The role and mechanism of glutamic NMDA receptor in the mechanical hyperalgesia in diabetic rats

Objectives: Some studies have shown that painful neuropathy is a common and costly complication of both type 1 and type 2 diabetes mellitus, and glutamate is involved in the process although the mechanisms are not clear. The purpose of the present study was to investigate the effect of N-methyl-D-aspartate (NMDA) receptor on mechanical hyperalgesia in diabetic rats and the possible mechanism.

Methods: Diabetic rat model was established by intraperitoneal injection of streptozotocin (STZ, 1%, 70 mg/kg) once, and evaluated by the change in the fasting blood glucose. The mechanical hyperalgesia was estimated by mechanical withdrawal threshold (MWT) using a set of calibrated Von Frey’s filaments. In addition, the expressions of phosphorylated NMDA NR1 and phosphorylated cAMP response element binding protein (pCREB) in L4/L5 dorsal horns of spinal cord were observed.

Results: Behavioral results showed that MK-801, an antagonist of NMDA receptor, could reduce the proportion of mechanical hyperalgesia in diabetic rats from 76.67 to 20.00%. Meanwhile, the mean MWTs in STZ group or saline-treated STZ group decreased significantly at 3–8 week, while, the MWTs in MK-801 treated STZ group were significant higher than those in STZ or saline-treated STZ group. In addition, the expressions of NMDA NR1 and pCREB in L4/5 dorsal horns of spinal cord were significant higher in diabetic rats, and MK-801 down-regulated their expressions partly.

Conclusion: All these results suggested that NMDA receptor and pCREB in the spinal cord were involved in the regulation of mechanical hyperalgesia in diabetic rats.     

Nerve root anomalies detected intra-operatively technical nuances towards achieving a successful surgical outcome: our experience of three case reports at a tertiary level centre

Objective: Analysis of three case reports of nerve root anomalies detected intra-operatively and its implications.

Design: Data collected during one year prospective non-randomised study using hospital records.

Setting: Single tertiary care centre.

Subjects: 3 patients in one year period.     

Possible error in the Danish version of the WHO Quality of Life (WHOQOL-BREF) Questionnaire

Background: The WHOQOL-BREF is widely used to measure quality of life.

Aims: The goal of the present study was to use the questionnaire in a doctoral study.

Methods: We studied all the instructions provided by the WHO.

Results: In the Danish version of the WHOQOL-BREF there is a discrepancy between the negatively phrased question 9 and both the syntax file and the verbal instructions for coding the data provided by the WHO.

Conclusions: This is a notification of possible error interpretations in projects that use the questionnaire. This could be corrected by manual correction in the coding process or by changing the negatively phrased question 9.     

Internal decompression for spinal stenosis (IDSS) for decompression and use of interlaminar dynamic device (CoflexTM) for stabilization in the surgical management of degenerative lumbar canal stenosis with or without mild segmental instability: our initial results

Introduction: Internal decompression of spinal stenosis (IDSS) and Posterior dynamic stabilization (PDS) form a bridge between decompression laminectomy alone and rigid fusion, by attempting to sustain beneficial effects of decompression and stabilization in an attempt to prevent bad effects of relentless degeneration.

Objective: To evaluate the clinical outcome in operated patient of posterior dynamic stabilization.

Design: Data were collected over 1 year in prospective, nonrandomized follow-up study using outcome scales.

Setting: Single surgeon, tertiary care centre in Mumbai, India.

Described here is the operative technique of posterior dynamic stabilization using CoFlex^TM and clinical outcome of 67 consecutive patients using Visual Analogue Scale and Oswestry Disability Score.     

Do depressive symptoms predict mortality in older people?

Context: Depressive symptoms are common in older persons, and may predict mortality.

Objectives: To determine: (1) If depressive symptoms predict mortality; (2) If there is a gradient in this effect; and (3) Which depressive factors predict mortality.

Population: In 1991–1992, 1751 community-dwelling older persons, sampled from a population-based registry, were interviewed.

