Effect of basic fibroblast growth factor on radiation-induced oral mucositis in male Syrian hamsters

Purpose: Oral mucositis is a frequent and dose-limiting side effect of radiotherapy or chemotherapy in cancer patients. We investigated the effect of basic fibroblast growth factor on radiation-induced oral mucositis in male Syrian hamsters.

Method: Oral mucositis was induced in male Syrian hamsters by a single dose of 30-Gy irradiation. Eight days after irradiation, treatment with gel containing trafermin (basic fibroblast growth factor) at 1 or 10?μg up to day-21 was initiated. Re-epithelialization was graded using a six-point scoring system for oral mucositis. Samples of hamster cheek pouches were removed for histopathologic analyses and immunohistochemistry.

Results: The oral-mucositis score decreased in a dose-dependent manner upon trafermin treatment. Trafermin (10 μg) improved oral mucositis significantly compared with vehicle. Histopathology revealed that the degree of re-epithelialization was improved by treatment with trafermin (10?μg) compared with treatment with vehicle.

Conclusions: Administration of trafermin (10?μg) can prevent mucosal damage to hamster cheek pouches induced by irradiation.     

Reduction of anterior glenohumeral dislocations: a new closed reduction technique

Objective: A new closed reduction technique for anterior glenohumeral dislocations and tuberosity fracture dislocations is introduced.

Methods: Forty-one consecutive patients with an acute anterior glenohumeral dislocation or tuberosity fracture dislocation underwent closed reduction by an orthopaedic surgeon employing this new method.

Results: Closed reduction was successful in 88% of patients using the reduction maneuver. Associated fracture with glenohumeral dislocation did not influence the success rate of the reduction maneuver. An assistant was needed in 15% of cases. No complications related to the reduction maneuver were noted amongst the cohort.

Conclusion: This novel reduction technique is safe demonstrating excellent success rates both for anterior shoulder dislocations and tuberosity fracture-dislocations.     

Whole body proton irradiation causes acute damage to bone marrow hematopoietic progenitor and stem cells in mice

Purpose: Exposure to proton irradiation during missions in deep space can lead to bone marrow injury. The acute effects of proton irradiation on hematopoietic stem and progenitor cells remain undefined and thus were investigated.

Materials and methods: We exposed male C57BL/6 mice to 0.5 and 1.0?Gy proton total body irradiation (proton-TBI, 150?MeV) and examined changes in peripheral blood cells and bone marrow (BM) progenitors and LSK cells 2 weeks after exposure.

Results: 1.0?Gy proton-TBI significantly reduced the numbers of peripheral blood cells compared to 0.5?Gy proton-TBI and unirradiated animals, while the numbers of peripheral blood cell counts were comparable between 0.5?Gy proton-TBI and unirradiated mice. The frequencies and numbers of LSK cells and CMPs in BM of 0.5 and 1.0?Gy irradiated mice were decreased in comparison to those of normal controls. LSK cells and CMPs and their progeny exhibited a radiation-induced impairment in clonogenic function. Exposure to 1.0?Gy increased cellular apoptosis but not the production of reactive oxygen species (ROS) in CMPs two weeks after irradiation. LSK cells from irradiated mice exhibited an increase in ROS production and apoptosis.

Conclusion: Exposure to proton-TBI can induce acute damage to BM progenitors and LSK cells.     

The drill wobble effect: oversizing the femoral tunnel during ACL reconstruction

Objectives: In ACL reconstruction, autologous tendon graft can be attached to the femur, within a boney tunnel, using an Endobutton device. The ultimate aim being to achieve biological fixation and incorporation into the bone. Accurate bone tunnel diameter to match the tendon graft is vital to biologic incorporation and strength. The common technique of in sequence passing a guide wire, a cannulated 4.5 mm Endobutton drill, then a cannulated femoral socket drill causes the guidewire to lose cortical fixation and stability before the femoral socket drill is passed.

