[Examination of urine in the child]

The examination of urine in children can be very complex, due to the difficulty to obtain clean urine specimens in infants and toddlers. Clean catch is an easy system to obtain urine but patience is needed. Transurethral catheterization or suprapubic aspiration is useful in infants and toddlers with sign of pyelonephritis. Urine bag specimens are not useful in the diagnosis of urinary tract infection because of the high rate of false positive cultures. The 24 hours urine collection is frequently replaced by a spot urine and the ratio of the measured substances with the urine creatinine are calculated. Urine microscopy is needed for the evaluation of pathological results in the dipstick testing: confirm that red urine is due to haematuria by demonstration of red blood cells on urine microscopy, dysmorphic cells and red-cell casts are pathognomonic of glomerular bleeding, white-cell casts signify glomerular inflammation and bacteria are easily seen in unstained urine. A urine culture is pathologic if the colony count exceeds 10(4) in the transurethral catheterization or clean void. In the suprapubic aspiration is any number of colony pathologic. Urate crystals in the urine of infants may cause a pink discoloration to nappies. Urine screenings are not very useful and should be performed only at the age of 5 years or by sexual-active adolescents.

Post-surgical follow-up (by ELISA and immunoblotting) of cured versus non-cured cystic echinococcosis in young patients

The study was designed to determine comparatively the prognostic value of immunoblotting and ELISA in the serological follow-up of young cystic echinococcosis (CE) patients exhibiting either a cured or a progredient (non-cured) course of disease after treatment. A total of 54 patients (mean age 9 years, range from 3 to 15 years) with surgically, radiologically and/or histologically proven CE were studied for a period up to 60 months after surgery. Additionally, some of the patients underwent chemotherapy. Based on the clinical course and outcome, as well as on imaging findings, patients were clustered into 2 groups of either cured (CCE), or non-cured (NCCE) CE patients. ELISA showed a high rate of seropositivity 4 to 5 years post-surgery for both CCE (57.1%) and NCCE (100%) patients, the difference found between the two groups was statistically not significant. Immunoblotting based upon recognition of AgB subcomponents (8 and 16 kDa bands) showed a decrease of respective antibody reactivities after 4 years post-surgery. Only sera from 14.3% of CCE patients recognized the subcomponents of AgB after 4 years, while none (0%) of these sera was still reactive at 5 years post-surgery. At variance, immunoblotting remained positive for AgB subcomponents in 100% of the NCCE cases as tested between 4 and 5 years after surgical treatment. Immunoblotting therefore proved to be a useful approach for monitoring post-surgical follow-ups of human CCE and NCCE in young patients when based upon the recognition of AgB subcomponents.

[Metaphylaxis of recurrent renal calcium stones]

Calcium containing renal stones represent a common medical problem and show a high rate of recurrence. Therefore, besides the treatment of acute stone episodes, also the prevention of new stone episodes is of crucial importance in the medical care of stone formers. To avoid stone recurrences, medical as well as dietary measures should be established based on the results of a thorough evaluation and the elaboration of an individual risk profile. This review article describes and discusses the currently established treatment options for the prophylaxis of calcium-containing renal stones.

Orthotopic transplantation of v-src-expressing glioma cell lines into immunocompetent mice: establishment of a new transplantable in vivo model for malignant glioma

OBJECT: The aim of this study was to develop and characterize a new orthotopic, syngeneic, transplantable mouse brain tumor model by using the cell lines Tu-9648 and Tu-2449, which were previously isolated from tumors that arose spontaneously in glial fibrillary acidic protein (GFAP)-v-src transgenic mice. METHODS: Striatal implantation of a 1-microl suspension of 5000 to 10,000 cells from either clone into syngeneic B6C3F1 mice resulted in tumors that were histologically identified as malignant gliomas. Prior subcutaneous inoculations with irradiated autologous cells inhibited the otherwise robust development of a microscopically infiltrating malignant glioma. Untreated mice with implanted tumor cells were killed 12 days later, when the resultant gliomas were several millimeters in diameter. Immunohistochemically, the gliomas displayed both the astroglial marker GFAP and the oncogenic form of signal transducer and activator of transcription-3 (Stat3). This form is called tyrosine-705 phosphorylated Stat3, and is found in many malignant entities, including human gliomas. Phosphorylated Stat3 was particularly prominent, not only in the nucleus but also in the plasma membrane of peripherally infiltrating glioma cells, reflecting persistent overactivation of the Janus kinase/Stat3 signal transduction pathway. The Tu-2449 cells exhibited three non-random structural chromosomal aberrations, including a deletion of the long arm of chromosome 2 and an apparently balanced translocation between chromosomes 1 and 3. The GFAP-v-src transgene was mapped to the pericentromeric region of chromosome 18. CONCLUSIONS: The high rate of engraftment, the similarity to the high-grade malignant glioma of origin, and the rapid, locally invasive growth of these tumors should make this murine model useful in testing novel therapies for human malignant gliomas.

