NSD1 duplication in Silver-Russell syndrome (SRS): molecular karyotyping in patients with SRS features.

Silver-Russell syndrome (SRS) is a growth retardation syndrome characterized by intrauterine and postnatal growth retardation, relative macrocephaly and protruding forehead, body asymmetry and feeding difficulties. Nearly 50% of cases show a hypomethylation in 11p15.5, in 10% maternal uniparental disomy of chromosome 7 is present. A significant number of patients with SRS features also exhibit chromosomal aberrations. We analyzed 43 individuals referred for SRS genetic testing by molecular karyotyping. Pathogenic variants could be detected in five of them, including a NSD1 duplication in 5q35 and a 14q32 microdeletion. NSD1 deletions are detectable in overgrowth disorders (Sotos syndrome and Beckwith-Wiedemann syndrome), whereas NSD1 duplications are associated with growth retardation. The 14q32 deletion is typically associated with Temple syndrome (TS14), but the identification of a patient in our cohort reflects the clinical overlap between TS14 and SRS. As determination of molecular subtypes is the basis for a directed counseling and therapy, the identification of pathogenic variants in >10% of the total cohort of patients referred for SRS testing and in >16% of characteristic individuals with the characteristic SRS phenotype confirms the need to apply molecular karyotyping in this cohort.

Dysfunction of SHANK2 and CHRNA7 in a patient with intellectual disability and language impairment supports genetic epistasis of the two loci.

Synaptopathies constitute a group of neurological diseases including autism spectrum disorders (ASD) and intellectual disability (ID). They have been associated with mutations in genes encoding proteins important for the formation and stabilization of synapses, such as SHANK1-3. Loss-of-function mutations in the SHANK genes have been identified in individuals with ASD and ID suggesting that other factors modify the neurological phenotype. We report a boy with severe ID, behavioral anomalies, and language impairment who carries a balanced de novo triple translocation 46,XY,t(11;17;19)(q13.3;q25.1;q13.42). The 11q13.3 breakpoint was found to disrupt the SHANK2 gene. The patient also carries copy number variations at 15q13.3 and 10q22.11 encompassing ARHGAP11B and two synaptic genes. The CHRNA7 gene encoding α7-nicotinic acetylcholine receptor subunit and the GPRIN2 gene encoding G-protein-regulated inducer of neurite growth 2 were duplicated. Co-occurrence of a de novo SHANK2 mutation and a CHRNA7 duplication in two reported patients with ASD and ID as well as in the patient with t(11;17;19), severe ID and behavior problems suggests convergence of these genes on a common synaptic pathway. Our results strengthen the oligogenic inheritance model and highlight the presence of a large effect mutation and modifier genes collectively determining phenotypic expression of the synaptopathy.

Y-chromosome markers in Turner syndrome: Screening of 130 patients.

BACKGROUND: The presence of Y-chromosome material in patients with Turner syndrome (TS) is a risk factor for the development of gonadoblastoma. Cytogenetic analysis detects Y-chromosome mosaicism in about 5% of Turner patients. However, if Y-chromosome sequences are present in only a few cells, they may be missed by routine analysis. The use of molecular techniques to detect the presence of Y-chromosome fragments in such patients is becoming increasingly important. AIM: The objective of our study was to analyze cryptic Y-chromosome derivatives in Hungarian TS patient population by real-time PCR (RT-PCR). SUBJECTS AND METHODS: Cytogenetic and RT-PCR methods were used to examine peripheral blood DNA of 130 Hungarian patients with TS for the presence of Y-chromosome. With RT-PCR, 4 regions throughout the Y-chromosome were analyzed. RESULTS: Initial cytogenetic karyotyping assessing 10-50 metaphases revealed 3 patients with Y-chromosome positivity. RT-PCR revealed further 6 patients with Y-chromosome, who were initially considered as Y-negatives by standard kayotyping. The consecutive cytogenetic analysis of a large number (about 100) of metaphases (in 5 patients) and/or FISH (in 6 patients) however, also confirmed the presence of the Y-chromosome in these patients. Prophylactic gonadectomy was carried out in all 9 patients and 1 of them was diagnosed as having bilateral gonadoblastoma without clinical symptoms. CONCLUSIONS: We recommend a routine molecular screening for hidden Y-chromosome sequences in Turner patients, who are negative for Y-chromosome by conventional cytogenetic analysis, in order to calculate the future risk of developing gonadoblastoma.