The Objective of this study is to analyze this common technique of femoral socket creation and determine if it results in unintentionally oversizing the femoral socket due to femoral socket drill-wobble over a destabilised guide wire.

Methods: 12 cadaveric femoral pairs equally divided between two groups underwent femoral socket creation in one of the two following sequences.

Group 1: Guidewire, 4.5 mm endobutton drill, 8 mm femoral socket drill. Group 2: Guidewire, 8 mm femoral socket drill, 4.5 mm endobutton drill. The created femoral tunnels apertures and calibres were measured and then compared for accuracy between the two groups.

Results: Passing the 4.5 mm drill before the 8 mm socket drill results in oversized tunnel apertures and calibres when compared to passing an 8 mm socket drill after the 4.5 mm drill has been passed (p<0.0001).

Conclusion: To most precisely create an 8 mm femoral socket in ACL reconstruction, the 8 mm femoral socket reamer followed by the 4.5 mm should be passed over the guide wire to prevent guide wire destabilization and drill-wobble.     

Heart rate recovery time in metabolically healthy and metabolically unhealthy obese children

Background: Autonomic dysfunction is an emerging non-traditional cardiovascular risk factor that correlates with obesity, components of metabolic syndrome, as well as cardiorespiratory fitness. As a simple and validated index of autonomic balance, heart rate recovery (HRR) has been reported as a useful biomarker for predicting cardiovascular morbidity and mortality.

Objectives: The aim of this study was to compare HRR in metabolically healthy vs. metabolically unhealthy obese children.

Methods: A total of 56 obese children of whom 31 had metabolic syndrome were examined. All the participants underwent the multistage submaximal cycle ergometer test and HRR was determined one minute after the test.

Results: The HRR was significantly lower (18.9 ± 3.7) in a group of metabolically unhealthy obese children compared to metabolically healthy obese children (24 ± 4.1) p < 0.001. Logistic regression analysis showed that reduction in HRR was also influenced by higher BMI.

Conclusion: Our findings implicate the presence of the autonomic dysfunction as reflected by impaired heart rate recovery (HRR) in obese children with metabolic syndrome.     

Cardiovascular sequel of neck irradiation in head and neck cancer patients

Purpose: The baroreflex is an important afferent mechanism controlling autonomic functions. As afferent nerves course through the neck, they are susceptible to damage by neck irradiation in head and neck cancer patients. With increased survival of head and neck cancer patients because of improved therapy, the cardiovascular morbidity and mortality in them have become apparent and this is of clinical concern. There are few case reports of baroreflex failure as a chronic sequel to neck irradiation.

Objectives: The present study evaluated the changes in cardio-autonomic tone and postural cardiovascular reflex in neck-irradiated patients.

Methods: Head and neck cancer patients who had received neck irradiation (n?=?15) and healthy controls (n?=?15) were evaluated for heart rate variability with time domain analysis of 5?min ECG recording. Postural cardiovascular reflexes were studied with changes in blood pressure and heart rate in the lying to standing test.

Results: Our results suggest that there is a reduction in overall time domain measures of heart rate variability and weakened postural reflexes in neck-irradiated patients.

Conclusion: Decreased heart rate variability in neck-irradiated patients reflects an independent risk of cardiovascular morbidity. The early detection of cardiovascular impairment in such patients may help healthcare professionals in providing better care. Furthermore, the dose delivered to the carotid sinus should be monitored and restricted.     

A systematic literature review of synovial chondromatosis and pigmented villonodular synovitis of the hip

Objectives: Benign synovial diseases of the hip including Synovial Chondromatosis (SC) and Pigmented Villonodular Synovitis (PVNS) are devastating diseases. Initially, patients present with hip pain unrelieved by conservative measures. The diagnosis of PVNS and SC are often delayed, leading to progression of joint damage.

The purpose of this review is to present the latest on the diagnosis, management, and prognosis of SC and PVNS of the hip.

