A new family with hyperthyroxinemia caused by transthyretin Val109 misdiagnosed as thyrotoxicosis and resistance to thyroid hormone--a clinical research center study.

Serum transthyretin (TTR) is a protein of liver origin that under normal conditions transports approximately 20% T4. Missense mutations of the TTR gene produce familial amyloidotic polyneuropathy and rarely, euthyroid hyperthyroxinemia (EHT). Of the 3 TTR variants so far identified with increased affinity for T4, Ser6, Thr109, and Met119, only TTR-Thr109 has high enough affinity for T4 to produce consistent hyperthyroxinemia in the heterozygous individuals. Because the mutation GCC-->ACC in codon 109 results in the loss of one Bso FI site in exon 4 of the TTR gene, the use of this enzyme was suggested to screen for TR-Thr109 in subjects with EHT. We investigated a family with dominantly inherited EHT, in which two of eight affected members received ablative thyroid treatment for presumed thyrotoxicosis, and one was misdiagnosed as having resistance to thyroid hormone. All affected individuals had serum reverse T3 concentrations above normal and average T4 50% above the mean of unaffected relatives. Total T3 and TSH levels were within the normal range. Although loss of the Bso FI site in one allele of the two TTR suggested the presence of Thr109, gene sequencing revealed a different mutation in the same codon (GCC-->GTC) producing TTR-Val109. T4-binding to TTR-Val109 was compared to that of the normal TTR-Ala109 and the formerly identified variant TTR-Thr109. Association constants were 1.3, 9.5, and 13.6 X 10(7) M-1 for TTR-Ala109, Val109, and Thr109, respectively. Thus, for equally expressed mutant and normal allele and 20% of serum T4 bound to TTR, the calculated mean serum T4 concentration of heterozygotes for TTR-Val109 should be 50% above the normal mean; the observed value being 55%. These results are in agreement with the observations based on the crystallographic structure of TTR-Thr109 indicating that the extra atoms in Val as in Thr, which are absent in the Ala of the wild type TTR, widen the ligand binding site.

Immunocytochemical detection of carcinoembryonic antigen in fine-needle aspirates from patients with diverse breast diseases.

Fine-needle aspirates and paraffin-embedded tissue sections from 91 cases with diverse breast diseases were immunostained with carcinoembryonic antigen (CEA) monoclonal antibody using a BioGenex StrAviGen kit based on the biotin-streptavidin amplified methodology. The results were compared with histopathologic tumor type and tumor stage. CEA was not expressed in fibrocystic changes with mild or florid epithelial hyperplasia (n = 23) and fibroadenomas (n = 8). On the other hand, 90% (56/60) of primary breast carcinomas showed positive cytoplasmic staining for CEA. No correlation was found between CEA expression, histopathologic tumor type, and tumor stage. We suggest that CEA immunocytochemistry will help in the accurate diagnosis of primary breast carcinoma in fine-needle aspirates in addition to the usual cytological criteria.

[The detection of metastases of ovarian carcinoma by immunoscintigraphy with monoclonal antibodies]. / Otkrivane na metastazi ot ovarialen kartsinom posredstvom imunostsintigrafiia s monoklonalni antitela.

Sixty eight women, operated for ovarian carcinoma, were studied by monoclonal antibodies anti-CA-125 labeled with 131I. 99m-Tc was used for the scintigraphy. Ninety-one metastases were discovered as 73 of them were established surgically. 52/61 were confirmed in the pelvis, 19/24 in the abdominal cavity and 3/6 in the liver. Higher precision of immunoscintigraphy was found in the diagnosis of liver metastasis, when it was compared with echographic and computed tomographic examinations.

[Electron microscopic study of the liver after experimentally resecting it and covering its surface with BAPP and BAPK]. / Elektronno-mikroskopicheskie issledovaniia pecheni posle ee rezektsii s pokrytiem poverkhnosti BAPP i BAPK v éksperimente.

An analysis of data of electron microscopic investigations of liver preparations within the terms of from 7 to 425 days after resection of the liver in which the liver wound was covered by the antimicrobial polycaproamid gauze made in Bulgaria has shown that the polymer material does not cause alterations in the liver structure and cell organelles of hepatocytes not preventing regeneration of the liver.

EPIDEMIOLOGICAL REGISTRY OF NEUROENDOCRINE TUMORS IN BULGARIA--A PILOT SURVEY.

