A neurosteroid analogue with T-type calcium channel blocking properties is an effective hypnotic, but is not harmful to neonatal rat brain.

BACKGROUND: More than 4 million children are exposed annually to sedatives and general anaesthetics (GAs) in the USA alone. Recent data suggest that common GAs can be detrimental to brain development causing neurodegeneration and long-term cognitive impairments. Challenged by a recent US Food and Drug Administration (FDA) warning about potentially neurotoxic effects of GAs in children, there is an urgent need to develop safer GAs. METHODS: Postnatal Day 7 (P7) rat pups of both sexes were exposed to six (repeated every 2 h) injections of equipotent hypnotic doses of ketamine or the neuroactive steroid (3ß,5ß,17ß)-3-hydroxyandrostane-17-carbonitrile (3ß-OH) for 12 h. Loss of righting reflex was used to assess hypnotic properties and therapeutic index; quantitative caspase-3 immunohistochemistry was used to assess developmental neuroapoptosis; patch-clamp recordings in acute brain slices were used to assess the effects of 3ß-OH on neuronal excitability and synaptic transmission. Cognitive abilities of rats exposed to ketamine, 3ß-OH, or vehicle at P7 were assessed in young adulthood using the radial arm maze. RESULTS: The neuroactive steroid 3ß-OH has a therapeutic index similar to ketamine, a commonly used clinical GA. We report that 3ß-OH is safe and, unlike ketamine, does not cause neuroapoptosis or impair cognitive development when administered to P7 rat pups. Interestingly, 3ß-OH blocks T-type calcium channels and presynaptically dampens synaptic transmission at hypnotically-relevant brain concentrations, but it lacks a direct effect on γ-aminobutyric acid A or glutamate-gated ion channels. CONCLUSIONS: The neurosteroid 3ß-OH is a relatively safe hypnotic that warrants further consideration for paediatric anaesthesia.

Reirradiation plus EGFR inhibition in locally recurrent and unresectable head and neck cancer: final results from a single institution.

PURPOSE: For some patients with recurrent, unresectable, and previously irradiated head and neck squamous cell carcinoma (HNSCC), reirradiation (re-RT) may be a curative option. Chemotherapy with epidermal growth factor receptor (EGFR) inhibition is established as palliative management. This retrospective single-institutional study investigates feasibility, toxicity, and outcome of reirradiation (re-RT) combined with EGFR blockade for these patients. PATIENTS AND METHODS: Between June 2008 and June 2012, 23 patients with inoperable and previously irradiated HNSCC were reirradiated. Concomitant EGFR blockade (cetuximab) was given initially at 400 mg/m2 two days prior to re-RT and weekly (250 mg/m2) thereafter. PET/CT imaging was fused with planning CT in 8 patients. RESULTS: One patient died of anaphylactic shock during the first cetuximab administration; two discontinued treatment on their own request. In all, 20 patients completed re-RT (50.4-66.6 Gy) and received cetuximab as prescribed. Grade 3 acute side effects were documented for dermatitis (35%), dysphagia (30%), acneiform rash (30%), and mucositis (15%). The 1-year overall survival rate was 34.8% Median overall and progression-free survival times were 9 and 4.3 months, respectively. A multivariable analysis using the Cox regression model showed significant positive impact of acneiform rash (hazard ratio [HR] 0.1531, 95% confidence interval [CI] 0.0383-0.6111), while a period from first radiation to re-RT longer than 120 months negatively (HR 0.1633, 95% CI 0.0305-0.8734) influenced patient survival. CONCLUSION: re-RT with concurrent cetuximab was feasible. Compared to platinum-based chemotherapy with fluorouracil and cetuximab, this therapeutic approach did not demonstrate survival benefit. Prolonged intervals from first treatment to re-RT seem to be unfavorable.

Relapsing high grade mucoepidermoid carcinoma. Long-lasting complete response following reirradiation and EGFR blockade.