Methods: An extensive systematic search of MEDLINE and PUBMED Databases was performed. Data parameters were set from 2005 to present day with set inclusion criteria. Systematic reviews were excluded.

Results: 427 abstracts were identified, with 12 articles meeting all inclusion criteria. Eight studies focused on SC, and 5 on PVNS. 233 patients with SC of the hip and 98 patients with PVNS of the hip were identified, a total of 331 patients.

Discussion: Benign Synovial disorders of the hip are rare. In patients with chronic hip pain secondary to benign synovial disorders, early diagnosis and surgical intervention demonstrate good outcomes, and patients may benefit due to prevention of morbidity from further joint destruction. There is no clear consensus between higher successes through open versus arthroscopic surgical debridement. In the final phase of benign synovial disorders of the hip, THA of different types based on the patient’s age should be considered.     

Role of NADPH oxidase in radiation-induced pro-oxidative and pro-inflammatory pathways in mouse brain

Purpose: The present study was designed to investigate our hypothesis that NADPH oxidase plays a role in radiation-induced pro-oxidative and pro-inflammatory environments in the brain.

Materials and methods: C57BL/6 mice received either fractionated whole brain irradiation or sham-irradiation. The mRNA expression levels of pro-inflammatory mediators, such as TNF-α and MCP-1, were determined by quantitative real-time RT-PCR. The protein expression levels of TNF-α, MCP-1, NOX-2 and Iba1 were detected by immunofluorescence staining. The levels of ROS were visualized by in situ DHE fluorescence staining.

Results: A significant up-regulation of mRNA and protein expression levels of TNF-α and MCP-1 was observed in irradiated mouse brains. Additionally, immunofluorescence staining of Iba1 showed a marked increase of microglial activation in mouse brain after irradiation. Moreover, in situ DHE fluorescence staining revealed that fractionated whole brain irradiation significantly increased production of ROS. Furthermore, a significant increase in immunoreactivity of NOX-2 was detected in mouse brain after irradiation. On the contrary, an enhanced ROS generation in mouse brain after irradiation was markedly attenuated in the presence of NOX inhibitors or NOX-2 neutralizing antibody.

Conclusions: These results suggest that NOX-2 may play a role in fractionated whole brain irradiation-induced pro-oxidative and pro-inflammatory pathways in mouse brain.     

The relationship of hip muscle performance to leg,ankle and foot injuries: a systematic review

Objectives: Hip control affects movement and muscle firing patterns in the leg, ankle and foot, and may contribute to overuse injuries. Muscle performance can be measured as strength, endurance or muscle activation patterns. Our objective was to systematically review whether hip muscle performance is associated with leg, ankle and foot injuries.

Data sources: A structured and comprehensive search of six medical literature databases was combined with forward and backward citation tracking (AMED, CINAHL, EMBASE, Medline, Scopus and SportDiscus).

Study selection: Eligible studies measured hip muscle performance in individuals with musculoskeletal injuries below the tibial tuberosity, using dynamometry or electromyography (EMG). All studies compared an injured group with a control group or compared the injured and non-injured limb in the same individual.

Data extraction: Data was extracted from each study independently by two authors.

Data synthesis: Twenty case-control and four prospective studies (n = 24) met the inclusion criteria. Injury classifications included chronic ankle instability (n = 18), Achilles tendinopathy (n = 2), medial tibial stress syndrome and tibial stress fracture (n = 1), posterior tibial tendon dysfunction (n = 1), and exertional medial tibial pain (n = 2). Eleven of the studies revealed differences in hip muscle performance indicating less strength, delayed onset activation and decreased duration of activation in the injured groups. Two studies found evidence for differences between groups only in some of their measurements. Three out of the four prospective studies revealed that hip muscle performance was not a risk factor for leg, ankle and foot injuries.

Conclusions: This review provides limited evidence that hip muscle performance variables are related to leg, ankle and foot injuries. Emerging evidence indicates this might be a result of the injury rather than a contributor to the injury.     