Nosocomial infection: A risk factor for a complicated course in children with respiratory syncytial virus infection - Results from a prospective multicenter German surveillance study

BACKGROUND: Nosocomially acquired respiratory syncytial virus infections (RSV-NI) may cause serious problems in hospitalized paediatric patients. Hitherto, prospectively collected representative data on RSV-NI from multicenter studies in Germany are limited. METHODS: The DMS RSV Ped database was designed for the prospective multicenter documentation and analysis of clinically relevant aspects of the management of inpatients with RSV-infection. The study covered six consecutive seasons (1999-2005); the surveillance took place in 14 paediatric hospitals in Germany. RESULTS: Of the 1568 prospectively documented RSV-infections, 6% (n=90) were NI and 94% (n=1478) were community acquired (CA). A significantly higher proportion in the NI group displayed additional risk factors like prematurity, chronic lung disease, mechanical ventilation (med. history), congenital heart disease, and neuromuscular impairment. Of all NI, 55% occurred in preterms (30.6% of all RSV-infections in preterms with severe chronic lung disease of prematurity were NI). Illness severity as well as the total mortality, but not the attributable mortality was significantly higher in the NI group. In the multivariate analysis, NI was significantly associated with the combined outcome 'complicated course of disease'. CONCLUSION: This is the first prospective multicenter study from Germany, which confirms the increased risk of a severe clinical course in nosocomially acquired RSV-infection. Of great concern is the high rate of (preventable) NI in preterms, in particular in those with severe chronic lung disease or with mechanical ventilation due to other reasons.

Stent placement in acute cerebral artery occlusion: use of a self-expandable intracranial stent for acute stroke treatment

Stent placement has been applied in small case series as a rescue therapy in combination with different thrombolytic agents, percutaneous balloon angioplasty (PTA), and mechanical thromboembolectomy (MT) in acute stroke treatment. These studies report a considerable mortality and a high rate of intracranial hemorrhages when balloon-mounted stents were used. This study was performed to evaluate feasibility, efficacy, and safety of intracranial artery recanalization for acute ischemic stroke using a self-expandable stent.

Procedural and 30-day outcomes following transcatheter aortic valve implantation using the third generation (18 Fr) corevalve revalving system: results from the multicentre, expanded evaluation registry 1-year following CE mark approval

AIMS: To describe the procedural performance and 30-day outcomes following implantation using the 18 Fr CoreValve Revalving System (CRS) as part of the multicentre, expanded evaluation registry, 1-year after obtaining CE mark approval. METHODS AND RESULTS: Patients with symptomatic severe aortic stenosis and logistic Euroscore > or =15%, or age > or =75 years, or age > or =65 years associated with pre-defined risk factors, and for whom a physician proctor and a clinical specialist were in attendance during the implantation and who collected the clinical data, were included. From April 2007, to April 2008, 646 patients with a mean age of 81 +/- 6.6 years, mean aortic valve area 0.6 +/- 0.2 cm2, and logistic EuroSCORE of 23.1 +/- 13.8% were recruited. After valve implantation, the mean transaortic valve gradient decreased from 49.4 +/- 13.9 to 3 +/- 2 mmHg. All patients had paravalvular aortic regurgitation < or = grade 2. The rate of procedural success was 97%. The procedural mortality rate was 1.5%. At 30 days, the all-cause mortality rate (i.e, including procedural) was 8% and the combined rate of death, stroke and myocardial infarction was 9.3%. CONCLUSIONS: The results of this study demonstrate the high rate of procedural success and a low 30-day mortality in a large cohort of high-risk patients undergoing transcatheter aortic valve implantation (TAVI) with the CRS.