BACKGROUND AND PURPOSE: The treatment strategy for inoperable recurrent mucoepidermoid carcinoma (MEC) is not well established. Here, we present a case of a relapsed high grade MEC of the salivary glands of the hard palate that was successfully treated with a reirradiation (re-RT) and cetuximab, an antibody against epidermal growth factor receptor (EGFR). CASE REPORT: Twelve years after resection and adjuvant radiotherapy for high grade MEC of the salivary glands, a patient presented with inoperable recurrent disease. She received another 59.4 Gy. In addition, 400 mg/m(2) cetuximab was administered in the first week, followed by six additional weekly courses at 250 mg/m(2). RESULTS: Treatment was well tolerated. The patient is doing well and continuous radiological complete response (CR) is documented for 25 months after completion of the combined treatment. CONCLUSION: Combined re-RT and targeted inhibition of EGFR with cetuximab may be a valuable therapeutic strategy in patients with recurrent localized high grade MEC who are not candidates for radical surgery.

Changes in telomerase activity after irradiation of human peripheral blood mononuclear cells (PBMC) in vitro.

Telomerase activity (TA) has been shown to be up-regulated by ionising radiation in immortal hematopoietic cell lines. The purpose of the present experiments was to test whether ionising radiation may regulate TA in normal human peripheral blood mononuclear cells (PBMC). A real-time PCR assay was established to quantify TA detected by the telomeric repeat amplification protocol. TA of PBMCs isolated from young healthy donors was highly increased by stimulation with phytohemagglutinin (PHA) for 72 h. Irradiation of PHA-stimulated PBMCs with 2-10 Gy of X rays showed up-regulated TA 4 h after irradiation with an enhancement at least as strong as for the human TK6 lymphoblastoid cell line. The present results show that TA is up-regulated by irradiation not only in immortal cell lines but also in mitogen-stimulated PBMCs. This supports a possible role for telomerase in the cellular radiation response.

[Intensity modulated radiotherapy (IMRT) of head and neck tumors. Increased biological effectiveness in high-risk situations by "integrated boost" therapy]. / Intensitätsmodulierte Bestrahlung (IMRT) von Kopf-Hals-Tumoren. Höhere biologische Wirksamkeit in Risikosituationen durch "integrierten Boost"

Primary tumors of the paranasal sinuses are rare entities which, because of precarious localization and frequently diffuse propagation into neighbouring cavities and the skull base, pose a significant therapeutic problem. Even after complete surgical resection, local relapses are frequent. Postoperative radiotherapy is therefore usually indicated. Intensity modulated radiotherapy (IMRT) is a new technique that helps creating dose distributions that conform closely to the target volume while maximally sparing the organs at risk. This results in the possibility of applying escalated doses to the target while still keeping the incidence of side effects low. What is especially appealing is the possibility of shaping the dose distribution within the target in such a way that areas with a presumably high tumor cell load receive increased doses, a concept which is best described by the term "integrated boost". We present the case of a patient with a sinunasal carcinoma and describe the implications of the clinical implementation of this technique.

Anthropometric characteristics of elite junior male and female javelin throwers.

The purpose of this study was to examine the anthropometric characteristics of elite junior javelin throwers on a sample of eleven male and twelve female finalists of the European Junior Championship in Athletics (MEPA 98). The chosen subjects were measured with a set of nine anthropometric variables, according to the methodology recommended by the International Biological Programme. The results show that no common constitutional type of a junior male or female javelin thrower exists, but that the anthropometric characteristics are very individually defined. At least two constitutional types exist for each gender, ensuring equal success in javelin. Correlational analysis shows that no statistically significant correlations exist between the individual anthropometric characteristics of the male and female throwers with their competitive result. Success in this track and field discipline is therefore more a synthesis of anthropometric characteristics and motor abilities, as well as an optimal technique.

Morphologic and kinematic characteristics of elite sprinters.

