Validation of a screening test for alcohol use,the Russian Federation

ObjectiveTo validate a Russian-language version of the World Health Organization’s Alcohol Use Disorders Identification Test (AUDIT).MethodsWe invited 2173 patients from 21 rural and urban primary health-care centres in nine Russian regions to participate in the study (143 declined and eight were excluded). In a standardized interview, patients who had consumed alcohol in the past 12 months provided information on their sociodemographic characteristics and completed the Russian AUDIT, the Kessler Psychological Distress Scale and the Composite International Diagnostic Interview to identify problem drinking and alcohol use disorders. We assessed the feasibility of administering the test, its internal consistency and its ability to predict hazardous drinking and alcohol use disorders in primary health care in the Russian Federation.FindingsOf the 2022 patients included in the study, 1497 were current drinkers with Russian AUDIT scores. The test was internally consistent with good psychometric properties (Cronbach’s α : 0.842) and accurately predicted alcohol use disorders and other outcomes (area under the curve > 75%). A three-item short form of the test correlated well with the full instrument and had similar predictive power (area under the curve > 80%). We determined sex-specific thresholds for all outcomes, as non-specific thresholds resulted in few women being identified.ConclusionWith the validated Russian AUDIT, there is no longer a barrier to introducing screening and brief interventions into primary health care in the Russian Federation to supplement successful alcohol control policies.     

Impact of COVID-19 pandemic lockdown on myocardial infarction care

European Journal of Epidemiology - The aim of this study was to evaluate the impact of the COVID-19 pandemic lockdown on acute myocardial infarction (AMI) care, and to identify underlying stressors...     

Focal sensory nerve abnormalities in patients with amyotrophic lateral sclerosis

Slowing of sensory nerve conduction is an unexplained finding in patients with sporadic amyotrophic lateral sclerosis (ALS). To study the frequency of these abnormalities and to study if a predisposition to the development of entrapment neuropathies is causal, 23 patients with definite ALS and 23 age-matched healthy volunteers were investigated prospectively. Antidromic sensory and motor nerve conduction velocities (NCVs) were measured in ulnar and median nerves. Median sensory NCV was abnormally low in three patients if compared with the lower limit of the control group; and median sensory NCV was abnormally low in nine patients (six right, eight left hands) if compared with ipsilateral ulnar sensory NCV. Sensory nerve conduction data did not correlate with clinical findings, such as forearm weakness or usage of canes. Motor nerve conduction data did not correlate with sensory nerve conduction data, with the exception of distal motor latency of right median nerves, which correlated with right median sensory NCV. Our findings show how affection of sensory fibers of distal segments of median nerves can be detected in individual patients with ALS. Nerve entrapment may contribute to this affection, but it is not the only cause. This should be considered in discussions about diagnostic criteria for ALS.     

Continuous monitoring of extracellular lactate concentration by microdialysis lactography for the study of rat muscle metabolism in vivo

A method is described for the measurement and on-line monitoring of muscular extracellular lactate concentration in both anaesthetized and freely moving rats. This method is based on microdialysis sampling and lactic dehydrogenase-catalysed nicotinamide adenine dinucleotide, reduced (NADH)-fluorescence detection techniques. In vivo calibration revealed a resting extracellular lactate concentration of 1.92±0.13 mmol/l (± SEM) in the gastrocnemius muscle of adult male Wistar rats (n=6), while the average whole-blood lactate level was 0.76±0.12 mmol/l (± SEM). This measured extracellular lactate concentration was 1.73-times higher than that deduced from the arterial lactate concentration. Blocking glycolysis with iodoacetate reduced the extracellular lactate concentration to 52±6% (± SEM, n= 4) of the resting level. The extracellular lactate concentration in rat gastrocnemius muscle had increased to significantly (P0.05) different levels, 2.4±0.03 (± SEM) or 4.0±0.55 (± SEM) times the control value, 1 h after aortic clamping (n=3) or cardiac arrest (n=3), respectively. Stimulation of the sciatic nerve induced elevations of the extracellular lactate concentration in the tibialis anterior muscle which were linearly related to the recorded isometric force-time integral. We also monitored on-line the changes in extracellular lactate concentration in the tibialis anterior muscle of a swimming rat. Our results indicate that microdialysis lactate reflects also intracellular metabolism. Lactography may be a useful alternative to biopsies and nuclear magnetic resonance spectroscopy in clinical medicine and physiology for the monitoring of metabolism in vivo.     

