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The role of the acute octreotide suppression test in detecting patients with neuroendocrine neoplasms
Get PDFBackground: Serum chromogranin A (CgA) is routinely used as a biomarker in patients with neuroendocrine neoplasms (NENs). Several conditions and comorbidities may be associated with falsely elevated CgA, often leading to extensive diagnostic evaluation, which may be costly and harmful. The aim of this study was to analyze the effectiveness of the acute octreotide suppression test (AOST) in differentiating falsely elevated serum CgA.
----- Methods: Our prospective study enrolled 45 patients from two different patient cohorts: (1) 29 patients with suspicion or presence of NENs (extensive workup and subsequent biopsy confirmed 16 NENs); (2) 16 consecutive patients admitted via the Emergency Department without NENs (non-NENs). AOST was performed after an overnight fast. Baseline CgA was measured, after which 0.25 mg of octreotide was administered subcutaneously. CgA was measured 3 and 6 h after administration.
----- Results: Baseline CgA levels were similar in NENs and non-NENs. At the end of the AOST, CgA decreased by a median of 83.3% (41.0-127.4) in non-NENs and 13.8% (0.0-43.6) in NENs (p < 0.001). In patients with increased baseline CgA, a decrease in CgA at the 6th hour of < 51.3% had 90.0% sensitivity and 88.9% specificity in detecting NENs. In patients with normal baseline serum CgA, a decrease in CgA at the 3rd hour of < 17.6% had 83.3% sensitivity and 81.8% specificity in detecting patients with NENs. The diagnostic accuracy of the AOST in the entire study population was 86.7%.
----- Conclusions: AOST is a promising tool to increase the diagnostic accuracy of serum CgA
The role of vitamin D in inflammatory bowel disease – assessing therapeutic and poreventive potential of supplementation and food fortification
Get PDFInflammatory bowel diseases are a group of chronic inflammatory conditions that affect gastrointestinal tract due to inapt and continuous immune activation in response to a myriad of predisposing factors (most notably genetics, environmental impact and gut microbiota composition). It has been shown that vitamin D status can also play a role in the disease pathogenesis, as its deficiency is commonly observed in two major forms of inflammatory bowel diseases - Crohn's disease and ulcerative colitis. Mounting evidence supports the concept of intricate relationship between gut dysbiosis and vitamin D metabolism, while suboptimal levels of this vitamin have been linked to increased clinical disease relapse rates, inadequate response to drugs, as well as decreased quality of life in patients with Crohn's disease and ulcerative colitis. Consequently, the pertinent question is whether increased vitamin D supplementation and (on a population level) food fortification may bring significant benefit to the affected individuals. In this short review we discuss the synthesis, functions, status and food sources of vitamin D, appraise biotechnological facets of vitamin D status analysis and food fortification, and concentrate on novel developments in the field that describe its influence on intestinal microbiota and inflammatory bowel disease
Opravdanost primjene heparina male molekulske mase u trudnica s nasljednom trombofilijom kao uzrokom opetovanih zadržanih pobačaja [Adequacy of low-molecural-weight heparin prophylaxis in pregnant women with hereditary trombophilia as a cause of recurrent pregnancy loss]
Get PDFINTRODUCTION: Approximately 1% of women trying to conceive experience recurrent
miscarriage. In 50% of the cases, the etiology of preceding miscarriages remains unknown.
For this reason, the appropriate treatment and medical approach to these women are very
challenging. Over the last 20 years, many studies have been analyzing the association
between inherited thrombophilia and recurrent miscarriages. The main goals of this research
were to investigate the perinatal outcome in hereditary thrombophilic patients with recurrent
missed abortions after treatment with low molecular weight heparin. Nevertheless, this study
evaluates the perinatal outcome in asymptomatic mutation carriers without LMWH
prophylaxis.
MATERIALS AND METHODS: The prospective study was conducted at the Department of
Gynaecology and Obstetrics, University Hospital Centre Zagreb, from 2011 to January 2018.