The purpose of the study was to ascertain the basic morphologic and kinematic characteristics of elite sprinters. The sample included 24 sprinters, with times over a 100 m distance between 10.21 s and 11.19 s. Morphologic characteristics of the sprinters were measured with a test battery of 17 measures, obtained according to the methodology prescribed by the International Biologic Programme (IBP). The kinematic variables were obtained from a flying start 20 m run and a 20 m run with a low start, with the technology of a contact carpet (ERGO TESTER-Bosco). Stride frequency and length, duration of contact and flight phases were registered. Time parameters were measured with a system of infrared photocells (BROWER Timing System). T-test showed that elite sprinters do not differ significantly in morphologic characteristics (p > 0.05) from the 100 m results point of view. However, statistically significant differences were obtained in starting acceleration and maximal velocity. The most important kinematic parameters for generating differences between the elite sprinters are contact time and stride frequency.

[Intestinal intussusception in children. Ultrasonic diagnosis]. / Invaginacija intestinuma kod dece. Dijagnostika ultrazvukom.

The aim of the paper is to demonstrate a successful use of ultrasound in the diagnosis of intestinal intussusception in children. Ultrasound decreases the number of irrigographic examinations and reduces diagnostic exposure of children to X-rays. In the last three years 35 children, aged from 3 months to 15 years (average 2 years), had a suspected clinical diagnosis of intussusception. The ultrasound studies revealed intestinal intussusception in 26 patients (74%). There were no false positive or false negative ultrasound findings. In four patients with secondary intussusception the main symptoms were identified (three solid lesions and two Meckel's diverticula). Intraluminal lesions at the apex of intussusception were confirmed by surgery. In 22 patients intussusception was idiopathic. In 15 of these patients (68%), hydrostatic desinvaginations, under combined ultrasound and radioscopic control, were successful. High grade unsuccessful hydrostatic reductions were associated with long persistence of symptoms (2 to 9 days). Ultrasound is reliable in diagnosis of intestinal intussusception and useful in control of hydrostatic reduction. In patients with expected intestinal perforation ultrasound should be combined with fluoroscopy.

Analysis of changes in indicators of functional and motor readiness of female basketball players within one-year training cycles.

The basic goal of this work was the evaluation of functional and motor preparedness of 13 top female basketball players during a one-year training cycle. Across of the six time points the preparedness of subjects was measured by means of a twelve-test battery measuring the basic and specific motor and functional abilities. The experimental training program was the yearly training macrocycle with all its components and duration. The differences among individual measurements in the space of twelve basic and specific functional and motor variables were analyzed by the statistical procedures in the framework of discriminant analyses. In comparison to the first measurement, the players achieved better results in the second, third, fourth, fifth and sixth measurements. On the multivariate level, only the analysis of differences between the first and third measurements indicated statistically significant differences. It can be concluded that the training process executed during the course of the preparation and competition periods (the transitional period was excluded from the analysis) induced positive changes.

LABORATORY EVOLUTION OF LIFE-HISTORY TRAITS IN THE BEAN WEEVIL (ACANTHOSCELIDES OBTECTUS): THE EFFECTS OF SELECTION ON DEVELOPMENTAL TIME IN POPULATIONS WITH DIFFERENT PREVIOUS HISTORY.

In this study we examined the direct and correlated responses for fast and slow preadult development time in three laboratory populations of the bean weevil (Acanthoscelides obtectus). The first population ("base," B) has experienced laboratory conditions for more than 10 years; the second ("young," Y) and the third ("old," O) populations were selected for early and late reproduction, respectively, before the onset of the present experiments. All three populations are successfully selected for both fast and slow preadult development. The realized heritabilities are very similar in all populations, suggesting a similar level of the additive genetic variance for preadult development. We studied the correlated responses on the following life-history traits: egg-to-adult viability, wet body weight, early fecundity, late fecundity, total realized female fecundity, and adult longevity. All life-history traits examined here, except for the egg-to-adult viability, are affected by selection for preadult development in at least in one of the studied populations. In all three populations, beetles selected for slow preadult development are heavier and live longer than those from the fast-selected lines. The findings with respect to adult longevity are unexpected, because the control Y and O populations, selected for short- and long-lived beetles, respectively, do not show significant differences in preadult development. Thus, our results indicate that some kind of asymmetrical correlated responses occur for preadult development and adult longevity each time that direct selection has been imposed on one or the other of these two traits. In contrast to studies with Drosophila, it appears that for insect species that are aphagous as adults, selection for preadult development entails selection for alleles that also change the adult longevity, but that age-specific selection (applied in the Y and O populations) mostly affects the alleles that have no significant influence on the preadult development. Implications of these findings on the developmental and evolutionary theories of aging are also discussed.

