Micro-scale vertebral features in postmenopausal women with alcohol-associated and metabolic-associated fatty liver disease: ex vivo bone quality analyses.

PURPOSE: Although epidemiological studies indicate increased fracture risk in women with alcohol-associated liver disease (AALD) and metabolic-associated fatty liver disease (MAFLD), data about their micro-scale bone features are still limited. We aimed to characterize bone quality changes in the anterior mid-transverse part of the first lumbar vertebral body collected from 32 adult postmenopausal females. Based on pathohistological assessment of the liver tissue, individuals were divided into AALD (n = 13), MAFLD (n = 9), and control group (n = 10). METHODS: We analyzed trabecular and cortical micro-architecture (using micro-computed tomography), bone mechanical properties (using Vickers microhardness tester), osteocyte lacunar network and bone marrow adiposity morphology (using optic microscopy). Data were adjusted to elude the covariant effects of advanced age and body mass index on our results. RESULTS: Our data indicated a minor trend toward deteriorated bone quality in MAFLD women, presented in impaired trabecular and cortical micro-architectural integrity, which could be associated with bone marrow adiposity alterations noted in these women. Additionally, we observed a significant decline in micro-architectural, mechanical, and osteocyte lacunar features in lumbar vertebrae collected from the AALD group. Lastly, our data indicated that vertebral bone deterioration was more prominent in the AALD group than in the MAFLD group. CONCLUSION: Our data suggested that MAFLD and AALD are factors that could play a part in compromised vertebral strength of postmenopausal women. Also, our data contribute to understanding the multifactorial nature of bone fragility in these patients and highlight the necessity for developing more effective patient-specific diagnostic, preventive, and therapeutic strategies.

The comparison of the effects of ketamine and etomidate on cardiodynamics, biochemical and oxidative stress parameters in Wistar male rats.

It is well known the use of ketamine and etomidate in clinical practice; however, the difference in the systemic effects of these two anesthetic agents is still debatable. Thus, in the present study we aimed to compare their effects on heart, and other organs through estimation of cardiodynamics, biochemical and hematological parameters. Male Wistar rats were divided in 2 groups containing of 2 subgroups (n = 7 in each subgroup, n = 28 in total): (1) bolus injection of anesthetic ketamine (40 mg/kg b.w., i.p. n = 14); (2) bolus injection of anesthetic etomidate (20 mg/kg b.w., i.p. n = 14). The experiments were done in vitro in one subgroup of each group: cardiodynamic variables (dp/dtmax, dp/dtmin, heart rate), coronary flow, oxidative stress in coronary effluent and cardiac tissue homogenate, and in vivo in another subgroup: biochemical and hematological parameters, and oxidative stress in haemolysate. Significantly increased left ventricular contractility (dp/dtmax) and relaxation (dp/dtmin) were noticed in etomidate group. Creatinine (CREA), HDL cholesterol and folate were significantly higher in etomidate group, whereas amylase (AMY) and eosinophils in ketamine group. Our results suggested that ketamine has more antioxidant potential compared to etomidate, and etomidate has more favorable effects regarding cardiac performance.

The micro-structural analysis of lumbar vertebrae in alcoholic liver cirrhosis.

Although vertebral fracture is more common among alcoholic liver cirrhosis patients when compared to general population, current data on three-dimensional micro-architecture are scarce. Our study showed significant trabecular deterioration in lumbar vertebrae obtained from alcoholic liver cirrhosis donors, suggesting that they should be advised to undergo early-stage screening for osteoporosis. PURPOSE: Recent studies showed an increased incidence of vertebral fractures in alcoholic liver cirrhosis (ALC) patients, while data about vertebral micro-structure are still limited. The aim of this study was to compare trabecular and cortical micro-architecture of lumbar vertebrae between ALC patients and healthy age- and sex-matched controls. METHODS: Our study included lumbar vertebral samples of male cadaveric donors, divided into ALC (n = 20, age: 59 ± 6 years) and control group (n = 20, age: 59 ± 8 years). Following pathohistological verification of liver cirrhosis, trabecular and cortical bone micro-architecture was analyzed by micro-computed tomography (micro-CT). RESULTS: Micro-CT evaluation of the trabecular bone in lumbar vertebrae showed a significant decrease in bone volume fraction, trabecular thickness, trabecular number, and connectivity (p < 0.01). In contrast to trabecular deterioration, prominent alteration in cortical parameters was not observed in lumbar vertebrae of ALC patients (p > 0.05). CONCLUSIONS: Our data indicate that susceptibility to non-traumatic fractures in ALC patients could be explained by alterations in trabecular bone micro-architecture. Thus, we genuinely recommend osteological screening of the lumbar spine for all ALC patients in order to evaluate individual fracture risk. Graphical abstract.

