Fluorescence in situ hybridization analysis of chromosome 12p in paraffin-embedded tissue is useful for establishing germ cell origin of metastatic tumors.

The over-representation of chromosome 12p sequences is crucial for the development of invasive testicular germ cell tumors. Testicular cancer patients may have metastatic tumors of diverse histologic types, including adenocarcinoma, undifferentiated carcinoma, sarcoma, or other malignancies that lack features of germ cell tumors. We sought to investigate the possible germ cell origin of such tumors using interphase fluorescence in situ hybridization. In all, 10 metastatic malignant somatic-type tumors from patients with histories of testicular cancer, as well as one malignant somatic-type tumor from a patient with primary mediastinal germ cell tumor were studied and included: adenocarcinoma (five cases), poorly differentiated carcinoma (one), sarcoma (four), and neuroendocrine carcinoma (one). The tumors were analyzed using fluorescence in situ hybridization using 12p spectrum green and 12 centromeric spectrum orange probes in paraffin sections. The patients ranged in age from 27 to 55 years (mean, 43). Colon and lung cancers from patients without germ cell tumors were used as controls. Adequate signals were observed in all tumors. Gain of chromosome 12p was seen in six tumors. None of the control tumors showed 12p amplification. Fluorescence in situ hybridization for 12p amplification in routinely processed surgical specimens is a useful adjuvant diagnostic tool in confirming the germ cell origin of metastatic tumors having the histologic appearance of somatic-type neoplasms.     

Lateral unicompartimental knee arthroplasty: indications,technique and short-medium term results

Lateral unicompartmental knee arthroplasty (UKA) is a valid alternative treatment in the event of arthritis confined to the lateral compartment. This paper examines its indications, technique and short to medium-term results. A total of 159 Miller–Galante cemented UKA prostheses (Zimmer, Warsaw, Indiana) were implanted consecutively (131 medial and 28 lateral) by the same surgeon. This study investigates 28 lateral UKAs in 27 patients. Twenty-five implants in 24 patients (including a subject operated bilaterally) were followed up for 12–60 months. Three patients were discarded on account of to short a follow-up period. The Hospital for Special Surgery (HSS) knee score was used to compare the pre- and post-operative results of the lateral UKA patients. The HSS score improved from a pre-op mean of 59.92 (range 48–68) to 88.04 (range 71–95) at the last follow-up. There was a positive increase in the pain, function and ROM components of the score. The lateral UKA prosthesis can be regarded as a sound alternative to total knee replacement. Correct patient selection on the basis of optimum surgical indications, however, is essential. No benefits of funds were received in support of the study.     

Relations of the pterygoid hamulus and hard palate in children and adults: anatomical implications for the function of the soft palate.

We investigated spatial relations of the pterygoid hamuli to the hard palate on 65 skull bases: 31 disarticulated sphenoidal bones from the newborn up to 9 years of age, 19 skulls of adult skeletons (21-59 age group), and 15 skulls aged 60-100 years. We measured: (a) width of the hard palate in the choanal region, (b) length of the hamulus, (c) inclination of the hamulus from the perpendicular line, and (d) distance between the tips of the contralateral hamuli. The width of the hard palate in the choanal region was smallest in children (mean +/- standard deviation, 21.5 +/- 2.6 mm) compared with adult skulls (26.8 +/- 2.3 mm in the 21-59 age group and 25.4 +/- 1.9 mm in the 60-100 age group; P<0.05, one-way analysis of variance (ANOVA) and Student-Newman-Keuls post hoc test). Children had the shortest hamulus (3.6 +/- 1.5mm), and its length increased in the adult age group to 6.9+1.7mm (P<0.05), and then again decreased to 5.0 +/- 1.9 mm in the 60-100 age group (P<0.05 vs. adults and children). The distance between the tips of the contralateral hamuli and their lateral inclination from the perpendicular plane were also greater in the adult age group (38.0 +/- 2.7mm and 35.9 +/- 13.7 degrees, respectively) than either in children (31.0 +/- 3.7mm and 19.6 +/- 12.1 degrees) or the elderly (32.7 +/- 3.9mm and 19.7 +/- 10.3 degrees) (P<0.05). Our study showed that the anatomical measures of the pterygoid hamulus and its relation to the surrounding structures change with age, and occur with the changes in the function of pharyngeal and palatal muscles in deglutition. These changes may have clinical relevance for sleep apnoea and snoring.     