The research covered three groups of women: the first group (LMWH+) included 133
pregnant women with the history of two or more early recurrent pregnancy loss and
hereditary trombophilia who were treated with a prophylactic dose of LMWH, the second
group (LMWH-) enrolled 35 women with habitual abortions and hereditary thrombophilia who
were not treated with a prophylactic dose of LMWH and, finally, the third (control) group
covered 55 healthy pregnant women (with a negative personal venous thromboembolism
and obstetric uteroplacental vascular insufficiency history) with hereditary thrombophilia who
were not treated with a prophylactic dose of LMWH. The definition of inherited thrombophilia
included the FVL, prothrombin G20210A mutation, antithrombin deficiency, protein C and
protein S deficiency, MTHFR mutation and PAI-1 mutation.
RESULTS: Pregnant women with inherited thrombophilia and habitual abortions who were
treated with prophylactic doses of LMWH heparin showed a statistically significant reduction
in miscarriages compared to women with inherited thrombophilia and two or more previous
early pregnancy loss who were not administered the prophylactic dose of LMWH (P= 0,001).
For a good perinatal outcome, it seems that application of LMWH is not necessary in the
group of asymptomatic carriers of mutations with hereditary thrombophilia and negative
personal and obstetric history.
CONCLUSION: LMWH has a role in preventing further pregnancy losses in patients with
hereditary thrombophilias and recurrent miscarriages. Nevertheless, the current findings show that LMWH is not required for a good perinatal outcome in asymptomatic carriers of a
thrombophilic defect
Prognostičko značenje izraženosti proteina NEDD9 u transbronhalnim bioptatima u bolesnika s karcinomom pluća [Prognostic significance of NEDD9 in small biopsies of lung cancer]
Get PDFLung cancer is the major cause of cancer mortality worldwide and includes several histologic subtypes evolving from numerous genetic and epigenetic changes emerging in alveolar, bronciolar and bronchial epithelium. Precise histologic diagnosis is the cornerstone of the individualised treatment of lung cancer.
Here we have demonstrated significantly higher accuracy and reproducibility of the diagnosis using immunohistochemistry in transbronchial biopsies of lung adenocarcinoma (p=0,005). Also, only 5.41% of all samples was finally diagnosed as NSCC NOS. Positivity for napsin A was seen in 45.33% of all adenocarcinoma samples along with consistant coexpression of TTF-1 in 90% of cases (p=0,289). As for CK7, homogenous immunoreactivity showed in 91.89% of all adenocarcinomas, and therefore staining for napsin A wasn't proven superior to neither CK 7 nor TTF-1 in adenocarcinoma immunotyping. Nevertheless, napsin A was negative in 95% of squamous cell carcinoma samples and consequently may be useful as an additional marker of glandular differentiation in less clear immunoprofiles (p<0,001).
Regulatory protein NEDD9 is involved in control of migration chemotaxis, apoptosis, cell cycle and cellular differentiation, playing the role of the hub-protein in the complex process of epithelial-mesenchimal transition. NEDD9 has recently been identified as integral part of aquisition of metastatic potential in mammary adenocarcinoma, glioblastoma and metastatic melanoma. We have demostrated both nuclear and cytoplasmatic expression of NEDD9 in transbronchial biopsies of lung adenocarcinoma, squamous carcinoma and also small cell carcinoma indicating the activation of the epithelial-mesenchimal transition in different lung cancer subtypes. Cytoplasmatic expression of NEDD9 was higher in comparison to nuclear in all carcinoma subtypes (p<0.001). The direct relationship between the expression of NEDD9 and survival wasn't established
Povezanost sastava gangliozida i izražaja neuroplastina s neurodegenerativnim promjenama [Association of ganglioside composition and neuroplastin expression with neurodegenerative changes]
Get PDFNeuroplastin is a highly glycosylated transmembrane protein whose membrane positioning is dependent on membrane ganglioside composition. In this thesis, we investigated changes of neuroplastin expression in neurodegeneration.
In human hippocampal tissue affected by sporadic Alzheimer's disease (AD), we show that neuroplastin immunoreactivity pattern is similar to control pattern, namely in cell bodies and dendrites of glutamatergic neurons of the trisynaptic pathway. Neuroplastin immunoreactivity is highly increased in AD, particularly in the dentate gyrus and subiculum in early stages of the disease.
