New evidence for,and challenges in,linking small CGG repeat expansion FMR1 alleles with Parkinson's disease

We recently reported a significant increase in the frequency of carriers of grey zone (GZ) alleles of FMR1 gene in Australian males with Parkinson's disease (PD) from Victoria and Tasmania. Here, we report data comparing an independent sample of 817 PD patients from Queensland to 1078 consecutive Australian male newborns from Victoria. We confirmed the earlier finding by observing a significant excess of GZ alleles in PD (4.8%) compared to controls (1.5%). Although both studies provided evidence in support of an association between GZ‐carrier status and increased risk for parkinsonism, the existing evidence in the literature from screening studies remains equivocal and we discuss the need for alternative approaches to resolve the issue.     

Radiofrequency is a secure and effective method for pancreatic transection in laparoscopic distal pancreatectomy: results of a randomized, controlled trial in an experimental model

Background

Postoperative pancreatic fistula (PPF) is the most frequent and serious complication after laparoscopic distal pancreatectomy (LDP). Our goal was to compare the performance, in terms of PPF prevention, and safety of a radiofrequency (RF)-assisted transection device versus a stapler device in a porcine LDP model.

Methods

Thirty-two animals were randomly divided into two groups to perform LDP using a RF-assisted device (RF group; n = 16) and stapler device (ST group; n = 16) and necropsied 4 weeks after surgery. The primary endpoint was the incidence of PPF. Secondary endpoints were surgery/transection time, intra/postoperative complications/deaths, postoperative plasmatic amylase and glucose concentration, peritoneal liquid amylase and interleukin 6 (IL-6) concentrations, weight variations, and histopathological changes.

Results

Two clinical and one biochemical PPF were observed in the ST and RF groups respectively. Peritoneal amylase concentration was significantly higher in the RF group 4 days after surgery, but this difference was no longer present at necropsy. Both groups presented a significant decrease in peritoneal IL-6 concentration during the postoperative follow-up, with no differences between the groups. RF group animals showed a higher postoperative weight gain. In the histopathological exam, all RF group animals showed a common pattern of central coagulative necrosis of the parenchymal surface, surrounded by a thick fibrosis, which sealed main and secondary pancreatic ducts and was not found in ST group.

Conclusions

The fibrosis caused by an RF-assisted device can be at least as safe and effective as stapler compression to achieve pancreatic parenchyma sealing in a porcine LDP model.     

Returning to work with aphasia: A case study

Background: For some people with aphasia, returning to work will be their eventual goal. While there are reports in the literature of incidence of return to work, and general discussion of success, there are few documented in depth studies of what this might entail for the individual with aphasia.

Aims: This paper explores returning to work with aphasia, and examines the complex relationship between the person, the aphasia and the demands of employment.

Methods & Procedures: This is a detailed case report, describing and reflecting on the experiences of GD, who returned to work following his stroke and aphasia. Therapy focused specifically on work requirements is described and the factors affecting GD's return to work explored. An interview was used to elicit GD's reflections on his experiences.

Outcome & Results: GD's language skills improved over time and with therapy, and he developed several strategies that facilitated his communication. He was able to return to work (part-time) in a modified role and this was successful initially. After an extended period (～19 months) his employment was terminated and GD explored other options. He moved on to a volunteering and charity trustee role.

Conclusions: The success (or not) of returning to work with aphasia is multi-faceted and does not rest solely with the person with aphasia. The nature of the work may have a strong bearing on success, as will the ability and willingness of the employer to engage in the process. Partnership with the person and constant review of goals and management is of overwhelming importance. We need to consider what “success” may mean in this context and the need to consider therapeutic and rehabilitation needs over a longer time frame.     

Interferon-inducible protein-10 identified as a mediator of tumor necrosis in vivo

Human Burkitt lymphoma cell lines give rise to progressively growing subcutaneous tumors in athymic mice. These tumors are induced to regress by inoculation of Epstein–Barr virus-immortalized normal human lymphocytes. In the present study, analysis of profiles of murine cytokine/chemokine gene expression in Burkitt tumor tissues excised from the nude mice showed that expression of the murine α-chemokine interferon-inducible protein-10 (IP-10) was higher in the regressing than in the progressive Burkitt tumors. We tested the effects of IP-10 on Burkitt tumor growth in nude mice. Inoculation of established Burkitt tumors either with crude preparations of murine IP-10 or with purified human IP-10 caused visible tumor necrosis in a proportion of the animals, although no complete tumor regressions were observed. Constitutive expression of murine IP-10 in Burkitt cells reduced their ability to grow as subcutaneous tumors, and caused visible tumor necrosis in a proportion of the animals. Histologically, IP-10-treated and IP-10-expressing Burkitt tumors had widespread evidence of tumor tissue necrosis and of capillary damage, including intimal thickening and vascular thrombosis. Thus, IP-10 is an antitumor agent that promotes damage in established tumor vasculature and causes tissue necrosis in human Burkitt lymphomas established subcutaneously in athymic mice.     

