High incidences of DNA ploidy abnormalities in tongue squamous cell carcinoma of young patients: an international collaborative study

Santos‐Silva A R, Ribeiro A C P, Soubhia A M P, Miyahara G I, Carlos R, Speight P M, Hunter K D, Torres‐Rendon A, Vargas P A & Lopes M A (2011) Histopathology  58 , 1127–1135
High incidences of DNA ploidy abnormalities in tongue squamous cell carcinoma of young patients: an international collaborative study Aims: This multi‐centre analysis assessed the DNA content of TSCC in 37 young patients (<40 years) and 28 old patients (>50 years) and determined the correlation of DNA ploidy findings with clinicopathological data. Methods and results: Image cytometry was carried out using an automated cellular imaging system on Feulgen‐stained histological sections to obtain high‐fidelity DNA histograms. Among young patients, 37.8% were females compared to 18.7% in the older group (P = 0.002). In total, 48.6% patients were non‐smokers and 40.5% were non‐drinkers compared to 10.7% non‐smokers and non‐drinkers in the older group (P < 0.0001). TNM, clinical stage of disease and histological grade of differentiation did not differ between groups. Tumour aneuploidy was detected in 86.5% and tetraploidy in 24.3% young patients; this was significantly greater than in the older group where 64.3% were aneuploid (P < 0.0001) and 7.2% tetraploid (P < 0.0001). The mean values of DNA index (DI) and DNA heterogeneity index as well as the percentage of cells with DI exceeding 5N were higher in young patients (P < 0.0001). Conclusions: Young patients with TSCC represent a distinct clinical entity. The high incidence of DNA ploidy abnormalities suggest that they may have increased genomic instability and indicates underlying genetic differences between TSCC in young and older patients.     

Use of the frontal assessment battery in evaluating executive dysfunction in patients with Huntington’s disease

The frontal assessment battery (FAB) is a bedside cognitive scale designed to measure executive functions. Huntington’s disease (HD) is a neurodegenerative disorder characterized by motor, behavioral, and cognitive dysfunction. The aim of this study was to check the validity of the FAB for the evaluation of cognitive impairment in patients with HD. Forty-one patients diagnosed with HD and 53 healthy controls matched by education, sex and age were evaluated with a validated Brazilian version of the UHDRS, the VFT, the SDMT, the SIT, the MMSE, and the FAB. The diagnosis of HD was made by DNA analysis. FAB scores were lower in patients than in the controls (p < 0.001) and had significant correlations with the VFT (r = 0.79; p < 0.05), the SDMT (r = 0.80; p < 0.05), the SIT (r = 0.72; p < 0.05), the MMSE (r = 0.83; p < 0.05), the FCS (r = 0.79; p < 0.05) and the motor section of the UHDRS (r = −0.80; p < 0.05). The FAB differentiated between HD patients in the initial and later stages of the disease. The one-year longitudinal evaluation revealed a global trend toward a worsening in the second score of the FAB. The results demonstrate that the FAB presents good internal consistency and also convergent and discriminative validity; therefore it is a useful scale to assess executive functions and to evaluate cognitive impairment in patients with HD.     

Unloading reaction to electrical stimulation at neutral and supinated ankle positions

An unloading reaction has been characterized as a modified flexor reflex (FR), in which the standing subjects decrease the load on the stimulated foot and increase the load on the contralateral side, but, without withdrawal of the stimulated foot. Different behavioral circumstances have been shown to modulate this reflex. It is not known whether unloading reactions can be modulated with a loaded supinated ankle position, which, in excess, may result in an ankle sprain injury. Since ankle sprain depends on the load applied to a supinated foot, our premise is that unloading reactions may protect the ankle from a sprain injury. Therefore, this study investigated how the unloading reactions were modulated during a loaded supinated ankle condition. We delivered non-nociceptive and nociceptive electrical stimulations on the lateral aspect of the ankle in standing subjects with the foot in neutral and in a supinated position. The magnitude and latencies of reflex responses were registered using kinetic and kinematic analyses and subsequently compared among the conditions. The analysis demonstrated greater reactions for the supinated ankle condition. The individuals also moved their whole body downwards and shifted the body weight to the non-stimulated foot. Therefore, this study suggested that a modified type of the classic flexion reflex, i.e., unloading reaction, may be used as a strategy to unload a supinated ankle and potentially minimize the risk of ankle sprain injuries.     