Metal-ion-dependent biological properties of a chelator-derived somatostatin analogue for tumour targeting

Somatostatin-based radioligands have been shown to have sensitive imaging properties for neuroendocrine tumours and their metastases. The potential of [(55)Co(dotatoc)] (dotatoc =4,7,10-tricarboxymethyl-1,4,7,10-tetraazacyclododecane-1-ylacetyl-D-Phe-(Cys-Tyr-D-Trp-Lys-Thr-Cys)-threoninol (disulfide bond)) as a new radiopharmaceutical agent for PET has been evaluated. (57)Co was used as a surrogate of the positron emitter (55)Co and the pharmacokinetics of [(57)Co(dotatoc)] were investigated by using two nude mouse models. The somatostatin receptor subtype (sst1-sst5) affinity profile of [(nat)Co(dotatoc)] on membranes transfected with human somatostatin receptor subtypes was assessed by using autoradiographic methods. These studies revealed that [(57)Co(dotatoc)] is an sst2-specific radiopeptide which presents the highest affinity ever found for the sst2 receptor subtype. The rate of internalisation into the AR4-2J cell line also was the highest found for any somatostatin-based radiopeptide. Biodistribution studies, performed in nude mice bearing an AR4-2J tumour or a transfected HEK-sst2 cell-based tumour, showed high and specific uptake in the tumour and in other sst-receptor-expressing tissues, which reflects the high receptor binding affinity and the high rate of internalisation. The pharmacologic differences between [(57)Co(dotatoc)] and [(67)Ga(dotatoc)] are discussed in terms of the structural parameters found for the chelate models [Co(II)(dota)](2-) and [Ga(III)(dota)](-) whose X-ray structures have been determined. Both chelates show six-fold coordination in pseudo-octahedral arrangements.

[Pediatric cardiac disease: indications for family screening and risk stratification]

In some forms of cardiac disease in childhood, familial occurrence is frequent. This implies the question whether family members should undergo cardiologic screening examinations. For cardiomyopathies the familiarity is so frequent and morbidity so important that examination by echo of all first degree relatives is recommended. As these cardiomyopathies may develop its phenotype all along a lifetime, repetitive examinations usually are indicated. For the primary electrical diseases the so called channelopathies the same is true, as for the high rate of familial occurrence and the high morbidity. Thus ECG screening of first degree relatives is recommended. In a child with congenital heart disease there are no recommendations with regard to familial screening and cardiological examinations usually are indicated only in case of clinical suspicion for heart disease.

[Tumor surveillance after resection of colorectal cancer]

Because recurrent adenocarcinoma of the colon and rectum (CRC) can still be treated with acceptable 5-year survival rates, tumor surveillance plays an important role. Early detection of recurrent disease from CRC allows for effective treatment with intention for cure. This is why, in 2007, an interdisciplinary group modified the popular "FAGAS" criteria, a proposition for surveillance after curative resection of colorectal cancer. Proposed are the 3-monthly follow-up of the tumor marker CEA (carcino embryonic antigen), which, in case of lower sigmoid or rectal cancer, would be completed by rectosigmoidoscopy and endosonography every 6 months. As a major change liver sonography is now proposed to be replaced by annual thoraco-abdominal CT scan. Colonoscopy within the first year after resection has its place in the surveillance due to a high rate of metachronous secondary tumors missed in the initial endoscopy. Once completed it needs not to be repeated for at least 3 years. Only in cases where early stage CRC was been completely resected no schematic surveillance must take place.

Double-lung transplantation in the rat: an acute, syngeneic in situ model

BACKGROUND. The high rate of reperfusion injury in clinical lung transplantation mandates significant improvements in lung preservation. Innovations should be validated using standardized and low-cost experimental models. METHODS. The model introduced here is analyzed by comparing global lung function after varying ischemic times (2, 4, 8, 16, and 24 hours). A rat double-lung block is flush-perfused, and the main pulmonary artery and left atrium are connected to the left pulmonary artery and vein of a syngeneic recipient using a T-shaped stent. With pressure side ports and incorporated flow crystals, measurement of vascular resistance and graft oxygenation can be performed. The transplant is ventilated separately, and compliance and resistance are determined. RESULTS. The increase in the ischemic interval from 2 to 24 hours caused an increase in the alveolar arterial oxygen difference from 220 +/- 20 to 600 +/- 34 mm Hg, pulmonary vascular resistance from 198 +/- 76 to 638 +/- 212 mm Hg.mL-1.min-1, and resistance to airflow from 274 +/- 50 to 712 +/- 30 cm H2O/L H2O, and a decrease in pulmonary compliance from 0.4 +/- 0.05 to 0.12 +/- 0.06 mL/cm H2O. CONCLUSIONS. This in situ, syngeneic rat lung transplantation model offers an alternative to large animal models for verification of lung preservation solutions and for modification of donor or recipient treatment regimens.

