Local control after craniospinal irradiation,intensity‐modulated radiotherapy boost,and chemotherapy in childhood medulloblastoma

BACKGROUND:

The current study was conducted to determine whether the use of cochlear‐sparing intensity‐modulated radiotherapy (IMRT) boost results in excess local failures in children with medulloblastoma.

METHODS:

Fifty children with a median age of 7.8 years underwent resection, craniospinal irradiation (CSI), IMRT posterior fossa (PF) and/or tumor bed (TB) boost, and cisplatin‐based chemotherapy for medulloblastoma. For standard‐risk patients, the CSI dose was 18 to 23.4 grays (Gy) and was followed either by an IMRT PF boost to 36 Gy and a TB boost of 54 to 55.8 Gy (n = 29) or by an IMRT TB boost to 55.8 Gy (n = 4). For high‐risk patients, the CSI dose was 36 to 39.6 Gy followed by an IMRT PF boost to 54 to 55.8 Gy (n = 8), an IMRT PF boost to 45 Gy and a TB boost to 55.8 Gy (n = 2), or an IMRT TB boost to 55.8 Gy (n = 7). For the TB boost, a 2‐cm margin around the surgical bed was treated in most patients.

RESULTS:

The 5‐year overall and progression‐free survival rates (±standard deviation) were 72% ± 6.6% and 68.3% ± 6.8%, respectively, for all patients; 77.8% ± 7.4% and 75.1% ± 7.6%, respectively, for standard‐risk patients; and 60.8% ± 12.8% and 55.4% ± 12.8%, respectively, for high‐risk patients. The 5‐year PF control rate was 90.5% ± 4.6%. TB failures occurred in 3 patients (including 2 patients who had distant failure), whereas an isolated non‐TB PF failure occurred in 1 patient.

CONCLUSIONS:

The use of IMRT was associated with excellent local control and did not result in excess PF failures outside of the TB. Cancer 2011. © 2010 American Cancer Society.     

Antimycobacterial Evaluation of Fifteen Medicinal Plants in South Africa

Fifteen plant species were collected from the Nelspruit Botanical Garden based on a list of plants provided by Phytomedicine Programme at the University of Pretoria and their ethnopharmacological information. Hexane, dichloromethane (DCM), acetone and methanolic extracts were screened for antimycobacterial activity against Mycobacterium smegmatis. The acetone extract of Milletia stulhimannii was the most active, showing activity against Mycobacterium smegmatis with minimum inhibitory concentration (MIC) value of 0.13 mg/ml. Acetone extracts for all plants had lower MIC values ranging between 0.11–1.25 mg/ml against M. smegmatis. Milletia stulhimannii, Albizia gummifera, Xanthocercis zambesiaca and Barringtonia racemosa have shown great potential as anti-tuberculosis agents. They were active against M. smegmatis with average MIC values of acetone extracts of 0.13 mg/ml.     

Single-center outcome analysis of 1,161 patients with St. Jude medical and ATS open pivot mechanical heart valves

BACKGROUND AND AIM OF THE STUDY: The clinical performance of mechanical heart valves and valve-related complications are important safety endpoints in patients after heart valve replacement. In this retrospective analysis, the mid- to long-term clinical outcomes of two similar bileaflet heart valves, routinely implanted at the authors' institution over an 11-year period, were compared. METHODS: Between January 1993 and December 2003, a total of 1,161 patients (758 males, 403 females) received either a St. Jude Medical (SJM) or ATS mechanical heart valve. Follow up was obtained via an in-house Quality Management Database, ascertained by telephone questionnaire of the patients and/or family physicians. Follow up was 98.9% complete; the median follow up was 4.6 years; total follow up was 5,624 patient-years (pt-yr). RESULTS: A total of 604 SJM and 601 ATS prostheses was implanted as isolated (n = 669) or combined (n = 492) procedures. The overall 30-day mortality for SJM and ATS was 4.1% and 3.4%, respectively (p = 0.45). Cumulative survival and freedom from valve-related mortality at 10 years for SJM and ATS valves were 66 +/- 3% versus 68 +/- 5% (p = 0.84) and 96 +/- 1% versus 97 +/- 1% (p = 0.36), respectively. No structural valve failure was encountered for both valve types. Freedom from overall valve-related complications at 10 years was 79 +/- 4% for SJM and 66 +/- 6% for ATS (p = 0.08). The linearized rates for valve-related adverse events for SJM and ATS valves, respectively, were: thromboembolism 0.9 and 1.1%/pt-yr; major bleeding requiring transfusion 0.3 and 0.5%/pt-yr; prosthetic endocarditis 0.03 and 0.1%/pt-yr; paravalvular leak 0.1 and 0.6%/pt-yr. CONCLUSION: On the basis of an 11-year experience, both bileaflet valves showed very good clinical results, with low incidences of adverse events during the mid-term outcome. Gender and/or concomitant coronary artery disease were not predictors for reduced life expectancy.     