Radiotherapy of meningioma: a treatment in need of radiobiological research

Purpose: Meningiomas account for one third of primary intracranial tumors; nevertheless information on meningioma cell lines and in vivo models is scant. Although radiotherapy is one of the most relevant therapeutic options for the treatment of patients with meningioma, radiobiological research to understand tumor response to this treatment is far from being thoroughly figured out. The aim of this report is to provide a comprehensive picture of the current literature on this field, so as to foster research in this regard.

Methods: We carried out a review of meningioma radiobiology based on a peer-reviewed PubMed search.

Results: Our findings confirm that the main limitation of radiobiological research into meningioma is the paucity of robust in vitro and in vivo models. Alternative approaches to overcome the already identified problems, and to allow better understanding of the entire histopathological spectrum of meningiomas have been explored.

Conclusions: A radiobiological perspective of meningioma may help to improve clinical results both in terms of tumor control and healthy tissue sparing. Although we are far from drawing any conclusions, this review can lead researchers to identify some clues for future areas of study.     

Immune responses of a wall lizard to whole-body exposure to radiofrequency electromagnetic radiation

Purpose During the last three decades, the number of devices that emit non-ionizing electromagnetic radiation (EMR) at the wireless communication spectrum has rapidly increased and possible effects on living organisms have become a major concern. The purpose of this study was to investigate the effects of radiofrequency EMR emitted by a widely used wireless communication device, namely the Digital Enhanced Communication Telephony (DECT) base, on the immune responses of the Aegean wall lizard (Podarcis erhardii).

Materials and methods Adult male lizards were exposed 24 h/day for 8 weeks to 1880–1900 MHz DECT base radiation at average electric field intensity of 3.2 V/m. Immune reactivity was assessed using the phytohemagglutinin (PHA) skin swelling and mixed lymphocyte reaction (MLR) tests.

Results Our results revealed a noticeable suppression (approximately 45%) of inflammatory responses in EMR-exposed lizards compared to sham-exposed animals. T cell-mediated responses were marginally affected.

Conclusion Daily radiofrequency EMR exposure seems to affect, at least partially, the immunocompetence of the Aegean wall lizard.     

6,7,3′,4′-Tetrahydroxyisoflavone improves the survival of whole-body-irradiated mice via restoration of hematopoietic function

Purpose: 6,7,3′,4′-tetrahydroxyisoflavone (T3) is a novel chemically synthesized compound reported in our previous study. This study was designed to explore the radioprotective effect of T3, and if so, its potential mechanisms.

Materials and methods: KunMing mice were exposed to various doses of γ irradiation (60 Co) after being treated with dimethyl sulfoxide (DMSO) or T3. Briefly, survival rate, dose reducing factor (DRF), body weight change (%), spleen index (SI) and thymus index (TI) of irradiated mice with or without different doses of T3 treatment were evaluated routinely. The hematopoietic function of bone marrow was emphatically investigated. In vitro experiments were performed to observe the protective effect of T3 on irradiated human lymphocyte AHH-1 cells by cell viability or flow cytometry (FCM) assays.

Results: A single dose of subcutaneous administration of T3 significantly improved the survival rate, and enhanced the restoration of hematopoietic function in irradiated mice. T3 also decreased the apoptosis of irradiated AHH-1 cells in vitro.

Conclusions: T3 protected mice against lethal γ irradiation-induced injury probably through the restoration of hematopoietic function. This implied that T3 could be further developed as a radioprotector.     

Transfer of useful variability of high grain iron and zinc from Aegilops kotschyi into wheat through seed irradiation approach

Purpose To transfer the 2S chromosomal fragment(s) of Aegilops kotschyi (2S^k) into the bread wheat genome which could lead to the biofortification of wheat with high grain iron and zinc content.

Materials and methods Wheat-Ae. kotschyi 2A/2S^k substitution lines with high grain iron and zinc content were used to transfer the gene/loci for high grain Fe and Zn content into wheat using seed irradiation approach.