The conservative treatment of phimosis in boys.

OBJECTIVE: To further test the application of topical steroids in boys referred to a paediatric surgical practice with pathological, non-retractable foreskins diagnosed as phimosis. PATIENTS AND METHODS: This prospective study comprised two groups of 20 boys each (mean age 4.1 years, range 3-6) diagnosed as having phimosis; twice daily, a topical steroid (0.05% betamethasone cream) was applied on the narrowed preputial skin in the first group and a neutral cream (Vaseline) in the second (control) group. Patients were treated for 4 weeks and the retractability of the foreskin and any side-effects assessed. RESULTS: Good retraction of the foreskin was achieved in 19 patients treated with betamethasone cream and the response was unsatisfactory in 16 patients from the control group; these 16 boys and one 6-year-old boy treated with betamethasone were circumsized. There were no side-effects or problems after the application of either cream. CONCLUSION: Treatment with 0.05% betamethasone cream is a simple and safe method for the treatment of phimosis in boys older than 3 years. An early operation is necessary in cases of genuine phimosis when 1 month of treatment with topical steroids has failed. We strongly support the saying, "The fortunate foreskin of an infant boy will usually be left well alone by everyone but its owner'.

Extravesical detrusor tunneling: a variant of antireflux procedure.

Detrusor tunneling procedure is an extravesical technique, which provides antireflux implantation of different tube systems (ureter, appendix, tubularized preputial flap, tapered ileum). The main characteristic of the technique is the formation of extravesical submucosal tunnel by creating a bridge from the unresected bladder muscle under which the tube is passed. During the period from January 1987 to July 1995, the technique was performed on 442 different tube systems: 402 ureters, 12 appendices, 26 tubularized preputial flaps and 2 tapered ileums. Patients were aged from 15 days to 42 years (mean 39 months). Follow-up was from 2 months to 8 years (mean 2.9 years). Postoperative complications occurred in 11 cases. There were 3 stenoses and 5 refluxes in ureteroneocystostomies, and one stenosis and 2 urine leakages in continent cutaneous vesicostomies. The extravesical detrusor tunneling procedure could be a very useful method for antireflux implantation of various tube systems.

[Cystic tumefaction in the minor pelvis--the agenesis-dysplasia syndrome (case report)]. / Cisticka tumefakcija u maloj karlici--sindrom agenezije-displazije (prikaz bolesnika)]

UNLABELLED: Ectopic kidney often shows signs of parenchyma maldifferentiation. Multicystic or dysplastic kidney is usually associated with congenital urogenital and skeletal system anomalies. In the Unilateral form of the agenesia-dysplasis syndrome, the kidney, if it is present, is small dysplastic and usually cystically changed. Ipsilateral uterus horn or vaginal agenesia are the most frequently associated anomalies. Case report. A six years old girl was clinically examined due to recurrent urinary tract infections. On ultrasound, the left kidney was enlarged, while the right kidney was absent in normal position. Cystic mass 4x5 cm was seen in the pelvis. The right kidney was not seen on IVP. CT scan showed a cystic formation in the pelvis, described as cystically changed dysplastic kidney. Pelviceal mass was extirpated. Exploration of the genital system revealed vaginal arch blinded in the hypoplastic right uterus horn. On pathohystology tumefaction corresponded to the dysplastic kidney. IN CONCLUSION: unilateral renal aplasia or dysplasia may indicate genital anomalies having in mind the hereditary character of unilateral form of the agenesia-dysplasia syndrome therefore, it could be helpful in prenatal diagnosis of cystic pelvic mass of fetus in families with this syndrome.

