Structural white matter abnormalities in patients with idiopathic dystonia

We investigated whether structural white matter abnormalities, in the form of disruption of axonal coherence and integrity as measured with diffusion tensor imaging (DTI), constitute an underlying pathological mechanism of idiopathic dystonia (ID), independent of genotype status. We studied seven subjects with ID: all had cervical dystonia as their main symptom (one patient also had spasmodic dysphonia and two patients had concurrent generalized dystonia, both DYT1‐negative). We compared DTI MR images of patients with 10 controls, evaluating differences in mean diffusivity (MD) and fractional anisotropy (FA). ID was associated with increased FA values in the thalamus and adjacent white matter, and in the white matter underlying the middle frontal gyrus. ID was also associated with increase in MD in adjacent white matter to the pallidum and putamen bilaterally, left caudate, and in subcortical hemispheric regions, including the postcentral gyrus. Abnormal FA and MD in patients with ID indicate that abnormal axonal coherence and integrity contribute to the pathophysiology of dystonia. These findings suggest that ID is not only a functional disorder, but also associated with structural brain changes. Impaired connectivity and disrupted flow of information may contribute to the impairment of motor planning and regulation in dystonia. © 2006 Movement Disorder Society     

Evaluation of a Membrane Filter Assay System, Ortho HCV Ab Quik Pack, for Detection of Anti-Hepatitis C Virus Antibody

A simple membrane immunoassay assay system, Quik Pack, for the detection of hepatitis C virus antibody was compared with two enzyme-linked immunosorbent assays (ELISAs) in a study of 600 serum samples. Quik Pack exhibited excellent sensitivity and specificity: 96.0 and 99.7%, respectively, versus the ELISA-2 and 99.7 and 99.4%, respectively, versus the ELISA-3.     

Fatal renal failure as the first manifestation of sarcoidosis diagnosed on necropsy in a young man: a case report

Renal involvement as the first manifestation of sarcoidosis is rare and has never been reported in India. This report describes a 35 year old man who was admitted to the emergency department with a clinical diagnosis of acute on chronic renal failure, secondary to obstructive uropathy. Postmortem examination unexpectedly revealed disseminated sarcoidosis.     

Intratumorous distribution of catecholaminergic clone cells of human neuroblastoma

Summary The intratumorous distribution of catecholaminergic clone cells in 23 human neuroblastomas was studied using Falck-Hillarp's method, and the findings compared with the catecholamine (CA) content within the tumour. All the specimens contained elements with CA fluorescence, and the pattern of fluorescence was classified from the distribution of CA-positive cells and neurofibrils, as diffuse cellular (DC); diffuse fibrillary (DF), sporadic (S), clustered (C), island-shaped (I), and bundled (B). The strength of CA fluorescence of both cellular and fibrillary elements correlated well with the CA content within the tumour. In addition, all tumours of urinary VMA-negative cases also contained significantly larger amounts of CA than other, non-functioning, tumours in the paediatric age group. The results of this study suggest that firstly, the ratio of CA-positive cells to CA-positive neuronal processes is proportionately higher in the poorly-differentiated neuroblastomas and that secondly, even tumours negative for urinary VMA or HVA might be polyclonal and contain catecholaminergic elements.This study was supported in part by a Research Grant from the Ministry of Education, Japan (No. 59570549)     

Quantitation of cytomegalovirus (hCMV) DNA and β-actin DNA by duplex real-time fluorescence PCR in solid organ (liver) transplant recipients

Even now rare human cytomegalovirus (hCMV) reactivation is still a life-threatening complication after solid organ transplantation. Although PCR techniques are regarded as the most sensitive detection methods for hCMV, their accuracy and reproducibility are limited. This is a major disadvantage with quantitative PCR assays, which are thought to provide valuable information about hCMV latency or active viral replication in transplant patients. To enhance the diagnostic safety of quantitative hCMV PCR, we developed a duplex real-time fluorescence PCR that is capable of quantifying hCMV DNA and beta-actin DNA as internal control simultaneously within one reaction. By the use of 6-carboxyfluorescein and hexa-chloro-6-carboxyfluorescein as reporter fluorophores and 4-(4'-dimethylamino-phenylazo) benzoic acid as dark quencher dye, hCMV DNA and beta-actin DNA could be quantified in parallel in a wide linear range from 10(1) to 10(7) copies, each. To test the clinical applicability of this approach, we investigated hCMV DNA kinetics in peripheral leukocytes of three hCMV antigen-positive and four antigen-negative patients after liver transplantation, as assessed by intracellular hCMV pp65 alkaline phosphate-anti-alkaline phosphate (APAAP) complex. While all APAAP-negative individuals remained PCR negative, kinetics of HCMV DNA in leukocyte DNA samples of APAAP-positive patients correlated closely with hCMV antigen tests. Here, comparison of separate and simultaneous target quantitation revealed identical results. It is of interest that, while single hCMV antigen positivity is commonly not regarded as a reliable parameter of viral reactivation, in our study a viral load greater than 10(4) copies/2x10(5) beta-actin DNA copies clearly indicated a subsequent increase in APAAP-positive leukocytes. We conclude that with the presented method the reliability of hCMV quantitation via real-time PCR can be substantially increased and may be used to monitor hCMV kinetics in vivo.     

Effect of aluminosilicates and bentonite on aflatoxin-induced developmental toxicity in rat.