Superiority of tacrolimus 0.1% ointment compared with fluticasone 0.005% in adults with moderate to severe atopic dermatitis of the face: results from a randomized, double-blind trial.

BACKGROUND: No specific data are available on tacrolimus ointment as a second-line treatment in adults with facial eczema. OBJECTIVES: To compare tacrolimus 0.1% and fluticasone 0.005% ointments in adults with moderate to severe atopic dermatitis (AD) of the face in whom conventional treatment was ineffective or poorly tolerated. METHODS: Patients were randomized to double-blind treatment of facial AD with twice-daily tacrolimus ointment (n = 288) or fluticasone ointment (n = 280) for 3 weeks or until clearance. After day 21, patients could continue without the study treatment, apply the same ointment once daily, or switch to the other medication twice daily, depending on lesion clearance and patient/physician satisfaction. The primary endpoint was the day-21 response [> or = 60% reduction in the modified Local Eczema and Severity Index (mLEASI) score]. Secondary endpoints included facial erythema and pruritus, global clinical response, treatment switching at day 21 and safety. RESULTS Response with tacrolimus ointment (93%) was superior to that with fluticasone (88%; P = 0.026). Improvements in mLEASI components were also greater with tacrolimus ointment. Facial erythema and pruritus improved in both groups. Global clinical response was rated 'marked improvement' or better in 88% and 79% of patients in the tacrolimus ointment and fluticasone groups, respectively. At day 21, 9% of patients switched from fluticasone to tacrolimus ointment, while 4.5% switched from tacrolimus ointment to fluticasone. Adverse events were more frequent with tacrolimus ointment as a result of the higher incidence of application-site skin burning sensation. Safety of both drugs was in line with their respective summary of product characteristics. CONCLUSIONS: Tacrolimus 0.1% ointment has superior efficacy to fluticasone 0.005% ointment for twice-daily treatment of adults with moderate to severe facial AD in whom conventional therapy was inadequately effective or not tolerated. Tacrolimus 0.1% ointment is a safe and effective second-line treatment for the control of moderate to severe AD of the face.

Synergistic interaction of ABCB1 and ABCG2 polymorphisms predicts the prevalence of toxic encephalopathy during anticancer chemotherapy.

Polymorphisms of the ABCB1 (MDR1) and ABCG2 (BCRP) genes were reported to alter the expression and function of these drug transporters. Both proteins are present at the main pharmacokinetic barriers including the blood-brain barrier. Data from 291 children with acute lymphoblastic leukaemia were analysed in this retrospective study. ABCB1 3435T>C, 2677G>T/A, 1236C>T and ABCG2 421C>A, 34G>A genotypes were determined. Encephalopathy episodes were more frequent among those with ABCB1 3435TT genotype than in the 3435CC/CT group (odds ratio (OR) 3.5; P=0.03). Patients with the ABCG2 421A allele tended to have more complications than wild type homozygotes (OR=2.0; P=0.25). The rate of the adverse effect was similar in those harbouring no or only one of the predisposing genotypes, that is, either ABCB1 3435TT or ABCG2 421AA/AC. However, significantly more children suffered encephalopathy in the group with both predisposing genotypes (OR=12.3; P=0.005). In conclusion, these variations exert synergistic effect in predisposing patients to toxic neurological complications of chemotherapy.

Laterality disturbance and hypopituitarism. A case report of co-existing situs inversus totalis and combined pituitary hormone deficiency.

