Fatty infiltration of the liver: evaluation by proton spectroscopic imaging

The reliability of proton spectroscopic imaging in evaluating fatty infiltration of the liver was investigated in 35 subjects (12 healthy volunteers and 23 patients with fatty livers). With this modified spin-echo technique, fatty liver could be separated from normal liver both visually and quantitatively. On the opposed image, normal liver had an intermediate signal intensity, greater than that of muscle, whereas fatty liver had a lower signal intensity, equal to or less than that of muscle. In normal livers, the lipid signal fraction was less than 10%, while in fatty livers it was greater than 10% and usually exceeded 20%. With this technique, nonuniform fatty infiltration of the liver can be differentiated from hepatic metastases, and the technique may prove useful in the differentiation of some hepatic disorders.     

Shifts in global immunisation goals (1984-2004): unfinished agendas and mixed results

The turn of the millennium has been marked by a large-scale mobilisation of resources for immunisation programmes in developing countries. The resources have been generated by public and private sector parties collaborating in the Global Alliance for Vaccines and Immunization (GAVI). GAVI was formed in response to deteriorating immunisation coverage rates occurring in the late 1990s. GAVI is the latest in a line of vaccine initiatives, which have operated over the past 20 years. This article reviews the five most important global immunisation initiatives that have taken place over those past 20 years. It analyses their origins, shifts in global immunisation goals, identifies key actors, assesses the initiatives' capacity to mobilise resources and increase immunisation coverage, and points to possible unintended effects of the initiatives. The study argues that shifts in global immunisation goals lead to fragmentation in the implementation of vaccine programmes at the local level in developing countries. It also suggests that global actors involved in the formulation of these initiatives appear to miss opportunities to build on past experiences and fail to learn from previous mistakes. This raises questions about the initiatives' sustainability and relevance to the overall objective of preventing vaccine-preventable deaths.     

Matrix metalloproteinases contribute to insulin insufficiency in Zucker diabetic fatty rats

To assess the molecular changes associated with pancreatic beta-cell dysfunction occurring during the onset of type 2 diabetes, we profiled pancreatic islet mRNAs from diabetic male and high-fat-fed female Zucker diabetic fatty (ZDF) rats and their nondiabetic lean counterparts on custom islet-specific oligonucleotide arrays. The most prominent changes in both the male and female models of type 2 diabetes were increases in the mRNAs encoding proteases and extracellular matrix components that are associated with tissue remodeling and fibrosis. The mRNAs for metalloproteinase (MMP)-2, -12, and -14 were sharply increased with the onset of islet dysfunction and diabetes. Zymography of islet extracts revealed a concurrent, >10-fold increase in MMP-2 protease activity in islets from 9-week-old male ZDF rats. Treatment of female ZDF rats receiving a diabetogenic diet with PD166793, a broad-spectrum MMP inhibitor, substantially prevented diabetes. The effect of this compound was due in part to marked beta-cell expansion. These studies indicate that MMPs contribute to islet fibrosis and insulin insufficiency in ZDF rats. Class-targeted protease inhibitors should be explored for their potential therapeutic utility in preservation of beta-cell mass in type 2 diabetes.     

Clinical and electroencephalographic correlates of the multiple independent spike foci pattern in children

The multiple independent spike foci (MISF) pattern on electroencephalograms occurred in 4.2% of 1,500 recordings obtained from patients between the ages of 6 months and 15 years. Among the 63 patients with MISF, 53 (84%) had a seizure disorder and 48 (76%) had generalized motor seizures. Half the study group had daily seizures and half had more than one type of attack. Sixty-eight percent of MISF patients were intellectually subnormal. The intellectual status varied according to age at seizure onset, findings on clinical neurological examination, incidence of spikes in the recording, number of spike foci, and presence of excessive delta activity.     

Domestic violence, alcohol and substance abuse

Domestic violence and substance abuse are common in primary care patients. Although these problems are associated with severe physical and psychological sequelae, they are often undiagnosed. This article provides an overview of the prevalence of these problems, the health-related consequences for adults, children and elderly, as well as the challenges for clinicians in screening, assessment and referral.     

Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE)

The International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE) have come to consensus definitions for the terms epileptic seizure and epilepsy. An epileptic seizure is a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition. The definition of epilepsy requires the occurrence of at least one epileptic seizure.     