Measures: The Center for Epidemiologic Studies – Depression (CES-D), age, gender, the Modified Mini-Mental State Examination, self-rated health, and functional status.

Outcome measure: Time to death.

Analysis: Those scoring 16+ on the CES-D were considered depressed. To determine if a gradient was present, the CES-D was treated as a continuous variable. Four depressive factors from the CES-D (depressed affect, positive affect, somatic, and interpersonal) were analyzed. Cox regression models were constructed.

Results: The mortality in those with depressive symptoms was higher in those without depressive symptoms (Hazard Ratio of 1.71, p < 0.001, Log rank test). In multivariable models, this association was no longer significant after accounting for self-rated health and functional status. There was a gradient in risk of mortality across the range of the CES-D. Somatic factors, depressed affect, and positive affect were all associated with mortality in bivariate analyses, but not in multivariable models adjusting for functional status. Interpersonal factors were not associated with mortality.

Conclusions: Depressive symptoms predict mortality in older persons.     

Cervical myelitis presenting as occipital neuralgia

Aim: Occipital neuralgia is a common form of headache that is characterized by paroxysmal severe lancinating pain in the occipital nerve distribution.

Methods: The exact pathophysiology is still not fully understood and occipital neuralgia often develops spontaneously. There are no specific guidelines for evaluation of patients with occipital neuralgia.

Result: Cervical spine, spinal cord and posterior neck muscle lesions can induce occipital neuralgia. Brain and spine imaging may be necessary in some cases, according to the nature of the headache or response to treatment.

Discussion: We report a case of cervical myelitis presenting as occipital neuralgia.     

Spinocerebellar ataxia type 3 presenting with writer's cramp without ataxia

Aim of the study: Spinocerebellar ataxia type 3 is the most common cause of autosomal dominant inherited ataxia worldwide.

Material and methods: Clinically, it exhibits wide phenotypic variability. Presentation as isolated dystonia is exceptional.

Results: Here, the case of a woman with writers cramp without ataxia is presented as a paucisymptomatic manifestation of this disease.

Conclusions: This association has not been described to date and extends the clinical variability of the disease.     

Consumer satisfaction with antipsychotic medication-monitoring appointments: the role of consumer–prescriber communication patterns

Objective: The study was designed to explore patterns of prescriber communication behaviors as they relate to consumer satisfaction among a serious mental illness sample.

Methods: Recordings from 175 antipsychotic medication-monitoring appointments between veterans with psychiatric disorders and their prescribers were coded using the Roter Interaction Analysis System (RIAS) for communication behavioral patterns.

Results: The frequency of prescriber communication behaviors (i.e., facilitation, rapport, procedural, psychosocial, biomedical, and total utterances) did not reliably predict consumer satisfaction. The ratio of prescriber to consumer utterances did predict consumer satisfaction.

Conclusions: Consistent with client-centered care theory, antipsychotic medication consumers were more satisfied with their encounters when their prescriber did not dominate the conversation.

Practice implications: Therefore, one potential recommendation from these findings could be for medication prescribers to spend more of their time listening to, rather than speaking with, their SMI consumers.     

Effects of repeated 9 and 30-day exposure to extremely low-frequency electromagnetic fields on social recognition behavior and estrogen receptors expression in olfactory bulb of Wistar female rats

Objective: We investigated the short- and long-term effects of extremely low-frequency electromagnetic fields (EMF) on social recognition behavior and expression of α- and β-estrogen receptors (ER).

Methods: Rats were exposed to 60-Hz electromagnetic fields for 9 or 30 days and tested for social recognition behavior. Immunohistochemistry and western blot assays were performed to evaluate α- and β-ER expression in the olfactory bulb of intact, ovariectomized (OVX), and ovariectomized+estradiol (E2) replacement (OVX+E2).

Results: Ovariectomization showed impairment of social recognition after 9 days of EMF exposure and a complete recovery after E2 replacement and so did those after 30 days. Short EMF exposure increased expression of β-ER in intact, but not in the others. Longer exposure produced a decrease in intact but an increase in OVX and OVX+E2.

