Electrophysiological evidence for presynaptic actions of phencyclidine on noradrenergic transmission in rat cerebellum

The actions of the psychotomimetic drug phencyclidine (PCP) were studied using Purkinje neurons in the cerebellum of urethane-anesthetized rats. PCP, applied by micropressure ejection through multibarreled micropipettes, depressed the spontaneous activity of these neurons as recorded by extracellular electrophysiological techniques. This depressant effect was blocked by neuroleptic drugs and lithium, both of which also block the depressant effects of norepinephrine, but not those of gamma-aminobutyric acid. PCP-elicited depressions could not be obtained in rats in which the cerebellar noradrenergic terminals had been lesioned selectively by pretreatment with the neurotoxin 6-hydroxydopamine. However, PCP was still an effective depressant in animals after destruction of non-noradrenergic intrinsic excitatory and inhibitory interneurons which synapse on the Purkinje cell by neonatal X-irradiation. Further treatment of the X-irradiated animal with 6-hydroxy-dopamine resulted in Purkinje neurons which were not responsive to PCP. Administration of magnesium ions, which reduces the release of neurotransmitters from afferent terminals, also blocked the depressant effects of PCP. The results of this study suggest that PCP acts in the cerebellum by a presynaptic mechanism involving the release of norepinephrine from intact, functioning noradrenergic terminals.     

Variation in emergency department visits for conditions that may be treated in alternative primary care settings

The purpose of this report is to examine Ontario's geographic variation in emergency department (ED) visits for conditions that may be treated in alternative primary care settings. We studied all visits to Ontario EDs in 2002/03 and calculated county-specific age-standardized rates. Overall in Ontario, there were 3174 ED visits per 100,000 population aged 1-74 for conditions that could be treated in alternate primary care settings, but rates varied widely across counties. They were higher in rural counties with rates up to 7-fold higher than the provincial average. Urban counties had lower rates, some were less than one-third of the provincial average. Further research is needed to determine the relationship between ED utilization and primary care capacity.     

Dietary Salt Intake and Discretionary Salt Use in Two General Population Samples in Australia: 2011 and 2014

The limited Australian measures to reduce population sodium intake through national initiatives targeting sodium in the food supply have not been evaluated. The aim was, thus, to assess if there has been a change in salt intake and discretionary salt use between 2011 and 2014 in the state of Victoria, Australia. Adults drawn from a population sample provided 24 h urine collections and reported discretionary salt use in 2011 and 2014. The final sample included 307 subjects who participated in both surveys, 291 who participated in 2011 only, and 135 subjects who participated in 2014 only. Analysis included adjustment for age, gender, metropolitan area, weekend collection and participation in both surveys, where appropriate. In 2011, 598 participants: 53% female, age 57.1(12.0)(SD) years and in 2014, 442 participants: 53% female, age 61.2(10.7) years provided valid urine collections, with no difference in the mean urinary salt excretion between 2011: 7.9 (7.6, 8.2) (95% CI) g/salt/day and 2014: 7.8 (7.5, 8.1) g/salt/day (p = 0.589), and no difference in discretionary salt use: 35% (2011) and 36% (2014) reported adding salt sometimes or often/always at the table (p = 0.76). Those that sometimes or often/always added salt at the table and when cooking had 0.7 (0.7, 0.8) g/salt/day (p = 0.0016) higher salt excretion. There is no indication over this 3-year period that national salt reduction initiatives targeting the food supply have resulted in a population reduction in salt intake. More concerted efforts are required to reduce the salt content of manufactured foods, together with a consumer education campaign targeting the use of discretionary salt.     

The postviral fatigue syndrome — an analysis of the findings in 50 cases

The clinical, pathological, electrophysiological, immunological and virological abnormalities in 50 patients with the postviral fatigue syndrome are recorded. These findings confirm the organic nature of the disease. A metabolic disorder, caused by persistent virus infection and associated with defective immunoregulation, is suggested as the pathogenetic mechanism.     

Insomnia: nonpharmacologic management by private practice physicians

We report a survey investigation on the perceived value of behavioral assessment and the use of nonpharmacologic treatment of insomnia by 159 physicians in private practice in Davidson County, Tennessee. They generally attributed limited value to behavioral assessment, and reported infrequent use of nonpharmacologic treatment. However, the more patients the physicians saw with insomnia as the chief symptom, the more they tended to value behavioral assessment and other diagnostic procedures. Endorsement of behavioral assessment and all other diagnostic practices was in turn related to the use of behavioral treatment techniques. We suggest that a lack of awareness of the value of alternative assessment and treatment strategies may account for physicians' limited use of nonpharmacologic approaches to this common yet frequently serious medical problem.     

