The role of neurotransmitters in the development of Parkinson's disease-related psychosis.

Psychotic symptoms are common, disabling non-motor features of Parkinson's disease (PD). Despite noted heterogeneity in clinical features, natural history and therapy response, current dogma posits that psychosis generally progresses in a stereotypic manner through a cascade of events that begins with minor hallucinations and evolves to severe hallucinations and delusions. Further, the occurrence of psychotic symptoms is believed to indicate a poor prognosis. Here we propose a classification scheme that outlines the pathogenesis of psychosis as it relates to dysfunction of several neurotransmitter systems. We hypothesize that several subtypes exist, and that PD psychosis is not consistently indicative of a progressive cascade and poor prognosis. The literature was reviewed from 1990 to 2017. An overview of the features of PD psychosis is followed by a review of data indicating the existence of neurotransmitter-related subtypes of psychosis. We found that ample evidence exists to demonstrate the presence of multiple subtypes of PD psychosis, which are traced to dysfunction of the following neurotransmitter systems: dopamine, serotonin and acetylcholine. Dysfunction of each of these systems is recognizable through their clinical features and correlates, and the varied long-term prognoses. Identifying which neurotransmitter system is dysfunctional may help to develop targeted therapies. PD psychosis has various subtypes that differ in clinical features, underlying pathology and pathophysiology, treatment response and prognosis. A novel classification scheme is presented that describes the clinical subtypes with different outcomes, which could lead to the development of targeted therapies. Future research should focus on testing the viability of this classification.

Cerebrospinal fluid biomarkers in Parkinson's disease with freezing of gait: an exploratory analysis.

We explore the association between three Alzheimer's disease-related and ten inflammation-related CSF markers and freezing of gait (FOG) in patients with Parkinson's disease (PD). The study population includes PD patients with FOG (PD-FOG, N = 12), without FOG (PD-NoFOG, N = 19), and healthy controls (HC, N = 12). Age and PD duration are not significantly different between groups. After adjusting for covariates and multiple comparisons, the anti-inflammatory marker, fractalkine, is significantly decreased in the PD groups compared to HC (P = 0.002), and further decreased in PD-FOG compared to PD-NoFOG (P = 0.007). The Alzheimer's disease-related protein, Aß42, is increased in PD-FOG compared to PD-NoFOG and HC (P = 0.001). Group differences obtained in individual biomarker analyses are confirmed with multivariate discriminant partial least squares regression (P < 0.001). High levels of Aß42 in PD-FOG patients supports an increase over time from early to advanced state. Low levels of fractalkine might suggest anti-inflammatory effect. These findings warrant replication.

Use of a novel technology for presenting screening measures to detect mild cognitive impairment in elderly patients.

BACKGROUND: Available screening tools for mild cognitive impairment (MCI), often a precursor to Alzheimer's disease, are insensitive or not feasible for administration in a busy primary care setting. Display Enhanced TEsting for Cognitive impairment and Traumatic brain injury (DETECT) addresses these issues by creating an immersive environment for the brief administration of neuropsychological (NP) measures. OBJECTIVE: The aim of this study was to determine if the DETECT cognitive subtests can identify MCI patients as accurately as standard pen and paper NP tests. METHODS: Twenty patients with MCI recruited from a memory disorders clinic and 20 age-matched controls were given both a full battery of NP tests (standard NP) and the DETECT screen. Logistic regression models were used to determine whether individual tests were predictive of group membership (MCI or control). Demographic variables including age, race, education and gender were adjusted as covariates. Selection methods were used to identify subset models that exhibited maximum discrimination between MCI patients and controls for both testing methods. RESULTS: Both the standard NP model (C-index = 0.836) and the DETECT model (C-index = 0.865) showed very good discrimination and were not significantly different (p = 0.7323). CONCLUSION: The DETECT system shows good agreement with standard NP tests and is capable of identifying elderly patients with cognitive impairment.

Diet as a Risk Factor for Cognitive Decline in African Americans and Caucasians with a Parental History of Alzheimer's Disease: A Cross-Sectional Pilot Study Dietary Patterns.