The National registry of patients with neuroendocrine tumors (NET) in Bulgaria was established in 2013 as a joint initiative of the Bulgarian Surgical Society and the Institute for Rare Diseases. The register aims to explore the epidemiology of NET in Bulgaria, as well as the different diagnostic and treatment approaches for the disease throughout the country. This the first of its kind retrospective study of NET in the country is covering the period January 2012 - January 2013. A total of 127 patients with NET were identified. At the time of the survey the average age of patients with NET was 58.61 ± 15.59 years. The data show almost equal distribution between the genders with a slight predominance of women. The largest relative part of NET is those of NET located in the gastrointestinal tract (54.10 ± 4.51%), followed by those located in the pancreas (12.30 ± 2.97%) and in the lungs (10.66 ± 2.79%). In 72.44 ± 3.96% of the patients a immunohistochemical diagnosis was performed. The study confirmed the leading role of the surgery method of the NET management. In 65.83 ± 4.33% of the patients a radical removal of the tumor was conducted, while the relative part of the undertaken partial resection was 7.50 ± 2.40%. A statistically significant association between the type of surgical treatment and during the follow-up of patients was found. An update of the information in the register will allow a more precise determining of the distribution and management of NET in Bulgaria.

Surgical treatment of chronic pancreatitis and its complications. Comparative analysis of results in 91 patients.

There is a large variety of proposed conservative, invasive, endoscopic and surgical methods for treatment of chronic pancreatitis and its complications. This study presents a comparative analysis of the results from each group of patients subjected to drainage, resection, denervation and other operative techniques for a total of 91 patients with chronic pancreatitis and its complications. Drainage and resection operative techniques yield comparable results in terms of postoperative pain control 93.1% and 100%, perioperative mortality--3.17% and 5.8%, perioperative morbidity--7.9% and 11.7%, respectively. There is a significant increase in the instances of diabetes in the resection group. Right-side semilunar ganglionectomy is a good method for pain control as an accompanying procedure in the course of another main operative technique.

Some aspects of the etiology and the pathogenesis of chronic pancreatitis.

The development of modern technology and advances in medical science make possible understanding of etiology of chronic pancreatitis. From a century ago, the ethanol is connected to chronic pancreatitis. In the last decades medical science made a big footstep in understanding of so called "idiopathic pancreatitis". Factors as autoimmune disturbances, toxins, gene mutations, geographic characteristics are already known as cornerstones in etiology and pathogenesis of the disease.

[Not Available]. / [Ethnographic studies and popular medicine]

In the work submitted, the author makes a brief historical review of Bulgarian ethnographic literature, related, among other things, also to popular medicine investigations. Reference is made to authors as Dr. Yuri Ivanovich Venelin (1825), G.S. Rakovsky (1859), and after the liberation of Bulgaria: Tzani Ginchev Shkeparnev, one of the outstanding protagonists for collecting facts and materials in the field of popular medicine in this country, M. Georgiev, Hr. Popstoilov, K. Irechek, Iv. D. Shishmanov and others. A description is made of the traditional methods of treatment with herbs, charms, healers and the like. Due attention is given also to the popular conceptions and explanation of the contributing factors of diseases, looking for the rationale in them and giving special consideration to the superstitious traces, inherited from the ancient Thracians. It is stressed that the items published heretofore in the "Comopilation of national folklore and literature", covering the field of popular medicine, constitute a great, unique in its significance, national wealth which is seldom found in other countries and which might be utilized by modern medicine as well as for drawing important ethnogenetic inferences.

[The immunoscintigraphic diagnosis of the metastases of colorectal cancer by using monoclonal antibodies]. / Imunostsintigrafska diagnostika na metastazi ot kolo-rektalen rak posredstvom monoklonalni antitela.

Sixty-four patients operated for colorectal cancer comprise the study group. CEA and CA-19.9 markers were used. The antibodies were labelled with 131I, using for the scintigraphy 99mTc as well. Eighty eight metastatic foci were detected, 67 of them (76.1 per cent) confirmed by the surgeon: Of 55 pelvic localizations, surgically detected were 47 (85.5 per cent), of 24 in the abdominal cavity 15 (62.5 per cent) were confirmed and of 9 in the liver--only 5 (55 per cent). Radioimmunoassay more accurate in pelvic localizations, whereas echography and computer tomography were more precise in liver examination (83.3 per cent).

[Diagnostic and therapeutic problems in typhoid fever complicated by severe enterorrhagia (apropos a patient successfully treated by surgery)]. / Diagnostichni i terapevtichni problemi pri koremen tif, uslozhnen s tezhka enteroragiia (po povod na bolen, uspeshno lekuvan s operatsii.