The effects of gasotransmitters inhibition on biochemical and haematological parameters and oxidative stress in propofol-anaesthetized Wistar male rats.

This study aimed to investigate the effects of propofol through evaluating its interaction with nitric oxide (NO), hydrogen sulfide (H2S), and carbon monoxide (CO). Wistar male rats were divided in 4 groups: (1) bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (2) Nω-nitro-l-arginine methyl ester (L-NAME; NO synthase inhibitor, 60 mg/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (3) DL-propargylglycine (DL-PAG; H2S synthase inhibitor, 50 mg/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (4) zinc protoporphyrin IX (ZnPPIX; CO synthase inhibitor, 50 µmol/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.). Increased levels of albumins, low-density lipoproteins, alkaline phosphatase, amylase, high-sensitivity Troponin T, and fibrinogen were found in L-NAME + propofol group. Platelet crit, platelet count, total cholesterol, and high-density lipoproteins were elevated in ZnPPIX + propofol group. Hydrogen peroxide was increased in all groups treated with gasotransmitters inhibitors. Reduced glutathione was reduced in all groups, superoxide dismutase activity only in L-NAME + propofol. The effect of propofol on various biochemical, haematological, and oxidative stress markers may be at least in part mediated through interaction with 3 estimated gasotransmitters.

Inhibition of gasotransmitters production and calcium influx affect cardiodynamic variables and cardiac oxidative stress in propofol-anesthetized male Wistar rats 1.

It has been assumed that the cardioprotective effects of propofol are due to its non-anesthetic pleiotropic cardiac and vasodilator effects, in which gasotransmitters (NO, H2S, and CO) as well as calcium influx could be involved. The study on isolated rat heart was performed using 4 experimental groups (n = 7 in each): (1) bolus injection of propofol (100 mg/kg body mass, i.p.); (2) L-NAME (NO synthase inhibitor, 60 mg/kg body mass, i.p.) + propofol; (3) DL-PAG (H2S synthase inhibitor, 50 mg/kg body mass, i.p.) + propofol; (4) ZnPPIX (CO synthase inhibitor, 50 µmol/kg body mass, i.p.) + propofol. Before and after the verapamil (3 µmol/L) administration, cardiodynamic parameters were recorded (dp/dtmax, dp/dtmin, systolic left ventricular pressure, diastolic left ventricular pressure, heart rate, coronary flow), as well as coronary and cardiac oxidative stress parameters. The results showed significant increases of diastolic left ventricular pressure following NO and CO inhibition, but also increases of coronary flow following H2S and CO inhibition. Following verapamil administration, significant decreases of dp/dtmax were noted after NO and CO inhibition, then increase of diastolic left ventricular pressure following CO inhibition, and increase of coronary flow following NO, H2S, or CO inhibition. Oxidative stress markers were increased but catalase activity was significantly decreased in cardiac tissue. Gasotransmitters and calcium influx are involved in pleiotropic cardiovascular effects of propofol in male Wistar rats.

Does the presence of an unerupted lower third molar influence the risk of mandibular angle and condylar fractures?

