Pitfals in recognition and management of trigeminal neuralgia.

BACKGROUND: Trigeminal neuralgia (TN) is a severe, disabling form of painful cranial neuropathy. Even though TN has a typical clinical picture, diagnosis it is often missed or delayed in clinical practice. In order to investigate the occurrence of diagnostic and therapeutic errors in TN, we studied 102 patients suffering from TN recruited through a multicentric survey. METHODS: We performed a Pubmed database search on errors and pittfalls in TN diagnosis and management. Then, patients with TN were consecutively enrolled in the period from February 2017 to October 2019, by several European Headache Centers participating in the study, following a call of the Headache and Pain Scientific Panels of the European Academy of Neurology (EAN). Diagnosis of Classical Trigeminal Neuralgia (CTN) was made according to the International Headache Society (IHS) criteria (Tölle et al., Pain Pract 6:153-160, 2006). All the patients were evaluated using telephone/frontal interviews conducted by headache/pain specialists using an ad hoc questionnaire. RESULTS: A number of 102 patients were recruited, mostly females (F:M ratio 2.64:1). Eighty-six percent of the patients consulted a physician at the time they experienced the first pain attacks. Specialists consulted before TN diagnosis were: primary care physicians (PCP) (43.1%), dentists (in 30.4%), otorhinolaryngologists (3.9%), neurosurgeons (3.9%), neurologists or headache specialists (14.7%), others (8%). The final diagnosis was made mainly by a neurologist or headache specialist (85.3%), and the mean interval between the disease onset and the diagnosis made by a specialist was 10.8 ± 21.2 months. The "diagnostic delay" was 7.2 ± 12.5 months, and misdiagnoses at first consultation were found in 42.1% of cases. Instrumental and laboratory investigations were carried out in 93.1% of the patients before the final diagnosis of TN. CONCLUSION: While TN has typical features and it is well defined by the available international diagnostic criteria, it is still frequently misdiagnosed and mistreated. There is a need to improve the neurological knowledge in order to promptly recognize the clinical picture of TN and properly adhere to the specific guidelines. This may result in a favorable outcome for patients, whose quality of life is usually severely impaired.

Unusual Listeria monocytogenes peritonitis in peritoneal dialysis patient with liver cirrhosis: a case report and review of literature.

Spontaneous Listeria peritonitis is well described in liver failure, but is uncommon in peritoneal dialysis patients. Atypical cases where peritonitis symptoms develop after systemic manifestations are rare and challenging for diagnostic. A 57-year-old peritoneal dialysis patient with history of ethylic cirrhosis was admitted after epileptic seizure. On admission, patient was soporous without signs of peritonitis and meningitis. Patient's peritoneal effluent was clear, with normal leukocytes. Cranial CT scan showed no abnormalities. Laboratory exams revealed positive inflammatory syndrome. Despite antibiotic therapy, next day, symptoms aggravated with coma development. Peritoneal effluent became cloudy and its leukocyte count rose up. Effluent microscopy revealed Gram-positive bacilli. Patient was started with intraperitoneal Vancomycin and Amikacin. Patient's clinical condition deteriorated with lethal outcome. Post-mortem analysis of effluent and blood culture showed growth of L. monocytogenes. Apart from idiopathic etiology, goat-milk curd, that patient had started consuming 10 days before admission, could theoretically be considered as possible infection vehicle. L. monocytogenes peritonitis in peritoneal dialysis patients is rare, but must be considered in immunocompromised or patients with concomitant liver failure, especially after Gram-positive bacilli identification in peritoneal effluent. In case of suspiscion of Listeria peritonitis, Ampicillin should be initiated, because bacteria often poorly respond to currently recommended empiric regimens.

Analytical studies of the Alexandrovo Thracian tomb wall paintings.

A profound study of samples obtained from Thracian tomb wall paintings at Alexandrovo, Bulgaria (dating back to the fourth century BC) were carried out by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and Attenuated Total Reflectance Fourier transform infrared spectroscopy (ATR FTIR), high-resolution transmission electron microscopy (HRTEM) and energy dispersive X-ray spectroscopy (EDS). The current work provides a glimpse of the ingenious construction and painting techniques used in Thracian tomb at Alexandrovo. The results suggest that beeswax was used as a paint binder and also revealed presence of various nano-materials.

Antihypertensive and cardioprotective effects of the dipeptide isoleucine-tryptophan and whey protein hydrolysate.