A quantitative study in the rat on the relationship between imipramine levels in brain and serum

Serum and brain levels of the tricyclic antidepressant drug imipramine (IMI) were studied in the rat under a variety of conditions. IV doses (range 1 nmol kg^-1 to 15 mol kg^-1, 350 ng–5mg kg^-1) and administered 5 min before death, were linearly correlated with IMI levels in serum, frontal cortex, and cerebellum. In this experiment, the highest levels of IMI were achieved in the frontal and occipital cortex and the lowest levels were found in the brain stem. The regional distribution was more even in rats pretreated with thiopental or -hydroxybutyric acid, drugs that alter cerebral blood flow. After 20 min or more, tracer amounts of IMI injected IV to IMI-pretreated rats [1 or 17 days, daily dose 2×36 mol kg^-1 (10 mg kg^-1), last dose 89 mol kg^-1 (25 mg kg^-1), 2–3 h before death] exhibited a distribution pattern in serum and various brain regions similar to that of the unlabeled drug. In the latter experiments, content (per volume) of the tracer or unlabeled IMI was more than 25-fold higher in various brain areas than in serum. It is concluded that despite large differences in drug levels in serum or brain, a close relationship is maintained under the conditions studied.deceased     

Splanchnic perfusion in intensive care patients

Splanchnic vasoregulation is poorly understood. The tissue perfusion in the splanchnic region may be compromised in critically ill patients both because of the underlying disease and therapeutic interventions. Inadequate perfusion, dysoxia, and ischemia-reperfusion may trigger and modify an inflammatory response which may itself cause deterioration of the splanchnic perfusion.     

Levels of soluble vascular endothelial growth factor (VEGF) receptor 1 in astrocytic tumors and its relation to malignancy, vascularity, and VEGF-A.

PURPOSE: Vascular endothelial growth factor (VEGF)-A isa key mediator of angiogenesis in malignant gliomas. Soluble VEGF receptor 1 (sVEGFR-1) can complex VEGF-A and reduce its bioavailability. In several animal models sVEGFR-1 inhibited angiogenesis and tumor growth. We analyzed the levels of endogenous sVEGFR-1 in gliomas of different malignancy grades in relation to tumor vascularity and VEGF-A. EXPERIMENTAL DESIGN: The concentration of sVEGFR-1 was determined by ELISA in 104 gliomas and normal brain. Levels of sVEGFR-1 were compared with malignancy grade, microvessel density, and VEGF-A concentration. Effects of sVEGFR-1 on glioma extract-induced endothelial cell chemotaxis were analyzed in vitro. RESULTS: The concentration of sVEGFR-1 correlated with the malignancy grade and was 12-fold higher in glioblastomas than in diffuse astrocytomas (P < 0.001), with intermediate levels for anaplastic astrocytomas. VEGF-A levels were 30-fold higher (P < 0.001) in glioblastomas than in diffuse astrocytomas. The sVEGFR-1:VEGF-A ratio was 0.27 in glioblastomas and 0.70 in diffuse astrocytomas. Both sVEGFR-1 and VEGF-A correlated with microvessel density (P < 0.001) and with each other (P < 0.001); sVEGFR-1 and VEGF-A also correlated with each other when only glioblastomas were analyzed (P = 0.001). In vitro, recombinant sVEGFR-1 inhibited endothelial cell chemotaxis induced by tumor extracts. CONCLUSIONS: Although absolute levels of sVEGFR-1 are increased in the more malignant gliomas, the sVEGFR-1:VEGF-A ratio is decreased 2.6-fold in glioblastomas compared with diffuse astrocytomas, suggesting that the ensuing increased bioavailability of VEGF-A favors angiogenesis. The inhibition of tumor extract-induced endothelial chemotaxis by sVEGFR-1 suggests that sVEGFR-1 could be useful as an angiogenesis inhibitor in the specific context of human gliomas.     

