X-linked Charcot-Marie-Tooth disease in pediatrics

Charcot-Marie-Toothova bolest (CMT) je klinički genetski i elektrofiziološki vrlo heterogena skupina nasljednih bolesti perifernih živaca. X-vezani oblik CMT (CMTX1) je drugi najčešći uzrok demijelinizirajućeg oblika CMT. Opisano je 6 tipova CMTX (CMTX1-CMTX6). CMTX1 je najčešća među njima i uzrokovana je mutacijom GJB1 gena čija je uloga kodiranje koneksina 32 (Cx32). Mijelinizirajuće Schwannove stanice ispoljavaju Cx32 koji sudjeluje u formiranju tijesnih spojeva među slojevima mijelina. Tijesni spojevi građeni od molekula Cx32 imaju važnu ulogu u homeostazi mijeliniziranih aksona. CMTX1 je X-vezani dominantni oblik CMT sa znakovima gubitka mijelina i aksona. Muškarci razvijaju umjerene do teške simptome, dok su žene heterozigoti blaže zahvaćene ili čak asimptomatske. Simptomi se razvijaju u kasnom djetinjstvu, kod dječaka nakon pete godine, a kod djevojčica nešto kasnije. Klinička slika je karakterizirana progresivnom atrofijom distalnih skupina mišića, slabošću, gubitkom osjeta, arefleksijom, deformacijama kostiju stopala (ekskavirano stopalo), skoliozom te kontrakturama. Kliničke manifestacije obično uključuju i atrofiju mišića šake, ponajprije tenarnih mišića. Oligodendrociti također ispoljavaju Cx32 pa se kod nekih pacijenata bolest manifestira znakovima zahvaćanja središnjeg živčanog sustava ili gubitka sluha. Bolesnici s CMTX1 tipično se prezentiraju s umjereno usporenom brzinom provođenja živaca. Budući da dosad nije otkrivena molekularna terapija bolesti, glavni terapijski pristup jest simptomatski, uz dugoročno multidisciplinarno praćenje bolesnika od strane dječjeg neurologa, fizijatra, ortopeda, kirurga i psihijatra.Charcot-Marie-Tooth (CMT) is a genetically, clinically and electrophysiologically heterogeneous group of inherited disorders of the peripheral nervous system. The X-linked form of Charcot-Marie-Tooth disease (CMTX1) is the second most common cause of a demyelinating type of CMT. There are 6 types of CMTX (CMTX1-CMTX6). CMTX1 is the most common one, and is caused by mutations in the GJB1 gene which encodes connexin 32 (Cx32). Myelinating Schwann cells express Cx32, which likely forms gap junctions between the layers of myelin sheath. Gap junctions formed by Cx32 play an important role in the homeostasis of myelinated axons. CMTX1 is an X-linked dominant type of CMT with both demyelinating and axonal features. Affected males have moderate-to-severe symptoms, whereas heterozygous females are usually mildly affected, or even asymptomatic. Symptoms develop in late childhood, usually after the age of five in males, and later in affected females. The clinical phenotype is characterized by progressive distal muscle atrophy, weakness, sensory loss, areflexia, skeletal deformities (high arched feet), scoliosis and contractures. Clinical features also include involvement of hand muscles with pronounced atrophy, particularly affecting thenar muscles. Oligodendrocytes also express Cx32, so several patients have manifestations of central nervous system involvement or hearing impairment. Patients with CMTX1 typically manifest intermediate slowing of nerve conduction velocity (NCV). There is no known molecular-based treatments for CMTX1. Treatment is symptomatic and affected individuals are often evaluated and managed by a team of children neurologists, physiatrists, ortopedic surgeons and psychiatrist