It has been suggested that unerupted lower third molars (M3) increase the fragility of the mandibular angle and simultaneously decrease the risk of condylar fracture. However, it is unknown whether this applies regardless of the direction and point of impact of the traumatic force. The aim of this study was to investigate the impact of an unerupted M3 on the fragility of the angle and condyle in terms of a force acting from different directions and affecting different regions of the mandible. Computed tomography scans of a human mandible and finite element methodology were used to obtain two three-dimensional models: a model with, and the other without an unerupted M3. A force of 2000N was applied to three different regions of the models: the symphysis, ipsilateral body, and contralateral body, respectively. When the force was applied to the mandibular body, the results revealed increased angle fragility in cases with unerupted M3. When the force was applied to the symphysis, the condyle region showed higher fragility, irrespective of the presence of an unerupted M3. In summary, fragility of the angle and condyle regions depends on the presence of an unerupted M3 and on the direction and point of impact of the force.

Mechanical weakening of devitalized teeth: three-dimensional Finite Element Analysis and prediction of tooth fracture.

AIM: To determine to which extent cavity preparation and each step of dentine removal in the process of root canal treatment (access cavity preparation and root canal enlargement) both individually and jointly contribute to the weakening of the tooth. METHODS: Numerical analysis using finite element method (FEM) of separate and combined influence of two-surface Class II preparation and root canal treatment was undertaken to evaluate the decrease in tooth strength. The influence of the two stages in root canal treatment, access cavity preparation and root canal enlargement, was also analysed separately and jointly. After each of these phases, the crown was restored with composite resin, and the FEA was performed only on restored teeth. To estimate the influence of all these procedures on tooth fracture resistance numerically, a Failure Index based on the maximum principal stress criterion (MPCS) was applied. Compressive and tensile stresses were analysed separately and corresponding Failure Indices were calculated. RESULTS: A two-surface resin composite restoration weakened the tooth by 23.25%. Nevertheless, the Failure Indices showed that this tooth was not likely to fracture even under high occlusal stress (710N). However, after access cavity preparation, the Failure Indices reached the point where, under high occlusal force that may occur in the posterior area, a tooth fracture occurred. The enlargement of root canals had an additional, but relatively small impact on tooth weakening, making the tooth even more susceptible to fracture. The combined influence of both cavity preparation and root canal enlargement led to weakening of 62.6% under a load of 710N, ultimately causing tooth fracture. CONCLUSION: The combined finite element method and the maximum principal stress analysis gave insight into the fracture mechanisms of teeth with two-surface composite restorations followed by root canal preparation. Removal of tooth tissue, despite its subsequent restoration with dental materials, weakened the tooth by changing the stress intensity and distribution through tooth structures. Access cavity preparation had the greatest influence on tooth strength whilst canal enlargement did not contribute to this process substantially.

Evidence of degraded BMD and geometry at the proximal femora in male patients with alcoholic liver cirrhosis.

UNLABELLED: We examined the association of alcoholic cirrhosis in 33 patients with areal bone mineral density (BMD) and the assessed bone geometric strength of their proximal femora. Lower areal BMD, cross-sectional area and section modulus, thinner cortex, and higher buckling ratio suggest that the alcoholic liver cirrhosis is associated with lower measures of bone strength. INTRODUCTION: Hepatic bone disease is an important complication of chronic liver disease and is associated with significant morbidity through fractures resulting in pain, deformity, and immobility. In this study, we examined the association of alcoholic cirrhosis and liver insufficiency stage with areal bone mineral density (aBMD) and additionally employed hip structure analysis (HSA) as an advanced method to assess bone geometric strength of the proximal femur in men with alcoholic liver cirrhosis. METHODS: The study included 33 male patients with alcoholic liver cirrhosis and a control group of 36 healthy patients. Laboratory testing included the following biochemical markers of bone turnover: serum levels of osteocalcin and C-telopeptide of type 1 collagen. Areal BMD was measured by dual x-ray absorptiometry on the proximal femora. Structural parameters were then derived from these scans using hip structure analysis software. RESULTS: After adjusting for age, body height, and weight, we found lower cross-sectional area (p = 0.005) and section modulus (p = 0.005), thinner cortex (p = 0.012), and higher buckling ratio (p = 0.043) in the neck region among patients with cirrhosis. The findings suggest that alcoholic liver cirrhosis is associated with lower measures of bone strength. These findings were consistent with decreased osteocalcin values and increased C-telopeptide of type 1 collagen in patients with cirrhosis, indicating reduction in bone formation and increased bone resorption. CONCLUSION: Our results emphasize that HSA-derived structural indices of proximal femoral structure may be an important index of greater fragility in patients with alcoholic cirrhosis.