Detection of anti-HTLV-I Tax antibodies in HTLV-I enzyme-linked immunosorbent assay-negative individuals

The HTLV-I tax gene protein (Tax) is not packaged within the mature viral particle from which the proteins for the commercially available enzyme-linked immunosorbent assay (ELISA) are derived. Screening of 162 individuals within a cohort of white intravenous (IV) drug abusers, previously identified as having an increased incidence of HTLV-I infection, demonstrated that seven of them had antibodies to the HTLV-I Tax protein but tested negative in HTLV-I ELISAs and Western blots prepared from purified virion proteins. Three out of 35 individuals in other behaviorally defined high-risk groups also displayed this limited pattern of reactivity to HTLV-I proteins. The presence of the anti-HTLV- I p40/Tax antibodies was determined by radioimmunoprecipitation assay (RIPA), which also revealed low levels of anti-env reactivity. The specificity of the anti-p40 reactivity was confirmed on specific Tax ELISAs and Western blots prepared from recombinantly produced Tax. In vitro gene amplification by the polymerase chain reaction (PCR) was used to establish the presence of sequences homologous to HTLV-I proviral DNA in four/four of these HTLV-I ELISA negative, Tax ELISA/Tax western blot/RIPA positive individuals. These data suggest that the true incidence of HTLV-I infection within high-risk cohorts is greater than previously reported.     

Development of Oxacillin Resistance in a Patient with Recurrent Staphylococcus aureus Bacteremia

Whole-genome sequencing was used to compare longitudinal isolates of Staphylococcus aureus that developed resistance to oxacillin (MIC up to 16 μg/ml). The mecA gene was absent. A novel 5-bp TATCC frameshift insertion in a gene encoding an ABC transporter similar to that of the teichoic acid translocation ATP-binding protein TagH and a 3-bp GCT nonframeshift insertion in the pdhA pyruvate dehydrogenase gene were detected in the oxacillin-resistant isolates.     

Influence of concurrent exercise or nutrition countermeasures on thigh and calf muscle size and function during 60 days of bed rest in women

AIM: The goal of this investigation was to test specific exercise and nutrition countermeasures to lower limb skeletal muscle volume and strength losses during 60 days of simulated weightlessness (6 degrees head-down-tilt bed rest). METHODS: Twenty-four women underwent bed rest only (BR, n = 8), bed rest and a concurrent exercise training countermeasure (thigh and calf resistance training and aerobic treadmill training; BRE, n = 8), or bed rest and a nutrition countermeasure (a leucine-enriched high protein diet; BRN, n = 8). RESULTS: Thigh (quadriceps femoris) muscle volume was decreased (P < 0.05) in BR (-21 +/- 1%) and BRN (-24 +/- 2%), with BRN losing more (P < 0.05) than BR. BRE maintained (P > 0.05) thigh muscle volume. Calf (triceps surae) muscle volume was decreased (P < 0.05) to a similar extent (P > 0.05) in BR (-29 +/- 1%) and BRN (-28 +/- 1%), and this decrease was attenuated (P < 0.05) in BRE (-8 +/- 2%). BR and BRN experienced large (P < 0.05) and similar (P > 0.05) decreases in isometric and dynamic (concentric force, eccentric force, power and work) muscle strength for supine squat (-19 to -33%) and calf press (-26 to -46%). BRE maintained (P > 0.05) or increased (P < 0.05) all measures of muscle strength. CONCLUSION: The nutrition countermeasure was not effective in offsetting lower limb muscle volume or strength loss, and actually promoted thigh muscle volume loss. The concurrent aerobic and resistance exercise protocol was effective at preventing thigh muscle volume loss, and thigh and calf muscle strength loss. While the exercise protocol offset approximately 75% of the calf muscle volume loss, modification of this regimen is needed.     

CHILDHOOD ONSET PERVASIVE DEVELOPMENTAL DISORDER

Two male children meeting criteria for Childhood Onset Pervasive Developmental Disorder (COPDD) are described. The current DSM-III category of COPDD may have value in separating these children from others with PDD. The authors suggest that these two children, and other children described in the literature as having dementia infantalis and/or disintegrative psychosis, have a distintegrative disorder resulting in muteness, profound mental retardation and severe autistic symptomatology. The term "pervasive disintegrative disorder" may be appropriate for such children and specific diagnostic criteria are suggested. The disorder appears to be extremely rare, with a prevalence estimate of 0.11 per 10,000.     

The role of protective antireflux procedures in neurologically impaired children: a decision analysis

Background/Purpose: Despite normal clinical history and preoperative radiologic and pH studies, gastroesophageal reflux (GER) can become apparent in neurologically impaired (NI) children after gastrostomy tube placement. An antireflux procedure performed at the time of gastrostomy tube placement may prevent postoperative GER and help avoid the need for a subsequent surgical procedure but is associated with a high morbidity and mortality rate in NI children. The purpose of this study was to determine the role of protective antireflux procedures in NI children undergoing gastrostomy tube placement. Methods: Decision analysis was used to evaluate the effect of a protective antireflux procedure on morbidity and mortality in NI children. The rate of postoperative GER, need for secondary antireflux procedures, and morbidity and mortality rates after gastrostomy tube placement with or without an antireflux procedure in NI children were estimated from the literature and expert opinion and used to construct decision trees. Results: At baseline values, gastrostomy tube placement resulted in a lower morbidity (11% v 13%) than gastrostomy tube placement with a protective antireflux procedure. One-way sensitivity analysis showed that gastrostomy tube placement was the favored approach when the morbidity of gastrostomy tube placement was less than 11% or the morbidity of antireflux surgery was greater than 10%. At baseline values, gastrostomy tube placement resulted in a lower mortality rate (0.3% v 0.8%) than gastrostomy tube placement with a protective antireflux procedure. Using 1-way sensitivity analysis, no threshold value of any variable was found that favored the use of a protective antireflux procedure with respect to mortality. Conclusions: Although a protective antireflux procedure may reduce the need for additional surgery, inclusion of this procedure is associated with a higher morbidity and mortality rate. Initial placement of a gastrostomy tube without a protective antireflux procedure is the favored approach for NI children without preoperative evidence of GER.