DN4 questionnaire as a useful tool for evaluating the pharmacotherapeutic response to opioid pharmacotherapy in malignant neuropathy.

Objective: Tapentadol is a drug of choice for neuropathic cancer pain. DN4 questionnaire quickly determines neuropathic pain component. The aim of this study is to determine the correlation between neuropathic malignant pain component by applying tapentadol antidolorose pharmacotherapy in combination with palliative radiotherapy of osseous neuropathic metastatic changes in breast cancer patients before and after palliative radiotherapy. Methods: The first patients group comprised 30 patients with primary breast cancer and proved painful bone secondary deposits with neuropathy for which tapentadol was prescribed, and they underwent palliative radiotherapy. The second group comprised 30 patients with primary breast cancer and proved painful bone metastases with neuropathy treated only with palliative antidolorose radiotherapy. Key findings : After two-months-follow up, tapentadol group patients had lower DN4 score values (Z=2,021; p=0.043). Significantly lower number of tapentadol group patients was without neuropathic pain after a three-month-follow up (χ ²=5,711; p=0.017). Significantly greater number of tapentadol group patients had best ECOG score 0 ( χ² =7,486; p=0.023). There was statistically significant positive correlation between tapentadol dose and DN4 score in patients after a month (ρ=0,471; p=0.009) and three months after the radiotherapy completion (ρ=0,610; p<0.001). Tapentadol is an opioid analgesic efficient for neuropathy relief in these patients and DN4 questionnaire is an efficient pharmacotherapy tool.

Differential diagnosis of liver diseases using serum biomarkers.

PURPOSE: Many human blood proteins are synthesised in the liver. Their serum levels may decrease or increase due to liver disorders and some of them serve as useful biomarkers. Determination of serum concentration of different biomarkers has important role in diagnosis of liver diseases and in monitoring the course of disease. In this work 3 serum markers associated with liver disorders were compared. The aim was to assess whether these biomarkers exhibit specific distribution pattern in different types of liver disease: liver neoplasia (primary hepatocellular carcinoma [HC] or metastatic liver disease [MLD] from colon cancer), viral hepatitis C (HCV) and the parasitic infection echinococcosis. METHODS: Serum concentrations of alpha-fetoprotein (AFP), ferritin and insulin-like growth factor I (IGF-I) were determined in patients with liver disease and compared between patient groups and with healthy persons. RESULTS: Serum AFP and ferritin levels exhibited similar pattern of change in patients with liver neoplasia or HCV, and concentrations of these 2 markers were significantly increased compared to the control group (p < 0.01 in each case). On the other hand, the concentration of IGF-I was significantly decreased in patients with liver neoplasia or echinococcosis compared to the control group (p < 0.05 for both). The concentration of IGF-I was significantly lower and the concentration of ferritin significantly higher in patients with HC than in patients with MLD from colorectal cancer (p < 0.01 for both). CONCLUSION: The results have shown that each hepatic pathology studied exhibited specific profile of the analysed set of biomarkers. Therefore, the simultaneous determination of the 3 mentioned biomarkers may help in differential diagnosis of liver diseases.

Carcinoembryonic antigen and related molecules in normal and transformed trophoblast.

Carcinoembryonic antigen (CEA, CD66e) and CEA-related cell adhesion molecules (CEACAMs) are important mediators in remodeling of diverse human tissues, and modulators of cell proliferation and differentiation. Expression by normal and transformed trophoblast of gestational trophoblastic diseases (GTDs), isolated cytotrophoblast and choriocarcinoma cell lines is presented here. Immunocyto/histochemistry of normal placenta (n=9), invasive mole (n=8), choriocarcinoma (n=7), a placental site trophoblastic tumor, cytotrophoblast in primary culture and JAr and JEG-3 cells was performed using polyclonal anti-CEA and specific monoclonal anti-CEA antibodies. Data were analyzed and scored using Mann-Whitney Test. CEA and CEA-related molecules were identified by Western blot and immunoaffinity chromatography in JAr and JEG-3 cells and extracts of 1st and 3rd trimester of pregnancy tissue and cytotrophoblast cell lysates. CEA is expressed throughout pregnancy, in first trimester predominantly in syncytiotrophoblast, but also in villous cytotrophoblast and extravillous trophoblast. Data presented here demonstrate that CEA is significantly increased in transformed trophoblast of GTDs (p<0.05). Both cytotrophoblast in primary culture and choriocarcinoma cell lines express CEA, with staining of granular deposits in JAr and cell membrane in JEG-3. The results suggest that CEA (CD66e) and other CEA-related protein(s) could be involved in trophoblast differentiation.