Epilepsy and family expressed emotion: results of a prospective study.

PURPOSE: To verify the emotional components expressed by the relatives of adult patients with a diagnosis of epilepsy, and whether they are related to adjustment to the illness and the course of the illness over time. METHODS: We studied a consecutive sample of 43 outpatients suffering from epilepsy and 43 key relatives using the Camberwell Family Interview (CFI), with the expressed emotion (EE) of the relatives being rated at baseline (T0). EE refers to a construct representing some key aspects of interpersonal relationships: the relatives were assigned to the high-EE group if they scored 3 or more on the emotional over involvement (EOI) scale, or showed hostility, or made 6 or more critical comments. The patients were clinically evaluated at baseline and for 1 year of appropriate treatment by an epileptologist who was blinded to the EE ratings. They also completed STAI XI, STAI X2 and Beck's Depression Inventory at baseline. RESULTS: Twenty-six relatives (60%) were rated as showing a high degree of EE. In the 12-month follow-up study, high EE and high EOI were found to be associated with a significantly higher seizure frequency than that recorded for the patients living in low-EE households (p<0.05). The patients from households assessed as reflecting a high degree of criticism showed poor drug compliance (p<0.01), whereas those with relatives assessed as having a high degree of warmth showed better clinical and pharmacological compliance (p<0.01). High family criticism scores also correlated with higher study entry levels of depression (p<0.05) and trait and state anxiety (p<0.05) among the patients. CONCLUSIONS: The study findings highlight the impact of particular components of the family emotional climate on the clinical course and psychological adjustment of patients with epilepsy.     

A new priority policy for patients with hepatocellular carcinoma awaiting liver transplantation within the model for end-stage liver disease system.

The best prioritization of patients with hepatocellular carcinoma (HCC) waiting for liver transplantation under the model for end-stage liver disease (MELD) allocation system is still being debated. We analyzed the impact of a MELD adjustment for HCC, which consisted of the addition of an extra score (based on the HCC stage and waiting time) to the native MELD score. The outcome was analyzed for 301 patients with chronic liver disease listed for liver transplantation between March 1, 2001 and February 28, 2003 [United Network for Organ Sharing (UNOS)-Child-Turcotte-Pugh (CTP) era, 163 patients, 28.8% with HCC] and between March 1, 2003 and February 28, 2004 (HCC-MELD era, 138 patients, 29.7% with HCC). In the HCC-MELD era, the cumulative dropout risk at 6 months was 17.6% for patients with HCC versus 22.3% for those patients without HCC (P = NS), similar to that in the UNOS-CTP era. The cumulative probability of transplantation at 6 months was 70.3% versus 39.0% (P = 0.005), being higher than that in the UNOS-CTP era for patients with HCC (P = 0.02). At the end of the HCC-MELD era, 12 patients with HCC (29.3%) versus 57 without HCC (58.8%) were still on the list (P = 0.001). Both native and adjusted MELD scores were higher (P < 0.05) and progressed more in patients with HCC who dropped out than in those who underwent transplantation or remained on the list (the initial-final native MELD scores were 17.3-23.1, 15.5-15.6, and 12.8-14.1, respectively). The patients without HCC remaining on the list showed stable MELD scores (initial-final: 15.1-15.4). In conclusion, the present data support the strategy of including the native MELD scores in the allocation system for HCC. This model allows the timely transplantation of patients with HCC without severely affecting the outcome of patients without HCC.     

