Malnutrition as a prognostic factor in lymphoblastic leukaemia: a multivariate analysis

One hundred and twenty eight Brazilian children with lymphoblastic leukaemia were intensively treated with a Berlin-Frankfurt-Munich based protocol. More children had a white cell count above 50 x 10(9)/l (31%) then observed in developed countries. After a median follow up of 31 months (11-58 months), the estimated probability of relapse free survival was 41% (7%) for the whole group. After adjustment in the Cox's multivariate model, malnutrition was the most significant adverse factor affecting duration of complete remission. Age above 8 years and high peripheral white cell count were also significant adverse factors. Among the nutritional indices, the height for age and weight for age z scores were both significant, whether the cut off points of z-2 or z = -1.28 were chosen to define malnutrition. A strong statistical association between the two indices was found; the contribution of height for age z score to the prediction of relapse free survival was more significant. Children with height for age z score < -2 had a relapse risk of 8.2 (95% confidence interval 3.1 to 21.9) relative to children with z score > -2. The results of this study suggest that socioeconomic and nutritional factors should be considered in the prognostic evaluation of children with leukaemia in developing countries.     

Breath and string test： A diagnostic package for the identification of treatment failure and antibiotic resistance of Helicobacter pylori without the necessity of upper gastrointestinal endoscopy

AIM: Helicobacter pylori (H pylori) resistance after failed eradication has a major impact on the outcome of a further treatment regimen. The aim of this study was to assess the validity of a non-invasive strategy using the 13C-urea breath test (UBT) and the gastric string test in identifying post-treatment resistance of H pylori. METHODS: The UBT was routinely performed 4 to 6 wk after H pylori eradication therapy. Forty-two patients (24 females, 18 males, mean age 48 years) with a positive UBT were included in the study. A gastric string test using a capsule containing a 90 cm-long nylon fiber was performed. Before the capsule was swallowed, the free end of the string was taped to the cheek. After one hour in the stomach, the string was withdrawn. The distal 20 cm of the string was inoculated onto an agar plate and processed under micro-aerophilic conditions. Following the string test, upper gastrointestinal endoscopy was performed to obtain gastric biopsies for conventional culture. RESULTS: H pylori was successfully cultured from the gastric string in 34 patients (81%), but not in 5 patients due to contamination with oropharyngeal flora. H py/oriwas cultured from the gastric biopsies obtained at endoscopy in 39 patients (93%). CONCLUSION: The UBT followed by the gastric string test in the case of treatment failure is a valid diagnostic strategy with the aim of determining the post-therapeutic antibiotic resistance of H pylori with little inconvenience to the patient. Upper Gl-endoscopy can be avoided in several cases by applying consequently this diagnostic package.     

Acute exacerbation of autoimmune hepatitis induced by Twinrix

We report on a 26-year-old man who presented with severe jaundice and elevated serum liver enzyme activities after having received a dose of Twinrix? In his past medical history, jaundice or abnormal liver function tests were never recorded. Following admission, an elevated immunoglobulin G level and antinuclear antibodies at a titer of 320 with a homogenous pattern were found. Histology of a liver biopsy showed marked bridging liver fibrosis and a chronic inflammation, compatible with autoimmune hepatitis. Treatment was started with budesonide and ursodeoxycholic acid, and led to complete normalization of the pathological liver function tests. We believe that Twinrix led to an acute exacerbation of an unrecognized autoimmune hepatitis in our patient. The pathogenesis remains to be clarified. It is tempting to speculate that inactivated hepatitis A virus and/or recombinant surface antigen of the hepatitis B virus -as seen in patients with chronic hepatitis C and unrecognized autoimmune hepatitis who were treated with interferon alpha-might have been responsible for disease exacerbation.     

Experimental stimulation of cell-mediated immunity without concomitant stimulation of humoral immunity in graft-versus-host immunosuppressed mice.

The immunosuppressive effect of the graft-versus-host (GVH) reaction was studied in CBA X A F1 (CAF1) mice which had been rendered immunologically unresponsive by the injection of parental A strain lymphoid cells (GVH mice). Suppression of both cell-mediated and humoral immune responses was demonstrated by the prolonged survival of C57BL/6 (B6) skin allografts and by the inability of GVH mice to produce detectable antibody following stimulation with sheep erythrocytes (SRBC). Appropriate stimulation of GVH mice induced cell-mediated immune reactions to xeno- and allogeneic antigens while the humoral immune responses to the same antigens remained suppressed. Multiple challenges of the GVH mice with B6 tissue caused a rapid rejection of subsequent B6 skin grafts but failed to stimulate the production of any detectable antibodies to B6 allotransplantation antigens. Sensitization of GVH mice with SRBC in Freund's complete adjuvant stimulated a delayed hypersensitivity response to SRBC, although no humoral response to SRBC could be detected, even after three challenges with SRBC. The experimental results are discussed in terms of a proposed model for GVH-induced immunosuppression.     

