The 'unified hypothesis' of Geddes et al. is not supported by the data

Inflicted head injury to the developing brain frequently results in serious disability. The pathogenesis of the neuraxial and ocular findings in infants believed to have suffered inflicted head injury remains the subject of considerable debate. Recent neuropathology studies of fatal cases of inflicted head injury and of a foetal/perinatal non-traumatic model have led to the proposal that there is a 'unified hypothesis', the essential feature of which is hypoxic brain swelling secondary to cervicomedullary injury. It has been suggested that less than violent forces may be involved and even that some cases may not be due to trauma at all. The purpose of this paper is to provide a critical review of the data upon which these suppositions are based on a background of what is already known. It is submitted that there are serious flaws in the methodology; the conclusions reached cannot logically be drawn from the data; and the 'unified hypothesis' is not supported by the evidence. On the basis of the data presented, it is also difficult to sustain the secondary hypothesis purporting to describe a minority cohort with 'infantile encephalopathy with subdural and retinal bleeding' of non-traumatic causation.     

Influence of antibody diversification on the mechanism of haplotype exclusion of immunoglobulin gene expression

Allelic, or haplotype, exclusion of immunoglobulin gene expression ensures that the products of a single allele or light chain isotype are expressed on the B cell surface. Evidence has accumulated in rodent and primate models to indicate that the products of successful rearrangement regulate this process. In contrast, haplotype exclusion of chicken immunoglobulin gene expression is regulated at the level of variable region gene rearrangement. We discuss here alternative models for ensuring haplotype exclusion that may operate in the chicken and extend the discussion to address the issue as to how two apparently distinct mechanisms may have evolved to yield the same outcome.     

A Simulation Modelling Approach to Evaluating Alternative Policies for the Management of the Waiting List for Liver Transplantation

A shortage of donor liver grafts unfortunately results in approximately 10% of patients dying whilst listed for a liver transplant in Europe and the United States. Thus it is imperative that all available organs are used as efficiently as possible. This paper reports upon the application of a simulation modelling approach to assess the impact of several alternative allocation policies upon the cost effectiveness of this technology at one liver transplant centre in the UK. The impact of changes in allocation criteria on the estimated net life expectancy, average net costs and overall cost effectiveness of the transplantation programme were evaluated. The incremental cost effectiveness ratio (ICER) for the base case allocation policy, based upon the time spent on the waiting list (i.e., longest wait first) was £11,557 at 1999 prices. The ICERs associated with an allocation policy based upon age (lowest age first), and an allocation policy based upon the severity of the pre-transplant condition of the patient (with most severely ill patients given a lower priority) were lower than the base case at £10,424 and £9077, respectively. The results of this modelling study suggest that the overall cost effectiveness of the liver transplantation programme could be improved if the current allocation policy were modified to give more weight to the age of the patient and the reduced chances of success of the most severely ill patients.     

Psychiatric morbidity and its recognition by doctors in patients with cancer

Psychiatric morbidity in patients with cancer is high and without appropriate treatment unremitting. We assessed the ability of 143 doctors to establish the psychological status of 2297 patients during outpatient consultations in 34 cancer centres and hospitals in the UK. Prior to seeing the doctor, consenting patients completed a short self-report questionnaire (GHQ12), designed for the psychological screening of large populations. At the end of the consultation, doctors completed visual analogue scales rating patients' distress. 837/2297 (36.4%) patients had GHQ scores suggestive of psychiatric morbidity. The doctors' sensitivity (true positive rate) was 28.87% (SD 25.29), specificity (true negative rate) 84.79% (SD 17.44). The misclassification rate was 34.7% (SD 13.79) meaning that for 797 patients the wrong assessment was probably made. These data show that much of the probable psychiatric morbidity experienced by patients with cancer goes unrecognized and therefore untreated. Doctors need communication skills training to elicit problems during consultations. Appropriate referrals to psychological services are necessary when patients requiring help are identified and ought to be an integral part of cancer care.     