[Surgical treatment of vesicoureteral reflux by tunnelling of the detrusor muscles]. / Hirursko lecenje vezikureterskog refluksa metodom tunelisanja misica detruzora.

Detrusor tunnelling is an extravesical surgical procedure of ureteral reimplantation. It is surely the least traumatic method of surgical correction of vesico-ureteral reflux because antireflux mechanism is achieved with minimal detrusor muscle dissection. This procedure simplifies implantation of dilated ureters, double ureters as well as the ureters shortened by previous antireflux surgical procedures. Ureteral tapering is unnecessary. One hundred and forty detrusor tunnelling uretero-cysto-neostomies in 102 patients have been performed in the University Children's Hospital between January 1990 and September 1994. The youngest patient was 1 month old and the eldest was 15 years (mean age 6.8 years). Indications for surgical treatment were primary (45.0%) and secondary (26.4%) megaureter as well as grade IV & V (international classification) vesico-ureteral reflux (28.6%). Follow up was 1-40 months (mean 26 months). Excellent postoperative results were achieved in 130 detrusor tunnelling uretero-cysto-neostomies, i.e. more than 90% of patients. Complication rate was 7.1% (6 patients-10 ureteral units) and about one third were classified as major-postoperative relapses or stenosis or minor-intraoperative mucosal perforation, hematuria, parahiatal diverticulum, spontaneous proximal migration of ureteral double J stent-about two thirds.

[An unusual spleen abscess in a 13-year-old girl after appendectomy]. / Apsces slezine kod 13-godisnje devojcice kao komplikacija apendicitisa.

Spleen abscess is not frequent in children. It may be caused by haematogenous seeding of the spleen with bacteria from primary septic focus; by direct spread of infection from adjacent structures, or by secondary infection in an area of the spleen damaged by infarction, trauma or parasitic infestation. A 13-year-old girl with spleen abscess following appendectomy is presented. Uneventful appendectomy was followed by prolonged unexplained sepsis that could not be controlled with high intravenous doses of different antibiotics. One month after appendectomy, exploration of the postoperative wound, pericecal and Douglas region was done, but neither pus or intra-abdominal foreign body were found. Abdominal ultrasonography and Nuclear Magnetic Resonance (NMR) revealed multiple spleen abscesses in the upper pole and the hilus region 44 days after appendectomy. Splenectomy with left subphrenic space drainage was performed, and an accessory spleen, 29 x 12 mm, was left intact. Left subphrenic abscess was revealed by echosonography 10 days later (5 days after abdominal drain has been removed), and image-guided percutaneous abscess drainage was therefore performed. Continous irrigation of the abscess cavity with adequate antibiotic solution, through pigtail drain left in position, was installed for next 12 days until the wash out was clear and sterile. Drain was removed and the patient discharged. Four months after discharge the patient was asymptomatic.

[Central venous access: our experience with Hickman and Broviac catheter in children]. / Centralni venski prisup--nasa iskustva s primenom katetera tipa Hikman-Brovijak kod dece.

We report the results of a 4-years-experience with Hickman-Broviac double lumen silicone catheters. The catheters were inserted in 51 dialysed and nondialysed children. Forty three catheters were placed for temporary or permanent dialysis access, 2 in patients for plasmapheresis, 4 in severely burnt patients, and 2 in neonates with the "short gut" syndrome. The youngest patient was 7 days old and the eldest 14.5 years (mean age 5.4 years). The catheters were implanted by open surgery into the right atrium through the right (92%) or left internal jugular vein (8%) in more than 80% of patients. Ten catheters were implanted in the femoral vein (three through the saphenous vein: in a patient with extensive burns in the thorax and neck area, and in seven patients with acute renal failure and high risk for anaesthesia). The complications, except the insufficient flow, were fewer and less dangerous than those reported in literature. Therefore, we strongly recommend insertion of these catheters as the method of choice for immediate vascular access in children in whom the creation of conventional vascular access is difficult or impossible, as well as in patients in whom provision of long- term intravenous nutrition or medication is essential.