Glycobiochemical characterization of salivary carcinoembryonic antigen.

PURPOSE: Carcinoembryonic antigen (CEA) is a highly glycosylated molecule, expressed in both normal and pathological conditions. This study was aimed at isolation and glycobiochemical characterization of human salivary CEA, and comparison of its structural properties with those of cancer-derived CEA. MATERIALS AND METHODS: CEA was isolated by immunoaffinity chromatography on an anti-CEA IgG-Sepharose 4B column. The isolated antigen was characterized by SDSPAGE, gel filtration on Sepharose 4B and lectin-affinity chromatography using a panel of 6 plant lectins. RESULTS: The isolated salivary CEA had a molecular mass of 180 kD and retained its structural and antigenic properties. Lectin-affinity chromatography indicated pronounced microheterogeneity of both salivary and cancer-derived CEA. Comparison of the lectin-binding patterns demonstrated lower relative amounts of distinct Phaseolus vulgaris agglutinin-reactive and Pisum sativum agglutinin-reactive glycoforms in salivary CEA than in cancer-derived CEA. CONCLUSION: The observed microheterogeneity of salivary CEA could have both functional and clinical relevance in relation to normal as well as to pathological oral physiology.

Low incidence of cardiac abnormalities in treated trichinosis: a prospective study of 62 patients from a single-source outbreak.

PURPOSE: The reported incidence of cardiac involvement in trichinosis is highly variable, ranging from 21% to 75%. This study sought to determine the incidence and type of cardiac lesions in trichinosis using serial echocardiographic examinations. SUBJECTS AND METHODS: Sixty-two consecutive patients admitted to the Banja Luka Medical Center during an outbreak of trichinosis (November to December 1996) were included in the study. Diagnosis was made by typical clinical presentation, positive epidemiologic history, serologic testing, and the detection of Trichinella larvae in contaminated meat. All patients underwent serial electrocardiograms and two-dimensional and Doppler echocardiographic examinations within 20 days after the onset of symptoms. Repeated echocardiographic examinations were performed weekly during the hospital stay in all patients with electrocardiographic abnormalities or an abnormal initial echocardiogram. RESULTS: Cardiac involvement (electrocardiographic and/or echocardiographic changes) was detected in 8 (13%) of the 62 patients. Nonspecific transient electrocardiographic ST-T changes were found in 6 patients (10%); 1 patient had frequent premature ventricular complexes. Echocardiographic examinations revealed pericardial effusions in 6 patients (10%), 5 of whom had minimal effusions without impairment of global and regional left ventricular systolic function. One patient had hypokinesis of the interventricular septum with a small pericardial effusion, both of which resolved within 2 weeks. Only 2 of the patients with electrocardiographic abnormalities lacked echocardiographic evidence of cardiac involvement. At 6-month follow-up, none of the patients had electrocardiographic or echocardiographic abnormalities. CONCLUSIONS: The incidence of cardiac involvement in trichinosis appears to be lower than previously reported. Pericardial effusion is the most common manifestation of cardiac involvement, and nonspecific transient electrocardiographic changes, traditionally ascribed to myocarditis, more frequently reflect pericarditis.

Acute pellucid marginal corneal degeneration.

