Slowly progressive aphasia without generalized dementia: studies with positron emission tomography

Slowly progressive aphasia without generalized dementia is a degenerative syndrome selectively affecting dominant hemisphere language areas. We report changes in regional glucose metabolism measured by positron emission tomography in two patients with this condition. Striking abnormalities of glucose utilization in the left cerebral cortex were demonstrated in both patients. The findings of other neurodiagnostic studies were relatively unremarkable. The first patient had a 3-year history of progressive anomia and impaired auditory verbal recall. An electroencephalogram was normal, and computed tomography showed mild left perisylvian atrophy. Positron emission tomography revealed profound hypometabolism in the left temporal regions. The second patient also had a 3-year history of progressive anomia. Electroencephalography, computed tomography, and magnetic resonance imaging scans were normal. Positron emission tomography showed a major reduction in left parietal glucose utilization, with a lesser decrement in left temporal metabolism. Neither patient demonstrated significant contralateral or global abnormalities such as those reported in positron emission tomographic studies of Alzheimer's disease with or without focal clinical features. These observations support the concept of adult-onset progressive aphasia without dementia as a clinical syndrome distinct from Alzheimer's disease.     

Properties of antigenic determinants that distinguish neurofibrillary tangles in progressive supranuclear palsy and Alzheimer's disease

Neurofibrillary tangles (NFT) in Alzheimer's disease (AD) and in progressive supranuclear palsy (PSP) differ in their location and morphology, but both appear to express the same or similar epitopes. These immunologic data may signify that both types of NFTs contain the same components and arise as a result of the same mechanisms. To explore this hypothesis, we probed PSP and AD samples of brain stem, where both PSP and AD NFTs occur, using a large panel of monoclonal antibodies (MAbs). The epitopes expressed in brain stem PSP and AD NFTs were compared with those in the NFTs of AD hippocampus. NFTs in PSP hippocampus were too infrequent for comparative analysis. The MAbs were raised to neurofilament and tau proteins, or to AD paired helical filaments. All MAbs raised to tau (three) and paired helical filaments (two) recognized brain stem PSP NFTs and AD NFTs in brain stem and hippocampus. However, 12 anti-NF MAbs specific for multiphosphorylation repeat domains or other phosphate-dependent and independent epitopes did not bind PSP NFTs, but they did detect AD NFTs in hippocampus, and 5 of these MAbs also recognized brain stem AD NFTs. We conclude that some populations of AD NFTs contain antigenic determinants that are not found in PSP NFTs. This may reflect the effect of different pathologic events specific to PSP and AD, or the selective formation of NFTs in different groups of neurons in each of these disorders.     

Association of apolipoprotein ɛ4 allele and neuropathologic findings in patients with dementia

Apolipoprotein E (APOE) is a lipoprotein expressed in liver and brain as one of three isoforms (APOE 2, APOE 3 and APOE 4). Recent findings suggest that the presence of APOE 4 is associated with an increased risk for both familial Alzheimer's disease and late-onset Alzheimer's disease. We extended these observations by determining the frequency of APOE alleles in patients with pathologically confirmed Alzheimer's Disease (AD), Parkinson's disease (PD), diffuse Lewy Body disease (DLBD), AD with concomitant PD pathology, demented PD patients without or with concomitant AD pathology and in schizophrenics with a progressive dementia (SCHIZ+DEM). The APOE genotype was determined by restriction digestion of polymerase chain reaction-amplified DNA isolated from frozen brain samples. The frequency of the APOE 4 allele was highest among sporadic AD and DLBD patients (0.30 and 0.38, respectively) and lowest in the SCHIZ+DEM and non-demented PD patients (0.06 and 0.1, respectively). Thus, the APOE 4 allele is over-represented selectively in patients with dementias associated with plaques and tangles and/or cortical Lewy bodies, but not in demented schizophrenics or non-demented PD patients.     

Targeting for thalamic deep brain stimulator implantation without computer guidance: assessment of targeting accuracy

The authors assess the accuracy of targeting nucleus ventralis intermedius (Vim) with fast spin echo inversion recovery (FSE/IR) magnetic resonance imaging (MRI) in 18 successful deep brain stimulator (DBS) implants for medically refractory tremor. FSE/IR-MRI-derived coordinates are compared to the final coordinates employed for DBS lead placement, selected with intraoperative neurophysiology. The authors conclude that FSE/IR MRI is sufficiently reliable to serve as the sole means of anatomically targeting Vim for DBS lead placement. An independent computer workstation is not required for accurate targeting; however, intraoperative neurophysiology remains essential.     