Micro-morphological properties of osteons reveal changes in cortical bone stability during aging, osteoporosis, and bisphosphonate treatment in women.

SUMMARY: We analyzed morphological characteristics of osteons along with the geometrical indices of individual osteonal mechanical stability in young, healthy aged, untreated osteoporotic, and bisphosphonate-treated osteoporotic women. Our study revealed significant intergroup differences in osteonal morphology and osteocyte lacunae indicating different remodeling patterns with implications for fracture susceptibility. INTRODUCTION: Bone remodeling is the key process in bone structural reorganization, and its alterations lead to changes in bone mechanical strength. Since osteons reflect different bone remodeling patterns, we hypothesize that the femoral cortices of females under miscellaneous age, disease and treatment conditions will display distinct osteonal morphology and osteocyte lacunar numbers along with different mechanical properties. METHODS: The specimens used in this study were collected at autopsy from 35 female donors (young group, n = 6, age 32 ± 8 years; aged group, n = 10, age 79 ± 9 years; osteoporosis group, n = 10, age 81 ± 9 years; and bisphosphonate group, n = 9, age 81 ± 7 years). Von Kossa-modified stained femoral proximal diaphyseal sections were evaluated for osteonal morphometric parameters and osteocyte lacunar data. Geometrical indices of osteonal cross-sections were calculated to assess the mechanical stability of individual osteons, in terms of their resistance to compression, bending, and buckling. RESULTS: The morphological assessment of osteons and quantification of their osteocyte lacunae revealed significant differences between the young, aged, osteoporosis and bisphosphonate-treated groups. Calculated osteonal geometric indices provided estimates of the individual osteons' resistance to compression, bending and buckling based on their size. In particular, the osteons in the bisphosphonate-treated group presented improved osteonal geometry along with increased numbers of osteocyte lacunae that had been formerly impaired due to aging and osteoporosis. CONCLUSIONS: The data derived from osteons (as the basic structural units of the cortical bone) in different skeletal conditions can be employed to highlight structural factors contributing to the fracture susceptibility of various groups of individuals.

Paranasal sinus osteoma: is there any association with anatomical variations?

BACKGROUND: Developmental disturbances of the paranasal sinuses are proposed as the cause of osteoma. We examined whether such disturbances may result in the frequent presence of anatomical variations of the paranasal sinuses in patients with osteoma. METHODOLOGY/PRINCIPAL: The study was performed retrospectively on 2,820 patients subjected to CT examination during 2005 - 2011. Demographic and CT characteristics of osteoma, and associated pathological findings were evaluated for 104 patients with diagnosed osteoma. The presence of anatomical variations was assessed for 51 osteoma patients with a complete medical history, and for 1,233 patients from a control group. RESULTS: The prevalence of osteomas was found to be 3.69%, with male to female ratio 1.08:1. The frontal sinus was most commonly affected. The presence of anatomical variations was more frequent in patients with osteoma than in controls, with significant differences confirmed for the sphenomaxillary plate, infraorbital cell, and crista galli pneumatization. CONCLUSIONS: The paranasal sinus osteoma is associated with higher prevalence of anatomical variations. This can be explained either by the stronger influence of genetic and/or environmental factors on the development of the paranasal sinuses in patients with osteoma, or by their higher susceptibility to above mentioned factors.

Oral status in patients receiving 5-fluorouracil for colorectal cancer.

