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.

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.

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.

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).

Alpha-fetoprotein in the serum of patients with neoplasms of the gastrointestinal tract.

Serum alpha-fetoprotein was estimated in 61 patients with neoplasms of the gastrointestinal tract, 29 healthy controls and 10 pregnant women. Almost half ot the patients had increased values of alpha-fetoprotein and no parellelism between alpha-fetoprotein and liver metastasis was found. Decreasing of the alpha-fetoprotein during the postoperative period could be considered a sign for a total removal of the tumor, and, on the contrary -- increasing of alpha-fetoprotein -- for a recurrence.

The results of clinical trial within the framework of CMEA on surgical methods of mammary gland carcinoma treatment.

The results of joint clinical investigation performed by 8 oncological centers within the framework of CMEA countries are reported. Out of 816 patients with mammary gland carcinoma (MGC) of lateral localization, stage T1-2N0-1aM0, classical radical mastectomy by Halsted was carried out in 230 patients, mastectomy by Patey in 318 patients and conservative operation of radical resection type--in 218 patients. Specific characteristics of the disease progression were studied considering the time of development and incidence rates of local relapse or distant metastases depending on the type of surgery and MGC stage. High rates of 5-year survival were found for all types of surgery, mastectomy by Patey proving somewhat superior.

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.

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.

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.

DNA aneuploidy and cell proliferation in breast tumors.

The cellular DNA content of 30 benign and 180 malignant breast tumors was analyzed by means of flow cytometry (FCM). All benign tumors exhibited a normal DNA content (diploid), whereas 65% of the malignant tumors showed an abnormal DNA content (aneuploid). The ploidy distribution of malignant tumors was bimodal with an increasing frequency near diploid DNA index (DI), and a second group had a DI ranging from triploid to tetraploid. In estimating the degree of malignancy eight independent histomorphologic and cytologic criteria were introduced. A good correlation was observed between DNA content abnormalities and the grade of differentiation of breast carcinomas. The percentage of S-phase cells of DNA aneuploid cell lines was significantly higher than in the diploid ones. The highly differentiated breast carcinomas (Grade 1) indicated lower S-phase values as compared to the undifferentiated (Grade 3) ones. S-phase values estimated by FCM were about two times higher than the 3H-thymidine labeling index (LI) obtained by an in vitro procedure. The data estimated in this study showed that DNA determinations as an adjunct to conventional histopathologic assessment may provide objective clinically relevant information with respect to the degree of malignancy and prognosis of patients with breast carcinoma.

[Autosomal recessive polycystic kidney]. / Avtozomno-retsesivna bubrechna polikistoza.

A case of a 22 years old woman with autosomal-recessive form of kidney polycystosis is presented. The diagnosis was made in early childhood. A combination of renal anomaly and hepatic fibrosis with manifestations of portal hypertension was present. No deviations from the other internal organs were found. At the age of 12 she entered into the stage of chronic renal failure. The last five years she is on dialysis treatment. She had survived several acute bleedings from esophageal varices. The authors are of the opinion that the case is of interest since patients with autosomal-recessive renal polycystosis very rarely reach majority.

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.

[Chronic pyelonephritis in polycystic kidney]. / Kum problema za khronichniia pielonefrit pri bubrechna polikistoza.

The characteristics of chronic pyelonephritis are studied in 37 patients out of a total of 53 patients with proved renal polycystosis. A group of 71 patients with chronic pyelonephritis selected at random are used as a control group. The frequency of chronic pyelonephritis among the patients with renal polycystosis is 69.8%. The difference between the mean age of the patients with renal polycystosis and chronic pyelonephritis and the patients with renal polycystosis without chronic pyelonephritis is 8.6 years. A significant difference is established between these two groups of patients concerning the frequency of symptomatic hypertension--89.2% for the patients with renal polycystosis and chronic pyelonephritis and 45% for the patients with uncomplicated renal polycystosis. A similar difference is established also for the renal failure--respectively 64.9% and 37.5%. The frequency of hypertension and chronic renal failure is lower in the control group of patients. 59% of the patients with renal polycystosis and chronic pyelonephritis have significant bacteriuria, E. coli and Proteus being the most frequently isolated bacteria but Pseudomonas shows the highest drug resistance. The isolated bacteria are most sensitive to nitroxoline and aminoglycoside antibiotics.

[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.

[Brain changes in patients on chronic hemodialysis recorded by computed axial tomography]. / Mozuchni promeni pri bolni na khroniokhemodializa, otchitani s kompiuturna aksialna tomografiia.

The brain changes in patients with chronic renal failure treated by chronic hemodialysis were studied with the help of computed tomography. The results showed the development of internal hydrocephalus in the patients in whose treatment "hard" water was used. In some of these patients the hydrocephalus was accompanied by clinical manifestations of the "disequilibrium" syndrome and the "hard water" syndrome. The patients dialyzed with "soft" water showed no brain changes and clinical signs. Hydrocephalus is probably the main pathogenetic factor for the development of the "hard water" syndrome which later develops in dialysis encephalopathy.

[Rare complications in polycystic kidney--the difficulties in their diagnosis and treatment]. / Redki uslozhneniia na bubrechnata polikistoza--trudnosti pri diagnostikata i lechenieto im.

The development of some rare complications of renal polycystosis is discussed. Four patients with chronic polycystosis with complications are followed up. In 3 of them (2 of them on chroniodialysis) the cysts suppurated and after an infective conservative treatment they were treated surgically-puncture, cyst excision and unilateral nephrectomy. To the fourth patient bilateral nephrectomy had been performed 5 years ago because of other reasons. All 4 patients are alive at present with a fairly good end result.

[Secondary cystic changes in the kidneys in chronic kidney failure]. / Vtorichni kistozni izmeneniia v bubretsite pri khronichna bubrechna nedostatuchnost.

In patients with chronic renal failure the presence and frequency of acquired cystic changes in the kidneys (acquired cystic renal disease) were studied. 46 patients, 21 to 62 years of age and duration of hemodialysis treatment from 2 up to 126 months, were examined. The patients with polycystic kidneys were excluded. Cysts were found in 67.4% of the patients. They were classified into five groups. Between the duration of the hemodialysis treatment (the chronic renal failure respectively) and the development of the cystic renal disease correlation was found. The correlation between the length of the kidneys and the cystic changes is statistically significant. There is no correlation with the sex, age, basic disease, hematologic indices, diuresis and arterial pressure of the patients. In 50% of the patients examined splenomegaly was found the cause of which is not known.