Discussion: Our findings suggest a significant role for β-estrogen receptors and a lack of effect for α-estrogen receptors on a social recognition task.

Abbreviations: EMF: extremely low frequency electromagnetic fields; ERs: estrogen receptors; OB: olfactory bulb; OVX: ovariectomized; OVX + E₂: ovariectomized + estradiol replacement; IEI: interexposure interval; β-ER: beta estrogen receptor; E₂: replacement of estradiol; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; WB: Western blot; PBS: phosphate-buffer saline; PB: phosphate-buffer     

Assessing family caregiver skill in managing behavioral symptoms of Alzheimer's disease

Objectives: This measurement study operationalized family caregiver skill in managing behavioral symptoms associated with Alzheimer's disease (AD) by testing a Caregiver Assessment of Behavioral Skill-Self-Report (CAB-SR) measure.

Method: A cross-sectional design was used. Caregivers had a family member with possible/probable AD, resided at home with the care recipient and provided the majority of care (N?=?82). The mail-administered assessment included the CAB-SR and other care recipient and caregiver measures.

Results: Preliminary CAB-SR reliability and validity were determined using reliability, factor analytic and correlational procedures.

Conclusion: This measure provides a preliminary assessment of caregiver skill in managing behavioral symptoms of AD and shows promise for use in research and clinical intervention settings.     

A randomized controlled trial comparing self-referral to inpatient treatment and treatment as usual in patients with severe mental disorders

Background: There has been a call for increased patient autonomy and participation in psychiatry. Some Community Mental Health Centres (CMHC) have implemented services called ‘self-referral to inpatient treatment’ (SRIT) for patients with severe mental disorders.

Aims: To investigate whether SRIT could yield better outcomes after 12 months in use of mental health services for people with severe mental disorders than Treatment As Usual (TAU).

Methods: This was a randomized controlled trial at a CMHC in Norway comparing SRIT and TAU in 12 months. Fifty-four patients with severe mental disorders were included. The patients in the SRIT group could admit themselves as inpatients for up to 5 days for each admission with at least a 2 weeks pause between the admittances.

Results: Twenty out of 26 participants (77%) in the SRIT group used the SRIT for a median of 1.5 admissions and 5 inpatient days. With the exception of a somewhat larger number of admissions at the CMHC in the SRIT group, no significant differences were found between the two groups in days as inpatients, admissions, outpatient contacts or coercion. Both groups reduced their inpatients days by 40%.

Conclusions: Both the SRIT and the TAU groups reduced their use of services during the 12 months intervention period. Giving patients with severe mental disorders the possibility to self-refer did not change the use of services.

Clinical implications: Self-referral to inpatient treatment for patients with severe mental disorders might increase patient autonomy, but does not seem to save use of inpatient services.     

Blockade of NMDA receptors decreased spinal microglia activation in bee venom induced acute inflammatory pain in rats

Objectives: Microglial cells in spinal dorsal horn can be activated by nociceptive stimuli and the activated microglial cells release various cytokines enhancing the nociceptive transmission. However, the mechanisms underlying the activation of spinal microglia during nociceptive stimuli have not been well understood. In order to define the role of NMDA receptors in the activation of spinal microglia during nociceptive stimuli, the present study was undertaken to investigate the effect of blockade of NMDA receptors on the spinal microglial activation induced by acute peripheral inflammatory pain in rats.

Methods: The acute inflammatory pain was induced by subcutaneous bee venom injection to the plantar surface of hind paw of rats. Spontaneous pain behavior, thermal withdrawal latency and mechanical withdrawal threshold were rated. The expression of specific microglia marker CD11b/c was assayed by immunohistochemistry and western blot.