BACKGROUND: African Americans (AA) are more likely to develop Alzheimer's disease (AD) than Caucasians (CC). Dietary modification may have the potential to reduce the risk of developing AD. OBJECTIVE: The objective of this study is to investigate the relationship between Southern and Prudent diet patterns and cognitive performance in individuals at risk for developing AD. DESIGN: Cross-sectional observational study. PARTICIPANTS: Sixty-six cognitively normal AA and CC individuals aged 46-77 years with a parental history of AD were enrolled. MEASUREMENTS: Participants completed a Food Frequency questionnaire, cognitive function testing, which consisted of 8 neuropsychological tests, and cardiovascular risk factor assessments, including evaluation of microvascular and macrovascular function and ambulatory blood pressure monitoring. RESULTS: Results revealed a relationship between the Southern diet and worse cognitive performance among AAs. AAs who consumed pies, mashed potatoes, tea, and sugar drinks showed worse cognitive performance (p<0.05) compared with CCs. In addition, gravy (p=0.06) and cooking oil/fat (p=0.06) showed negative trends with cognitive performance in AAs. In both CC and AA adults, greater adherence to a Prudent dietary pattern was associated with better cognitive outcomes. Cardiovascular results show that participants are overall healthy. AAs and CCs did not differ on any vascular measure including BP, arterial stiffness and endothelial function. CONCLUSION: Research shows that dietary factors can associate with cognitive outcomes. This preliminary cross-sectional study suggests that foods characteristic of the Southern and Prudent diets may have differential effects on cognitive function in middle-aged individuals at high risk for AD. Results suggest that diet could be a non-pharmaceutical tool to reduce cognitive decline in racially diverse populations. It is possible that the increased prevalence of AD in AA could be partially reduced via diet modification.

[Monitoring of antibiotic resistance of gram negative anaerobes]. / Surveillance de la résistance aux antibiotiques des anaérobies stricts à Gram négatif.

MATERIAL AND METHOD: Using an agar reference method (Norma M11-A5, National Committee for Clinical and Laboratory Standards) the minimal inhibitory concentrations of nine antibiotics were determined for 376 anaerobic strains. The following strains were investigated: 254 Bacteroides fragilis group (including 143 B. fragilis), 122 other gram-negative anaerobes (Bacteroides spp., Prevotella, Fusobacterium, Porphyromonas, Suterella, Desulfomonas, Veillonella). RESULTS: In the B. fragilis group resistance rates were: coamoxyclav 2.8%, ticarcillin 27.5%, ticarcillin-clavulanic acid 1.9%, piperacillin-tazobactam 1.9%, cefoxitin 6.2%, imipenem 0.8%, clindamycin 28.3%, respectively. Based on previous studies, resistance to imipenem remained low in 2003 and was only observed for B. fragilis. Resistance to clindamycin was maintained around 25%. No metronidazole resistance was observed, but decreased susceptibility was found for B. fragilis, B. merdae and Prevotella, as in 4.3% of gram-negative anaerobes. DISCUSSION: This study confirms the high resistance rate of gram-negative anaerobes to clindamycin, the efficient activity of imipenem, beta-lactam/beta-lactamase inhibitor combinations and metronidazole. However, reduced metronidazole susceptibility seems to be increasing.

Combating resistance in a challenging, changing environment.

The prevalence of antimicrobial resistance for both Gram-positive and Gram-negative pathogens is escalating worldwide. Outbreaks of community- and hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) are being reported more frequently. Although antimicrobial resistance is well recognised as a global problem, decisions about appropriate intervention and treatment should be made at the level of the local hospital or healthcare system. Thus, local surveillance to identify prevalent pathogens, detect bacterial resistance and identify particular strains is necessary for selecting optimal treatment regimens. In addition, bactericidal antimicrobial agents with novel mechanisms of action and activity against multidrug-resistant bacteria, together with improved infection control measures, are needed to address this growing medical problem more effectively.

The DETECT system: portable, reduced-length neuropsychological testing for mild traumatic brain injury via a novel immersive environment.

Undiagnosed mild traumatic brain injury (mTBI) often leads to poor patient management and significant morbidity. The lack of an efficient screening tool is especially apparent in the athletic setting, where repetitive injuries can lead to prolonged disability. We have developed the Display Enhanced Testing for Concussions and mTBI system (DETECT), in order to create a portable immersive environment that could eliminate visual and audio distractions. Neuropsychological tests sensitive to mTBI were modified for use with the system and allow rapid neurological assessment independent of the environment or trained personnel. We evaluated the immersive qualities of the DETECT system in 42 uninjured controls. The system was successful in blocking out external audiovisual stimuli. The neuropsychological test results obtained in a stimulus rich environment were equivalent to those obtained in a controlled quiet environment. The immersive environment, portability, and brevity of the DETECT system allow for real-time cognitive testing in situations previously deemed impractical or unavailable for mTBI patients.

