Recurrent missense mutations at the first and second base of codon Arg243 in human lipoprotein lipase in patients of different ancestries

Mutations in the lipoprotein lipase (LPL) gene are the most common cause of familial chylomicronemia. Here we define the molecular basis of LPL deficiency in four patients of German, French, Dutch, and Chinese descent. We show that two of the probands of Dutch and Chinese origin have a previously described Arg²⁴³His mutation while the patients of German and French descent have a novel Arg²⁴³ Cys substitution in their LPL gene. Haplotype analysis is in favour of two separate origins for the Arg²⁴³ Cys substitution which together with the Arg²⁴³ His mutation would implicate three recurrent mutations involving the first and second nuclcotides of the codon encoding Arg²⁴³ of the LPL gene. The recurrent mutations affecting the first and second nucleotide of CGC coding for the normal Arg residue are support for the high mutability of CpG dinucleotides within the LPL gene. © 1994 Wiley-Liss, Inc.     

Atraumatic Restorative Treatment (ART): Rationale, Technique, and Development

Despite long-term efforts to use appropriate dental equipment for treating dental caries in economically less developed countries, the predominant treatment remains extraction. The reasons for this failure to save teeth are given in this paper. Supported by results of research undertaken in economically developed countries, a 15-step treatment module for dental caries is presented. This technique, which is called Atraumatic Restorative Treatment (ART), is based on removing decalcified tooth tissue using only hand instruments and restoring the cavity with an adhesive filling material. The technique does not require electricity. The advantages and limitations of the technique are discussed and its use in a school oral health program in Zimbabwe presented. We conclude that ART can make restorative oral care more available to a larger part of the world population than it is today.     

Neutrophils in cancer

Neutrophils play an important role in cancer. This does not only relate to the well-established prognostic value of the presence of neutrophils, either in the blood or in tumor tissue, in the context of cancer progression or for the monitoring of therapy, but also to their active role in the progression of cancer. In the current review, we describe what is known in general about the role of neutrophils in cancer. What is emerging is a complex, rather heterogeneous picture with both pro- and anti-tumorigenic roles, which apparently differs with cancer type and disease stage. Furthermore, we will discuss the well-known role of neutrophils as myeloid-derived suppressor cells (MDSC), and also on the role of neutrophils as important effector cells during antibody therapy in cancer. It is clear that neutrophils contribute substantially to cancer progression in multiple ways, and this includes both direct effects on the cancer cells and indirect effect on the tumor microenvironment. While in many cases neutrophils have been shown to promote tumor progression, for instance by acting as MDSC, there are also protective effects, particularly when antibody immunotherapy is performed. A better understanding of the role of neutrophils is likely to provide opportunities for immunomodulation and for improving the treatment of cancer patients.     

Muscle computed tomography in adult-onset acid maltase deficiency

Nine patients with adult-onset acid maltase deficiency (Pompe's disease) were examined clinically and with computed tomography (CT). The CT scan showed early and severe involvement of the muscles of trunk and thighs, with selective sparing of the tensor fasciae latae, short head of biceps femoris, gracilis, and sartorius muscles. Shoulder and leg muscles were less affected. The disease spread over the years from trunk to extremities. Muscle strength and CT findings were positively correlated. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:398–400, 1998.     

Pain and activity levels before and after platelet-rich plasma injection treatment of patellar tendinopathy: a prospective cohort study and the influence of previous treatments

Purpose

The aim of this study was to evaluate the outcome of patients with patellar tendinopathy treated with platelet-rich plasma injections (PRP). Additionally, this study examined whether certain characteristics, such as activity level or previous treatment affected the results.

Methods

Patients (n = 36) were asked to fill in the Victorian Institute of Sports Assessment – Patellar questionnaire (VISA-P) and visual analogue scales (VAS), assessing pain in activities of daily life (ADL), during work and sports, before and after treatment with PRP. Of these patients, 14 had been treated before with cortisone, ethoxysclerol, and/or surgical treatment (group 1), while the remaining patients had not been treated before (group 2).

Results

Overall, group 1 and group 2 improved significantly on the VAS scales (p < .0.05). However, group 2 also improved on VISA-P (p = .0.003), while group 1 showed less healing potential (p = 0.060). Although the difference between group 1 and group 2 at follow-up was not considered clinically meaningful, over time both groups showed a clinically significant improvement.

Conclusion

After PRP treatment, patients with patellar tendinopathy showed a statistically significant improvement. In addition, these improvements can also be considered clinically meaningful. However, patients who were not treated before with ethoxysclerol, cortisone, and/or surgical treatment showed the improvement.     