The epidemiology of Parkinson's disease. A case-control study of young-onset and old-onset patients

While the cause of Parkinson's disease (PD) remains unknown, recent evidence suggests that certain external factors, ie, environmental agents, may act as neurotoxins, initiating the chain of oxidative reactions that ultimately destroy neurons in the substantia nigra. Young-onset PD might result from greater exposure to a putative neurotoxin. This hypothesis has rekindled interest in the epidemiology of PD. We therefore conducted a detailed analysis of various environmental exposures and early life experiences in 80 patients with old-onset PD (at an age older than 60 years), 69 young-onset patients (younger than 40 years), and 149 age- and sex-matched control subjects. Contrary to previous reports, we were unable to implicate well water or exposure to herbicides, pesticides, or industrial toxins as significant PD risk factors. A residential history of rural living was reported by more patient cases than control subjects and was marginally significant. On the other hand, at least one episode of head trauma "severe enough to cause vertigo, dizziness, blurred or double vision, seizures or convulsions, transient memory loss, personality changes, or paralysis" occurred significantly more often prior to disease onset in patients with both young-onset and old-onset PD than in control subjects (odds ratio = 2.7). When adjusted for head trauma and rural living, smoking was inversely associated with PD, as has been previously reported (odds ratio = 0.5). There were no significant differences in early life experiences or environmental exposures between young-onset and old-onset patients. We suggest that the risk of developing PD is influenced by a variety of factors.(ABSTRACT TRUNCATED AT 250 WORDS)     

The association between social support and the mental health of social workers and police officers who work with unaccompanied asylum-seeking refugee children’s forced repatriation: A Swedish experience

This study aims to contribute to the knowledge of social support and its association with mental health amongst social workers and police officers in forced repatriation work of unaccompanied asylum-seeking refugee children. Nationally distributed surveys to social workers and police officers with and without experience of forced repatriation were used, measured by an abbreviated version of the Interview Schedule for Social Interaction (ISSI), and analyzed by univariate and multivariable regression models. Social workers in forced repatriation showed significantly poorer mental health than other social workers, but simultaneously relatively high access to social support. Irrespective of working with forced repatriation, police officers reported relatively high access to social support, but no difference in mental health. Furthermore, low levels of satisfaction with social interaction and close emotional support increased the odds of psychological disturbances for police officers in forced repatriation. Findings are discussed with special regard to the complexity of forced repatriation, particularly when children are the focus.     

Platelet‐rich plasma enhances the integration of bioengineered cartilage with native tissue in an in vitro model

Current therapies for cartilage repair can be limited by an inability of the repair tissue to integrate with host tissue. Thus, there is interest in developing approaches to enhance integration. We have previously shown that platelet‐rich plasma (PRP) improves cartilage tissue formation. This raised the question as to whether PRP could promote cartilage integration . Chondrocytes were isolated from cartilage harvested from bovine joints, seeded on a porous bone substitute and grown in vitro to form an osteochondral‐like implant. After 7 days, the biphasic construct was soaked in PRP for 30 min before implantation into the core of a donut‐shaped biphasic explant of native cartilage and bone. Controls were not soaked in PRP. The implant–explant construct was cultured for 2–4 weeks. PRP‐soaked bioengineered implants integrated with host tissue in 73% of samples, whereas controls only integrated in 19% of samples. The integration strength, as determined by a push‐out test, was significantly increased in the PRP‐soaked implant group (219 ± 35.4 kPa) compared with controls (72.0 ± 28.5 kPa). This correlated with an increase in glycosaminoglycan and collagen accumulation in the region of integration in the PRP‐treated implant group, compared with untreated controls. Immunohistochemical studies revealed that the integration zone contained collagen type II and aggrecan. The cells at the zone of integration in the PRP‐soaked group had a 3.5‐fold increase in matrix metalloproteinase‐13 gene expression compared with controls. These results suggest that PRP‐soaked bioengineered cartilage implants may be a better approach for cartilage repair due to enhanced integration.     

Vaccination against the M protein of Streptococcus pyogenes prevents death after influenza virus:S. pyogenes super-infection

Influenza virus infections are associated with a significant number of illnesses and deaths on an annual basis. Many of the deaths are due to complications from secondary bacterial invaders, including Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Streptococcus pyogenes. The β-hemolytic bacteria S. pyogenes colonizes both skin and respiratory surfaces, and frequently presents clinically as strep throat or impetigo. However, when these bacteria gain access to normally sterile sites, they can cause deadly diseases including sepsis, necrotizing fasciitis, and pneumonia. We previously developed a model of influenza virus:S. pyogenes super-infection, which we used to demonstrate that vaccination against influenza virus can limit deaths associated with a secondary bacterial infection, but this protection was not complete. In the current study, we evaluated the efficacy of a vaccine that targets the M protein of S. pyogenes to determine whether immunity toward the bacteria alone would allow the host to survive an influenza virus:S. pyogenes super-infection. Our data demonstrate that vaccination against the M protein induces IgG antibodies, in particular those of the IgG1 and IgG2a isotypes, and that these antibodies can interact with macrophages. Ultimately, this vaccine-induced immunity eliminated death within our influenza virus:S. pyogenes super-infection model, despite the fact that all M protein-vaccinated mice showed signs of illness following influenza virus inoculation. These findings identify immunity against bacteria as an important component of protection against influenza virus:bacteria super-infection.     

Use of Cortisone and Antibiotics in Resistant Pelvic Infections

Although the incidence of resistant pelvic infections has been decreased, they are still a problem in spite of adequate antibiotic therapy. A new approach to such cases, in the subacute stage, is described, and the method, rationale and dangers outlined. Results obtained in the cases described, as well as in others treated subsequently, have been excellent.