Interobserver variation in respiratory signs of severe malaria

Respiratory abnormalities are common presentations of malaria and acute respiratory tract infection, both of which are major causes of childhood mortality and morbidity in sub-Saharan Africa. Appropriate management depends on accurate assessment of disease severity which for the majority of children must be based on clinical signs alone. Choosing which signs best serve this purpose remains a considerable problem particularly in malaria endemic areas. As part of a prospective study to define clinical signs indicative of life threatening malaria video recordings were used to examine the level of agreement between clinicians for potentially important respiratory signs in 51 children. Overall agreement was good for recession, severe recession, and nasal flaring (kappa = 0.57, 0.50, and 0.60 respectively) and substantial for deep breathing and the summary impression of respiratory distress (kappa = 0.70 and 0.69 respectively). However, within this substantial variation in interpretation was apparent between individual observers from slight to almost perfect agreement (kappa values 0.10-0.92). Video is a useful tool to demonstrate interobserver variation and it may also allow training in recognition of signs and a means of standardising clinical signs between centres.     

Reduced aggression in mice lacking the serotonin transporter

Abstract Rationale. The possible role of γ-aminobutyric acid (GABA) in human aggression was evaluated by administering baclofen, a GABA-B agonist and comparing the effects on laboratory measures of aggression and escape among subjects with and without a history of conduct disorder. Methods. Twenty male subjects with a history of criminal behavior participated in experimental sessions, which measured aggressive and escape responses. Ten subjects had a history of childhood conduct disorder (CD+) and ten control subjects had no history of CD. Aggression was measured using the point subtraction aggression paradigm (PSAP), which provides subjects with aggressive, escape, and monetary-reinforced response options. Results. Acute doses (0.07, 0.14 and 0.28 mg/kg) of baclofen had remarkably different effects on aggressive responses among CD+ subjects relative to control subjects. Aggressive responses of CD+ subjects decreased, while aggressive responses of control subjects increased following baclofen administration. Baclofen decreased escape responses for both CD+ and control subjects. No changes in monetary-reinforced responses were observed, indicative of no central nervous system stimulation or sedation. Conclusions. The GABA-B agonist baclofen suppressed aggressive responses in subjects with a history of childhood CD, while producing the opposite effect in control subjects. These suggest a possible unique role for GABA in the regulation of aggression in CD+ population. Electronic Publication     

Pharmacokinetics and anticonvulsant effects of diazepam in children with severe falciparum malaria and convulsions

AIMS: Convulsions are a common complication of severe malaria in children and are associated with poor outcome. Diazepam is used to terminate convulsions but its pharmacokinetics and pharmacodynamics have not been studied in this group. Accordingly, we carried out a comparative study of the pharmacokinetics of intravenous (i.v.) and rectal (p.r.) diazepam. METHODS: Twenty-five children with severe malaria and a convulsion lasting >5 min were studied. Sixteen children received diazepam intravenously (i.v.; 0.3 mg kg(-1)) and nine rectally (p.r.; 0.5 mg kg(-1)). Plasma diazepam concentrations were measured by reversed phase high-performance liquid chromatography. The duration of convulsions, depth of coma, respiratory and cardiovascular parameters were monitored. RESULTS: Median maximum plasma diazepam concentrations of 634 (range 402-1507) ng ml(-1) and 423 (range 112-1953) ng ml(-1) were achieved at 5 and 25 min following i.v. and p.r. administration, respectively. All patients except three (one i.v. and two p.r.) achieved plasma diazepam concentration >200 ng ml(-1) within 5 min. Following p.r. administration, plasma diazepam concentrations were more variable than i.v. administration. A single dose of i.v. diazepam terminated convulsions in all children but in only 6/9 after p.r. administration. However, nine children treated with i.v. and all those treated with p.r. diazepam had a recurrence of convulsions occurring at median plasma diazepam concentrations of 157 (range: 67-169) and 172 (range: 74-393) ng ml(-1) , respectively. All the children in the i.v. and four in the PR diazepam group who had recurrence of convulsions required treatment. None of the children developed respiratory depression or hypotension. CONCLUSIONS: Administration of diazepam i.v. or p.r. resulted in achievement of therapeutic concentrations of diazepam rapidly, without significant cardio-respiratory adverse effects. However, following p.r. administration, diazepam did not terminate all convulsions and plasma drug concentrations were more variable.     