AIMS: Angiotensin-converting enzyme inhibitors are treatment of choice in hypertensive patients. Clinically used inhibitors exhibit a structural similarity to naturally occurring peptides. This study evaluated antihypertensive and cardioprotective effects of ACE-inhibiting peptides derived from food proteins in spontaneously hypertensive rats. METHODS AND RESULTS: Isoleucine-tryptophan (in vitro IC50 for ACE = 0.7 µm), a whey protein hydrolysate containing an augmented fraction of isoleucine-tryptophan, or captopril was given to spontaneously hypertensive rats (n = 60) over 14 weeks. Two further groups, receiving either no supplement (Placebo) or intact whey protein, served as controls. Systolic blood pressure age-dependently increased in the Placebo group, whereas the blood pressure rise was effectively blunted by isoleucine-tryptophan, whey protein hydrolysate and captopril (-42 ± 3, -38 ± 5, -55 ± 4 mm Hg vs. Placebo). At study end, myocardial mass was lower in isoleucine-tryptophan and captopril groups but only partially in the hydrolysate group. Coronary flow reserve (1 µm adenosine) was improved in isoleucine-tryptophan and captopril groups. Plasma ACE activity was significantly decreased in isoleucine-tryptophan, hydrolysate and captopril groups, but in aortic tissue only after isoleucine-tryptophan or captopril treatment. This was associated with lowered expression and activity of matrix metalloproteinase-2. Following isoleucine-tryptophan and captopril treatments, gene expression of renin was significantly increased indicating an active feedback within renin-angiotensin system. CONCLUSION: Whey protein hydrolysate and isoleucine-tryptophan powerfully inhibit plasma ACE resulting in antihypertensive effects. Moreover, isoleucine-tryptophan blunts tissue ACE activity, reduces matrix metalloproteinase-2 activity and improves coronary flow reserve. Thus, whey protein hydrolysate and particularly isoleucine-tryptophan may serve as innovative food additives with the goal of attenuating hypertension.

Use of self-actuating and self-sensing cantilevers for imaging biological samples in fluid.

In this paper, we present a detailed investigation into the suitability of atomic force microscopy (AFM) cantilevers with integrated deflection sensor and micro-actuator for imaging of soft biological samples in fluid. The Si cantilevers are actuated using a micro-heater at the bottom end of the cantilever. Sensing is achieved through p-doped resistors connected in a Wheatstone bridge. We investigated the influence of the water on the cantilever dynamics, the actuation and the sensing mechanisms, as well as the crosstalk between sensing and actuation. Successful imaging of yeast cells in water using the integrated sensor and actuator shows the potential of the combination of this actuation and sensing method. This constitutes a major step towards the automation and miniaturization required to establish AFM in routine biomedical diagnostics and in vivo applications.

Safety investigation of team performance in accidents.

The paper presents the capacities of the performance evaluation of teamwork (PET) method. Its practicability and efficiency are illustrated by retrospective human reliability analyse of the famous nuclear and maritime accidents. A quantitative assessment of operators' performance on the base of thermo-hydraulic (T/H) calculations and full-scope simulator data for set of NPP design basic accidents with WWER is demonstrated. The last data are obtained on the 'WWER-1000' full-scope simulator of Kozloduy NPP during the regular practical training of the operators' teams. An outlook on the "evaluation system of main control room (MCR) operators' reliability" project, based on simulator data of operators' training is given.

Rheological evaluation of the influence of sterilisation on ocular gels using an experimental design.

Different rheological characterisation methods are employed to investigate the influence of the sterilisation method (autoclaving), the polymer concentration (0.50, 0.75 and 1.00%) and the dispersing medium (i.e. isotonic phosphate buffer and mannitol solution) on Carbopol 974 P NF dispersions, used as ocular gels. The evaluation of the different polyacrylic acid-based dispersions was performed using flow and oscillatory shear measurements, and herewith an experimental design was set up. The rheological data show that the choice of the dispersing medium has a significant influence on the rheological behaviour of the ocular gels prepared. The dispersions in mannitol exhibit higher elastic properties than those made in the phosphate buffer solution (PBS). Sterilisation increases only the elastic properties of the 0.50% (w/w) Carbopol 974 P NF/PBS dispersion but has no influence on the other dispersions prepared.

Angiotensin-converting enzyme activity and the ACE Alu polymorphism in autosomal dominant polycystic kidney disease.