Numerous studies have established that aflatoxin is a potent developmental toxin in animals. Previous research has demonstrated that a phyllosilicate clay, hydrated sodium calcium aluminosilicate (HSCAS or Novasil), tightly binds and immobilizes aflatoxins in the gastrointestinal tract of animals and markedly reduces the bioavailability and toxicity of aflatoxin. Our objective in this study was to utilize the pregnant rat as an in vivo model to compare the potential of HSCAS and bentonite to prevent the developmental toxicity of aflatoxin. Aluminosilicates (HSCAS) and bentonite were added to the diet at a level of 0.5% (w/w) and fed to the pregnant rat throughout pregnancy (i.e. days 0-20). Test animals were fed an aflatoxin-contaminated diet (2.5 mg kg(-1) diet) with or without sorbents during gestation days 6-15. Evaluations of toxicity were performed on day 20. These included maternal (mortality, body weights, feed intake and litter weights), developmental (embryonic resorptions and fetal body weights) and biochemical (ALT, AST and AP) evaluations. Sorbents alone were not toxic and aflatoxin alone resulted in significant maternal and developmental toxicity. Animals treated with phyllosilicate (plus aflatoxin) were comparable to controls following evaluations for resorptions, live fetuses and fetal body weights, as well as biochemical parameters. While bentonite plus aflatoxin resulted in significant reduction in fetal body weight, none of the fetuses from HSCAS or bentonite plus aflatoxin-treated groups had any gross, internal soft tissue or major skeletal malformations.     

Studies of chemical and biological properties of 99mTc-DMS (dimercaptosuccinic acid) — Renal imaging agent

Studies of the chemistry of preparation of tin chelate 2.3-dimercaptosuccinic acid (DMS) complexed with ^99mTc with respect to its biological properties have been made. We have varied molar ratio of reactants (DMS:Sn/II/), concentration of Sn-DMS chelate and pH of ^99mTc-DMS injection solution and examined their influence on biodistribution. Biodynamics of labeled solution at time intervals of from 0.5 to 4 h have also been measured. Animal experiments were carried out on mice and rats.Radiochemical purity was checked by paper chromatography, thin-layer chromatography, and gel-filtration through Bio-Gel P-2.A sterile, pyrogen-free lyophilized kit for labeling, stable for 6 months, was made on the basis of achieved results.The results of its clinical application are also reported.Report presented at the I European Congress of Nuclear Medicine, Lausanne, May 12/15, 1976     

PLGA-modified Syloid®-based microparticles for the ocular delivery of terconazole: in-vitro and in-vivo investigations

The eye is an invulnerable organ with intrinsic anatomical and physiological barriers, hindering the development of a pioneer ocular formulation. The aim of this work was to develop an efficient ocular delivery system that can augment the ocular bioavailability of the antifungal drug, terconazole. Mesoporous silica microparticles, Syloid^® 244 FP were utilized as the carrier system for terconazole. Preliminary studies were carried out using different drug:Syloid^® weight ratios. The optimum weight ratio was mixed with various concentrations (30 and 60%w/w) of poly (lactic-co-glycolic acid) (PLGA), ester or acid-capped and with different monomers-ratio (50:50 and 75:25) using the nano-spray dryer. Results revealed the superiority of drug:Syloid^® weight ratio of 1:2 in terms of yield percentage (Y%), SPAN and drug content percentage (DC%). Furthermore, incorporation of PLGA with lower glycolic acid monomer-ratio significantly increased Y%. In contrast, increasing the glycolic acid monomer-ratio resulted in higher DC% and release efficiency percentage (RE%). Additionally, doubling PLGA concentration significantly reduced Y%, DC%, drug loading percentage (DL%) and RE%. Applying desirability function in terms of increasing DC%, DL% besides RE% and decreasing SPAN, the selected formulation was chosen for DSC, XRD and SEM investigations. Results confirmed the successful loading of amorphized terconazole on PLGA-modified Syloid^® microparticles. Moreover, pharmacokinetic studies for the chosen formulation on male Albino rabbits’ eyes revealed a 2, 6.7 and 25.3-fold increase in mean residence time, C_max and AUC_0–24-values, respectively, compared to the drug suspension. PLGA-modified Syloid^® microparticles represent a potential option to augment the bioavailability of ocular drugs.     

Factors for Effective Identification of Patients at Nutritional Risk in Clinical Practice: Thematic Analysis of Qualitative Research

IntroductionDespite the high prevalence of malnutrition in patients at all levels of healthcare, early prevention and treatment of malnourished patients are often neglected and overlooked in clinical practice. The aim of this systematic literature review was to identify the factors considered most important by healthcare professionals in the identification and treatment of malnourished patients or those at risk of malnutrition.MethodsA systematic literature review of qualitative research was conducted. Documents published in scientific journals in English from 2011 to 2021 were searched in the PubMed (MEDLINE), CINAHL and ProQuest databases. The results were analysed with a thematic analysis of qualitative research findings.ResultsFrom the search set of 1010 results, 7 sources were included in the final analysis. Factors identified by health professionals as important in the identification and treatment of malnourished patients in clinical practice were grouped into five themes: unclear organizational structure; indefinite structure of nutritional care; poor continuity of nutritional care; lack of knowledge and skills of health professionals; lack of time and human resources.ConclusionsHealth policy must provide resources for nutritional care for patients at all levels of health care on the initiative of the highest professional bodies at the state level. To improve the nutritional care of patients in clinical practice, the management of health care institutions must promote and enable the professional and organizational establishment of clinical nutrition as a regular medical activity of the institution, develop clinical nutritional pathways, and promote evidence-based clinical practice and interprofessional collaboration.