Results: After bee venom treatment, it was found that rats produced a monophasic nociception characterized by constantly lifting and licking the injected hind paws, decreased thermal withdrawal latency and mechanical withdrawal threshold; immunohistochemistry displayed microglia with enlarged cell bodies, thickened, extended cellular processes with few ramifications, small spines, and intensive immunostaining; western blot showed upregulated expression level of CD11b/c within the period of hyperalgesia. Prior intrathecal injection of MK-801, a selective antagonist of NMDA receptors, attenuated the pain behaviors and suppressed up-regulation of CD11b/c induced by bee venom.

Conclusion: It can be concluded that NMDA receptors take part in the mediation of spinal microglia activation in bee venom induced peripheral inflammatory pain and hyperalgesia in rats.     

Neurological impairments in hypoxic neonates and lactate levels

Introduction: Metabolic acidosis with increasing lactate concentration develops due to the lack of oxygen in the tissues.

Objectives: The effect of lactic acidosis on neurological development in the first year of life.

Materials and Methods: Our study included 50 newborns with perinatal hypoxia requiring oxygen therapy and 50 healthy newborns. pH, pCO2, pO2, base excess (BE) and lactates from arterialized capillary blood were determined in both groups of newborns, in the first and second hours after birth, and neurological development in the first year of life was estimated.

Results: pH, pCO2, pO2, BE and lactates differed significantly between the groups in the first and second hours after birth p < 0.01. Hypotonia was recorded in 20/50 cases and hypertonia was recorded in 10/50 cases in the first year of life.

Conclusion: Lactate concentration may be an indicator of neurological damage in neonates with perinatal hypoxia.     

A novel ETFDH mutation in an adult patient with late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency

Aim of the study: To report a novel mutation in the electron transfer flavoprotein dehydrogenase (ETFDH) gene in an adult patient with late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency.

Materials and methods: The genomic DNAs from a patient whose main clinical presentations are muscles weakness and hypoglycemia was analysed.

Results: The patient was identified to carry compound heterozygous mutations in ETFDH gene. Two missense mutations c.814 G > A and c.389 A > T were found.

Conclusion: This is the first report of c.814G > A mutation in ETFDH in adult patient with MADD.     

Attitudes towards people with depression and schizophrenia among social service workers in Denmark

Background: Mental health-related stigma is a major public health issue, and is an obstacle to the possibility for successful treatment, recovery, and reintegration.

Aim: To examine attitudes towards mental illness among employees in the social services.

Methods: The study design was part of a large randomized trial, and data presented in this study are baseline data from this trial. Respondents completed a baseline questionnaire to assess the respondents’ attitudes.

Results: A significant difference was found between employees’ personal attitudes towards depression and schizophrenia. The same significant difference was found in the employees’ perceived attitudes. Furthermore, a significant difference was found between the employees’ personal and perceived attitudes. A significant difference was found between the respondents wish for social distance towards depression and schizophrenia in all cases, except regarding the willingness to provide a job at one’s own workplace.

Conclusion: Employees in the social services are comparable to the general public concerning attitudes towards mental illness.

Implications: The results indicate that the employees in social services could have great use of gaining more knowledge about mental illness and ways in which to recognize a mental illness, in order to be able to offer the right kind of help and reduce the treatment gap concerning people suffering from mental illness.     

Effects of ERK1/2 kinases inactivation on the nigrostriatal system of Krushinsky-Molodkina rats genetically prone to audiogenic seizures

Recently, we demonstrated that inhibition of ERK1/2 activity by SL-327 treatment blocks seizure behavior in Krushinsky-Molodkina (KM) rats, which was mediated by altering of GABA and glutamate release mechanism in the hippocampus. Basal ganglia representing various subcortical cell groups play a significant role in the regulation of motor activity, including epileptiform seizures.

Objectives: To verify if nigrostriatal system could be also affected by SL-327 treatment we analyzed the expression of tyrosine hydroxylase, D1 and D2 dopamine receptors, NR2B subunit of NMDA receptor as well as vesicular glutamate transporter VGLUT2 and glutamic acid decarboxylases GAD65/67 in the striatum and substantia nigra of KM rats.