BACKGROUND: Previous studies concerning Alu I/D polymorphism in the ACE gene and ADPKD severity have used the Alu genotypes as a representative of the true biological variable, namely ACE activity. However, wide individual and ethnic differences in the proportion of variance in ACE activity explained by the I/D genotype may have confounded these studies. This investigation examines the association between ADPKD severity and ACE in terms of plasma enzyme activity and I/D genotypes in individuals from three different countries. METHODS: Blood samples were collected from 307 ADPKD patients (116 Australian, 124 Bulgarian and 67 Polish) for determination of ACE activity levels and I/D genotypes. Chronic renal failure (CRF) was present in 117 patients and end-stage renal failure (ESRF) in 68 patients. RESULTS: ACE activity was related to the I/D genotype, showing a dosage effect of the D allele (P=0.006). The proportion of variance due to the Alu polymorphism was 14%. No difference in ACE activity and I/D genotype distribution was found between patients with CRF versus normal renal function (P=0.494; P=0.576) or between those with ESRF versus those without ESRF (P=0.872; P=0.825). No effect of the I/D genotype on age at development and progression to renal failure (CRF; ESRF) was detected in the overall group, and in subgroups based on ethnic origin, linkage status and sex. CONCLUSION: ACE is not likely to play a role as a determinant of ADPKD phenotype severity.

Differential regulation of cathepsin B and prorenin gene expression in renal juxtaglomerular cells.

Cathepsin B (cathB) is a lysosome cysteine proteinase. It has been suggested to process prorenin to renin in the renin producing juxtaglomerular (JG) cells of the afferent arterioles (AA) of the kidney. Whether cathB expression is regulated similarly to prorenin production is yet unknown. We have measured prorenin and cathB mRNA levels as well as cathB protein levels in renal AA of Sprague-Dawley rats subjected to low (0.02% w/w) salt diet and ramipril treatment (10 mg/kg/day), or to normal (0.6%) or high (4%) salt diet. Prorenin and cathB expression were also analyzed in the JG cell line As4.1. Prorenin mRNA levels in animals on normal (plus ramipril), low or high salt diet correlated as 1:10:0.5, respectively, while cathB mRNA levels correlated as 1:1:0.6, respectively. Treatment of the As4.1 cells with 100 nM phorbol-12-myristate-13-acetate (PMA) for 16 h inhibited prorenin mRNA expression 3-fold relative to the control conditions. CathB mRNA abundance was not different between the PMA treated and the control As4.1 cells. Western analysis of the cathB protein abundance has shown no difference between the rats on normal and low salt diet, and decrease by 50% in the rats on high salt diet. The results of this study suggest that prorenin and cathB gene expression in renal JG cells are differentially regulated.

Screening the 3' region of the polycystic kidney disease 1 (PKD1) gene in 41 Bulgarian and Australian kindreds reveals a prevalence of protein truncating mutations.

Screening for disease-causing mutations in the unique region of the polycystic kidney disease 1 (PKD1) gene was performed in 41 unrelated individuals with autosomal dominant polycystic kidney disease. Exons 34-41 and 43-46 were assayed using PCR amplification and SSCP analysis followed by direct sequencing of amplicons presenting variant SSCP patterns. We have identified seven disease-causing mutations of which five are novel [c.10634-10656del; c.11587delG; IVS37-10C>A; c.11669-11674del; c.13069-13070ins39] and two have been reported previously [Q4010X; Q4041X]. Defects in this part of the gene thus account for 17% of our group of patients. Five of the seven sequence alterations detected are protein-truncating which is in agreement with mutation screening data for this part of the gene by other groups. The two other mutations are in-frame deletions or insertions which could destroy important functional properties of polycystin 1. These findings suggest that the first step toward cyst formation in PKD1 patients is the loss of one functional copy of polycystin 1, which indirectly supports the "two-hit" model of cystogenesis where a second somatic mutation inactivating the normal allele is necessary to occur for development of the disease condition.

Screening for mutations in the peripheral myelin genes PMP22, MPZ and Cx32 (GJB1) in russian charcot-marie-tooth neuropathy patients; irina V. Mersiyanova, sookhrat M. Ismailov, alexandr V. Polyakov, elena L. Dadali, valeriy P. Fedotov, eva nelis, ann Lofgren, vincent timmerman, christine van broeckhoven, and oleg V. Evgrafov (Article was originally published in human mutation 15:340-347, 2000)

The authors wish to correct a mistake which occurred in the reporting of one of the mutations. The mutation in Cx32 Met34Lys is wrongly described as 100A>G. The correct description of the mutation should be 101T>A (Met34Lys).