Surgical resection of pulmonary metastatic lesions in children with hepatoblastoma

Background

Although the most common site of metastasis for hepatoblastoma is the lung, the role of thoracotomy and surgical resection of pulmonary metastasis remains uncertain. In this study, we aimed to determine the long-term outcome of patients with hepatoblastoma who have a surgical resection of pulmonary metastatic lesions.

Methods

Patients with hepatoblastoma in the Children's Oncology Group INT-0098 were reviewed. Detailed reports enabling comprehensive review were available for 175 of 181 eligible patients. Prognostic factors (histology, tumor margin, surgical complications, α-fetoprotein) were also reviewed.

Results

Thoracotomy for initial pulmonary metastasis: 38 patients presented with pulmonary metastasis, Children's Oncology Group stage IV. Nine of these 38 underwent thoracotomy and pulmonary metastectomy either before (2), simultaneous (5), or after (2) resection of their primary liver tumor. Eight of these 9 patients with metastectomy were long-term survivors. Thoracotomy for tumor relapse: 20 patients who had previously achieved complete tumor clearance experienced subsequent pulmonary relapse of their tumor (11 stage I or III, 9 stage IV). All 20 patients with pulmonary relapse had salvage chemotherapy; 13 also had thoracotomy and pulmonary metastectomy (8) or thoracotomy and biopsy (5). Only 4 of 13 were long-term survivors: 2 were stage I and 2 were stage IV.

Conclusions

As pediatric surgeons, we varied tremendously in our timing and surgical approach to the management of pulmonary metastasis in hepatoblastoma. This large multicenter review suggests that thoracotomy should be used cautiously in the management of pulmonary relapse and perhaps more aggressively in the management of metastases present at diagnosis that persist after neoadjuvant chemotherapy.     

Cerebral MRI abnormalities associated with vigabatrin therapy

Purpose:   Investigate whether patients on vigabatrin demonstrated new-onset and reversible T₂-weighted magnetic resonance imaging (MRI) abnormalities.
Methods:   MRI of patients treated during vigabatrin therapy was reviewed, following detection of new basal ganglia, thalamus, and corpus callosum hyperintensities in an infant treated for infantile spasms. Patients were assessed for age at time of MRI, diagnosis, duration, and dose, MRI findings pre-, on, and postvigabatrin, concomitant medications, and clinical correlation. These findings were compared to MRI in patients with infantile spasms who did not receive vigabatrin.
Results:   Twenty-three patients were identified as having MRI during the course of vigabatrin therapy. After excluding the index case, we detected new and reversible basal ganglia, thalamic, brainstem, or dentate nucleus abnormalities in 7 of  22  (32%) patients treated with vigabatrin. All findings were reversible following discontinuation of therapy. Diffusion-weighted imaging (DWI) was positive with apparent diffusion coefficient (ADC) maps demonstrating restricted diffusion. Affected versus unaffected patients, respectively, had a median age of 11 months versus 5 years, therapy duration 3 months versus 12 months, and dosage  170  mg/kg/day versus 87 mg/kg/day. All affected patients were treated for infantile spasms; none of 56 patients with infantile spasms who were not treated with vigabatrin showed the same abnormalities.
Discussion:   MRI abnormalities attributable to vigabatrin, characterized by new-onset and reversible T₂-weighted hyperintensities and restricted diffusion in thalami, globus pallidus, dentate nuclei, brainstem, or corpus callosum were identified in 8 of 23 patients. Young age and relatively high dose appear to be risk factors.     