Contrasting dynamics in the same plant-herbivore interaction

Long-term studies of two-species interactions under field conditions are unusual; most long-term field studies are of single species dynamics (1-6). Concurrent long-term studies on the dynamics of the same two interacting species in different locations are very rare. This result has led to the tacit assumption that different cases of the same two-species interaction would involve essentially quantitative differences (e.g., context-specific differences in the numeric values of demographic parameters like fecundity or death rates). Here, we show that for one of the best-known two-species systems (ragwort and cinnabar moth), this finding does not hold. The interaction between the plant and its herbivore is fundamentally different in coastal dunes in The Netherlands and in grasslands in Southeast England. In the first case, the dynamics are cyclic and the interaction involves both direct and delayed density dependence; in the second case, the insect has little impact on plant dynamics and there are no time lags in density dependence. The difference is caused by differences in the importance of seed-limitation in plant recruitment in the two locations.     

Reducing dose at barium enema: radiographers do it digitally

It has been previously shown that, whilst radiographers in our hospital can undertake barium enema examinations with the same degree of diagnostic accuracy as consultant radiologists, there was a dose penalty to the patient arising from the use of a restrictive protocol requiring radiographers to take a series of plain radiographs for reporting purposes. For the past 3 years radiographers at this hospital have worked to a new protocol that replaces all routine radiographs with digital spot films. In the present study, dose-area product (DAP) measurements for 801 barium enema examinations performed by consultant radiologists and radiographers, using the revised protocol, were analysed and compared to ascertain whether there were still significant differences in radiation dose to the patient depending on the category of staff performing the examination. All examinations were reported by a consultant radiologist. The radiologists' reports were analysed against the known outcomes to compare the diagnostic accuracy of the examination when carried out by the two categories of staff. This study shows that using a modified protocol, in which digital spot films replace the series of overcouch radiographs for reporting, our radiographers are able to perform barium enemas without dose penalty to the patient, and without compromizing diagnostic accuracy. Means with 95% confidence intervals for DAP in the two groups were 9.8 Gycm(2) (9.4-10.3 Gycm(2)) and 10.7 Gycm(2) (10.2-11.1 Gycm(2)) for radiographers and radiologists, respectively.     

Is breast MRI ever useful in a mammographic screening programme?

OBJECTIVE: To establish the diagnostic impact of breast magnetic resonance imaging (MRI), on the management of cases in our mammographic screening programme. METHODS AND MATERIALS: We analysed the cases examined from July 1997 to December 2000 during which time 44,000 population screening mammograms and 85 MRI studies were undertaken on women identified by computer overlap. The studies were reviewed to find the reason for the MRI study and its diagnostic impact. RESULTS: Of 83 studies analysed, 31 were for recurrence of tumour, 33 in newly diagnosed cancer, 22 to assess extent, 11 to monitor primary chemotherapy. In a small diagnostic subset of 19 cases MRI was used to find or characterize a lesion. The 11 cases in which MRI results caused a measurable beneficial change in management were from the query recurrence and diagnostic groups. In 52 cases from all groups, MR increased diagnostic confidence. In 11 cases MRI results were indeterminate, and in six of these stimulated more studies. CONCLUSION: MRI is an expensive investigation and its use must be justified. There is a limited, but valuable role for breast MRI in selected cases from screening assessment. Misinterpretation of enhancing lesions may generate additional procedures. Diagnostic impact was greatest for the detection of tumour recurrence.     

Nasal inflammation and chronic ear disease in Australian Aboriginal children

Objective : Chronic middle ear disease is common in Aboriginal children, and may be linked to nasal inflammation and Eustachian tube dysfunction. The pattern of nasal inflammation is unknown. The study reported here was performed to define the role of allergy and infection in causing nasal inflammation in Aboriginal children with chronic middle ear disease.
Methodology : Thirty-one Aboriginal children aged between 3 and 7 years underwent clinical assessment, audiometry and allergy skin tests. Nasal swabs for bacterial culture and cytology were performed during the winter and again in spring to identify any seasonal variation. A randomized trial of nasal beclomethasone for 8 weeks was conducted in children with abnormal tympanometry to identify the effect of therapy upon nasal cytology.
Results : Twenty-six of the 31 children had abnormal tympanograms. Average hearing levels were reduced in nine children. Pathogenic organisms were isolated from most children: Streptococcus pneumoniae (82%), Haemophilus influenzae (79%), Moraxella catarrhalis (39%) and Staphylococcus aureus (29%). Eight of the 31 children (26%) were atopic. Nasal cytology disclosed a marked neutrophil infiltrate (80% of cells) during the winter, which fell significantly in spring to 52% of cells. Only two subjects had nasal eosinophilia of >10%. There was no effect of beclomethasone on nasal cytology.
Conclusions : Chronic ear disease in Aboriginal children is associated with nasal inflammation, neutrophil infiltration and the presence of bacteria. These features suggest respiratory infection as the main cause of chronic nasal inflammation in Aboriginal children with middle ear disease. There is a seasonal variation in the severity of the nasal infiltrate, consistent with increased infections during winter. Despite a high prevalence of atopy, allergic nasal disease was uncommon.