Monitoring of vancomycin serum levels for the treatment of staphylococcal infections.

Vancomycin serum concentrations were determined for 1,737 patients treated with either 2 x 1 g of vancomycin or 4 x 500 mg daily (780 patients), according to current nomograms, or by continuous infusion (957 patients) with a loading dose (1 g) and a total of 2-6 g daily. Trough serum concentrations were determined after 36-48 h. Adequate serum levels for the treatment of a normal methicillin-resistant Staphylococcus aureus (MRSA) and a glycopeptide-intermediate S. aureus (GISA) were observed in 81% and 20.9% of patients, respectively. The data support theoretical arguments that higher and more sustained serum levels of vancomycin, obtained by continuous infusion, may enhance clinical efficacy.

European Committee on Antimicrobial Susceptibility Testing (EUCAST) Technical Notes on antimicrobial susceptibility testing.

The main objectives of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are to harmonise breakpoints for antimicrobial agents in Europe, and to act as the breakpoint committee for the European Medicines Agency (EMEA) during the registration of new antimicrobial agents. Detailed EUCAST procedures for harmonising and setting breakpoints for antimicrobial agents are available on the EUCAST website. Beginning with the current issue, a series of EUCAST Technical Notes will be published in CMI, based on the rationale documents produced by EUCAST for each of the antimicrobial agents studied, with the aim of highlighting important background information underlying decisions on breakpoints made by EUCAST.

Chronic Q fever. Ninety-two cases from France, including 27 cases without endocarditis.

OBJECTIVE: Chronic Q fever is seldom recognized; before 1989, only 234 cases had been reported in the literature. The 92 cases of chronic Q fever collected at the French National Reference Center for Rickettsioses from 1982 through 1990 represent the largest series ever reported. PATIENTS: The patients included in the study were diagnosed between July 31, 1982, and August 1, 1990, at the French National Reference Center for Rickettsioses as having chronic Q fever by the following criteria: presence of antibody against Coxiella burnetii phase I antigen at a titer greater than or equal to 800 for IgG and 50 for IgA by the indirect immunofluorescence test. Epidemiologic, clinical, laboratory, and treatment data were collected from 39 different collaborative hospitals throughout France. MAIN OUTCOME MEASURE: For each serologically selected patient, a computerized questionnaire was utilized to record 188 different items of demographic, epidemiologic, clinical, laboratory, and therapeutic data, which were analyzed. RESULTS: Chronic Q fever occurs more frequently in city dwellers than in rural inhabitants, and exposure to domestic ruminants and raw milk is an important feature. Immunocompromising conditions (20.2%) and underlying heart disease (88.4%) or vascular disease are the most important risk factors to consider in potential cases of chronic Q fever. The mortality in these patients with endocarditis was high (23.5%). The clinical spectrum of 84 patients included 57 cases of endocarditis, three cases of vascular prosthesis infection, three cases of aneurysmal infection, three cases of osteoarthritis, four cases with lung localizations, nine asymptomatic cases, three cases of hepatitis, and two cases with cutaneous forms of the disease. CONCLUSIONS: In patients with unexplained fever, negative blood cultures, and a history of underlying vascular or cardiac disease, Q fever should be considered.

[Efficacy and safety of telithromycin in the treatment of acute maxillary sinusitis]. / Efficacité et tolérance de la télithromycine dans le traitement des sinusites maxillaires aiguës.

UNLABELLED: The aim of this study was to evaluate the efficacy and tolerance of 5 days of telithromycin (800 mg once a day) in the treatment of bacteriologically proven acute maxillary sinusitis (AMS). DESIGN: Two hundred and sixty-three patients with a clinically diagnosed AMS and purulent rhinorrhea were included in this prospective, multicenter, non-comparative open-labeled French study. Pus was sampled from the middle meatus before inclusion. The bacterial origin of the infection was confirmed by a scientific committee (presence of leucocytes/bacteria on direct microscopic examination of pus, and positive culture). RESULTS: Seven to 14 days after the end of the treatment the clinical success rate (cure and improvement) was 91% (63/69 patients) in the per protocol bacteriologically documented (PPb) population and 90% (231/257 patients) in the modified intent-to-treat population. The main strains identified in the 69 patients of PPb population were Streptococcus pneumoniae (47.8%, of which 15 strains with reduced susceptibility to penicillin and 15 erythromycin resistant strains), Haemophilus influenzae (14.5%), Branhamella catarrhalis (8.7%) and Streptococcus aureus (29.0%). Drug tolerance was assessed on 263 patients as satisfactory with mainly gastro-intestinal disorders considered to be related to the treatment in 7.6% of patients. No serious adverse event related to the study drug was reported. CONCLUSION: The efficacy of telithromycin 800 mg once daily for 5 days is confirmed in the treatment of AMS, even for those due to S. Pneumoniae.

