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.     

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     

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.     

Length-dependent gametic CAG repeat instability in the Huntington's disease knock-in mouse

The CAG repeats in the human Huntington's disease (HD) gene exhibit striking length-dependent intergenerational instability, typically small size increases or decreases of one to a few CAGs, but little variation in somatic tissues. In a subset of male transmissions, larger size increases occur to produce extreme HD alleles that display somatic instability and cause juvenile onset of the disorder. Initial efforts to reproduce these features in a mouse model transgenic for HD exon 1 with 48 CAG repeats revealed only mild intergenerational instability ( approximately 2% of meioses). A similar pattern was obtained when this repeat was inserted into exon 1 of the mouse Hdh gene. However, lengthening the repeats in Hdh to 90 and 109 units produced a graded increase in the mutation frequency to >70%, with instability being more evident in female transmissions. No large jumps in CAG length were detected in either male or female transmissions. Instead, size changes were modest increases and decreases, with expansions typically emanating from males and contractions from females. Limited CAG variation in the somatic tissues gave way to marked mosaicism in liver and striatum for the longest repeats in older mice. These results indicate that gametogenesis is the primary source of inherited instability in the Hdh knock-in mouse, as it is in man, but that the underlying repeat length-dependent mechanism, which may or may not be related in the two species, operates at higher CAG numbers. Moreover, the large CAG repeat increases seen in a subset of male HD transmissions are not reproduced in the mouse, suggesting that these arise by a different fundamental mechanism than the small size fluctuations that are frequent during gametogenesis in both species.      

Anatomical correlates of functional plasticity in mouse visual cortex

Much of what is known about activity-dependent plasticity comes from studies of the primary visual cortex and its inputs in higher mammals, but the molecular bases remain largely unknown. Similar functional plasticity takes place during a critical period in the visual cortex of the mouse, an animal in which genetic experiments can readily be performed to investigate the underlying molecular and cellular events. The experiments of this paper were directed toward understanding whether anatomical changes accompany functional plasticity in the developing visual cortex of the mouse, as they do in higher mammals. In normal mice, transneuronal label after an eye injection clearly delineated the monocular and binocular zones of area 17. Intrinsic signal optical imaging also showed monocular and binocular zones of area 17 but revealed no finer organization of ocular dominance or orientation selectivity. In normal animals, single geniculocortical afferents serving the contralateral eye showed great heterogeneity and no clustering consistent with the presence of ocular dominance patches. Growth and elaboration of terminal arbor continues beyond postnatal day 40 (P40), after the peak of the critical period. After prolonged monocular deprivation (MD) from P20 to P60, transneuronal labeling showed that the projection serving the ipsilateral eye was severely affected, whereas the effect on the contralateral eye's pathway was inconsistent. Optical imaging also showed profound effects of deprivation, particularly in the ipsilateral pathway, and microelectrode studies confirmed continued functional plasticity past P40. Reconstruction of single afferents showed that MD from P20 to P40 promoted the growth of the open eye's geniculocortical connections without causing the closed eye's contralateral projection to shrink, whereas MD from P20 to P60 caused an arrest of growth of deprived arbors. Our findings reveal numerous similarities between mouse and higher mammals in development and plasticity, along with some differences. We discuss the factors that may be responsible for these differences.     

Acute renal failure caused by Klebsiella pneumoniae pyelonephritis.

We report a 34-year-old male patient without prior medical history who presented with acute renal failure due to acute bacterial pyelonephritis. Both blood and urine cultures grew Klebsiella pneumoniae. Although a kidney biopsy revealed extensive necrosis and no viable glomeruli, renal function recovered to near normal after intermittent hemodialysis and antibiotic therapy. We believe that it is important to include this entity in the differential diagnosis of acute renal failure since proper diagnosis and treatment is essential for recovery of renal function. Furthermore, we would like to draw attention to Klebsiella pneumoniae as an important potential pathogen in such cases, in addition to Escherichia coli.