Results Bread wheat plants derived from 40 krad-irradiated seeds showed the presence of univalents and multivalents during meiotic metaphase-I. Genomic in situ hybridization analysis of seed irradiation hybrid F₂ seedlings showed several terminal and interstitial signals indicated the introgression of Ae. kotschyi chromosome segments. This proves the efficacy of seed radiation hybrid approach in gene transfer experiments. All the radiation-treated hybrid plants with high grain Fe and Zn content were analyzed with wheat group 2 chromosome-specific polymorphic simple sequence repeat markers to identify the introgression of small alien chromosome fragment(s).

Conclusion Radiation-induced hybrids showed more than 65% increase in grain iron and 54% increase in Zn contents with better harvest index than the elite wheat cultivar WL711 indicating effective and compensating translocations of 2S^k fragments into wheat genome.     

Proteome analysis of irradiated endothelial cells reveals persistent alteration in protein degradation and the RhoGDI and NO signalling pathways

Purpose: Epidemiological studies indicate that radiation doses as low as 0.5?Gy increase the risk of cardiovascular disease decades after the exposure. The aim of the present study was to investigate whether this radiation dose causes late molecular alterations in endothelial cells that could support the population-based data.

Materials and methods: Human coronary artery endothelial cells were irradiated at 0.5?Gy (X-ray) and radiation-induced changes in the proteome were investigated after different time intervals (1, 7 and 14 d) using ICPL technology. Key changes identified by proteomics and bioinformatics were validated by immunoblotting and ELISA.

Results: The radiation-induced alteration of the endothelial proteome was characterized by sustained perturbation of Rho GDP-dissociation inhibitor (RhoGDI) and nitric oxide (NO) signalling pathways. At later time-points, this was accompanied by reduced proteasome activity, enhanced protein carbonylation indicating augmented oxidative stress, and senescence.

Conclusions: These molecular changes are indicative of long-term premature endothelial dysfunction and provide a mechanistic framework to the epidemiological data showing increased risk of cardiovascular disease at 0.5?Gy.     

Intra-sheath versus extra-sheath ultrasound guided corticosteroid injection for trigger finger: a triple blinded randomized clinical trial

Objective: The aim of this study is to compare clinical results of ultrasound-guided corticosteroid injection, intra-sheath versus extra-sheath of the finger flexor tendon.

Methods: A total of 166 patients with trigger finger were evaluated in a triple blind randomized clinical trial study. All the patients were injected with 1ml of 40mg/ml methyl prednisolone acetate, under the guidance of ultrasound. Half the patients were injected extra sheath, while the other half were injected intra sheath at the level of first annular pulley.

Results: The two groups were comparable in baseline characteristics (age, gender, dominant hand, involved hand and finger, and the symptoms duration). No significant difference was observed in the two groups with regards to Quinnell grading. In the final visit, 94% of patients from each group were symptom free.

Conclusion: Results of corticosteroid injection intra-sheath or extra-sheath of the finger flexor tendon under ultrasound guidance in patients with trigger finger are comparably alike. Extra-sheath injection at the level of A1 pulley is as effective as an Intra-sheath administration.     

DNA repair pathway choice at various conditions immediately post irradiation

Purpose: To clarify which DNA double-strand break repair pathway, non-homologous end-joining (NHEJ), homologous recombination repair (HRR) or both, plays a key role in potentially lethal damage repair (PLDR).

Methods and materials: Combining published data and our new potentially lethal damage repair (PLDR) data, we explain whether similar to sublethal damage repair (SLDR), PLDR also mainly depends on NHEJ versus HRR. The PLDR data used the same cell lines: wild type, HRR or NHEJ-deficient fibroblast cells, as those SLDR data published by our laboratory previously. The PLDR condition that we used was as commonly described by many other groups: the cells were collected immediately or overnight post ionizing radiation for colony formation after cultured to a plateau phase with a low concentration of serum medium.

Results: Enough data from other groups and our lab showed that wild type or HRR-deficient cells had efficient PLDR, but NHEJ deficient cells did not.