The authors present the case history of a 52-yr-old male patient with a unique association of combined pituitary hormone deficiency (CPHD) and situs inversus totalis. Except for signs and symptoms of pituitary hormone deficiency, the patient had no dysmorphic features, and hearing impairment, primary mental or neurological defects were also absent. Pituitary magnetic resonance imaging (MRI) scan showed hypoplasia of the anterior lobe of the pituitary gland and an ectopic posterior pituitary lobe. Despite the presence of situs inversus totalis, the patient was right-handed and functional MRI demonstrated left-hemisphere activation during language tests. Kartagener syndrome was considered, but immunofluorescence analysis showed normal localization of the outer dynein arm protein in respiratory epithelial cells obtained from the nasal mucosa. Direct DNA sequencing of all coding exons of the pituitary transcription factor 1 (PIT1) and prophet of PIT1 (PROP1) genes failed to detect disease-causing mutations, suggesting that these genes were not involved in the development of CPHD in our patient. More interestingly, the potential role of the paired like homeodomain transcription factor 2 (PITX2) gene, which has been implicated not only in CPHD, but also in left-right patterning in animal models, was also excluded, as sequencing showed the absence of mutations in coding exons of this gene. To our knowledge, PITX2 gene mutations have not been investigated in CPHD patients who had situs inversus totalis. We conclude that in contrast to animal models, the PITX2 gene is not involved in the development of situs inversus totalis, at least not in our CPHD patient.

Sitting to standing postural changes: Energy expenditure and a possible mechanism to alleviate sedentary behavior.

Background and aims Sedentary lifestyles have recently been identified as potential mechanism for obesity and associated metabolic diseases linked to ill health. The aim of this study was to investigate the effects of standing and sitting-standing positional changes on energy cost and consequently interrupting sedentary sitting time while working. Methods A total of 26 healthy male volunteers performed normal typing and editing work for 100 min under three conditions. The conditions included sustained sitting, sustained standing, and sitting-standing alternation every 20 min using a sit-stand desk. Respiratory parameters measured included minute ventilation (VE), oxygen consumption (VO2), and energy expenditure (EE). Measurements were recorded using a calibrated Cosmed K4b2 portable gas analysis system. Results The mean value for VE was the highest in the standing position (VE = 13.33 ± 0.71), followed by sitting-standing alternation (VE = 12.04 ± 0.62). Both were significantly different from sitting (VE = 10.59 ± 0.69). The maximum VE and EE for standing (VE = 14.81 ± 0.43 and EE = 1.84 ± 0.10) and sitting-standing alternation (VE = 14.80 ± 0.40 and EE = 1.93 ± 0.08) were significantly higher than that of sitting (VE = 12.15 ± 0.42 and EE = 1.67 ± 0.07). No significant differences were observed in the mean VO2 among the three conditions. However, the maximum VO2 for both standing (VO2 = 5.40 ± 0.20) and sitting-standing alternation (VO2 = 5.14 ± 0.17) had shown to be significantly higher than sitting (VO2 = 4.50 ± 0.18). There were no significant differences observed in the mean EE levels between sitting (EE = 1.43 ± 0.07) and sitting-standing alternation (EE = 1.55 ± 0.08). However, the mean EE while standing (EE = 1.62 ± 0.09) significantly increased compared to sitting. Conclusions The findings of this study indicate that sitting-standing alternations may be implemented as an effective intervention to interrupt prolonged sitting while working.

National registry of patients with juvenile idiopathic inflammatory myopathies in Hungary--clinical characteristics and disease course of 44 patients with juvenile dermatomyositis.