Endogenous nitric oxide attenuates erythropoietin gene expression in vivo.

This study aimed to investigate the role of endogenous nitric oxide (NO) in erythropoietin (EPO) gene expression in mice in vivo. For this purpose EPO mRNA was semiquantitated by ribonuclease protection assay in livers and kidneys of three groups of mice: wild-type (wt), endothelial NO-synthase (NOS) knockout mice (eNOS-/-), and wt treated with the NOS inhibitor N(G)-nitro-L-arginine methyl ester (50 mg x kg(-1) x day(-1)) for 4 days (wt+L-NAME). EPO gene expression was stimulated by normobaric hypoxia (8% O2) or by 0.1% carbon monoxide (CO) inhalation for 4 h each, or by intraperitoneal injection of 60 mg/kg cobaltous chloride (CoCl2) for 6 h. Renal EPO mRNA in wt increased 12-, 40-, and 13-fold over normoxic levels in response to hypoxia, CO and CoCl2 respectively. EPO mRNA was detectable in the livers only after CO exposure. Renal and hepatic EPO gene expression in wt+L-NAME appeared moderately increased relative to wt with a maximal 2.5-fold enhancement after CO exposure. EPO mRNA levels in eNOS-/- mirrored those of wt+L-NAME, but the effects were less prominent. Our data suggest that endogenous NO attenuates EPO gene expression in mice. This effect is dependent on the rate of EPO gene induction.

Single dose recombinant human erythropoietin reduces transforming growth factor beta in patients on chronic haemodialysis.

Short-term effects of recombinant human erythropoietin on serum levels of transforming growth factor beta-1, interleukin 1-alpha, interleukin 3, interferon gamma, and tumour necrosis factor alpha in patients with chronic renal failure on chronic haemodialysis were investigated. Recombinant human erythropoietin was applied subcutaneously in a dose of 75 IU/kg on 19 patients. Serum levels of transforming growth factor beta-1, interleukin 1-alpha, interleukin 3, interferon gamma, tumour necrosis factor alpha and erythropoietin, red blood cell parameters: red blood cell count, haemoglobin, haematocrit, and erythrocyte indices were determined before and after recombinant human erythropoietin single application. Transforming growth factor beta-1 serum levels were decreased after recombinant human erythropoietin (22.70 +/- 1.51 ng/ml versus 18.77 +/- 1.70 ng/ml (p < 0.01). None of the other investigated parameters was influenced significantly by recombinant human erythropoietin. Recombinant human erythropoietin in patients with chronic renal failure on chronic haemodialysis may influence anaemia not only through its stimulating effect on erythropoiesis, but also by direct oxygen-independent decrease of at least one of the negative regulators of erythropoiesis--the transforming growth factor beta.

Genetic heterogeneity of polycystic kidney disease in Bulgaria.

Linkage analysis was performed on 22 Bulgarian families with polycystic kidney disease (PKD) ascertained through the hemodialysis centers of two medical schools. A total of 128 affected and 59 unaffected individuals, and 54 spouses have been investigated using eight polymorphic markers linked to PKD1 and nine markers to PKD2. The results demonstrate locus heterogeneity with 0.67 as the maximum likelihood value of alpha, i.e., the proportion of families linked to PKD1. In five families, the results suggest linkage to PKD2 and observed recombinants place the gene between loci D4S1544 and D4S1542. In one family, two double recombinants for closely linked markers on chromosome 16 and on chromosome 4 give evidence for the lack of linkage to either PKD1 or PKD2, thus suggesting the involvement of a third locus. Analysis of clinical data in the PKD1 group versus the unlinked group shows no significant differences in the severity of the disease.

[Urinary electrolyte excretion in autosomal dominant polycystic kidney]. / Urinna ekskretsiia na elektroliti pri avtozomna dominantna bubrechna polikistoza.

In 33 patients with autosomal dominant renal polycystosis the urine excretion of the electrolytes sodium and potassium was examined and analyzed in relation to the renal function and the arterial pressure. The clearances, the urine ratio and the excreted fractions of both electrolytes were calculated. It was established that by normal renal function and without arterial hypertension there were no significant differences in the parameters studied between the patients and the healthy controls. In the patients with arterial hypertension and preserved renal function the sodium clearance and urine excretion were lower, but the differences with the normotensive patients were not statistically significant. In the patients with chronic renal failure (when diuretic was applied) higher mean values of the excreted fractions of sodium and potassium were established. The results support the thesis that hypertension in renal polycystosis is of volumetric character.