Conclusion: NHEJ contributes more to PLDR than HRR in mammalian cells, which is similar to SLDR. Since both SLDR and PLDR are relevant to clinical tumor status while undergoing radiotherapy, such clarification may benefit radiotherapy in the near future.     

Epinephrine-induced pulmonary edema during hip arthroscopy: a report of two cases and a review of the literature

Objectives: Hip arthroscopy utilization has significantly increased in recent years. While it is a relatively safe procedure, it is not without risk. Life-threatening complications, albeit rare, can potentially occur and must be appropriately recognized and treated. We describe 2 cases in which patients’ undergoing hip arthroscopy developed pulmonary edema and their respective courses of treatment.

Methods: Both patients were being treated for symptomatic femoroacetabular impingement (FAI), with labral tears, requiring operative management after a failed trial of conservative management. The complication occurred during a primary hip arthroscopy procedure and a retrospective review of their clinical records and intra-operative notes was performed.

Results: Hip arthroscopy was performed under spinal anesthetic in the supine position in both patients. In both procedures, patients developed severe hypertension and tachycardia, with subsequent oxygen desaturations with noted pulmonary edema. The postulated etiology was systemic effects from intra-articular epinephrine, causing acute pulmonary edema with corresponding cardiovascular changes. With supportive ventilation, selective alpha-adrenergic blocker and furosemide administration, and cessation of epinephrine exposure, vital signs normalized and both patients experienced symptom resolution.

Conclusion: During arthroscopy, if acute hypertension, tachycardia and hypoxia develop, epinephrine-induced pulmonary edema should be considered as a cause by the treating orthopedic surgeon and anesthesiologist in order to initiate an appropriate treatment plan.     

Increasing levels of saliva alpha amylase in electrohypersensitive (EHS) patients

Purpose: To assess the level of various salivary and urinary markers of patients with electromagnetic hypersensitivity (EHS) and to compare them with those of a healthy control group.

Materials and methods: We analyzed samples from 30 EHS individuals and a matched control group of 25 individuals (non-EHS) aged between 22 and 66. We quantified cortisol both in saliva and urine, alpha amylase (sAA), immunoglobulin A and C Reactive Protein levels in saliva and neopterin in urine (uNeopterin).

Results: sAA was found to be significantly higher (p?<?0.005) in the EHS group. uNeopterin and sAA analysis showed a significant difference based on the duration of EHS.

Conclusion: Higher levels of sAA in EHS participants may suggest that the sympathetic adrenal medullar system is activated. However, most of the analyzed markers of the immune system, sympathetic activity and circadian rhythm did not vary significantly in the EHS group. There is a trend to the higher levels of some variables in subgroups according to the EHS duration.     

Resveratrol ameliorates ionizing irradiation-induced long-term immunosuppression in mice

Purpose: Ionizing radiation has been associated with adverse effects on the immune system. Currently, there are no effective treatment options to ameliorate these effects. The aim of the present study was to investigate the protective effects of resveratrol against radiation-induced long-term immunosuppression in mice.

Materials and methods: Mice were exposed to total body irradiation and treated with resveratrol or vehicle. Several immune parameters were measured, including thymus and spleen weights, T-lymphocyte and B-lymphocyte count in peripheral blood, concanavalin A and lipopolysaccharide induced lymphocyte proliferation. To explore the mechanism, we investigated intracellular ROS level of lymphocytes and mice plasma cytokine levels.

Results: Treatment with resveratrol ameliorated TBI-induced atrophy of the thymus and spleen, reduction of lymphocyte count and decline of lymphocyte proliferation. TBI exhibited significantly reduced level of IL-2, IL-4, IL-7 and IFN-γ compared with the control mice and treatment with resveratrol attenuated the reduction.

Conclusion: The results of the present study suggest that treatment with resveratrol could ameliorate irradiation induced long-term immune malfunction at least partly via modulation of plasma cytokine.