Pellucid marginal corneal degeneration is a bilateral disease characterized by a narrow band of corneal thinning localized 1-2 mm from the inferior limbus. The disease is diagnosed usually between 20 and 50 years of life, and its etiology remains obscure. During the clinical course and evolution of pellucid marginal corneal degeneration, acute hydrops with corneal edema in the lower half may develop (acute pellucid marginal corneal degeneration). However, since cases of acute pellucid marginal corneal degeneration are not frequently encountered in clinical practice, each new patient is evaluated and managed with the utmost care to contribute to our better understanding of this disease. This is a report of two cases of acute pellucid marginal corneal degeneration that had a relatively favorable functional outcome when treated medically, so that corneal grafting was not necessary.

ASA score as prognostic criterion for incidence of postoperative complications after transhiatal esophagectomy.

The aim of this study is to point out the importance of the American Society of Anesthesiologists risk score (ASA score) as a very cheap and simple prognostic criterion for the incidence and severity of postoperative complications of transhiatal esophagectomy (THE). During the past ten years, twenty-nine patients were operated for cancer of the esophagus using the THE method at the University Hospital Center "Rijeka". Patients' preoperative physical status was estimated using the 19 parameters of ASA score and they were classified into ASA risk groups. The incidence and severity of the two most common and potentially fatal postoperative complications of THE--aspiration pneumonia and anastomotic leak--were compared with the patients ASA score as well as with the duration of postoperative hospital stay and operative mortality. Postoperative complications after THE, even with lethal outcome occurred only in patients with high ASA score (ASA risk group IV and V). Our conclusion is that ASA score has proven to be a reliable and useful prognostic criterion for the development of postoperative complications after THE and for the incidence of operative mortality.

Expression of galectin-3 and carcinoembryonic antigen in the trophoblast of the gestational trophoblastic disease.

PURPOSE: Galectin-3, an endogenous beta-galactoside- binding protein, has been implicated in the regulation of many physiological and pathological cellular processes through specific interactions with complementary ligands. The level of galectin-3 expression has been correlated with metastatic potential in many tumor types. The present study was designed to investigate possible correlation of the expression of galectin-3 with carcinoembryonic antigen (CEA), one of the putative galectin-3 ligands, in the transformed trophoblast of the gestational trophoblastic diseases (GTDs) compared to the invasive trophoblast (interstitial and endovascular) of the normal first trimester of pregnancy placenta. MATERIALS AND METHODS: Double immunohistochemistry was used to examine paraffin sections of 9 specimens of normal placenta, 8 cases of invasive mole and 7 cases of choriocarcinoma. Immunoreactivity was scored semiquantitatively to include both the percent of trophoblast cells stained as well as the intensity of staining. RESULTS: Data presented here demonstrate similar patterns of expression for galectin-3 and CEA in transformed GTDs trophoblastic cells, as well as in normal invasive trophoblast. Upregulation of galectin-3 in transformed GTDs trophoblast was followed by high levels of CEA expression in the same tissue specimen (significant differences at < 0.05, Mann-Whitney Rank Sum Test). CONCLUSION: These results may point to the CEA as one of the ligands for galectin-3 in transformed trophoblast, which merits further investigation.

Manual ability and manual dexterity in children with cerebral palsy.

INTRODUCTION: Manual ability and performance of dexterity tasks require both gross and fine hand motions and coordination. The aim of this study was to determine the level of manual dexterity (capacity) and investigate its relationship with manual ability (performance) in children with cerebral palsy. METHOD: This study was designed as a cross-sectional study of 30 children with cerebral palsy (aged 8-15 years). In order to assess gross manual dexterity the Box and Block Test was used. Manual ability was assessed according to Manual Ability Classification System (MACS). RESULTS: A relationship between the level of manual ability impairment and performance on manual dexterity tasks was expressed. Participants at MACS level IV demonstrated slowest times and transferred the smallest number of blocks (p<0.01). This study also found that correlation between Gross Motor Function Classification Scale (GMFCS) and MACS is statistically significant (p<0.001). All hand skills were more impaired in the non-dominant hand compared to the dominant hand but there were no statistically significant difference (p=0.06). CONCLUSION: The results suggest that gross manual dexterity is a good predictor of manual abilities in children with cerebral palsy. These results provide better understanding of the relationship between manual dexterity and activity limitations and lend credibility to the use of these classification systems and assessments in order to optimize treatment planning and evaluate interventions and progress. Hippokratia 2014; 18 (4): 310-314.

