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Clinical neurophysiology of multiple sclerosis
Get PDFDifferent neurophysiological methods such as evoked potentials (EP), testing of the autonomic nervous system (ANS) or polysomnography have the potential to detect clinically silent lesions or to confirm the existence of an association between a clinical symptom and multiple sclerosis (MS); previously undetected by MRI. Therefore, in the most recent MRI criteria for the diagnosis of MS (MAGNIMS consensus guidelines), neurophysiological confirmation of optic nerve dysfunction (slowed conduction on visual EP), support dissemination in space and, in patients without concurrent visual symptoms, dissemination in time. In this chapter we will review the existing evidence regarding the role of different neurophysiological tests (specifically the role of EPs, autonomic nervous system testing and sleep testing in MS) in the diagnosis and management of MS
Polimorfizam promotorske regije gena inhibitora aktivatora plazminogena-1 u bolesnika s moždanim udarom
Get PDFStroke (MU) is the leading cause of disability in modern society. In developed countries, the MU is in second place among the causes of mortality and in Croatia leading causes of death. Due to changing lifestyles and reducing risk factors, better management of patients with stroke, the incidence of stroke in developed countries declined, and mortality is reduced. Yet the treatment of stroke is far from satisfactory. In the last decade MU is finally recognized as emergency in medicine.
Furthermore, treatment of stroke, primary and secondary prevention and rehabilitation in the specialized departments, have proven to be effective methods. In recent years several recommendations for the treatment of stroke were published. The goal of primary prevention is to reduce the risk of stroke in asymptomatic individuals. Lifestyle and certain diseases have been identified as a risk factor for stroke. The most common risk factors include inadequate diet, alcohol consumption, smoking, reduced physical activity, hypertension, diabetes, elevated cholesterol levels, myocardial infarction, atrial fibrillation and carotid stenosis. Stress, taking high amounts of oral contraceptives, polymorphism 4G/5G as a risk factor for lacunar stroke, while the incidence of 4G/4G mentioned as a protective factor in the elderly. Therefore, the gene polymorphism 4G/5G could be useful in identifying individuals at risk for developing cardiovascular disease, and dosing of patients fibrinolytic agents, like t-PA
Dipeptidyl peptidase-4 activity is associated with urine albumin excretion in type 1 diabetes
No full textAIMS:
The inability of kidneys to prevent urinary protein leakage represents the earliest sign of renal damage in diabetic kidney disease (DKD). Recent data suggest the possible nephroprotective role of the dipeptidyl peptidase-4 (DPP-4) inhibitors. We aimed to investigate whether serum DPP-4 activity is associated with urine albumin excretion (UAE) in patients with type 1 diabetes (type 1 DM). -----
METHODS:
DPP-4 activity and UAE measurement were performed in 113 patients with type 1 DM and glomerular filtration rate (GFR) within normal range. They were divided into three groups according to UAE tertiles. -----
RESULTS:
Worse lipid profile and higher waist circumference were observed in the group with highest DPP-4 activity. Patients within lowest UAE tertile group had lowest DPP-4 activity value (p<0.001) compared to group within second and third tertile of UAE. DPP-4 activity correlated with systolic blood pressure (ρ=0.142; p=0.001), HbA1c (ρ=0.133; p=0.013) and UAE (ρ=0.349; p<0.001). In the linear regression analysis when DPP-4 activity was adjusted for age, gender, disease duration, HbA1c, waist circumference, the use of ACEI and hypolipemic agents the association remained significant; UAE increased for 8.136mg/24h by each increase of DPP-4 activity of 1U/L (p<0.008). -----
CONCLUSION:
Our results indicate that serum DPP-4 activity is associated with albuminuria in type 1 diabetes. This arises the question whether the use of DPP-4 inhibitors might serve as an additional therapeutic strategy to prevent proteinuria in patients with DKD
Diabetic ketosis during hyperglycemic crisis is associated with decreased all-cause mortality in patients with type 2 diabetes mellitus
No full textPatients with type 2 diabetes mellitus have impaired ketogenesis due to high serum insulin and low growth hormone levels. Evidence exists that ketone bodies might improve kidney and cardiac function. In theory, improved ketogenesis in diabetics may have positive effects. We aimed to assess the impact of diabetic ketosis on all-cause mortality in patients with type 2 diabetes mellitus presenting with hyperglycemic crisis. We analyzed 486 patients with diabetic ketosis and 486 age and sex-matched patients with non-ketotic hyperglycemia presenting to the emergency department. Cox proportional hazard models were used to analyze the link between patient characteristics and mortality. During an observation time of 33.4 months, death of any cause occurred in 40.9 % of the non-ketotic hyperglycemia group and 30.2 % of the DK group (hazard ratio in the diabetic ketosis group, 0.63; 95 % confidence interval 0.48-0.82; P = 0.0005). Patients with diabetic ketosis had a lower incidence of symptomatic heart failure and had improved renal function. They used less furosemide and antihypertensive drugs, more metformin and lower insulin doses, all of which was independently associated with decreased mortality. Plasma glucose and glycated hemoglobin levels were similar in both groups. Patients with hyperglycemic crisis and diabetic ketosis have decreased all-cause mortality when compared to those with non-ketotic hyperglycemia. diabetic ketosis might be a compensatory mechanism rather than a complication in patients with hyperglycemic crises, but further prospective studies are warranted