Neer Award 2007: Reversion of structural muscle changes caused by chronic rotator cuff tears using continuous musculotendinous traction. An experimental study in sheep

HYPOTHESIS: Chronic rotator cuff tears are associated with irreversible architectural muscle changes and a high rate of repair failure. The changes observed in man and their irreversibility with a single stage repair can be reproduced in sheep. It was the purpose of this experiment to test the hypothesis that slow, continuous elongation of a retracted musculotendinous unit allows reversal of the currently irreversible structural muscle changes. MATERIALS AND METHODS: The infraspinatus tendon of 12 sheep was released using a greater tuberosity osteotomy and allowed to retract for 4 months. Then, a new device was mounted on the scapular spine and used to extend the infraspinatus muscuculotendinous unit transcutaneously by 1 mm per day. Thereafter, the tendon was repaired back to the greater tuberosity. We assessed the muscular architecture using magnetic resonance imaging, macroscopic dissection, histology, and electron microscopy. Fatty infiltration (in Hounsfield units 1/4 HU) and muscular cross-sectional area (in % of the control side) were monitored with computed tomography at tendon release, initiation of elongation, repair, and at sacrifice. RESULTS: Sixteen weeks after tendon release, the mean tendon retraction was 29 +/- 6 mm (14% of original length, P = .008). In 8 sheep, elongation was achieved as planned (group I), but in 4, the elongation failed technically (group II). The mean traction time was 24 +/- 6 days with a mean traction distance of 19 +/- 4 mm. At sacrifice, the mean pennation angle in the infraspinatus of group I was not different from the control side (29.8 degrees +/-7.5 degrees vs. 30 degrees +/-6 degrees , P = .575). In group II, the pennation angle had increased from 30 degrees +/-6 degrees to 55 degrees +/-14 degrees (P = .035). There was no fatty infiltration at the time of tendon release. After retraction, there was a significant increase in fatty infiltration of the infraspinatus muscle and a decrease of its cross-sectional area to 57% of the contralateral side (P = .0001). During traction, the degree of fatty infiltration remained unchanged (36 HU to 38 HU, P = .381), and atrophy improved to a muscle square area of 78% of the contralateral side (P = .0001) in group I. In group II, an increase of fatty infiltration was measured from 36 HU to 28 HU; however, this increase was not significant (P = .144). Atrophy did not change in group II (57-55%, P = .946). At sacrifice, the remaining muscle mass was 64% in group I and 46% in group II (P = .019). DISCUSSION: Our preliminary results document, that continuous elongation of a retracted, fatty infiltrated and atrophied musculotendinous unit is technically feasible. CONCLUSION: In the sheep, continuous elongation can lead to restoration of normal muscle architecture, to partial reversal of muscle atrophy, and to arrest of the progression of fatty infiltration. LEVEL OF EVIDENCE: Basic science level 2; Prospective comparative therapeutic study.

Quality of life of grown-up congenital heart disease patients after congenital cardiac surgery

BACKGROUND: Due to better early and long-term outcome, the increasing population of grown-ups with congenital heart disease (GUCH) brings up unexpected quality of life (QoL) issues. The cardiac lesion by itself is not always the major problem for these patients, since issues pertaining to QoL and psychosocial aspects often predominate. This study analyses the QoL of GUCH patients after cardiac surgery and the possible impact of medical and psychosocial complications. PATIENTS AND METHODS: A questionnaire package containing the SF-36 health survey (health related QoL), the HADS test (anxiety/depression aspects) and an additional disease specific questionnaire was sent to 345 patients (mean 26+/-11 years) operated for isolated transposition of the great arteries (TGA), tetralogy of Fallot (TOF), and ventricular septal defect (VSD). The scores were compared with age- and gender-matched standard population data and in relation to the underlying congenital heart disease (CHD). RESULTS: In all SF-36 and HADS health dimensions the GUCH patients showed excellent scores (116+/-20), which are comparable to the standard population (100+/-15), regardless of the initial CHD (p=0.12). Eighty-two percent of the patients were found to be in NYHA class I and 83% patients declared that they do not consider their QoL to be limited by their malformation. Complications like reoperations (p=0.21) and arrhythmias (p=0.10) do not show significant impact on the QoL. The additional questionnaire revealed that 76% of adult patients have a fulltime job, 18% receive a full or partial disability pension, 21% reported problems with insurances, most of them regarding health insurances (67%), and 4.4% of adult patients declared to have renounced the idea of having children due to their cardiac malformation. CONCLUSION: QoL in GUCH patients following surgical repair of isolated TOF, TGA and VSD is excellent and comparable to standard population, this without significant difference between the diagnosis groups. However, these patients are exposed to a high rate of complications and special psychosocial problems, which are not assessed by standardized questionnaires, such as the SF-36 and HADS. These findings highlight the great importance for a multidisciplinary and specialized follow-up for an adequate management of these complex patients.