Benefits of physical exercises in developing certain fitness levels in children with hyperactivity.

The objectives of this study were to assess the effects of participating in regular physical activity on the fitness of children with hyperactivity. The study compared a sample of children who were assessed as hyperactive with the same number of children rated as non-hyperactive. The Conners' Rating Scale was used for hyperactivity evaluation, while fitness levels were assessed using a battery of six motor tests prior to and following the completion of the physical exercise programme. The findings indicated that while overall fitness levels of both groups improved, the differences were not statistically significant. However, improvements shown within the group of hyperactive children with regard to coordination of the whole body, trunk strength and agility were statistically significant. Physical activity may be associated with enhanced levels of some aspects of physical fitness.

The proposed mechanism of action during different pain management techniques on expression of cytolytic molecule perforin in patients after colorectal cancer surgery.

The postoperative period is accompanied with neuroendocrine, metabolic and immune alteration which is caused by tissue damage, anesthesia, postoperative pain and psychological stress. Postoperative pain contributes to dysfunction of immune response as a result of interaction between central nervous and immune system. The postoperatively activated hypotalamo-pituitary-adrenocortical axis, sympathic and parasympathic nerve systems are important modulators of immune response. According to bidirectional communication of immune and nervous system, appropriate postoperative pain management could affect immune response in postoperative period. Although the postoperative suppression of immune response has been reported, a very little are known about the influences of different pain management techniques on cytotoxic function of immune cells in patients with colorectal cancer in early postoperative period. Perforin is a cytotoxic molecule expressed by activated lymphocytes which has a crucial role in elimination of tumor cells and virus-infected cells, mostly during the effector's phase of immune response. Immune compromise during the postoperative period could affect the healing processes, incidence of postoperative infections and rate and size of tumor metastases disseminated during operation. The pharmacological management of postoperative pain in patients with malignancies uses very different analgesic techniques whose possible influence on cytotoxic functions of immune cells are still understood poor. For decades the most common way of treating postoperative pain after colorectal cancer surgery was intravenous analgesia with opiods. In the last decade many investigations pointed out that opiods can also contribute to postoperative suppression of immune response. Epidural analgesia is a regional anesthesia technique that acts directly on the origin of pain impulses and pain relief can be achieved with small doses of opiods combined with local anesthetics. Local anesthetics potentate analgesic properties of opiods but per se are also acting as antiinflammatory drugs. Afferent neural blockade by epidural analgesia attenuates neuroendocrine stress response. We propose that epidural analgesia could be more convenient that intravenous analgesia in maintenance of immunological homeostasis that is altered by surgical stress, tumor growth and pain.

Human carcinoma-associated and salivary mucins detected by anti-bovine submaxillary mucin antibodies.