[Shoulder arthritis due to Haemophilus aphrophilus]. / Arthrite d'épaule à Haemophilus aphrophilus.

We report a case of shoulder arthritis due to Haemophilus aphrophilus. The patient, a 56 year-old woman, was immunocompetent. She presented with a septic arthritis of the left shoulder without portal of entry. A synovial fluid sample was cultured and positive for a gram-negative bacillus after 8 days. It was identified as Haemophilus aphrophilus, in the HACCEK group, by PCR ARN 16S. We did not find any associated endocarditis. The patient recovered. As far as we know, this is only the 5th reported case of arthritis due to this microorganism.

Gist recall in multiple sclerosis.

This study examined gist recall (memory for important story ideas) in patients with multiple sclerosis. Twelve patients with clinically probable or definite multiple sclerosis and 10 neurologically intact control subjects were read prose passages from the Wechsler Memory Scale-Revised Logical Memory subtest. The idea units from these passages contained low, medium, and high information content to the stories. In comparison with the control subjects, the patients recalled fewer total elements over immediate and delayed conditions. However, similar to controls, they recalled more ideas that were of high rather than low or medium importance. These results suggest that semantic sensitivity to important ideas of narratives is a relatively preserved feature in multiple sclerosis.

Treatment trial of oxiracetam in Alzheimer's disease.

Twenty-four carefully assessed patients with probable Alzheimer's disease were enrolled in a double-blind, placebo-controlled treatment study of oxiracetam, a nootropic agent reported to improve memory performance in patients with dementia. A broad battery of neuropsychological tests failed to reveal any improvement in the treated group or in any treated patient when individual test scores were analyzed. These findings indicate that oxiracetam is ineffective in reducing cognitive impairment due to Alzheimer's disease.

Apolipoprotein E and age at onset of Alzheimer's disease in African American patients.

The authors examined whether the APOE-epsilon4 allele is associated with an earlier age at onset of AD in 71 African American patients with probable AD. The authors found a linear dose effect in which each copy of the epsilon4 allele was associated with a 3.6-year earlier onset of AD, indicating a dose-dependent relationship between APOE-epsilon4 and age at onset of AD in African Americans.

Strategies in aminoglycoside use and impact upon resistance.

Assessment of amikacin resistance over a 10-year period at our institution revealed that the number of resistant strains remained stable. Qualitatively, amikacin-resistant Enterobacteriaceae and Pseudomonas were fairly stable. There was a slight increase in amikacin-resistant Acinetobacter and staphylococci. Different factors influencing the emergence and spread of resistant hospital bacteria have been studied at different periods and compared with similar data on gentamicin-resistant strains. Transmissible plasmids, multiple mechanisms of resistance, and high levels of resistance were more frequent in gentamicin-resistant strains. In the amikacin-resistant strains, the level of resistance was 16 to 32 mg/liter with few autotransferable plasmids. A synergistic or additive effect with cephalosporins, which may be a factor in decreasing the risk of selection of the resistant strains since there is no plasmid-mediated resistance to cephalosporins, was demonstrated in Enterobacteriaceae. To control the development of aminoglycoside resistance in hospitals, it may be necessary to restrict the use of more than the one drug to which resistance is developing; to use the antibiotic at the right dosage and, when necessary, in a combination that may prevent the emergence of resistant organisms and plasmids; and to develop measures to control bacterial and R factor transmission.

Single- versus triple-lumen central catheter-related sepsis: a prospective randomized study in a critically ill population.