Idiopathic inflammatory myopathies (IIMs) are systemic autoimmune diseases characterized by chronic muscle inflammation resulting in progressive weakness and frequent involvement of internal organs, mainly the pulmonary, gastrointestinal and cardiac systems which considerably contribute to the morbidity and mortality of the IIMs. Aim of this study was to present clinical characteristics, disease course, frequency of relapses and survival in patients with juvenile dermatomyositis (DM). A national registry of patients with juvenile IIMs was elaborated by the authors in Hungary. We have summarized data of the register according to signs and symptoms, disease course, frequency of relapses and survival of patients with juvenile IIM. Analysis was performed using data of 44 patients with juvenile DM diagnosed between 1976 and 2004 according to Bohan and Peter's criteria. Survival probability was calculated by Kaplan-Meier method. Data of patients with juvenile DM were compared with data of 66 patients with adult DM. The most frequent cutaneous features were facial erythema and heliotrope rash. Extramuscular and extraskeletal manifestations of the disease were more frequent in adult patients. The most common extramuscular feature was arthralgia in both groups of patients with juvenile or adult DM. Cardiac manifestation of the disease was not observed in juvenile patients. Respiratory muscle involvement and interstitial lung disease (ILD) were more frequent among adult DM patients than cardiac manifestation of the myositis. In view of the disease course, the authors found that frequency of polycyclic and monophasic subtypes of the disease were mainly similar. The hazard of relapse was found higher during the first year after the remission. None of the juvenile patients died. Among adult patients four disease-specific deaths occurred. There was no correlation between relapse free survival and initial therapeutic regimen. Many of our patients had polycyclic or chronic disease. As relapses can occur after a prolonged disease-free interval, patients should be followed up for at least 2 years. Although we found favourable survival probability, further investigations are needed to assess functional outcome.

Mutational spectrum of steroid 21-hydroxylase and the genotype-phenotype association in Middle European patients with congenital adrenal hyperplasia.

OBJECTIVE: To analyze the mutational spectrum of steroid 21-hydroxylase (CYP21) and the genotype- phenotype correlation in patients with congenital adrenal hyperplasia (CAH) registered in the Middle European Society for Pediatric Endocrinology CAH database, and to design a reliable and rational approach for CYP21 mutation detection in Middle European populations. DESIGN AND METHODS: Molecular analysis of the CYP21 gene was performed in 432 CAH patients and 298 family members. Low-resolution genotyping was performed to detect the eight most common point mutations. High-resolution genotyping, including Southern blotting and sequencing was performed to detect CYP21 gene deletions, conversions, point mutations or other sequence changes. RESULTS: CYP21 gene deletion and In2 and Ile172Asn mutation accounted for 72.7% of the affected alleles in the whole study group. A good genotype-phenotype correlation was observed, with the exception of Ile172Asn and Pro30Leu mutations. In 37% of patients low resolution genotyping could not identify the causative mutation or distinguish homozygosity from hemizygosity. Using high-resolution genotyping, the causative mutations could be identified in 341 out of 348 analyzed patients. A novel mutation Gln315Stop was found in one simple virilising CAH (SV-CAH) patient from Austria. In the remaining seven patients polymorphisms were identified as the leading sequence alteration. The presence of elevated basal and ACTH-stimulated 17-hydroxyprogesterone, premature pubarche, advanced bone age and clitoral hypertrophy directly implicated Asn493Ser polymorphism in the manifestation of nonclassical- (NC) and even SV-CAH. CONCLUSIONS: By genotyping for the most common point mutations, CYP21 gene deletion/conversion and the 8 bp deletion in exon 3, it should be possible to identify the mutation in 94-99% of the diseased alleles in any investigated Middle European population. In patients with a mild form of the disease and no detectable mutation CYP21 gene polymorphisms should be considered as a plausible disease-causing mutation.

Disease course, frequency of relapses and survival of 73 patients with juvenile or adult dermatomyositis.

OBJECTIVE: Our aim is to present the disease course, frequency of relapses and survival of juvenile and adult dermatomyositis (JDM/DM) patients. METHODS: Analysis was performed using data on 73 patients. The median follow-up for 38 JDM patients was 32 months and 78 months for 35 adult DM patients. RESULTS: 23/38 JDM patients (60%) had monophasic, 12/38 (31.6%) had polycyclic and 3/38 (7.9%) had chronic disease. Among children treated only with glucocorticoids, 12/20 (60%) had monophasic and 8/20 (40%) had polycyclic disease. 10/17 (58.8%) children, who required second-line immunosuppressive agents, had monophasic and 4/17 (23.5%) had polycyclic disease. 18/35 DM (51.4%) patients had monophasic, 13/35 (37.1%) had polycyclic, 1/35 (2.9%) had chronic disease and 3/35 (8.6%) had fulminant myositis. Among DM patients requiring only glucocorticoids, 12/20 (60%) were monophasic and 8/20 (40%) were polycyclic. In patients requiring second-line immunosuppressive agents, 6/15 patients (40%) had monophasic and 5/15 (33.3%) had polycyclic disease. Among patients with polycyclic disease, the risk of relapse was higher during first year than later in the disease course. None of the JDM patients have died, while 4 disease-specific deaths occurred in adult patients. There was no significant difference between the survival of JDM and DM patients. DISCUSSION: There was no correlation between relapse-free survival and the initial therapeutic regimen. Many of our patients had polycyclic or chronic disease. As relapses can occur after a prolonged disease-free interval, patients should be followed for at least 2 years. Although we found a favourable survival rate, further investigations are needed to assess functional outcome.