PURPOSE: Oral complications are frequent and troublesome symptoms for those undergoing chemotherapy for cancer. Several antineoplastic agents are proved to have stomatotoxic potential, among them 5-fluorouracil (5-FU). The aim of the present study was to evaluate the oral status and patient experiences during chemotherapy with 5-FU for colorectal cancer. METHODS: Twenty-eight patients treated with 5-day 5-FU plus leucovorin entered this study. Positive data about oral symptoms were taken by anamnesis. Mucositis severity index, gingival index, plaque index, probing pocket depth and bleeding on probing have been used to assess oral mucosa and periodontal status of the patients. Patients were examined prior to chemotherapy and 14 days after the start of the chemotherapy cycle. RESULTS: Mild to moderate subjective complaints concerning oral cavity were reported by 17.9% of patients before and 39.2% of patients after chemotherapy. Clinical examination revealed oral mucosa damage in 10.7% and 35.7% of patients, with mean mucositis score of 0.14 and 0.54 before and after chemotherapy, respectively. Although mean values of all periodontal indices were elevated after chemotherapy, only increase in gingival index was statistically significant (p=0.035). Mucositis was significantly correlated with oral pain (p=0.00), xerostomia (p=0.00), and plaque index (p=0.077), while the correlation between mucositis and the rest of the examined parameters was not significant. CONCLUSION: Oral complications were not highly expressed in this study. Although 5-FU is considered to exert significant stomatotoxic effect, severe mucositis was far less common in this study compared to studies reported elsewhere.

Bcl-2 expression and its possible influence on malignant transformation of oral lichen planus.

PURPOSE: The aim of this study was to investigate the malignant potential of oral lichen planus (OLP) on the basis of the expression of the Bcl-2 marker in healthy individuals (H), patients with OLP and patients with squamous cell carcinoma (SCC), and to establish potential interdependence between expression of Bcl-2 and the different clinical and histopathological parameters in H, OLP, and SCC. METHODS: Immunohistochemistry for Bcl-2 was carried out using an avidin-biotin peroxidase complex method. Tissue sections were treated with mouse monoclonal antibody against Bcl-2 (124, DAKO A/S, Denmark; dilution 1/100). Immunohistochemical parameters measured included total tissue area, total stained area and intensity of stain. RESULTS: Keratinocytes were not Bcl-2 positive in H and were sparsely positive in OLP. The number of lymphocytes stained with Bcl-2 was significantly lower in H as compared to patients with SCC and OLP. Bcl-2 staining was weak to moderate in OLP, and moderate to intense in SCC. Bcl-2-positive lymphocytes were more expressed in older OLP patients (>55 years), and in OLP specimens with orthokeratinized epithelium, less developed acanthosis and highest grade of lymphocyte expression. CONCLUSION: Bcl-2 may not serve as a prognostic biomarker in oral cancer development from OLP, but it could help in selecting patients with higher need of follow up to prevent malignancy.

Adolescent health in medieval Serbia: signs of infectious diseases and risk of trauma.

Although pattern of health in adults has been frequently assessed in past human populations, health status of adolescents as a distinct life stage has usually been overlooked. Inconsistency in number and meaning of recognised age categories in anthropological literature, as well as chronological age ranges used to define them, further complicate the interpretation of adolescent health. In this study, we analysed signs of pathological conditions on skeletal remains of 81 adolescents from a medieval site of Stara Torina (northern Serbia). Diagnostic palaeopathological procedures comprised gross examination, digital radiography, and histological analysis. Skeletal signs of anaemia such as cribra orbitalia and other porotic phenomena as well as signs of non-specific bone infection were observed frequently, while evidence of bone trauma was recorded in a very low percentage of individuals. In addition, we recorded two conditions relatively rarely observed in palaeopathological contexts: a case of skull and vertebral asymmetry indicative of congenital muscular torticollis, and a case of a fibrous cortical defect on distal femur. Comparison with available information from other medieval adolescent samples from Serbia demonstrated that while mortality was relatively constant throughout the sample, Stara Torina showed a much higher occurrence of bone disease. Characteristics of observed skeletal conditions, supported by available historical reports, suggest that the health of medieval adolescents in the examined population was most significantly affected by infectious processes.

Effect of sucrose concentration on the products of Kombucha fermentation on molasses.