Targeting working memory to modify emotional reactivity in adult attention deficit hyperactivity disorder: a functional magnetic resonance imaging study

Understanding the neural mechanisms of emotional reactivity in Attention-Deficit/Hyperactivity Disorder (ADHD) may help develop more effective treatments that target emotion dysregulation. In adult ADHD, emotion regulation problems cover a range of dimensions, including emotional reactivity (ER). One important process that could underlie an impaired ER in ADHD might be impaired working memory (WM) processing. We recently demonstrated that taxing WM prior to the exposure of emotionally salient stimuli reduced physiological and subjective reactivity to such cues in heavy drinkers, suggesting lasting effects of WM activation on ER. Here, we investigated neural mechanisms that could underlie the interaction between WM and ER in adult ADHD participants. We included 30 male ADHD participants and 30 matched controls. Participants performed a novel functional magnetic resonance imaging paradigm in which active WM-blocks were alternated with passive blocks of negative and neutral images. We demonstrated group-independent significant main effects of negative emotional images on amygdala activation, and WM-load on paracingulate gyrus and dorsolateral prefrontal cortex activation. Contrary to earlier reports in adolescent ADHD, no impairments were found in neural correlates of WM or ER. Moreover, taxing WM did not alter the neural correlates of ER in either ADHD or control participants. While we did find effects on the amygdala, paCG, and dlPFC activation, we did not find interactions between WM and ER, possibly due to the relatively unimpaired ADHD population and a well-matched control group. Whether targeting WM might be effective in participants with ADHD with severe ER impairments remains to be investigated.

     

Suppression of conditioned nicotine and sucrose seeking by the cannabinoid-1 receptor antagonist SR141716A

The present study shows that the selective cannabinoid CB1 receptor antagonist SR141716A attenuated responding for both nicotine- and sucrose-associated stimuli in a long-term extinction-reinstatement model. The results suggest that endocannabinoids play a general role in modulating cue reactivity or conditioned reinforcement following prolonged abstinence of both drug and natural reinforcers. In line with previous preclinical and recent clinical observations, our results provide a strong rationale for the use of CB1 antagonists in the treatment of addictive behaviors.     

Back to basics: managing gunshot injuries in East Timor

BACKGROUND: The management of patients following severe trauma requires a combination of skills. Among these are accurate clinical assessment, basic resuscitation measures, basic general surgical skills and techniques, good decision making and team leadership. More technically advanced imaging and investigations are often useful and can enhance clinical assessment but should not replace the basic elements. In situations where more advanced investigations are not available good outcomes can be achieved by application of the basic principles in trauma management and surgery. This article describes a mass casualty situation of gunshot wounds managed with limited resources and the outcomes. METHODS: A series of gunshot wounds managed in a single day at Dili National Hospital, Dili, East Timor is described. The presentation of the patients, initial assessment of injuries and haemodynamic stability are detailed in addition to the subsequent surgical treatment, complications and outcomes. The information was obtained from hospital records and personal recollection of the treating doctors. All injuries were documented with digital photography. All patients were managed by two surgeons who also supervised their postoperative course and reported on their outcomes. Surgical procedures on all of the patients were performed by the named two consultant surgeons and one basic surgical trainee. RESULTS: Fourteen patients were treated for gunshot injuries. All were single bullet injuries. Six trajectories involved the thoracic or abdominal cavity (one trajectory traversed both). Eight injuries were to limbs or soft tissue of the pelvis and included four compound fractures. Surgical intervention was needed for all patients ranging from emergency laparotomy for haemodynamic instability through to wound debridements. Thirteen patients survived and were discharged from hospital within 3 weeks. One patient died of uncontrolled haemorrhage. CONCLUSIONS: In the present series of gunshot injuries managed with limited resources a good outcome was achieved with the application of basic principles. The present series emphasizes the importance of basic trauma management as outlined in courses such as Emergency Management of Severe Trauma and the use of basic surgical techniques as taught during the Advanced Surgical training program.     

A single exposure to morphine induces long-lasting behavioural and neurochemical sensitization in rats

Repeated exposure to drugs of abuse causes persistent behavioural sensitization and associated adaptations in striatal neurotransmission, which is thought to play an important role in certain aspects of drug addiction. Remarkably, even a single exposure to psychostimulant drugs such as amphetamine or cocaine can be sufficient to elicit long-lasting sensitization. The present study was designed to evaluate whether long-lasting behavioural and neurochemical sensitization can also be evoked by a single exposure to morphine, an opiate drug of abuse. Rats were pretreated once with morphine (2, 10 or 30 mg/kg). Three weeks later, the locomotor effects of morphine and amphetamine, as well as the electrically evoked release of [3H]dopamine and [14C]acetylcholine from slices of nucleus accumbens and caudate-putamen, was assessed. In morphine-pretreated rats, the psychomotor effects of morphine and amphetamine were sensitized. In addition, the electrically evoked release of [3H]dopamine and [14C]acetylcholine was augmented in slices of nucleus accumbens and caudate-putamen from morphine-pretreated animals. Although the sensitization of the locomotor effect of morphine was less profound than previously observed after repeated intermittent morphine treatment, the enduring behavioural and neurochemical consequences of a single and repeated intermittent morphine treatment appear to be highly comparable. We therefore conclude that a single exposure to morphine induces long-lasting behavioural sensitization and associated neuroadaptations.