Screening for mutations of 21-hydroxylase gene in Hungarian patients with congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders, causing impaired secretion of cortisol and aldosterone from the adrenal cortex, with subsequent overproduction of adrenal androgens. The most common enzyme defect causing CAH is steroid 21-hydroxylase deficiency. To determine the mutational spectrum in the Hungarian CAH population, the CYP21 active gene was analyzed using PCR. A total of 297 Hungarian patients with 21-hydroxylase deficiency are registered in the 2nd Department of Pediatrics, Budapest, Hungary, and their clinical status was evaluated. Blood samples for CYP21 genotype determination could be obtained from 167 patients (representing 306 unrelated chromosomes and 56.2% of the total group of patients). Eight of the most common mutations were screened [In2 (intron 2 splice mutation), I172N, Del (Del: apparents large gene conversion), Q318X, R356W, 1761Tins, ClusterE6, V281L] using allele-specific amplification. The most frequent mutation in the Hungarian CAH population was found to be In2. Our results have shown a good genotype/phenotype correlation in case of most mutations; the In2 mutation is associated mostly with the severe form of the disease, whereas I172N was expressed in a wide spectrum of phenotypes. 1999)

Transthyretin mutation (serine 84) associated with familial amyloid polyneuropathy in a Hungarian family.

A Hungarian family with familial amyloid polyneuropathy (FAP) was studied. The disease presented in two individuals with carpal tunnel syndrome in the fourth and fifth decades of life. The proband subsequently developed vitreous opacities requiring vitrectomy and now has evidence of cardiomyopathy. Single strand conformation polymorphism analysis and direct DNA sequencing revealed a variant AGC (serine) codon at amino acid position 84 of the amyloid precursor protein, transthyretin (TTR). The same single amino acid substitution in TTR was detected in an Indiana kindred with Swiss/German origin. Six individuals of the 11 tested being at risk for FAP proved to have the mutation in the present Hungarian kindred. This is the first description of this TTR gene mutation in Europe. Despite TTR gene haplotype analysis which suggests that the Hungarian and Indiana kindreds may have a common origin, no genealogical link has been identified between the families living in Indiana and Hungary.

3-Chloro-1,3,5-pregnatriene derivatives with glucocorticoid activity.

Novel synthetic glucocorticoid analogues were tested for receptor binding and glucocorticoid activity. They were of unusual structure, insofar as they had a 3-chloro rather than a 3-oxo function. 3-Chloro analogues of fluorinated glucocorticoids formed extremely stable complexes with the rat liver glucocorticoid receptor. 3-Chloro derivative of fluocinolone acetonide also had in vivo glucocorticoid activity. It induced tyrosine aminotransferase in the liver and repressed thymidine kinase in the thymus very effectively. It is concluded that 3-chloro analogues may retain glucocorticoid activity as well as the ability to bind to the glucocorticoid receptor protein.

Limited value of serum steroid measurements in identification of mild form of 21-hydroxylase deficiency.