PURPOSE: A prospective randomized study was conducted over a 23-month period in an adult medical-surgical intensive care unit to determine whether triple-lumen catheters reduce the need for peripheral vascular access and whether they are associated with a higher rate of infection than single-lumen catheters. PATIENTS AND METHODS: After the insertion route, internal jugular or subclavian, was selected by the physician, patients were randomized either to single-lumen or triple-lumen catheter groups. Complementary peripheral vascular access was allowed in both groups. Catheters were removed according to preestablished defined reasons: suspicion of catheter-related sepsis, uselessness of central venous access, duration of catheterization of more than 21 days, discharge from the intensive care unit, or death. RESULTS: Data on 129 central venous catheters were collected from 91 consecutive patients. Twenty-five of 68 patients from the single-lumen group and 1 of 61 patients from the triple-lumen group needed peripheral vascular access (p less than 0.001). Catheter-related sepsis rates, defined either by clinical signs and positive qualitative tip cultures (8.9% versus 11.5%) or by quantitative tip cultures (16.2% versus 11.5%), were identical in the single-lumen and triple-lumen groups (type II error: 8%). CONCLUSION: In intensive care units, the use of triple-lumen catheters is associated with a dramatic decrease in the need for peripheral vascular access. The incidence of central venous catheter-related sepsis appears identical for single- and triple-lumen catheters.

Feline analgesia following central administration of opioids.

Activity of opioids in cats was assessed by employing the tail-flick method. Microinjection of morphine (100 micrograms) or etorphine (2.5 micrograms) into the ventrolateral periaqueductal gray (VLPAG) region resulted in significant analgesia. Smaller doses of morphine (10 and 50 micrograms) or etorphine (0.62 and 1.25 micrograms) were without significant effect. Methadone likewise produced no significant analgesic action in doses as large as 360 micrograms in the ventrolateral periaqueductal gray. Rank order potency, i.e. etorphine greater than morphine much greater than methadone, was similar following systemic administration. Increased latency of tail-flick response after injection of etorphine was diminished by administration of naloxone, either systemically or centrally, thus indicating a specific opiate-mediated response.

Effect of chronic treatment with tricyclic antidepressants upon antinociception induced by intrathecal injection of morphine and monoamines.

The effects of acute and chronic treatment with tricyclic antidepressants (TCA) upon antinociception induced by intrathecally administered serotonin (5-HT), norepinephrine (NE), and morphine were assessed at weekly intervals by the tail-flick method in the rat. Acute pretreatment with either clomipramine (28.5 mumol/kg, s.c.) or desipramine (85.5 mumol/kg, s.c.) enhanced the analgesia induced by both intrathecally-administered morphine (7.5 nmol) and 5-HT (241 nmol), compared to saline (1 ml/kg) but only desipramine facilitated the effects of intrathecally administered NE (0.49 nmol). The chronic (22 day) administration of both tricyclic antidepressants resulted in loss of the enhancement of the effects of morphine (day 22) and 5-HT (day 15); only desipramine (day 15) abolished the facilitation of NE. In a similar study, acute pretreatment with the non-tricyclic antidepressant inhibitor of the reuptake of NE, nisoxetine, (97.5 mumol/kg, s.c.), amplified the effects of intrathecally administered NE and morphine but not 5-HT-induced analgesia. Although chronic (22 day) treatment with nisoxetine caused a loss of the effects of enhancement of morphine (day 8), there was no effect upon the action of NE and antinociception induced by 5-HT was facilitated (day 22). Receptor binding studies indicated that chronic (22 day) treatment with clomipramine, desipramine or nisoxetine reduced the affinity of opiate [3H]naloxone) receptors in the spinal cord. These results demonstrate that (1) acute treatment with trycyclic antidepressants enhanced analgesia induced by intrathecally injected morphine, and (2) the chronic administration of trycyclic antidepressants resulted in a loss of enhancement of the effects of morphine, given intrathecally, which appeared to be independent of alterations in the activity of NE or 5-HT but may be associated with the development of subsensitive opiate receptors.

Epidemiology of quinolone resistance: Europe and North and South America.

After nearly 10 years of fluoroquinolone usage for a wide range of bacterial infections, a striking difference has been observed in the incidence of bacterial resistance to fluoroquinolones between bacteria responsible for community- and hospital-acquired infections, respectively. Resistance is only rarely encountered among common pathogens. In most studies, 97 to 100% of all pathogens are fully susceptible to fluoroquinolones. In contrast, resistance to fluoroquinolones has emerged and increased among bacteria responsible for nosocomial infections. The incidence of resistance to fluoroquinolones varies between bacterial species, clinical settings and countries, and is related to local epidemic spread of a few clones. The highest incidence of resistance is observed in Pseudomonas aeruginosa, Acinetobacter spp., Serratia marcescens and, particularly, methicillin-resistant Staphylococcus aureus (MRSA): some investigators have reported 95 to 100% fluoroquinolone resistance among MRSA. Follow-up of trends in the resistance to fluoroquinolones based upon surveillance programmes are needed.