Unstable recent intracapsular femoral neck fractures in young adults: Osteosynthesis and primary valgus osteotomy using broad dynamic compression plate

Background:

Displaced intracapsular femoral neck fractures continue to be a difficult problem to treat. Various treatment modalities and their modifications have been proposed to improve the outcome. Osteosynthesis and primary valgus angulation osteotomy is one of them. Technique and outcome in a consecutive series of recent intracapsular femoral neck fractures in young adults, from a single center, is presented.

Materials and Methods:

Fifty-five patients of recent (<3 weeks old) displaced intracapsular fracture neck femur (Garden III and IV, Pauwels III, with or without comminution) in the age group 20-50 years (mean 35.4±10.4 years) were subjected to osteosynthesis and primary valgus intertrochanteric osteotomy using contoured broad dynamic compression plate (DCP). The patients were followed up from two to six years (mean 4.6 years).

Results:

Fifty-one fractures united by six months of the index procedure (92.7% union range). Avascular necrosis (AVN) developed in six patients (11%). The other complications were shortening (six), coxa vara (two), infection (two) and delayed union at osteotomy site (one). Excellent results were achieved in 48, good/fair in four and poor in three patients.

Conclusion:

Osteosynthesis with cancellous screw and primary valgus intertrochanteric osteotomy stabilized by a contoured broad DCP is a simple, easy to perform, biological treatment. Failure in a particular case can be treated with any appropriate second procedure.

Level of Evidence:

IV     

Detection of precursor Th cells in mesenteric lymph nodes after oral immunization with protein antigen and cholera toxin

We have characterized the earliest antigen-specific Th cells in murine mesenteric lymph nodes (MLN), following oral immunization with the hen egg lysozyme (HEL) as antigen and cholera toxin (CT) as adjuvant. We did this by analyzing in vitro proliferation and cytokine production in response to HEL by the MLN T cells. MLN cells taken 5 days after a single oral immunization with HEL and CT provided the earliest source of proliferating HEL-specific T cells. This proliferation was completely inhibited by anti-IL-2, but not inhibited by anti-IL-4 antibody. IL-2 protein was detected in culture supernatants but not IL- 4 using ELISA or bioassays. IL-4 mRNA was not found in responding cells using RT-PCR. Some of the day 5 MLN cultures produced IFN-gamma in response to HEL, but isolated T cells from the same MLN did not. Exogenous IL-4 alone did not stimulate day 5 MLN T cells, but IL-4 did synergize with HEL to induce a large proliferative response. The data indicate that the HEL-specific CD4 T cell pool in MLN 5 days after oral immunization is composed of undifferentiated precursor Th cells. These cells have the potential for IL-2 production and IL-4R expression upon re-stimulation in vitro.      

Lung oxidative stress as related to exercise and altitude. Lipid peroxidation evidence in exhaled breath condensate: a possible predictor of acute mountain sickness