Expression of receptor activator of nuclear factor kappaB ligand on bone marrow plasma cells correlates with osteolytic bone disease in patients with multiple myeloma.

PURPOSE: Increased bone resorption is a hallmark of multiple myeloma and is attributable to osteoclast activation. Recent studies showed that the receptor activator of nuclear factor kappaB ligand (RANKL) is the key mediator of osteoclastogenesis and plays a crucial role in bone destruction in malignant bone disease. We found that human myeloma cells express RANKL and analyzed the association of the RANKL expression with the presence of osteolytic bone disease in patients with multiple myeloma. EXPERIMENTAL DESIGN: Flow cytometry was performed on bone marrow samples derived from controls and multiple myeloma patients with or without osteolytic bone lesions on conventional radiography. Plasma cells were identified as CD38++/CD138+ cells. The level of RANKL expression on the surface of bone marrow plasma cells was correlated with the bone status of the patients. RESULTS: The bone marrow plasma cells from controls showed no or only a weak surface expression of RANKL, and the median mean fluorescence index (MFI) was 6. In contrast, expression of RANKL could be detected on bone marrow plasma cells from all of the patients with multiple myeloma, and median MFI was 47. The difference in MFI for RANKL expression of bone marrow plasma cells from controls and myeloma patients was highly significant (P < 0.0005). Myeloma patients with osteolytic bone lesions showed a significantly higher expression of RANKL (median MFI = 60; range, 16-2494) compared with patients without osteolysis (median MFI = 16; range, 6-229; P < 0.0005). CONCLUSIONS: These results show for the first time that the level of RANKL expression by myeloma cells correlates significantly with osteolytic bone disease.     

Pseudophakic accommodation with translation lenses – dual optic vs mono optic

PURPOSE: To investigate the pseudophakic accommodation effect in dual and mono optic translation accommodative intraocular lenses (AIOL) using linear matrix methods in the paraxial space. METHODS: Dual (anterior optic of power +32 D linked to a compensatory posterior optic of negative power) and mono lens power was determined in the non-accommodated state using linear geometric optics based on the Gullstrand model eye. The position of the AIOL was calculated from a regression formula. Pseudophakic accommodation was assessed with three systems: (1) forward shift of the mono optic lens, (2) anterior translation of the anterior optic in the dual optic lens system with an unchanged position of the posterior minus lens and (3) symmetrical anterior and posterior translation of the anterior and posterior lens. The Gullstrand model eye was modified by changing the axial length (and proportionally changing the phakic anterior chamber depth) to investigate the accommodative effect in myopic and hyperopic eyes. RESULTS: The dual optic lens system (2) yields a nearly constant accommodation amplitude of 2.4-2.5 D mm(-1) movement over the total range of axial lengths. The mono optic lens (1) provides a higher accommodative effect only in extremely short eyes (high refractive power of the lens), whereas for normal eyes (1.4-1.5 D mm(-1) movement) and for long (myopic) eyes the accommodative effect is much less than the dual optic lens. The dual optic lens system under condition (3) yields less accommodation amplitude compared with the dual optic system under condition (2) over the total range of axial length but provides higher accommodation amplitude compared with the mono optic lens system (1) with axial lengths greater than 22.3 mm (lens power 25.5 D). In the accommodated state, with lens translation of 1 mm, the absolute value of the lateral magnification increases with the refractive power of the mono optic lens (1) and decreases in both dual optic lens systems (under conditions 2 and 3). CONCLUSIONS: A mathematical strategy is presented for calculation of the accommodative effect of mono-optic and dual optic AIOL. The dual optic lens yielded a nearly constant accommodation amplitude of about 2.4-2.5 D mm(-1) translation, whereas the mono optic lens yielded an accommodative response of <2 D mm(-1) translation in long myopic or normal eyes. Only in extremely short eyes is the accommodative amplitude of the mono-optic lens higher than the dual optic lens.