Polyclonal rabbit anti-bovine submaxillary mucin antibodies, anti-BSM IgG, were analyzed by autoradiography and densitometry (after SDS electrophoresis and blotting), ELISA, and IRMA assays for reactivity against native antigen BSM, deglycosylated and desialylated BSM, and human salivary and carcinoma-associated mucins. Known human tumor marker CA19-9 antigen reacted with rabbit anti-BSM IgG under different conditions, either soluble or immobilized. As soluble antigen, in IRMA it reacted with anti-BSM antibodies used both as a catcher and a tracer, as well as in combination with monoclonal anti-CA19-9 antibodies as a catcher. MUC1 mucin is a carrier of this carbohydrate antigen, CA19-9, or sialyl-Lewis(a), as well as of CA15-3 antigen, a known breast tumor marker. Autoradiography and densitometry demonstrated binding of anti-BSM IgG to intact MUC1 in a sample of commercial standard preparation of CA19-9 antigen. The same method and analysis demonstrated binding of anti-BSM IgG to MUC1 and to smaller antigens of 85-120 kD in samples containing CA15-3 antigen: commercial standard preparation, human breast tissue, and human milk. In a sample of whole human saliva, reactions of both isoforms of MUC7 were detected by autoradiography, as bands of 85 and 115 kD, and densitogram analysis also demonstrated reaction with MUC5B. Chemical modifications performed as periodate oxidation and desialylation of the BSM demonstrated carbohydrate (i.e., sialic acid) epitope sensitivity for anti-BSM IgG. The results presented in this work indicate that polyclonal anti-BSM antibodies are specific for sialylated carbohydrate structure on mucins and could serve as a tool for investigation of human carcinoma-associated and salivary mucins.

Azathioprine and cytarabine applied topically prolong corneal graft survival in rabbits.

Azathioprine and cytarabine applied topically as 0.1% solution in the grafted rabbit eye significantly prolong corneal allograft survival time. Mean corneal graft survival time was 61 +/- 27.76 days and 55 +/- 26.79 days in the group treated with azathioprine and cytarabine, respectively, while mean corneal graft survival time in the control group of rabbits with no immunosuppressive therapy was 19 +/- 4.47 days. After completion of the immunosuppressive treatment, the achieved azathioprine effect lasted longer than the cytarabine effect. Favourable azathioprine and cytarabine effects on corneal allograft survival in rabbits were obtained with no serious local and systemic side effects. Only moderate hyperemia of the palpebral and bulbar conjunctiva was recorded during the first days of treatment. No other side effects were observed.

[Terrien's marginal corneal degeneration]. / Terienova marginalna degeneracija roznjace.

Terrien's marginal corneal degeneration is an uncommon disease from the group of peripheral corneal degenerations. Although this corneal degeneration, as a special entity in ophtalmological practice, has been known for more than 90 years, its clinical essence, and especially aetiopathogenesis and methods of surgical treatment, still intrigue ophthalmologists and ophthalmic surgeons. The uncommon and interesting corneal degeneration is studied in great detail according to referential literature and experience of the author in the light of the latest discoveries and achievements. Special attention was paid to the facts suggesting immunological nature of the disease and soma new information related to clinical course and evolution of the disease. All procedures and methods of conservative and surgical treatment of this type of corneal degeneration are described in the paper.

[Successful treatment of people with severe body injuries caused rabid animal bites]. / Uspjesno tretiranje lica sa tezim ozljedama tijela nakon ugriza bijesnih zivotinja.

Seven patients were presented with severe injuries seeking medical help 3-10 days after being bitten by rabid animals. Just one of those subjects underwent timely and correct surgical management. Three patients were with complete, and four with incomplete antirabic prophylaxis. Two patients did not receive human rabies immunoglobulin, and another two did not receive HDC-RV vaccine. At least 3 patients were expected to develop rabies, but it did not happen. The course of these cases could be explained by the existence of less pathogenic strains of virus in Banja Luka region.

[Ophthalmologic manifestations in patients with ichthyosis]. / Oftalmoloske pojave kod obolelih od ihtioze.

Different manifestations on some ocular and adnexal structures may accompany ichthyosis. Some ophthalmological manifestations in the clinical course of ichthyosis may endanger the eye and even lead to the sight loss. The paper reports a case of a patient with congenital ichthyosiform erythrodermia and ophthalmological manifestations on the lids and cornea. In addition to ichthyosis of the lid skin, squamous blepharitis and cicatricial ectropium of the lower lids were also present, while signs of exposure keratitis on the right eye and corneal leucostaphyloma on the left eye were also noted. Presence of lagophthalmos and permanent exposure of both eyeballs led to deterioration of the condition which may result in the sight loss on the right eye, as well. Therefore, contracture release of both lower lids was performed followed by full-thickness skin graft. Surgical procedure and the postoperative course were uneventful. The operation successfully corrected position of the lower lids and enabled formation and reestablishment of the precorneal tears film which led to improvement of the condition of the cornea. The effect has been maintained for six postoperative years now.