Low-dose lithium combined with captopril prevents stroke and improves survival in salt-loaded, stroke-prone spontaneously hypertensive rats

OBJECTIVE: A number of potential interactions between angiotensin-converting enzyme inhibitors and lithium have been described in the literature. In the present study, we investigated the effects of a low-dose combination treatment with lithium and captopril on survival and stroke prevention in salt-loaded, stroke-prone spontaneously hypertensive rats (SHRSP). METHODS: Eight-week-old saline-drinking SHRSP (n = 21 per group) were treated with vehicle, LiCl (1 mmol/kg per day), captopril (25 mg/kg per day) and captopril plus LiCl for up to 37 weeks. Body weight, salt water intake blood pressure and mortality were recorded throughout the experimental period. Plasma renin activity, plasma lithium concentration and urinary excretion of albumin, sodium and potassium were measured at different time points. RESULTS: Captopril treatment doubled the life expectancy when compared with vehicle-treated rats. Lithium alone had minor effects on survival but led to a dramatic increase in survival when added to captopril (mean survival time > 237 versus 147 days, P < 0.001). Systolic blood pressure increased with age in all treatment groups but was comparable in the captopril-treated and the captopril-plus-lithium-treated groups. Plasma renin activity as well as urinary sodium and potassium excretion did not differ between both groups. In the captopril group a striking fivefold increase of albuminuria occurred between 14 and 26 weeks of age, while this progression was completely abolished by the addition of lithium. CONCLUSIONS: Our results demonstrate that the addition of lithium to captopril dramatically prolong the effects of the angiotensin-converting enzyme inhibitor on survival in salt-loaded SHRSP. This effect was independent of a reduction in blood pressure.     

Homicide risk across race and class: a small-area analysis in Massachusetts and Rhode Island

Areas with higher absolute poverty and higher income inequality have been associated with higher risk of homicide victimization. In addition, studies of differential homicide rates have indicated that black persons are at a higher risk of homicide compared to white persons. However, few studies directly compared risk of homicide offending or victimization between Hispanic persons and non-Hispanic white persons, and few studies have attempted to examine the interaction between race and residential neighborhood socioeconomic measures on homicide risk. This population-based retrospective study comprised all white, black, and Hispanic 15-to 44-year-old men included in the 1990 US Census as Rhode Island or Massachusetts residents. Vital statistics registries were linked to 1990 US Census data to provide information on small-area characteristics. Overall, we observed a trend of increasing homicide risk as block-group socioeconomic position descended. The data indicated that block-group poverty, female-headed households, home ownership, and higher education were all strongly associated with homicide risk after stratifying by race and age of victim and adjusting for other block-group socioeconomic characteristics. Race was a strong modifier for absolute risk difference for the relation between risk of homicide and socioeconomic surroundings. Our analyses suggested that area-based interventions that would improve neighborhood social and economic conditions would be effective in decreasing risk of homicide for men.     

Spared somatomotor and cognitive functions in a patient with a large porencephalic cyst revealed by fMRI

To date functional magnetic resonance imaging (fMRI) has not been extensively used in presurgical evaluation of patients with intractable epilepsy. Patient S.P. presented with left frontal originating seizures, secondary to a large porencephalic cyst that encompassed much of his occipital and temporal cortex and a substantial portion of ipsilateral parietal cortex. Nevertheless, S.P. did not demonstrate any gross impairments of praxis or speech. Scalp electroencephalogram (EEG) telemetry revealed reduced background activity in the left hemisphere, an absence of identifiable normal sleep states, and confirmed the left frontal origin of his seizures with a prolonged postictal state, suggesting that the remaining cortex in S.P.'s left hemisphere did not function normally despite his apparently normal appearance. Dichotic listening results also suggested that S.P. had an atypical language representation suggestive of either bilateral or right hemisphere speech representation. Surgical intervention to remove the remaining left hemisphere cortex was a serious consideration for treatment of S.P.'s seizures. We used fMRI to evaluate whether or not the remaining cortex in S.P.'s left hemisphere supported any cognitive or motor functions. Even though the volume of cerebral cortex was severely reduced and displaced in the left hemisphere, fMRI revealed significant activation in this remaining tissue in response to motor, somatosensory, and word generation tasks. In other words, we were able to demonstrate using fMRI that the remaining tissue in S.P.'s left hemisphere continued to support some motor and cognitive functions. The possible implications of these findings in terms of functional reorganisation are discussed briefly.