Fermentation of 1.5g/l of Indian black tea, sweetened with adequate quantities of molasses (containing approx. 70g/l, 50g/l and 35g/l of sucrose), was conducted using domestic Kombucha. Inoculation was performed with 10% of fermentation broth from a previous process. The fermentation in cylindrical vessels containing 2l of liquid phase, was carried out at 22±1°C for 14 days, with periodical sampling, to measure pH, content of acids (total, acetic and l-lactic), content of remaining sucrose, and the yield of biomass at the end of fermentation. A product with 70g/l sucrose from molasses corresponds to an optimal concentration of carbon source, which provided metabolites with high pH, a low content of less desired acetic acid, a high content of highly desired l-lactic acid, an acceptable content of total acids and the highest possible level of utilisation of sucrose.

MECP2 mutations in Serbian Rett syndrome patients.

BACKGROUND: Rett syndrome is a severe neurodevelopmental X-linked dominant disorder affecting 1/15,000 girls worldwide. Eight years ago, the MECP2 gene was associated with the devastating clinical features observed in Rett syndrome patients. OBJECTIVES: To investigate the spectrum and the frequency of MECP2 mutations in Serbian Rett syndrome patients. PATIENTS AND METHODS: We screened the MECP2 coding region by conventional mutational screening (single-strand conformation polymorphism/sequencing) in 24 patients of Serbian origin and in their 41 unaffected family members. In search for gene dosage alterations in seemingly mutation-negative girls, we developed a new, specific quantitative PCR method. RESULTS: Nineteen patients (79%) carried MECP2 mutations, five of which were novel (one nonsense mutation, one duplication and three deletions). Fourteen previously described disease-causing sequence changes and one polymorphism were also detected. Detailed case reports are given for the carriers of the novel mutations. Large MECP2 rearrangements cause Rett syndrome in a significant number of girls without 'classic' mutations in this gene. Therefore, we developed a specific quantitative PCR method, covering MECP2 exons 3 and 4, which previously has not been used for screening. No dosage alterations of the two exons were found in the four tested mutation-negative girls. CONCLUSIONS: This is the first genetic study of Rett syndrome in Serbian patients describing the MECP2 mutational and phenotypic spectrum in this population. Detailed clinical descriptions of this ethnically homogeneous patient population add to our knowledge of genotype/phenotype correlations in this severe condition.

Presence of herpes simplex virus on the oral mucosa in patients undergoing chemotherapy.

BACKGROUND: The aim of this study was to confirm the presence of herpes simplex virus type 1 and 2 on the oral mucosa, in patients undergoing chemotherapy, by means of polymerase chain reaction (PCR). METHODS: The research was carried out on 40 patients receiving chemotherapy as treatment for different malignancies. The status of oral mucosa and viral presence were assessed in all patients at the initial examination (prior to chemotherapy), and at the control examination (two weeks after the initiation of the chemotherapeutic cycle). RESULTS: The presence of HSV-1 was detected in 28 patients (70%) prior to chemotherapy, of whom 7 (25%) manifested oral complications. The control examination showed the presence of HSV-1 in 35 patients (87.5%), of whom 23 (65.7%) presented oral mucosa changes. HSV-2 has not been detected in any of the patients.

Gunshot injury to the face with a missile lodged in the upper cervical spine without neurological deficit.

An unusual case of facial gunshot injury with the missile lodged in the cervical spinal canal, but without any neurological impairment is reported. The extent of tissue damage and missile track termination in a male patient who sustained gunshot trauma to the face was assessed by plain radiography and by CT scans. The patient was treated conservatively and observed for clinical manifestations of neurological deficit for 3 weeks. CT of the head and neck performed 13 years after injury with the three-dimensional (3D) reconstruction of skeletal elements revealed healed fractures of the right nasal bone, the labyrinth of the right ethmoid bone, and position of the missile on the medial aspect of the right lateral mass of the atlas. There was no migration of the missile during this period. This case report of gunshot wound to the face associated with injury of the cervical spine indicated possibility of survival and atypical absence of clinical manifestation that may occur even when a bullet remains in the spinal canal.