Cyanoacrylate glue in the treatment of corneal ulcerations.

The application of tissue adhesives to treat different corneal diseases has been used extensively in recent years. Owing to the widespread application, it has been possible to establish the advantages and disadvantages of this method of treatment. Keeping in mind the disadvantages (primarily the toxicity of cyanoacrylate glue for the corneal endothelium and lens when it comes into direct contact with these structures), the application of cyanoacrylate glue was restricted to the treatment of progressive corneal ulcerations where the risk of corneal perforation was recognized. This method of treatment was applied in 30 patients with corneal melting in dry eye associated with rheumatoid arthritis (12), trophic postherpetic ulcerations of the cornea (9), chemical corneal burns (7), neurotrophic corneal ulceration (1) and Mooren's ulcer (1). The defect healed and anterior corneal surface epithelization occurred in 73.33% of patients in contrast to the additional treatment, most commonly penetrating keratoplasty, required in the remaining patients (26.67%).

Surgical treatment of sympathetic ophthalmia.

We report the case of a 12-year-old girl who was hospitalized for bilateral uveitis that occurred 2 years after a penetrating injury of the left eye. On admission, all clinical signs of sympathetic ophthalmia were present with visual function reduced to light perception and intact projection in the right eye and light perception without intact projection in the left. Ultrasonography confirmed that the retina was in its proper place in both eyes. Since abrasion of the corneal epithelium and decalcification of the cornea with ethylene diamine tetra-acetic acid had been performed on the right eye, it was decided to proceed with pars-plana lensectomy and vitrectomy in the same (better preserved) eye. The surgery was performed as planned, with an uneventful postoperative course. Three years later, the eye operated upon had no signs of inflammation, and the visual acuity achieved with the aphakic correction was 0.8.

Increase of corneal graft survival by use of topically immunosuppressive agents in rabbits.

Corneal graft survival in rabbits was significantly prolonged by topical treatment of the recipient eye with cyclophosphamide (0.1% in sterile isotonic NaCl) and methotrexate (0.1% in arachis oil) applied four times daily for 4 weeks. A control group of animals was treated with dexamethasone in the same way. The mean graft survival time was 52 +/- 18.5 days in the group treated with dexamethasone and 80 +/- 18.2 and 73 +/- 23.5, respectively, in the groups treated with cyclophosphamide and methotrexate. Cyclophosphamide and methotrexate applied topically produced no systemic side effects, and only one mild and transient local side effect in the form of hyperemia of the bulbar and palpebral conjunctiva. These two immunosuppressive drugs were more effective than the corticosteroid currently in clinical use, i.e., dexamethasone.

Effects of prostaglandin E2 and cholinergic drugs on intraocular pressure.

Effects of prostaglandin E2 (PGE2) and cholinergic drugs on intraocular pressure (IOP) have been studied in the rabbit. PGE2 injected intracamerally in a dose of 5 micrograms produced a long-lasting increase in IOP. Topical pretreatment with carbachol, physostigmine and pilocarpine abolished the rise of IOP after the intracameral injection of PGE2. When the IOP had already been increased by PGE2 topical application of pilocarpine and physostigmine did not change it. Carbachol even potentiated the pressor effect of PGE2. Topical application of cholinergic drugs only slightly increased protein content of the aqueous humor. Intracameral injection of PGE2 significantly increased protein content of the aqueous humor, and subsequent application of carbachol produced further elevation of protein content. On the other hand, when PGE2 was injected after topical application of cholinergic drugs, protein content was the same as after PGE2 alone. The relationship between PGE2 and cholinergic drugs regarding the IOP was thus demonstrated.