BACKGROUND: ACTH stimulation test is widely used as a basic diagnostic method for non-classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD). However, the interpretation of this test has not been definitely established. To determine the cut-off values of basal and post-ACTH serum 17-OHP concentrations, data of patients with suspected 21-OHD has been analysed. PATIENTS AND METHODS: Two hundred and eighty-seven patients with postnatal/peripubertal virilization were investigated. Serum steroid concentrations were measured by RIA, urinary steroid profile was determined by capillary gas chromatography and mutation analysis of CYP21 gene was performed by allele specific PCR. 21-OHD was diagnosed by elevated serum 17-OHP concentrations, high level of the urinary 17-OHP metabolites and/or homozygosity for CYP21 mutations. RESULTS: Twenty-one patients of the total of 287 subjects (7.3 %) were identified as having 21-OHD. The numbers of 21-OHD patients compared to total numbers of patients with different ranges of serum 17-OHP were as follows: basal values below 3.5 ng/ml (mean + 1 SD) 0/225; between 3.5 - 6.6 ng/ml 3/41; above 6.6 ng/ml (mean + 2 SD) 18/21. Post-ACTH values below 6.4 ng/ml (mean + 1 SD) 0/226, between 6.4 - 10.3 ng/ml 0/35, above 10.3 ng/ml (mean + 2 SD) 21/26. CONCLUSION: There are patients with inappropriate peripubertal virilization who have slightly elevated 17-OHP concentrations. In this subgroup of patients more sensitive and specific methods are needed to establish the diagnosis of 21-OHD. Therefore we suggest performing an ACTH stimulation test in patients with a morning 17-OHP level above 3.5 ng/ml. Furthermore, urinary steroid profile and/or CYP21 gene analysis are needed in patients with a stimulated 17-OHP value between 10 and 30 ng/ml. These tests will distinguish between patients with non-classical 21-OHD and patients with other disorders.

A new route, jet-injection for anesthetic induction in children: I. Midazolam dose-range finding studies.

In order to assure rapid anesthetic induction in children and to prevent the psychological and physical trauma associated with restraint during mask induction or intramuscular injection, we evaluated the utility of a jet-injector and the effectiveness of midazolam for anesthetic co-induction in a dose-range finding study. Forty children (age: 1-6 yrs), whose parents gave a valid consent approved by the Institutional Review Board (IRB) and who underwent minor surgery, were randomized into four equal groups: A. midazolam 100 micrograms/kg by jet-injection (JI); B. midazolam 150 micrograms/kg JI; C. midazolam 200 micrograms/kg JI; D. midazolam 80 micrograms/kg i.m by conventional syringe-needle. As a drying agent, atropine 20 micrograms/kg JI or i.m. was also added to the midazolam solution. The onset and full sedative effect of midazolam, the scoring of sedation and emotional state, the ease of placement of the intravenous catheter, the speed of recovery by Aldrete-scores and the time for safe discharge were evaluated. No demographic differences were observed among the four groups with similar mean duration of surgery and anesthesia. The mean sedation score was reduced in Group C the most, less in the B, A and D groups. The onset of sedation ranged from 3-5 min in groups A, B or C as compared to 5-9 min in D. Ideal conditions for the start of i.v. catheter were best achieved in group C (8:8) and B (8:10) in contrast to groups A (2:10) and D (0:10). Whereas no i.v. start was difficult in B and C, 6:10 were difficult in D and A. None of the children in the three JI groups (A, B and C) experienced unpleasant recall or pain from the injection during the whole procedure. Response to verbal stimuli recovered in 3 min after the end of anesthesia and the children were discharged 8-9 minutes afterward. None of the children needed a longer than 15-minute interval to reach an Aldrete score of 10. No differences among the groups were observed as to the time of recovery or discharge. This new route of midazolam administration with the jet-injector allows pain-free and stress-free induction of anaesthesia after rapid placement of an intravenous catheter and prevents the transmission of infections.

A new route, jet-injection for anesthetic induction in children - II. ketamine dose-range finding studies.