Smjernice za dijagnostiku i liječenje gnojnog hidradenitisa (hidradenitis suppurativa) [Guidelines for the diagnostics and treatment of hidradenitis suppurativa]
Get PDFCroatian dermatovenerologic society and Croatian society for plastic, reconstructive and esthetic surgery of the Croatian Medical Association formed the working group which consists of physicians with experience in diagnostics and treatment of hidradentitis suppurativa. After a critical analysis of relevant scientific papers, the working group has developed practice guidelines for the diagnosis and treatment
Significance of intraoperative findings in revision tympanomastoidectomy
Get PDFPURPOSE:
The study was designed to assess correlations between intraoperative findings in revision tympanomastoidectomy as predictors of cholesteatoma recurrence. -----
MATERIALS AND METHODS:
A retrospective single-institution cohort of 101 patients who underwent surgical treatment for recurrent chronic otitis media in a tertiary referral otology centre. -----
RESULTS:
Out of 101 patients, 65 had canal wall up and 36 canal wall down revision surgery. There were 35 cholesteatoma recurrences. Sites most commonly associated with recurrent disease were residual facial ridge cells in 46 (45.5%), ossicular chain sites in 46 (45.5%) patients, posterior external auditory canal wall erosions in 38 (37.6%) patients and mastoid apex recurrence in 35 (34.7%) patients. Ossicular and posterior external auditory canal wall erosion and incomplete removal of mastoid apex cells correlate well with cholesteatoma recurrence accompanied by canal wall up surgery (p=0.009). Residual mastoid apex cells, posterior external auditory canal wall erosion and presence of residual facial ridge cells were identified as the strongest positive predictors of cholesteatoma recurrence, identifying high risk patients associated with canal wall down procedures (p=0.0036). -----
CONCLUSIONS:
Correlations between intraoperative findings and cholesteatoma recurrence could improve preoperative and intraoperative planning and reduce the rates of postoperative failures1 due to mismanagement of high risk areas
Non-linear actions of physiological agents: Finite disarrangements elicit fitness benefits
Get PDFFinite disarrangements of important (vital) physiological agents and nutrients can induce plethora of beneficial effects, exceeding mere attenuation of the specific stress. Such response to disrupted homeostasis appears to be universally conserved among species. The underlying mechanism of improved fitness and longevity, when physiological agents act outside their normal range is similar to hormesis, a phenomenon whereby toxins elicit beneficial effects at low doses. Due to similarity with such non-linear response to toxins described with J-shaped curve, we have coined a new term "mirror J-shaped curves" for non-linear response to finite disarrangement of physiological agents. Examples from the clinical trials and basic research are provided, along with the unifying mechanisms that tie classical non-linear response to toxins with the non-linear response to physiological agents (glucose, oxygen, osmolarity, thermal energy, calcium, body mass, calorie intake and exercise). Reactive oxygen species and cytosolic calcium seem to be common triggers of signaling pathways that result in these beneficial effects. Awareness of such phenomena and exploring underlying mechanisms can help physicians in their everyday practice. It can also benefit researchers when designing studies and interpreting growing number of scientific data showing non-linear responses to physiological agents
Melphalan modifies the bone microenvironment by enhancing osteoclast formation
Get PDFMelphalan is a cytotoxic chemotherapy used to treat patients with multiple myeloma (MM). Bone resorption by osteoclasts, by remodeling the bone surface, can reactivate dormant MM cells held in the endosteal niche to promote tumor development. Dormant MM cells can be reactivated after melphalan treatment; however, it is unclear whether melphalan treatment increases osteoclast formation to modify the endosteal niche. Melphalan treatment of mice for 14 days decreased bone volume and the endosteal bone surface, and this was associated with increases in osteoclast numbers. Bone marrow cells (BMC) from melphalan-treated mice formed more osteoclasts than BMCs from vehicle-treated mice, suggesting that osteoclast progenitors were increased. Melphalan also increased osteoclast formation in BMCs and RAW264.7 cells in vitro, which was prevented with the cell stress response (CSR) inhibitor KNK437. Melphalan also increased expression of the osteoclast regulator the microphthalmia-associated transcription factor (MITF), but not nuclear factor of activated T cells 1 (NFATc1). Melphalan increased expression of MITF-dependent cell fusion factors, dendritic cell-specific transmembrane protein (Dc-stamp) and osteoclast-stimulatory transmembrane protein (Oc-stamp) and increased cell fusion. Expression of osteoclast stimulator receptor activator of NFκB ligand (RANKL) was unaffected by melphalan treatment. These data suggest that melphalan stimulates osteoclast formation by increasing osteoclast progenitor recruitment and differentiation in a CSR-dependent manner. Melphalan-induced osteoclast formation is associated with bone loss and reduced endosteal bone surface. As well as affecting bone structure this may contribute to dormant tumor cell activation, which has implications for how melphalan is used to treat patients with MM
Varijacije u kliničkoj slici i epidemiologiji dubokih dermatomikoza vlasišta [The clinical pattern variations and epidemiology of deep seated tinea capitis]
Get PDFTinea capitis caused by Microsporum canis is usually noninflammatory.