MODEL POLYPEPTIDES FOR α-HELIX COILED COIL PROTEINS:

A polyheptapeptide poly (Ala-Leu-Lys-Glu-Ala₂-Glu) has been synthesized by polymerization of the blocked heptamer and by sequential synthesis. The former method yields molecular weights up to 40, 000, the latter a product of rather uniform D.P = 25, i.e. a molecular weight M_r= 18, 250. The polypeptide was designed to have a repeat sequence of hydrophobic residues of the type expected in α-keratin and in tropomyosin and was designed to optimize hydrophobic bonding between two chains. Preliminary characterization indicates that in aqueous solution the polypeptides are random at all pH, but high molecular weight material shows a small amount (up to 20%) of α-helix. However, crystallization of the material from certain solvents and solvent mixtures including chloroform I trifluoroacetic acid and hexafluoroisopropanol, produces α-helical material which in some cases is crystalline. Electron microscopy of the crystalline material shows lozenge-shaped crystals of about 1 μ in maximum side and ? 300 Å thick. Diffuse electron diffraction has been obtained with d = 16.1 Å. The hexafluoroisopropanol-precipitated material, which is α-helical by infrared spectroscopy and film circular dichroism, gives a diffuse X-ray diffraction pattern with d = 5.1 å and d = 2.5 å. Attempts to orient the material caused distortion toβ-sheet form. The diffraction studies are consistent with an α-helix coiled coil and a tentative cell packing arrangement is described.     

Sympathetic nervous system, genes and human essential hypertension

The sympathetic nervous system (SNS) is the first line of defense in the response to environmental stress through its regulation of second-to-second changes in blood pressure (BP). Both the activity of the SNS and the therapeutic responses to SNS agonists and antagonists are known to be highly variable in the population. "Small" changes caused by single nucleotide polymorphisms (SNPs) of SNS genes may have considerable impact on SNS function and individualized hypertension treatment. In this review, we first describe the physiology of the SNS and its influence on cardiovascular and renal mechanisms of BP regulation. A thorough review of the role of genetic variability of various SNS genes in relation to the development of BP and essential hypertension (EH) follows. Given the vast number of SNS components, evaluations of multiple SNPs from multiple SNS genes are necessary for future association studies of BP and EH. One way to surpass the limitations and inconsistencies of previous association studies is to use a gene-based approach also referred to as indirect association, which takes all common variation within a candidate gene into account. In order to determine how SNS genes are differentially expressed or silenced, activated or inactivated against various environmental backgrounds, it is important to assess not only environmental and lifestyle risk factors such as diet, climate, chronic stress, but also personality characteristics such as hostility and coping styles. Uncovering relevant gene-gene and gene-environment interactions within the SNS cascade will not only enable early detection of EH risk but will also aid in the treatment of hypertensives through both non-pharmacological and pharmacological means.     

The development and validation of a risk score to predict the probability of postoperative vomiting in pediatric patients

Risk scores to predict the occurrence of postoperative vomiting (PV) or nausea and vomiting that were developed for adult patients do not fit for children, because several risk factors are difficult to assess or are usually not applicable in pediatric patients (e.g., smoking status). Thus, in the present study, we sought to develop and to validate a simple score to predict PV in children (POVOC-score). Development and validation of the new score was based on data from 4 independent institutions of 1257 children (aged 0-14 yr) undergoing various types of surgery under general anesthesia without antiemetic prophylaxis. Preoperatively, several potential risk factors were recorded. Postoperatively, the occurrence of PV was observed for up to 24 h. The dataset was randomly split into an evaluation set (n = 657) that was analyzed using a forward logistic regression technique and a validation set (n = 600) that was used to confirm the accuracy of prediction by means of the area under a receiver operating characteristic curve. Four independent risk factors for PV were identified in the final analysis: duration of surgery >/=30 min, age >/=3 yr, strabismus surgery, and a positive history of PV in the children or PV/postoperative nausea and vomiting in relatives (mother, father, or siblings). The incidence of PV was 9%, 10%, 30%, 55%, and 70% for 0, 1, 2, 3, and 4 risk factors observed. Using these incidences as cut-off values in the validation dataset, the area under the receiver operating characteristic curve was 0.72 (95% confidence interval: 0.68-0.77). Our data suggest that PV can be predicted with an acceptable accuracy using a four-item simplified risk score.     

Frameless image guidance improves accuracy in three-dimensional interstitial brachytherapy needle placement

PURPOSE: The aim of this work was to adapt a computer-assisted real-time three-dimensional (3D) navigation system for interstitial brachytherapy procedures. METHODS AND MATERIALS: The 3-D navigation system Surgical Planning and Orientation Computer System (SPOCS; Aesculap, Tuttlingen, Germany) was adapted for use in interstitial brachytherapy. A special needle holder with mounted infrared-emitting diodes (IRED) for 3D navigation-based needle implantation was developed. Measurements were made on a series of different phantoms to study the feasibility and the overall accuracy and precision of the navigation system with regard to single-needle application and volume implants (multiple-needle implantations). In all, 250 single implants and 20 volume implants were performed. Accuracy was measured as the target registration error (TRE) between the preoperatively defined and the achieved target position. RESULTS: Analyses of the 250 different targets showed a mean TRE for single-needle applications of 1.1 mm (SD +/- 0.4 mm), 0.9 mm (SD +/- 0.3 mm), and 0.7 mm (SD +/- 0.3 mm) in the x, y, and z direction, respectively. The maximal deviation was 2.3 mm. The corresponding TRE in the x, y, and z direction for volume implants was 1.6 mm (SD +/- 0.4 mm), 1.9 mm (SD +/- 0.6 mm), and 1.0 mm (SD +/- 0.4 mm), respectively. The maximum deviation was 2.9 mm. CONCLUSIONS: The adaptation of a commercially available surgical planning and navigation system to interstitial brachytherapy is feasible. It enables virtual planning and improved accuracy in 3D interstitial needle implantation.