The relationship of input and output phonological processing: An evaluation of models and evidence to support them

In this paper, we review studies of the relationship between input and output phonological processing and discuss the means by which an interactive activation model that assumes a single phonological network or functionally connected input and output phonological networks could account for apparent dissociations of these two pathways. Following this, we report data from 24 aphasic subjects with word processing deficits that indicate associations between input and output phonological processing. Input phonological measures correlated with output phonological measures, but not with output lexical-semantic measures. Input lexical-semantic measures did not significantly correlate with any of the output measures. We identified one subject, EF, who did not show this overall pattern. She performed well on two measures of phonological input processing (discrimination and rhyme judgements), but produced a high rate of phonological errors in picture naming. On an auditory lexical decision task, however, EF produced a high rate of false alarm errors (misperception of nonwords as words). False alarm errors have been attributed to a disturbance in input phonological processing. Consistent with this hypothesis, the rates of false alarm errors made by this group of subjects on the same auditory lexical decision task correlated with (1) input tasks that require maintaining activation of phonological representations and (2) a measure of output phonological processing (rates of phonologically related nonword errors in picture naming). These results are discussed with reference to current approaches to the study of input and output phonological processing and possible future investigations of this question.     

Sensory phenomena: Clinical correlates and impact on quality of life in adult patients with Tourette syndrome

Tourette syndrome (TS) is a neurodevelopmental condition characterised by multiple tics, with frequent behavioural co-morbidity. Sensory phenomena (SP) are unpleasant sensations which provide involuntary urges to tic in patients with TS. While SP have a central role in tic expression, little is known about their clinical correlates or association with health-related quality of life (HR-QOL) in TS. We conducted a cross-sectional study on 72 adult outpatients with TS, recruited at a specialist clinic. All participants completed a comprehensive battery of psychometric measures, including the Premonitory Urges for Tics Scale (PUTS) to assess SP and a disease-specific quality of life scale (GTS-QOL) to assess HR-QOL. SP were very common (97.2% of patients), with a median PUTS total score of 28/40. Bivariate analyses showed that PUTS scores were most significantly correlated with self-report measures of vocal tic severity and compulsivity. PUTS scores were also significantly correlated with GTS-QOL scores, most notably with the psychological subscale. SP are frequently reported by adults with TS, are associated with perceived tic severity and compulsivity, and can significantly affect psychological well-being. Standardised measurement of SP should be incorporated into routine assessment of patients with TS to optimise their clinical management.     

The spatial relationship between neurons and astrocytes in HIV-associated dementia

Specific neuronal spatial distributional patterns have previously been correlated with increasing severity of HIV-associated dementia (HAD). As astrocytes are also a putative site of neurotoxicity, we investigated the spatial relationships of astrocytes with pyramidal and interneurons in the superior frontal gyrus from 29 patients who died from acquired immunodeficiency syndrome. Frontal cortical brain tissue was taken from diseased HIV patients who had been assessed for the presence and severity of HAD using the Memorial Sloan-Kettering Scale. No correlation was found between neuronal density and severity of dementia. However, the pattern of astrocytes became more clustered as dementia progressed. Bivariate spatial pattern analysis of neuronal populations with astrocytes revealed that, with increasing dementia severity, astrocytes and large pyramidal neurons increasingly “repelled” each other, while astrocytes and interneurons evidenced increasing “attraction.” This implies that astrocytes may be more likely to be situated in the vicinity of surviving interneurons but less likely to be situated near surviving large pyramidal neurons in the setting of progressing HAD.     

Natural immunity to SARS-CoV-2 and breakthrough infections in vaccinated and unvaccinated patients with cancer

Background Consolidated evidence suggests spontaneous immunity from SARS-CoV-2 is not durable, leading to the risk of reinfection, especially in the context of newly emerging viral strains. In patients with cancer who survive COVID-19 prevalence and severity of SARS-CoV-2 reinfections are unknown.Methods We aimed to document natural history and outcome from SARS-CoV-2 reinfection in patients recruited to OnCovid ({"type":"clinical-trial","attrs":{"text":"NCT04393974","term_id":"NCT04393974"}}NCT04393974), an active European registry enrolling consecutive patients with a history of solid or haematologic malignancy diagnosed with COVID-19.Results As of December 2021, out of 3108 eligible participants, 1806 COVID-19 survivors were subsequently followed at participating institutions. Among them, 34 reinfections (1.9%) were reported after a median time of 152 days (range: 40–620) from the first COVID-19 diagnosis, and with a median observation period from the second infection of 115 days (95% CI: 27–196). Most of the first infections were diagnosed in 2020 (27, 79.4%), while most of reinfections in 2021 (25, 73.5%). Haematological malignancies were the most frequent primary tumour (12, 35%). Compared to first infections, second infections had lower prevalence of COVID-19 symptoms (52.9% vs 91.2%, P = 0.0008) and required less COVID-19-specific therapy (11.8% vs 50%, P = 0.0013). Overall, 11 patients (32.4%) and 3 (8.8%) were fully and partially vaccinated against SARS-CoV-2 before the second infection, respectively. The 14-day case fatality rate was 11.8%, with four death events, none of which among fully vaccinated patients.Conclusion This study shows that reinfections in COVID-19 survivors with cancer are possible and more common in patients with haematological malignancies. Reinfections carry a 11% risk of mortality, which rises to 15% among unvaccinated patients, highlighting the importance of universal vaccination of patients with cancer.Subject terms: Oncology, Public health