Cytogenetic findings in 14 benign cartilaginous neoplasms

Benign cartilaginous tumors represent a spectrum of neoplastic processes with variable clinical and pathologic presentations. These tumors are histologically characterized by the presence of chondrocytes surrounded by a cartilaginous matrix. Few studies describe karyotypic abnormalities in these benign lesions. We report a series of 14 chondromas from a single institution. Conventional cytogenetics was performed on short term cultures from all cases. Clonal chromosome aberrations were found in nine tumors. One soft tissue chondroma contained three clones with t(6;12)(q12;p11.2), t(3;7)(q13;p12), and der(2)t(2;18)(p11.2;q11.2). Three periosteal chondromas displayed random structural aberrations of chromosomes 2, 3, 6, 7, and 11 and loss of chromosome 13. Among the enchondromas, three tumors displayed chromosome losses, one contained a complex translocation involving chromosomes 12, 15, and 21 as well as an inv(2)(p21q31),t(12;15;21)(q13;q14;q22) and a separate enchondroma showed a translocation involving chromosomes 12 and 22. Our data suggest that considerable cytogenetic heterogeneity exists among benign chondromatous tumors.     

Uncaria tomentosa stimulates the proliferation of myeloid progenitor cells

Ethnopharmacological relevance

The Asháninkas, indigenous people of Peru, use cat's claw (Uncaria tomentosa) to restore health. Uncaria tomentosa has antioxidant activity and works as an agent to repair DNA damage. It causes different effects on cell proliferation depending on the cell type involved; specifically, it can stimulate the proliferation of myeloid progenitors and cause apoptosis of neoplastic cells. Neutropenia is the most common collateral effect of chemotherapy. For patients undergoing cancer treatment, the administration of a drug that stimulates the proliferation of healthy hematopoietic tissue cells is very desirable.It is important to assess the acute effects of Uncaria tomentosa on granulocyte-macrophage colony-forming cells (CFU-GM) and in the recovery of neutrophils after chemotherapy-induced neutropenia, by establishing the correlation with filgrastim (rhG-CSF) treatment to evaluate its possible use in clinical oncology.

Materials and methods

The in vivo assay was performed in ifosfamide-treated mice receiving oral doses of 5 and 15 mg of Uncaria tomentosa and intraperitoneal doses of 3 and 9 μg of filgrastim, respectively, for four days. Colony-forming cell (CFC) assays were performed with human hematopoietic stem/precursor cells (hHSPCs) obtained from umbilical cord blood (UCB).

Results

Bioassays showed that treatment with Uncaria tomentosa significantly increased the neutrophil count, and a potency of 85.2% was calculated in relation to filgrastim at the corresponding doses tested. An in vitro CFC assay showed an increase in CFU-GM size and mixed colonies (CFU-GEMM) size at the final concentrations of 100 and 200 μg extract/mL.

Conclusions

At the tested doses, Uncaria tomentosa had a positive effect on myeloid progenitor number and is promising for use with chemotherapy to minimize the adverse effects of this treatment. These results support the belief of the Asháninkas, who have classified Uncaria tomentosa as a ‘powerful plant’.     

Role of nitric oxide in motor control: implications for Parkinson's disease pathophysiology and treatment

According to classical thinking about Parkinson's disease, loss of dopaminergic input from the substantia nigra pars compacta leads to overactivity and underactivity of the indirect and direct output pathways, respectively, in the basal ganglia. Administration of the dopamine precursor L-DOPA (l-3, 4-dihydroxyphenylalanine) is proposed to induce changes in the opposite directions. L-DOPA is the most used drug to treat Parkinson`s disease symptoms. After repeated treatment with this compound, however, disabling secondary effects such as the abnormal involuntary movements usually appear. Nitric oxide is a free radical that can also act as an atypical neurotransmitter and influences dopamine-mediated neurotransmission. In this paper we will briefly review the role of nitric oxide on motor control and in Parkinson's disease, particularly a possible role of nitric oxide in L-DOPA induced dyskinesia in rodents. Recent results show that nitric oxide synthase inhibition reduces L-DOPA-induced dyskinesia in rats and mice. The effect is dose-dependent, does not suffer tolerance nor interferes with L-DOPA positive motor effects. These preclinical findings suggest that nitric oxide is a promising therapeutic target for the reduction of L-DOPA-induced dyskinesia.