Lung oxidative stress (OS) was explored in resting and in exercising subjects exposed to moderate and high altitude. Exhaled breath condensate (EBC) was collected under field conditions in male high-competition mountain bikers performing a maximal cycloergometric exercise at 670 m and at 2,160 m, as well as, in male soldiers climbing up to 6,125 m in Northern Chile. Malondialdehyde concentration [MDA] was measured by high-performance liquid chromatography in EBC and in serum samples. Hydrogen peroxide concentration [H₂O₂] was analysed in EBC according to the spectrophotometric FOX₂ assay. [MDA] in EBC of bikers did not change while exercising at 670 m, but increased from 30.0±8.0 to 50.0±11.0 nmol l⁻¹ (P<0.05) at 2,160 m. Concomitantly, [MDA] in serum and [H₂O₂] in EBC remained constant. On the other hand, in mountaineering soldiers, [H₂O₂] in EBC under resting conditions increased from 0.30±0.12 μmol l⁻¹ at 670 m to 1.14±0.29 μmol l⁻¹ immediately on return from the mountain. Three days later, [H₂O₂] in EBC (0.93 ±0.23 μmol l⁻¹) continued to be elevated (P<0.05). [MDA] in EBC increased from 71±16 nmol l⁻¹ at 670 m to 128±26 nmol l⁻¹ at 3,000 m (P<0.05). Changes of [H₂O₂] in EBC while ascending from 670 m up to 3,000 m inversely correlated with concomitant variations in HbO2 saturation (r=−0.48, P<0.05). AMS score evaluated at 5,000 m directly correlated with changes of [MDA] in EBC occurring while the subjects moved from 670 to 3,000 m (r=0.51, P<0.05). Lung OS may constitute a pathogenic factor in AMS.     

Critical appraisal of the revised Ghent criteria for diagnosis of Marfan syndrome

Radonic T, de Witte P, Groenink M, de Bruin‐Bon RACM, Timmermans J, Scholte AJH, van den Berg MP, Baars MJH, van Tintelen JP, Kempers M, Zwinderman AH, Mulder BJM. Critical appraisal of the revised Ghent criteria for diagnosis of Marfan syndrome. Marfan syndrome (MFS) is a connective tissue disorder with major features in cardiovascular, ocular and skeletal systems. Recently, diagnostic criteria were revised where more weight was given to the aortic root dilatation. We applied the revised Marfan nosology in an established adult Marfan population to define practical repercussions of novel criteria for clinical practice and individual patients. Out of 180 MFS patients, in 91% (n = 164) the diagnosis of MFS remained. Out of 16 patients with rejected diagnosis, four patients were diagnosed as MASS (myopia, mitral valve prolapse, borderline non‐progressive aortic root dilatation, skeletal findings and striae) phenotype, three as ectopia lentis syndrome and in nine patients no alternative diagnosis was established. In 13 patients, the diagnosis was rejected because the Z‐score of the aortic root was <2, although the aortic diameter was larger than 40 mm in six of them. In three other patients, the diagnosis of MFS was rejected because dural ectasia was given less weight in the revised nosology. Following the revised Marfan nosology, the diagnosis of MFS was rejected in 9% of patients, mostly because of the absence of aortic root dilatation defined as Z‐score ≥2. Currently used Z‐scores seem to underestimate aortic root dilatation, especially in patients with large body surface area (BSA). We recommend re‐evaluation of criteria for aortic root involvement in adult patients with a suspected diagnosis of MFS.     

Value of allohaemagglutinins in the diagnosis of a polysaccharide antibody deficiency

Polysaccharide antibody deficiency is characterized by a poor or absent antibody response after vaccination with an unconjugated pneumococcal polysaccharide vaccine. Allohaemagglutinins (AHA) are antibodies to A or B polysaccharide antigens on the red blood cells, and are often used as an additional or alternative measure to assess the polysaccharide antibody response. However, few studies have been conducted to establish the clinical significance of AHA. To investigate the value of AHA to diagnose a polysaccharide antibody deficiency, pneumococcal polysaccharide antibody titres and AHA were studied retrospectively in 180 subjects in whom both tests had been performed. Receiver operating characteristic curves for AHA versus the pneumococcal vaccine response as a marker for the anti-polysaccharide immune response revealed an area under the curve between 0·5 and 0·573. Sensitivity and specificity of AHA to detect a polysaccharide antibody deficiency, as diagnosed by vaccination response, were low (calculated for cut-off 1/4–1/32). In subjects with only low pneumococcal antibody response, the prevalence of bronchiectasis was significantly higher than in subjects with only low AHA (45·5 and 1·3%, respectively) or normal pneumococcal antibody response and AHA (2·4%). A logistic regression model showed that low pneumococcal antibody response but not AHA was associated with bronchiectasis (odds ratio 46·2). The results of this study do not support the routine use of AHA to assess the polysaccharide antibody response in patients with suspected immunodeficiency, but more studies are warranted to clarify the subject further.