Investigating women's preferences for intrapartum care: home versus hospital births

There is an increasing amount of evidence to suggest that the clinical outcomes associated with a home birth for low risk women are at least as good, if not better than, the clinical outcomes associated with giving birth in hospital. If it is the case that there is little or no difference in clinical outcomes between the two modes of delivery, then traditional measures of benefit used in health economics, e.g. quality adjusted life years (QALYs), would detect little or no difference between the alternative modes of delivery. From this, the conclusion would be that the utility values associated with each mode of delivery are similar. However, women may still have clearly defined preferences relating to the way in which maternity care is provided. This paper uses the economic technique of conjoint analysis to assess the relative value attached to several main characteristics associated with the process of maternity care during the intrapartum stage for women who have actively chosen to give birth at home relative to women who have given birth in hospital. It was found that respondents who had chosen a home birth valued continuity of carer, a homely environment and the ability to make their own decisions about what happens during labour and delivery. In contrast, hospital birth respondents placed a relatively high value on access to an epidural for pain relief and not needing to be transferred to another location during labour if a problem arose. The results of the study suggest that women have clearly defined preferences for characteristics associated with the process of intrapartum care that would be unlikely to be detected by traditional benefit measures used in health economics. This finding is important where policy issues relating to aspects of maternity care service delivery are being considered.     

Cardiopulmonary complications following cardiac surgery

Opinion statement There are numerous cardiac and pulmonary complications that can occur after operations that involve the use of cardiopulmonary bypass (CPB). We have chosen to focus on perioperative myocardial ischemia, left ventricular (LV) dysfunction, ventricular arrhythmias, atrial arrhythmias, and inflammation and pulmonary dysfunction as the most important. If left untreated, these complications can be life-threatening. Moreover, their presence is associated with higher hospital expenses due to therapies and longer inpatient stays.     

The effect of diastolic stiffness on ventricular function after partial ventriculectomy: a finite element simulation

Partial ventriculectomy (PV) has been proposed by Batista and colleagues to improve cardiac function in patients with dilated cardiomyopathy (DCM); however, results have been mixed. We tested the hypothesis that preoperative diastolic function affects the stroke volume/end-diastolic pressure (Starling) relationship after PV. A previously described finite element simulation of DCM and PV was used. Diastole and end systole were represented by separate elastic finite element models with different unloaded shapes and nonlinear material properties. Left ventricular (LV) end-systolic elastance (E(ES)), diastolic compliance (DC), and Starling relationships were calculated. DC was varied by changing Ogden material property alpha(i) from 12 (compliant) to 20 (stiff). PV was simulated at 20% LV mass reduction. The slope of the Starling relationship increased from 1.82 to 1.21 as alpha(i) increased from 12 to 20. Partial ventriculectomy increased the Starling relationship in each case from 1.34 to 1.01 respectively. However, the net result in each case is a decrement in the Starling relationship with resection, and the smallest decrement was associated with the highest diastolic stiffness (alpha(i) = 20). Partial ventriculectomy depressed the Starling relationship for all values of diastolic compliance. It is expected that patients with a higher diastolic stiffness should do better.     

Cationic lipid-mediated gene transfer to the growing murine and human airway

Gene therapy in patients with cystic fibrosis may need to be commenced before the onset of lung disease which may be evident as early as 4 weeks after birth. We assessed the efficacy of cationic lipid-mediated transfer of a reporter gene, chloramphenicol acetyltransferase, in the growing murine and human respiratory tract. Gene expression was greater in adult mice (greater than 8 weeks old) compared with 9- and 16-day-old animals, despite a relatively greater proportion of complex delivered to the younger mice. Subsequent experiments compared 16-day-old and adult mice. Whilst higher gene expression occurred in the parenchyma compared with conducting airways in both groups, significantly greater expression was seen in the conducting airway of adult mice compared with 16-day-old animals. This expression persisted beyond 18 days in the adults but was undetectable in the younger group at this time-point. In an ex vivo model there was no difference in gene expression between the two groups. Further, no differences were observed in gene expression between growing (age 5 weeks to 14 years 8 months) and adult human lung tissue in either parenchyma or conducting airway. These data suggest age-dependent differences in gene transfer in vivo, which are not seen in an ex vivo setting. Proof-of-principle has been demonstrated for cationic-lipid mediated gene transfer to the growing human lung. Gene Therapy (2000) 7, 273-278.