In a transgenic mouse model of familial AD, neuroplastin and plasma membrane calcium ATP-ase expression are decreased in cortex and hippocampus when compared to wild-type mice. This finding may be attributed to changed molecular mechanisms of learning and memory disorder. Neuroplastin expression and its positioning within membrane domains is highly dependent on ganglioside composition and thus directly affected when membrane ganglioside composition is altered, as shown by analysis of isolated membrane fractions derived from brain tissue of different mice models with aberrant ganglioside synthesis. In vitro studies showed that GM1, a complex a-series ganglioside, predominantly co-localizes with neuroplastin and is probably responsible for its positioning within lipid rafts.
Based on joined data of already described alterations of membrane domains in neurodegeneration and here presented association of expression and membrane positioning of neuroplastin with ganglioside composition, we conclude that neuropathological cascade in Alzheimer’s disease affects cell-adhesion molecule neuroplastin. Changed neuroplastin expression leads to altered cell calcium signaling and inability to maintain learning and memory molecular mechanisms
Učinci pentadekapeptida BPC 157, L-NAME i L-arginina na serijski prijelom rebara u štakora
Get PDFIntroduction: Rib fractures, in particular serial fractures (3 or more fractured ribs ipsilateral)
have serious consequences on the human body and quality of life and represent an important
medical and socioeconomic problem.
Aim: To determine the effects of pentadecapeptide BPC 157, L-arginin and L-NAME on
healing of serial rib fracture in rats.
Materials and methods: After intraperitoneal anesthesia, in male Winstar albino rats was
performed the vertical transection of 8-10 ribs of right hemithorax at the lateral edge of the
paravertebral muscles. The pentadecapeptide BPC 157 was administered intraperitoneal or
orally.It was applied intraperitoneal (doses of 10 μg/kg and 10 ng/kg) immediately following
a surgical procedure and then once daily and the last application 24 h before sacrifice. Orally
(0.16 μg/ml and 0.16 ng/ml, a total of 12 ml/day) was applied in drinking water, from waking
up to the animal sacrifice. In order to test the interaction with the NO system, L-NAME (5
mg/kg/day i.p.) and/or L-arginin (100 mg/kg/day i.p.) were administered alone or with BPC
157 to specific animal groups. The control groups were treated with 0.9% NaCl i.p. or with
pure drinking water p.o. The daily clinical status of the animal (respiration frequency, chest
movement) was observed, and on 20th day, during the first sacrifice interval, aortic blood was
taken to analyze the acid-base status and the calcium and phosphate serum levels. At the same
time, the local finding was verified in the sense of the formation of endothoracic fascia and
scar, and then the right hemitorax was taken for further radiographic and histological analysis.
After 60 days, the animals were sacrificed for biomechanical testing.
Results: Animals treated with BPC 157 did not show pathological alterations in acid-base
status. Calcium and phosphate serum levels were normal in all animal groups. BPC 157 alone
or in combination with L-arginin and/or L-NAME leads to earlier healing of the rib fracture
and increased creations of callus without scarring and adhesions at the place of fracture, as
confirmed by radiographic and histological analysis. Biomechanical testing has shown that
bone tissue of animals treated with BPC 157 on the site of fractures is stronger.
Conclusion: The pentadecapeptide BPC 157 leads to earlier healing of fractured ribs and
formation of stronger bones at the site of the fractures, and this is the effect of interacting with
the NO system. The positive effect of pentadecapeptida BPC 157 is achieved regardless of the
way of administration (oral or intraperitoneal) and the administered dose (10 μg or 10 ng)
Korelacija histoloških i imunohistoloških svojstava T-staničnoga limfoma kože (Mycosis fungoides) s kliničkom slikom, stadijem i ishodom bolesti u desetogodišnjem razdoblju [Correlation of histological and immunohistochemical properties of T-cell skin lymphoma (mycosis fungoides) with the clinical picture, stage and patient outcome in ten-year period]
Get PDFThe aim of this study was to identify predictors of disease progression and death in patients with early stage mycosis fungoides (MF). Eighty-three patients diagnosed with early-stage MF at the Departments of Dermatovenerology and Pathology, UHC Zagreb between 01/2003 and 12/2012 were included in this retrospective-prospective study. Following parameters were analyzed: clinical picture, response to therapy, disease progression, lichenoid dermal lymphocyte infiltrate, „guardian“ lymphocytes, atypical lymphocytes and loss of surface CD2, CD3, CD5 and/or CD7 markers on T lymphocytes.