X-linked Charcot-Marie-Tooth disease in pediatrics

Charcot-Marie-Toothova bolest (CMT) je klinički genetski i elektrofiziološki vrlo heterogena skupina nasljednih bolesti perifernih živaca. X-vezani oblik CMT (CMTX1) je drugi najčešći uzrok demijelinizirajućeg oblika CMT. Opisano je 6 tipova CMTX (CMTX1-CMTX6). CMTX1 je najčešća među njima i uzrokovana je mutacijom GJB1 gena čija je uloga kodiranje koneksina 32 (Cx32). Mijelinizirajuće Schwannove stanice ispoljavaju Cx32 koji sudjeluje u formiranju tijesnih spojeva među slojevima mijelina. Tijesni spojevi građeni od molekula Cx32 imaju važnu ulogu u homeostazi mijeliniziranih aksona. CMTX1 je X-vezani dominantni oblik CMT sa znakovima gubitka mijelina i aksona. Muškarci razvijaju umjerene do teške simptome, dok su žene heterozigoti blaže zahvaćene ili čak asimptomatske. Simptomi se razvijaju u kasnom djetinjstvu, kod dječaka nakon pete godine, a kod djevojčica nešto kasnije. Klinička slika je karakterizirana progresivnom atrofijom distalnih skupina mišića, slabošću, gubitkom osjeta, arefleksijom, deformacijama kostiju stopala (ekskavirano stopalo), skoliozom te kontrakturama. Kliničke manifestacije obično uključuju i atrofiju mišića šake, ponajprije tenarnih mišića. Oligodendrociti također ispoljavaju Cx32 pa se kod nekih pacijenata bolest manifestira znakovima zahvaćanja središnjeg živčanog sustava ili gubitka sluha. Bolesnici s CMTX1 tipično se prezentiraju s umjereno usporenom brzinom provođenja živaca. Budući da dosad nije otkrivena molekularna terapija bolesti, glavni terapijski pristup jest simptomatski, uz dugoročno multidisciplinarno praćenje bolesnika od strane dječjeg neurologa, fizijatra, ortopeda, kirurga i psihijatra.Charcot-Marie-Tooth (CMT) is a genetically, clinically and electrophysiologically heterogeneous group of inherited disorders of the peripheral nervous system. The X-linked form of Charcot-Marie-Tooth disease (CMTX1) is the second most common cause of a demyelinating type of CMT. There are 6 types of CMTX (CMTX1-CMTX6). CMTX1 is the most common one, and is caused by mutations in the GJB1 gene which encodes connexin 32 (Cx32). Myelinating Schwann cells express Cx32, which likely forms gap junctions between the layers of myelin sheath. Gap junctions formed by Cx32 play an important role in the homeostasis of myelinated axons. CMTX1 is an X-linked dominant type of CMT with both demyelinating and axonal features. Affected males have moderate-to-severe symptoms, whereas heterozygous females are usually mildly affected, or even asymptomatic. Symptoms develop in late childhood, usually after the age of five in males, and later in affected females. The clinical phenotype is characterized by progressive distal muscle atrophy, weakness, sensory loss, areflexia, skeletal deformities (high arched feet), scoliosis and contractures. Clinical features also include involvement of hand muscles with pronounced atrophy, particularly affecting thenar muscles. Oligodendrocytes also express Cx32, so several patients have manifestations of central nervous system involvement or hearing impairment. Patients with CMTX1 typically manifest intermediate slowing of nerve conduction velocity (NCV). There is no known molecular-based treatments for CMTX1. Treatment is symptomatic and affected individuals are often evaluated and managed by a team of children neurologists, physiatrists, ortopedic surgeons and psychiatrist

Gender differences in risk factors and cardiovascular outcomes in symptomatic peripheral artery disease patients

AIM: To compare the influence of gender on adverse cardiovascular events in patients with sympto- matic peripheral artery disease (PAD) based on their clinical presentation (intermittent claudication or critical limb ischemia, CLI). PATIENTS AND METHODS: A prospective, registry-based study involving patients with symp- tomatic peripheral artery disease was conducted. Patients were divided according to initial clinical presentation (intermittent claudication or CLI) and gender and were analyzed separately. Risk factors, prognosticators and longitudinal events (major adverse cardiovascular events, MACE: myocardial infarction, stroke, death) were collected. Data were obtained prospectively from hospital records and death certificates. RESULTS: 1084 patients (35% women) with symptomatic PAD were included in the study. Mean follow-up period was 45 months, and 371 patients (34%) experienced MACE. Compared to males, females were older (p <0.001) and were more likely to have CLI (p=0.006) and impaired renal func- tion (p <0.001). Diabetes (p=0.043) and smoking (p <0.001) were more prevalent in men, as well as polyvascular disease (p=0.024). No significant difference was found regarding the use of medications. No differences were observed in MACE-free survival between women and men, both in subgroups of patients with intermittent claudication (log-rank p=0.759) and CLI (log-rank p=0.558). CONCLUSIONS: Our study showed no gender differences in the occurrence of MACE based on initial clinical presentations of PAD

Efficiency of ultrasonic Vertex III hypsometer compared to the most commonly used hypsometers in Croatian forestry

The article investigates the efficiency of the ultrasonic Vertex hypsometer in tree height measurements in relation to some of the most commonly used hypsometers in Croatian forestry. The whole measurement process consists of three steps: time needed to reach the measurement zone, time needed to determine the distance to a tree, and time needed to measure and read the height of a tree. Measurements were conducted with four hypsometers: Vertex, Blume-Leiss, Bitterlich\u27s Spiegel Relaskop with a standard scale (RO) and Bitterlich\u27s Spiegel Relaskop with a CP scale (with the horizontally /RCPH/ or vertically /RCPV/ positioned staff). Research results do not show any statistically important differences among the hypsometers in terms of time needed to reach the measurement zone. In measuring tree heights in a stricter sense (without the element of reaching the measurement zone), the least amount of time was required by the Vertex (28.4 cmin) on average. The Vertex is followed by the relaskop with a CP scale, the horizontally (57.4 cmin) or vertically positioned staff (86.1 cmin), then the Blume-Leiss (84.0 cmin) and finally the relaskop with a standard scale (106.8 cmin). The differences between the Vertex and other hypsometers are statistically significant. Despite a slightly higher price of the Vertex, its speed, precision, accuracy and simplicity of use, as well as the possibility of simple circular plot forest inventories rank it above all the other instruments