However, progressive number of severe kerion like tinea capitis (TC) due to M. canis
has been recently registered. Providing that the same fungal species might evoke
different clinical patterns, interspecies polymorphism within M. canis isolates might
have been responsible for this phenomenon.
The aim of this study was to examine genotypic variability among isolates of
M. canis from patients with superficial and deep seated tinea capitis.
Sixty strains of M. canis from patients with both superficial and deep seated
tinea capitis have been isolated and identified to the species level using standard and
advanced mycological procedure techniques. Morphological identification was
confirmed by molecular methods PCR-RFLP (Polymerase Chain Reaction-Restriction
Fragment Length Polymorphism). After amplification of ITS1-5.8S-ITS2 region, the
PCR product was exposed to restriction enzyme HinfI. All strains of M. canis had
identical pattern on gel electrophoresis. For sub typing of M. canis isolates the RAPD
(Random Amplified Polimorphic DNA) has been perfomed using (ACA)5 and (GACA)4
primers. After RAPD amplification with (ACA)4 primer, among all M. canis isolates
only one RAPD profile was determined, whereas using (GACA)4 primer two different
band patterns were confirmed.
According to the results of the epidemiological part of our study M. canis
remained the main causative agent of TC in Croatia. The incidence of TC remained
high during the ten-years period (2006-2015), but decrease in the incidence of TC
was observed in the first 5 years, with stable incidence of TC during the last 5 years
of the study period. A statistically significant increase of TC among all fungal skin
infections during the last 3 years was observed. The association between RAPD profiles and certain clinical type of tinea
capitis was not determined by the use of GACA4 primer . Results of most molecular
studies show that there is no clonal differentiation within M. canis. Moreover, using
the same (GACA)4 primer M. canis was found not to be genotypically unique.
However, furhter investigations on larger group of patiens might be required in order
to elucidate this problem more precisely
Analiza gena i proteina signalnih puteva Wnt i Sonic Hedgehog u primarnoj i sekundarnoj mijelofibrozi [Analysis of genes and proteins of WNT and Sonic Hedgehog signaling pathways in primary and secondary myelofibrosis]
Get PDFPrimary (PMF) and secondary myelofibrosis (SMF) are malignant diseases originating from transformed hematopoietic stem cell. WNT and SHH signaling pathways are involved in processes of cell cycle regulation, fibrosis and neoangiogenesis that are typically deranged in these diseases.
Using immunohistochemistry and real-time-polymerase-chain-reaction (RT-PCR) we investigated WNT3a, β-catenin, Sclerostin/SOST, SHH and GLI1 expression in totally 66 diseased (51 PMF, 15 SMF) and 18 healthy bone marrow samples. Correlations with clinical parameters were made.
Canonical-WNT signaling pathway elements were globally higher expressed in PMF and SMF than in controls and might potentiate anemia. SMF β-catenin expression profile is more similar to PMF than to PRV/ET. Sclerostin expression did not differ between diseased and healthy patients, but positively affected overall survival in diseased patients. SHH signaling pathway elements were higher expressed in megakaryocytes of PMF and SMF than in controls, but were not globally higher expressed. SHH expression was higher in leukemic transformation of disease. Expression of particular elements of both signaling pathways positively correlated together which is in line with the model that these pathways are a part of larger interconnected network.
Our results suggest that canonical-WNT and SHH signaling pathways play a role in pathogenesis of PMF and SMF