Poststroke DNA immunization against neurite growth inhibitors is beneficial to the recovery from local cerebral ischemia in rats

BACKGROUND： Inhibitory signals, i.e. neurite growth inhibitors （NGIs）, presenting on central nervous system （CNS） myelin have been shown to play a crucial role in inhibiting lesioned axonal sprouting and leading to less functional recovery. Vaccines targeting NGIs may provide multifactorial protection against brain insults by overcoming the inhibitory effects of these NGIs and boosting the body＇s immune repair mechanisms. OBJECTIVE： To evaluate the effect of poststroke DNA immunization against NGIs on the rehabilitation for sensorimotor function of rat models of local cerebral ischemia. DESIGN： Completely randomized grouping design, and controlled experiment. SETTING： Brain Injury Research Laboratory, Department of Neurosurgery, National Neuroscience Institute, Singapore. MATERIALS： Sixty adult male Sprague-Dawley rats ranging in age from 45 to 120 days and in weight from 180 to 250 grams were provided by Animal Center of Department of Anatomy, Faculty of Medicine, National University of Singapore. pcDNA3.1（＋）-neurite growth inhibitors （pcDNA-NGIs） a gift was provided by Dr. Xiao from Department of Clinical Research, Singapore General Hospital, Singapore. METHODS： The experiment was carried out at Brain Injury Research Laboratory, Department of Neurosurgery, National Neuroscience Institute, Singapore from August 2003 to April 2005. （1）The involved rats were randomized into 3 groups： pcDNA-NGIs group （group A）, pcDNA3.1 （＋） group （group B） and model group （group C）, with 20 rats in each group. Left focal cerebral ischemia （FCI） was permanently induced through middle cerebral artery occlusion （MCAO） with the assistance of an operating microscope. Successful MCAO was determined by a 20% decrease to baseline in the ipsilateral cerebral blood flow. 100 μg of pcDNA-NGIs eluted in phosphate-buffered saline （PBS） was intramuscularly injected into the tibial muscle once a week after MCAO for 6 weeks in group A. As control, pcDNA3.1 （＋） was also administrated in the same way in group B and nothing was administrated in group C. （2） The modified neurological severity score （mNSS）, a composite of motor, sensory, reflex and balance tests, was used to test the sensorimotor deficit. The mNSS was graded on a scale of 0 - 18, i.e. normal score was 0, maximal deficit score was 18, and 1 point was warded for the inability to perform the tasks or the lack of a tested reflex. （3） The newly generated axons of corticorubral projection were traced by stereotaxic guided injection of 100 g/L biotinylated dextran amine. Rats were sacrificed two weeks after tracing, and cryostat coronal sections of midbrains （30μm） were reacted to BDA according to the manufacturer＇s instruction by the free-floating method. Images were captured on a DM RXA2 LEICA Microscope with a Spot Digital Camera system （Germany）, and the numbers of labeled axons on the denervated side in four standard coronal sections including the red nucleus were manually quantified. MAIN OUTCOME MEASURES： （1） The number of newly generated axons of corticorubral projection. （2）The improvement in sensorimotor deficit. RESULTS： All the involved 60 rats entered the stage of final analysis. （1） The number of newly generated axons of corticorubral projection of rats： Only ipsilateral axons of CRP were noted with little evidence of fibers crossing to the contralateral red nucleus in rats of groups B and C. More BDA-positive fibers crossing the midline and terminating in the contralateral red nucleus in appropriate target areas mirroring the non-differentiated red nucleus were found in rats of group A. Quantitative analysis showed that BDA-labeled axons in the denervated side of rats in group A were more than those in group B （P 〈 0.05）. （2） Improvement in sensorimotor deficit of rats： At 2 weeks after immunization, significant improvement in sensorimotor deficit was found in rats of group A. There were significant differences of improvement in sensorimotor deficit of rats between group A and group B or group C at 12 and 14 weeks after immunization （P 〈 0.05）. CONCLUSION： （1） Poststroke DNA immunization against NGIs leads to increased sensorimotor recovery following FCI and compensatory newly growth of axons from corticorubral projection.     

Development and proliferation of lymphocytes in mice deficient for both interleukins-2 and -4

Interleukin (IL)-2 and IL-4 are considered as important regulators of growth and differentiation of lymphocytes. We report that in mice made deficient for both IL-2 and IL-4 by gene targeting all major T cell subsets and B cells were normal, indicating that IL-2 and IL-4 are not essential for development of the immune system. Paradoxically, proliferation of T cells was increased in both IL-2- and IL-4-deficient homozygous mice.