Ketamine (K) i.m. has been widely used for anesthetic induction in small children in the last decades, if mask induction has failed. In many instances, however, physical restraint was required. In order to eliminate the pain of i.m. injection and to prevent the psychological and physical trauma associated with restraint, we evaluated the utility of jet-injection (j.i.) of K for anesthetic induction in a dose-range finding study. Thirty children (age 1-6 years), whose parents gave a valid consent approved by the IRB and were scheduled for minor surgeries, were randomized into 3 equal groups: A/ketamine 6.0 mg/kg j.i., B/ketamine 3.5 mg/kg j.i., C/ketamine 2.5 mg/kg j.i. As a drying agent atropine 20 microg/kg was also given i.v. The onset of full amnesic/sedative effect of K, the scoring of sedation and emotional state, the ease of placement of the i.v. catheter, the speed of recovery by Aldrete scores, and the time for safe discharge were evaluated. Although no demographic differences were observed among the groups the duration of surgery and anesthesia were longer in the B group (41 and 49 min) than in the A or C groups. The onset of sedation was significantly (p < 0.05) faster in group A (174 sec) than in group B (312 sec) or C (303 sec). However, no significant difference was observed in the onset of complete sedation among the groups. The sedation index was the lowest representing the best sedation in group A (4.2) while in group B and C were somewhat higher (4.6 and 4.4). There were no differences in the ease of i.v. cannulation among the groups. Recovery from anesthesia was the slowest in group A, although the differences among the 3 groups did not reach statistical significance. The mean discharge times ranged from 10-13 min with no differences among the groups. Laryngospasm occurred in 4:10 in group A and 1:10 in groups B and C. Evidently the high dose of K, 6.0 mg/kg caused a proneness to laryngospasm. Since no additional benefit was derived from this high dose, the lower doses (3.0 mg/kg) of K may be sufficient for routine use. None of the children experienced unpleasant recall or pain for the injection or the whole procedure. This new route of anesthetic induction with the jet-injector utilizing K may provide pain-free and stress-free induction as compared to its i.m. injection. This technique also prevents transmission of infection and is [correction of and cost] cost effective since simultaneous and/or sequential injection can be given from a single vial of K.

A new route, jet injection for anesthetic induction in children. IV. Midazolam plasma levels.

The jet injector route for midazolam was used in 40 children 1 - 6 years of age undergoing various short duration surgical procedures. A randomly selected dose of 100, 150, and 200 microg/kg was given by a jet injector and compared to 80 microg/kg by conventional i.m. injection with syringe and needle to induce sedation/anesthesia. Because of clinical limitations, plasma midazolam levels were measured for only up to 32 min post-injection. Peak levels were 70.4, 105.8, 157.3, and 135.5 ng/ml in the corresponding groups. Plasma levels reached their peak faster after 200 microg/kg jet injection than after 80microg/kg i.m. midazolam. Furthermore, midazolam plasma levels were sustained longer after 200 microg/kg by jet injection. Larger doses of midazolam are required by jet injection than by i.m. injection. Individual subjects showed considerable variability in plasma levels of midazolam by both methods of administration, although jet injection was more convenient and less traumatic.

A new route, jet injection for anesthetic induction in children--III. Ketamine pharmacokinetic studies.

The jet injector route for ketamine was used on 30 children 1-6 years of age undergoing various surgical procedures. A randomly selected dose of 2.5, 3.5, or 6.0 mg/kg of ketamine was given to induce anesthesia. Peak plasma ketamine levels did not follow a simple arithmetic increment related to dose. Dosage based on mg/m2 body surface area or mg/kg body weight provided similar blood levels of ketamine. The beta-phase t1/2 of ketamine in these children was shorter than that found in adults. Considerable individual variability was observed in both the plasma levels to a given dose of jet-injected ketamine and in the beta-phase t1/2. The ketamine beta-t1/2s were not dose related.

Relaxation: evaluation and applications.

Probabilistic relaxation labeling processes are iterative parallel schemes that use contextual information to reduce local ambiguities. The behavior of these processes can be described by examining the rates of change and entropies of the probability vectors at each iteration. Examples are given comparing three relaxation processes as applied to several basic image analysis tasks.

[Gallbladder torsion in infants]. / Kisdedkori epehólyagtorsio.

The infrequent case of gallbladder torsion and accompanying Meckel's diverticulum in a 3-year-old girl, is described. Detorquation, cholecystectomy and resection of the diverticulum were performed. Condition of the development of the disease as well as its clinical aspects and therapy are discussed. It is suggested to explore the abdominal cavity for other developmental anomalies in the course of the operation. The patient recovered without complications and left the hospital 14 days after the operation.