Early serum procalcitonin, interleukin-6, and 24-hour lactate clearance: useful indicators of septic infections in severely traumatized patients

BACKGROUND: Elevated lactate and interleukin-6 (IL-6) levels were shown to correlate with mortality and multiple organ dysfunction in severely traumatized patients. The purpose of this study was to test whether an association exists between 24-hour lactate clearance, IL-6 and procalcitonin (PCT) levels, and the development of infectious complications in trauma patients. METHODS: A total of 1757 consecutive trauma patients with an Injury Severity Score (ISS) > 16 admitted over a 10-year period were retrospectively analyzed over a 21-day period. Exclusion criteria included death within 72 h of admission (24.5%), late admission > 12 h after injury (16%), and age < 16 years (0.5%). Data are stated as the median (range). RESULTS: Altogether, 1032 trauma patients (76.2% male) with an average age of 38 years, a median ISS of 29 (16-75), and an Acute Physiology, Age, and Chronic Health Evaluation (APACHE) II score of 14 (0-40) were evaluated. The in-hospital mortality (>3 days) was 10%. Patients with insufficient 24-hour lactate clearance had a high rate of overall mortality and infections. Elevated early serum procalcitonin on days 1 to 5 after trauma was strongly associated with the subsequent development of sepsis (p < 0.01) but not with nonseptic infections. The kinetics of IL-6 were similar to those of PCT but did differentiate between infected and noninfected patients after day 5. CONCLUSIONS: This study demonstrates that elevated early procalcitonin and IL-6 levels and inadequate 24-hour lactate clearance help identify trauma patients who develop septic and nonseptic infectious complications. Definition of specific cutoff values and early monitoring of these parameters may help direct early surgical and antibiotic therapy and reduce infectious mortality.

Taxane-containing induction chemotherapy followed by definitive chemoradiotherapy. Outcome in patients with locally advanced head and neck cancer

BACKGROUND Induction chemotherapy followed by definitive chemoradiotherapy is an intensified treatment approach for locally advanced squamous cell carcinoma of the head and neck (HNSCC) that might be associated with high rates of toxicity. MATERIALS AND METHODS The data of 40 consecutive patients who underwent induction chemotherapy with docetaxel-containing regimens followed by intensity-modulated radiotherapy (IMRT) and concomitant systemic therapy for unresectable locally advanced HNSCC were retrospectively analyzed. Primary objectives were RT-related acute and late toxicity. Secondary objectives were response to induction chemotherapy, locoregional recurrence-free survival (LRRFS), overall survival (OS), and influencing factors for LRRFS and OS. RESULTS The median follow-up for surviving patients was 21 months (range, 2-53 months). Patients received a median of three cycles of induction chemotherapy followed by IMRT to 72 Gy. Three patients died during induction chemotherapy and one during chemoradiotherapy. Acute RT-related toxicity was of grade 3 and 4 in 72 and 3 % of patients, respectively, mainly dysphagia and dermatitis. Late RT-related toxicity was mainly xerostomia and bone/cartilage necrosis and was of grade 3 and 4 in 15 % of patients. One- and 2-year LRRFS and OS were 72 and 49 % and 77 and 71 %, respectively. CONCLUSION Induction chemotherapy followed by chemoradiotherapy using IMRT was associated with a high rate of severe acute and late RT-related toxicities in this selected patient cohort. Four patients were lost because of fatal complications. Induction chemotherapy did not compromise the delivery of full-dose RT; however, the use of three cycles of concomitant cisplatin was impaired.