Patients with initial stage IIA had inferior overall and progression-free survival than those with initial stage IB and IA. Patients with plaques also had inferior survivial than those with patches. Worse overall and progression-free survival was noted in patients with a premycotic stage lasting 48 months or less in comparison to those lasting more than 48 months. The same was seen in patients with more than 30 „guardian“ lymphocytes/100 keratinocytes (compared to those with 30 and less). Patients with more than 50% atypical lymphocytes had a faster progression rate than those with 50% or fewer atypical lymphocytes. Patients with loss of CD7 have faster progression than those without it. Initial disease stage IIA, presence of plaques in the initial clinical presentation, skin lesion encompassing >10% of total body surface, enlarged lymph nodes, disease progression, disease without response to therapy, dense lichenoid dermal infiltrate of lymphocytes and >30 „guardian“ lymphocytes/100 keratinocytes increase the risk for mortality within five years of diagnosis. Response to therapy statistically significantly affects the progression of the disease in the first five years after the diagnosis. Disease unresponsive to therapy increases the risk of progression within five years of diagnosis, while a complete response reduces this risk.
This study identified potential new prognostic factors for early stage MF. Larger studies are needed to confirm these results that could improve our ability to identify patients with increased risk of disease progression and poor prognosis
Usporedba djelovanja trajne infuzije i pojedinačnih doza rokuronija u anesteziji za lumbalnu diskektomiju na mišićnu snagu i kvalitetu oporavka bolesnika [Comparison of the effect of continuous infusion and bolus doses of rocuronium during anesthesia for lumbal discectomy on muscle strength and quality of patient recovery]
Get PDFRocuronium is a non-depolarising neuromuscular blocking agent that can be administered in bolus doses or via continuous infusion during general anesthesia. Due to the specificity of the knee-chest position in a lumbar discectomy, many complications during anesthesia and surgery are possible. Therefore an effective and balanced intraoperative neuromuscular block is needed.
Studies so far have not included a comparison on muscle strength and quality of patient recovery of the effect of continuous infusion and bolus doses of rocuronium during anesthesia for lumbar discectomy.
The hypothesis of this research was that the continuous infusion of rocuronium during general anesthesia for a lumbar discectomy enables better muscle strength recovery, and a better quality of patient recovery as measured by questionnaire.
The aim was to compare the influence of the continuous infusion and bolus doses of rocuronium on patient recovery. Therefore we assessed how continuous infusion and bolus doses of rocuronium affect the recovery of muscle strength as measured by a hand-grip dynamometer. The quality of patient recovery was assessed by standardised questionnaire (Qor-40 - Quality of recovery questionnaire).
The aim was also to evaluate the applicability of the Croatian version of Qor-40 questionnaire in clinical practice.
The research involved 80 patients with ASA classifications I and II, between 18 and 65 years of age, for whom a lumbar discectomy was planned. They were randomly divided into two groups of 40 patients. In both groups, the general anesthesia was maintained with propofol and remifentanil, with standard anesthetic monitoring, BIS and TOF. In the control group, rocuronium was administered in separate bolus doses with the TOF ratio of 5%, while in the experimental group rocuronium was administered via continuous infusion so that theTOF ratio was 5%.
Hand-grip muscle strength was measured with a dynamometer on three occasions: before general anesthesia, in the early post-anesthesia period in the operating room, and 24 hours after anesthesia.
The quality of patient recovery was assessed with a Qor-40 questionnaire before anesthesia, 24 hours after anesthesia, and 30 days after anesthesia and surgery.
The results show there is no statistically significant difference between groups in hand-grip muscle strength as measured with a dynamometer in the early postoperative period, or in the period 24 hours after anesthesia and surgery.