[Our experience of postoperative saving of drainage blood in orthopaedic surgery].

Postoperative saving of drainage blood presents postoperative autologous transfusion and that means group of action of collection patients blood and its late reinfision. The conditions of orthopaedic surgery join with arthroplasty of coxae and knee are connected with signicifant loss of blood (800-1200 ml). With the aim of reducing the need for use of heterologous blood and elimination of potentional risks because of her application, we investigate the possibility of application the system of posteoperative saving of drainage blood in the study group of 48 patients in relation of control group of 25 patients. Postoperative blood saving has been derived after the first 4-8 hours, after the and of surgical operation. In the study group only 4 patients (8%) need additional heterologous transfusions. Postoperative blood saving and its reinfusion have not significant effect at hemostasis and sistem of coagulation. During six months postoperative, no patients in the study group have not any complication after orthopaedic surgery.

[West syndrome--new therapeutic approach]. / Westov sindrom--novi terapijski pristup.

West syndrome (WS) is an age dependent epileptic syndrome caused by various brain disorders. WS has been frequently classified in two groups, cryptogenic and symptomatic. As symptomatic WS consists of patients with numerous types of brain lesions, the prognosis and evolutional changes may be different among the types of brain lesions. WS is resistant to treatment to most conventional antiepileptic drugs, and only valproic acid, benzodiazepines, adrenocorticotropic hormone (ACTH), corticosteroids and vigabatrin have been found efficacious. Benzodiazepine, notably nitrazepam, and less clonazepam had been effective in bringing spasms under control but emerging tolerance and significant side effects (hypotonia and drowsiness) precluded its wider use. ACTH has been the treatment of choice for infantile spasms ever since Sorel and Dusaucy-Bouloye described its effectiveness in 1958. Despite the empirical approach steroids were capable of controlling the spasms and normalizing EEG in about 60% of cases. Corticotropin (ACTH) was used in doses from 5 to 180 I.U. daily, prednizolone 2-10 mg/kg daily, hydrocortisone 5-10 mg/kg daily and dexamethason 0.3-0.5 mg/kg. However, poor consensus was defined regarding the best steroid molecule to use, the dosage, and the duration of treatment. Also frequent and sometimes serious side effects have occurred during ACTH therapy, notably serious infections and hypertension that promoted continuous search for alternative and safer drugs tolerated outpatient treatment, good tolerance and minor side effects. Recently a specific visual field loss has been reported in treated adults that raised concern about safety of vigabatrin. New reports in children claim that vigabatrin treatment of children and adolescents has a lower risk for visual field defect than in adults, because of reported reversibility. Vigabatrin paediatric advisory group recommend the trial of vigabatrin for 12-14 days as first treatment for WS and in the case of good clinical response continuation of therapy for six months. Other new antiepileptic drugs (lamotrigine, topiramate, felbamate and zonisamide) have shown significant efficacy in the treatment of resistant WS to previous medication. The current task is to determine risk/benefit ratios of these two drugs (vigabatine, ACTH) and to delineate the group of patients with WS where their use would be optimal.

Association of Krabbe leukodystrophy and congenital fiber type disproportion.

Hypotonia and weakness developed in a 12-month-old boy whose psychomotor development had previously been normal. The muscle biopsy demonstrated a disparity in the mean diameters of type 1 and type 2 fibers and satisfied major histologic criteria for diagnosis of congenital fiber type disproportion (CFTD). However, deterioration of motor and mental function, which developed subsequently, strongly suggested progressive encephalopathy. Examination of leukocyte cerebral enzymes at 15 months of age revealed a complete lack of galactosylceramide-beta-galactosidase. Selective type 1 fiber atrophy with type 1 fiber predominance has been observed in various conditions, including Krabbe disease. We report an additional case of Krabbe leukodystrophy associated with CFTD. The finding on the molecular level will resolve the dilemma of whether CFTD is a congenital myopathy or whether these patterns of disproportion may result from a number of different processes that interfere with the maturation of the developing motor unit.