessed in a neuropsychiatry clinic. A list of probe questions on the nature of the stereotypy was administered to parents (and to children if developmentally ready). Questionnaires administered included the Stereotypy Severity Scale, Short Sensory Profile, Strengths and Difficulties Questionnaire, Repetitive Behavior Scale – Revised, and the Developmental Coordination Disorder Questionnaire. The stereotyped movement patterns were directly observed and in some cases further documented by video recordings made by parents. The probe questions were used again on follow‐up at a mean age of 10 years 7 months (SD 4y 4mo). Results Mean age at onset was 17 months. Males exceeded females by 3:1. Family history of a pattern of SMD was reported in 13 and neuropsychiatric comorbidity in 30 (attention‐deficit–hyperactivity disorder in 16, tics in 18, and developmental coordination disorder in 16). Obsessive–compulsive disorder occurred in only two. The Short Sensory Profile correlated with comorbidity (p<0.001), the Stereotypy Severity Scale (p=0.009), and the Repetitive Behavior Scale (p<0.001); the last correlated with the Stereotypy Severity Scale (p=0.001). Children (but not their parents) liked their movements, which were usually associated with excitement or imaginative play. Mean length of follow‐up was 4 years 8 months (SD 2y 10mo). Of the 39 children followed for longer than 6 months, the behavior stopped or was gradually shaped so as to occur primarily privately in 25. Misdiagnosis was common: 26 were initially referred as tics, 10 as ASD, five as compulsions, and one as epilepsy. Co‐occurring facial grimacing in 15 children and vocalization in 22 contributed to diagnostic confusion. Interpretation SMD occurs in children without ASD or intellectual disability. The generally favorable clinical course is largely due to a gradual increase in private expression of the movements. Severity of the stereotypy is associated with sensory differences and psychopathology. Differentiation of SMD from tics and ASD is important to avoid misdiagnosis and unnecessary treatment.     

Delphi survey of research priorities

Aim  To identify nurses' priorities for topics and issues to be addressed by a developing nursing research program at a county hospital.
Background  Delphi surveys have been effective at other hospitals to identify research priorities of nurses.
Methods  A Delphi survey was performed in two rounds. Questionnaires were distributed to all 415 nurses who worked at the hospital.
Results  A total of 274 nurses returned the Round I questionnaire (response rate, 66%), and 249 returned the Round II questionnaire (response rate, 60%).
Conclusions  The Delphi survey was successfully used to identify nurses' research priorities at a county hospital. A total of 39 topics were identified from content analysis of research areas described by nurses. Factor analysis revealed three factors: work environment, newborn issues and effects of leadership.
Implications for nursing management  The Delphi survey is a useful way to begin a program of research. Nurses who have a successful experience with research are more likely to become further involved in research, which will allow them to more effectively participate in decision making and improving the work environment. In addition, items were identified that needed to be addressed by nursing managers.     

Sweat Sodium Related to Amount of Sweat after Sweat Test in Children with and without Cystic Fibrosis

ABSTRACT. The sweat concentration of sodium was found to be inversely correlated with the amount of sweat obtained after a sweat test according to the method of Gibson & Cook in children without and with cystic fibrosis. Reference intervals for sweat sodium overlapped for the two groups but two-dimensional reference distributions for the amount of sweat (range 20-440 mg) correlated with its sodium content were completely separated. The establishment of similar distributions in centres carrying out sweat tests could serve to assess the performance of this investigation at local level.     

Psychosexual trauma of an abnormal cervical smear

Summary. The psychosexual sequelae of diagnosis and treatment of pre-invasive cervical atypia were assessed in three groups of women. The first group included 30 women referred to a colposcopy clinic with an abnormal cervical smear indicating cervical intraepithelial neoplasia (CIN), the second comprised 50 women who were traced as sexual partners of men with penile human papillomavirus (HPV) infection; 26 of them had histologically proven cervical atypia and 24 had no such evidence. The third group included 25 women traced as partners of men with non-specific urethritis and who did not have cervical disease. Before and after questionnaires assessed six aspects of sexual behaviour and responses before diagnosis and 6 months after treatment in women with cervical atypia. These were compared with answers given by women investigated and treated, if necessary, as partners of men with sexually transmitted disease (control group). There were statistically significant adverse psychosexual sequelae associated with diagnosis and treatment of pre-invasive cervical epithelial disease.