As far as the quality of patient recovery as measured by Qor-40 questionnaire is concerned, the results show a statistically significant difference between groups in terms of physical independence. The group where rocuronium was administered via continuous infusion displayed better physical independence both in period 24 hours after anesthesia and surgery and in the 30 days after. With regard to the other four parameters (pain, patient support, emotional state and physical comfort) there were no differences between the groups.
The Croatian version of the Qor-40 questionnaire is a valid instrument for measuring the quality of recovery after surgery and anaesthesia.
Further research, conducted on a larger sample and with the longer follow-up interval, could additionally explain the influence of the continuous infusion of rocuronium on patient recovery after a lubar discectomy
Stupanj metilacije gena ASC/TMS1 i MyD88 u uzorcima zdravog tkiva i tkiva karcinoma pločastih stanica grkljana
Get PDFLaryngeal Cancer is the most frequent Head and Neck Cancer comprising high mortality rate.
Almost 90% of all Laryngeal Cancers develop due to genetical and epigenetical changes caused by lifestyle and environmental factors. More than 95% of all laryngeal cancers are Squamous Cell Carcinoma. To date there are no established biomarkers to facilatate the diagnosis, prognosis and treatment of patients suffering from this malignant disease. Recent studies showed that inadequate control of inflammation and presence of infection are tightly related with developing and promotion of the cancer. Innate immue system has a very important role in the control of inflammation. Innate immunity defense mechanisms activate pattern recognition receptors (PRRs) and adaptor molecules play the key role in all signalling pathways. In this study, we hypothesized that the changes in the methylation status of promotor regions of ASC/TMS1 and MyD88 genes, responsible for activation and regulation of inflammation, in healthy and laryngeal cancer tissue might be related with development and progression of cancer. The aim of this study is to investigate is there a difference in the methylation status of this genes in healthy and tumor tissue and does it correlate with protein expression. In recent literature the methylation status of this genes has still not been analyzed in Laryngeal Cancer and the pyrosequencing method in methylation status determination as performed in this study has not been used in other cancers. Results of this study show that the overall methylation level of the promotor region of MyD88 gene is statistically significantly higher in healthy laryngeal tissue in relation to cancer tissue and this finding correlate with protein expression level. The overall methylation level of promotor region of ASC/TMS1 gene is unchanged in Laryngeal Cancer and healthy laryngeal tissue. The protein expression level of ASC/TMS1 is statistically significantly higher in cancer in relation to healthy laryngeal tissue. Taking into account there is no difference in the overall methylation level of the promotor region of ASC/TMS1 gene in healthy and tumor tissue we assume that the observed difference in ASC/TMS1 protein expression (higher expression in tumor tissue) is the outcome of other posttranscriptional regulation mechanisms.
We consider that the results of this study in the future may lead to earlier detection, treatment and follow-up of Laryngeal Squamous Cell Carcinoma and reveal new scientific discoveries of the role of ASC/TMS1 and MyD88 genes
Artroskopija prvoga metatarzofalangealnog zgloba [Arthroscopy of the first metatarsophalangeal joint]
Get PDFArthroscopy of the first metatarsophalangeal joint (MTP-1) has become indispensable method of surgical care to injuries and their consequences and damages that affect the MTP-1 joint. The advantages of arthroscopy of the 1st MTP joint in comparison to classical open surgery are multiple. Primarily, arthroscopy allows an excellent view of intra-articular structures and thus a detailed overview of the entire joint which enables us to perform complete surgery without opening the joint. Furthermore, morbidity is significantly smaller, rehabilitation is faster, and return to daily activities is also faster. Basic requirements for successful application of arthroscopy of the MTP-1 joint are careful planning of the procedure, very good knowledge of regional anatomy, strictly following the rules of performing the procedure, and an experienced surgeon with arthroscopy skills. Primary indications for the arthroscopy of the MTP-1 joint include early stages of hallux rigidus, osteochondral lesions, synovitis, and pathological conditions of sesamoid bones. In this article we describe the indications, technique, complications and the prospect of the arthroscopy of the MTP-1 joint, with a detailed overview of contemporary literature data