[Diagnosis of ureteral duplication associated with complications]. / Dijagnostika dvostrukog uretera pracenog komplikacijama.

In three patients (mean age about 3 years) we established excretory tract duplication with obstructed ectopic ureter, a function of the upper pole and ectopic ureterocele. Diagnostic procedure was different in each case. Ultrasonography was the most important diagnostic method in all cases; it usually showed all main morphological details, regardless of functional ability of the kidney. To complete diagnosis, we used additional methods: antegrade pyelography and percutaneous nephrotomy. Excretory urography and voiding cystography gave only indirect signs of a functional part of duplicated excretory tract. The methods we used were complementary and they should rationally be combined in order to complete the diagnosis of ureteral duplication with complications.

[Diagnostic and therapeutic significance of percutaneous nephrostomy in children]. / Dijagnosticki i terapijski znacaj perkutane nefrostomije u dece.

During the period from April 1986 to March 1988 on the Pediatric Clinic in Belgrade a total of 12 percutaneous nephrotomies were performed to relieve obstruction of the upper urinary tract. The youngest patient was a two-month old with giant hydronephrosis, and the oldest was a 12-year old girl with an acute kidney obstruction caused by impaction of wedging the poured off stone. The most common reasons for obstruction of the upper urinary tract were congenital stenoses and postoperative scars, urethrocystoneostomia and pyeloplasty. The most frequent clinical manifestations in patients on whom nephrotomy was carried out as an emergency operation were infection, palpable tumor (cyst) and acute kidney insufficiency. Percutaneous nephrostomy was always performed with basal sedation and local infiltrative anesthesia under X-ray control. Surgery was necessary in all cases, but no complications needing surgical intervention occurred. Mild hematuria can be expected at almost every punction, so it should not be treated as a complication. Dislocation of the nephrostoma catheter immediately after surgery can be a complication which necessitates reintervention, but if this happens after more than ten days, the catheter can easily be replaced through the formed fistulous channel. In one case percutaneous placing of the catheter was not possible, so it was placed surgically in the kidney and skin to enable drainage of the infected urinome a month after rupture of the ureteropyelic segment. Percutaneous placing of a catheter through the nephrostoma is the method of choice for urgent and temporary relief of obstructions of the upper urinary system regardless of etiology, and this procedure achieves immediate therapeutic and, if necessary, diagnostic effect which enables recovery of the patient and preparation for definitive surgery which in such a situation could be hazardous.

[Surgery in recurrence of undescended testes]. / Hirurgija recidiva nesputenog testisa.

In the period from Jan. '80 to Dec. '87 at the Pediatric Surgical Clinic in Belgrade 119 patients were operated upon or 147 recurrencies of undescended testes; in 28 cases (23.52%) there were bilateral recurrences. 4 patients were twice unsuccessfully operated on at the same side. The authors analyse the causes of failures of orchiopexy; the proved mistakes were divided into four groups: a) Mistakes due to the undiscovering of the testis, b) unpreparation, or insufficiently preparated the testis from surrounding tissues, c) insufficiently shortening of the testis' way toward the scrotum, and d) mistakes being occasionally arised during the fixation of the testis into the scrotum. During the first unsuccessful operation 20 testes have atrophied, so that a reintervention consisted only in the exploration. In other cases the testis was placed into the scrotum regardless whether it was normal or hypotrophic. In two cases a Fowler-Stephens procedure was carried out, and in one case an autotransplantation of the testis was done. An improvement was found in 89 testes (60.57%), while 38 cases (25.85%) remained with the same characteristics, as they were in the course of our surgical interventions.