The case history of a 69-year-old patient with typhoid fever is described. The disease ran an atypical course; with early jaundice syndrome, severe enterorrhagia and late appearance of roseola. He was successfully treated by surgical intervention--hemicolectomy. The need of surgical treatment of patients with typhoid fever, who have severe, life-threatening enterorrhagia, is emphasized.

[The pathomorphological changes in the pleura of rabbits with artificial pneumothorax and uropolin pleurography]. / Patomorfologichni promeni v plevrite na zaitsi pri artifitsialen pnevmotoraks i plevrografiia s uropolin.

The results from artificial pneumothorax in 25 rabbits with intrapleural administration of Uropolin (10 rabbits) as well as of 10% solution of NACl (7 rabbits) were described. Thoracotomy was made on 7th, 14th and 12 21st day and the parietal, diaphragmatic and visceral pleura with underlaying tissues were examined. Proliferation of the mesothelium [correction of mesother] and growth of the connective tissue, which were more manifested in rabbits treated with Uropolin, were established histologically. The authors think that pathohistological examinations confirm the clinical observed favourable effect of intrapleural administration of Uropolin for obliteration of the pleural cavity.

[The role of the laser in gastrointestinal surgery]. / Miastoto na lazera v gastrointestinalnata khirurgiia.

In a series of 2500 operations with laser in the gastrointestinal region the authors used laser CO2 with up to 90 W strength and Nd--Yag with up to 80 W strength, both alone and in combination. Principal application of this technique is in oncologic surgery: resection of liver, volatilization of hepatic and other metastases, destruction of inoperable carcinoma in the middle and distal portion of the rectum and in other fields of proctologic surgery. In this aspect, laser technique is a powerful palliative means in the general arsenal of surgery.

Using the spectral asymmetry of TEA CO2 laser pulses to determine the Doppler-shift sign in coherent lidars with low frequency stability.

We develop a method for determinating the relative positions of the lidar transmitter (LT) and the local oscillator (LO) frequencies in Doppler CO2 lidars. It uses the weak spectral asymmetry of TEA CO2 laser pulses, defined by a number of secondary peaks at the high-frequency side of the main spectrum peak. Depending on the sign of the beat frequency, these peaks may appear in the demodulated spectrum at either the high- or the low-frequency side. Each laser pulse spectrum is compared with reference spectra with two types of asymmetry, with the cross-correlation coefficients used as criteria. The performance of the method at different values of signal-to-noise ratio is analyzed numerically. The method is also applied to raw data from the lidar reference channel and demonstrates good performance at noise levels lower than the secondary peaks in the pulse spectrum or at a signal-to-noise ratio of > or = 20 dB. Application of the pulse spectrum asymmetry for lidar frequency stabilization is analyzed. Lidar operation without frequency stabilization is considered as well. The method offers a simple Doppler lidar hardware for the creation of low-cost coherent lidars, velocimeters-rangefinders, etc.

[Experimental study of the dynamics of alkaline phsophatase activity after a liver wound]. / Eksperimentalni prouchvaniia vurkhu dinamikata na alkalnofosfataznata aktivnost pri chernodrobna rana.

The investigation of alkaline phosphatase activity on 80 rabbits with an experimental model of liver wound showed the following results: 1. Alkaline phosphatase in blood serum was elevated considerably during the first postoperative days, but after the fifth day was close to the normal ranges. 2. Tissue alkaline phospatase sharply fell up to the third day. Its values began to raise after the 20th day and reached the normal level in the end of the experimental period (30th day). 3. Histochemical studies of liver wound showed a positive reaction for alkaline phosphatase in the cells of the inflammatory infiltrate during the first days. Increased phosphatase activity was demonstrated in fiber structures, epithelium of bile canals and capillary endothelium. The dynamics of alkaline phosphatase activity in blood serum is a reflection of the delicate biochemical and histochemical changes in the liver wound. The follow-up of serum alkaline phosphatase together with the clinical course of healing could be an useful index for evaluation of diet and working capacity of the patient.

The alveolar lining film in experimental pulmonary collapse.

Obstructive pulmonary collapse was produced by ligation of lobar bronchus in 41 healthy dogs. The atelectatic lung was examined electronmicroscopically by means of vapour fixation, ruthenium red procedure and tricomplex flocculation. The equilibration stability index of Pattle was determined and compared to the electromicroscopic findings. The experimentally produced obstructive pulmonary collapse was a mechanical phenomenon which secondarily caused qualitative changes in the production of the alveolar lining layer.