Methods: Animals were injected i.p. with SL-327 (50 mg/kg) 60 min before audio stimulation. After audiogenic stimulation the brains of control and SL 327 treated rats were removed for further immunohistochemical and biochemical analysis.

Results: Obtained results demonstrated a decrease activity in synapsin I, and accumulation of VGLUT2 in the striatum after blockade of audiogenic seizure (AGS) by SL 327 that could lead to inhibition of glutamate release. While in the striatum GAD65/67 level was diminished, in the substantia nigra GAD65/67 was increased showing enhanced inhibitory output to the compact part of the substantia nigra. Analysis of dopaminergic system showed a significant reduction of tyrosine hydroxylase activity and expression in the substantia nigra, and decreased D1 and D2 receptor expression in the striatum.

In summary, we propose that changes in the nigrostriatal system could be mediated by inhibitory effect of SL 327 on AGS expression.     

Use of patient-controlled psychiatric hospital admissions: mental health professionals’ perspective

Background: In a patient-controlled admission (PCA) programme, the decision about hospital admission is made solely by the patient, with no gatekeeper function allocated to the mental health professionals (MHPs). Current knowledge about how MHPs experience and evaluate PCA is sparse.

Aims: This Danish multi-centre study examined the MHP assessment of the PCA programme in daily clinical practice, and compared PCA evaluations made by MHPs and patients.

Methods: A questionnaire was developed and a survey conducted over the course of a year at all Danish mental health units included in the PCA programme. MHPs made an overall evaluation of the PCA programme. At each unique PCA, both patient and MHP evaluated the specific admission when the patient entered the unit and at discharge.

Results: In total, 546 questionnaires were included in the survey, based on 252 unique MHPs. The MHPs rated the PCA programme positively. The MHPs believed that PCA helped patients receive early help and avoid long admissions. Overall, agreement was poor when comparing patients’ and MHPs’ evaluation of the same PCA.

Conclusion: MHPs (and patients) seem to be in favour of implementing the PCA programme. However, results revealed that MHPs and patients have different views of what caused the patient to admit themselves and why patients were discharged.

Clinical implications: MHPs should be aware that patients might have other reasons for admitting and discharging themselves than what seems most obvious to the MHP.     

Morphological vs. phonological explanations for affix errors in agrammatism

Background: There has been no consensus as to what explains the well-attested problems with inflection in individuals with agrammatic aphasia. Some studies point to a predominantly phonological influence while others view morphological factors as primary.

Aims: The present study aims to investigate what morphological and phonological factors influence the production of inflectional suffixes in agrammatism.

Methods & Procedures: Seven non-dysarthric and non-apraxic English-speaking agrammatic patients (mean age 53.2 years, range 35–69 years, at least 2 years post onset) were given a production task in which the morphological or phonological complexity of the environment of the inflectional morpheme was varied.

Outcomes & Results: Analysis indicates that morphological factors (number and type of morpheme, real vs. pseudo stems), rather than phonological factors (sonority, suffix syllabicity, stem length) resulted in significantly higher error rates.

Conclusion: Once morphological and phonological influences are teased apart in a controlled experiment, we see that morphological environments in the production of affixed forms in agrammatic aphasia play a greater role than phonological factors.     

Neurobrucellosis presenting as clinically definite amyotrophic lateral sclerosis

Purpose/Aim: We describe the first case of a patient with neurobrucellosis presenting with clinically-definite ALS.

Material and methods: A 48-year old male patient, in whom the diagnoses of systemic brucellosis and clinically definite ALS were undoubtedly confirmed and were eventually causally interrelated. The disease-specific antibiotic therapy was unsuccessful to slow the evolution of the motor neuron disease and the patient became non ambulatory over time.

Results: Considering the close temporal association of ALS onset with the systemic Brucella infection and consequent antigenic stimuli, we might suggest that human brucellosis might have triggered a process of motor neuron degeneration in keeping with neurobrucellosis, primarily due to parainfectious mechanism.

Conclusion: Our case helps to shed light on the factors that may trigger or only fasten motor neuron disease manifestations.