Taking a Better History for Behavioral Issues Pre‐ and Post‐Deep Brain Stimulation: Issues Missed by Standardized Scales

Objectives: To screen for potentially underreported behavioral changes in patients with idiopathic Parkinson's disease (PD) pre‐ and post‐deep brain stimulation (DBS), a retrospective data base review was performed. Methods: In total, 113 patients who underwent unilateral or bilateral DBS at the University of Florida in either subthalamic nucleus or globus pallidus internus for PD were screened for behavioral issues by asking about the presence or absence of seven neuropsychiatric symptoms (panic, fear, paranoia, anger, suicidal flashes, crying, and laughing). Results: There was a high prevalence of fear (16.3%), panic (14.0%), and anger (11.6%) at baseline in this cohort. In the first six months following DBS implantation, anger (32.6%), fear (26.7%), and uncontrollable crying (26.7%) were the most frequent symptoms reported. Those symptoms also were present following six months of DBS surgery (30.2%, 29.1%, and 19.8%, respectively). New uncontrollable crying occurred more in the acute postoperative stage (less than or equal to six months) (p= 0.033), while new anger occurred more in the chronic postoperative stage (greater than six months) (p= 0.017). The frequency of uncontrollable laughing significantly increased with bilateral DBS (p= 0.033). Conclusions: Many of the neuropsychiatric issues were identified at preoperative baseline and their overall occurrence was more than expected. There was a potential for worsening of these issues post‐DBS. There were subtle differences in time course, and in unilateral vs. bilateral implantations. Clinicians should be aware of these potential behavioral issues that may emerge following DBS therapy, and should consider including screening questions in preoperative and postoperative interviews. Standardized scales may miss the presence or absence of these clinically relevant issues.     

A nonsense mutation (R220X) in the alpha-galactosidase A gene causes typical Fabry disease in both genders

BACKGROUND: Fabry disease is an X-linked recessive disorder resulting from a deficiency of lysosomal alpha-galactosidase A (alpha-Gal A). Chronic renal failure is an important cause of death in patients with Fabry disease. We report on patients with Fabry disease (a hemizygous male and his mother) due to a nonsense mutation (R220X) in the alpha-Gal A gene. METHODS: The proband, a 41-year-old man, and his 71-year-old mother presented with renal and cardiac manifestations of Fabry disease. Histological examination and molecular analysis of the alpha-Gal A gene were performed. RESULTS: Typical histological findings of Fabry disease were observed in a renal biopsy specimen from the proband and in renal and myocardial necropsy specimens from the mother. Sequencing of a full-length alpha-Gal A cDNA from the proband indicated a C-T transition at codon 220, resulting in substitution of the predictable termination for arginine (R220X). Examination of genomic alpha-Gal A DNA revealed that the proband was a hemizygote and the mother was a heterozygous carrier for the mutation. CONCLUSION: This is the first detailed report of family members with Fabry disease due to a nonsense mutation (R220X) in the alpha-Gal A gene. Our study indicates that this mutation causes the typical disease in both genders.     

Stenting in obstruction of superior vena cava; clinical experience with the self-expanding endovascular prosthesis

From August 1997 to December 2002, 14 consecutive patients with superior vena cava syndrome with the self-expanding endovascular prosthesis. Diagnoses were adenocarcinoma in 6, small cell carcinoma in 4, squamous cell carcinoma in 1, metastatic lung cancer in 2, and invasive thymoma in 1. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured on their admission and perioperative period. Expecting only 1 patient complete symptomatically relieved within 3 days of stent implantation. Superior vena cava pressure or radial pressure of the stent was sufficient to relieve obstruction. Preoperative ANP level were normal, BNP level were increased. Postoperatively both ANP level and BNP level were slightly increased under intravenous dopamine hydrochloride. Implantation of the self-expanding stent endovascular prosthesis for superior vena cava syndrome provides rapid symptomatic relief and improves the patient's quality of life.     

Evaluation of absorbed dose in respiratory-gated radiotherapy using a phantom system that simulates patient respiration

Respiratory-gated (RG) radiotherapy is useful for minimizing the irradiated volume of normal tissues resulting from the shifting of internal structures caused by respiratory movement. In this technique, although improvement in the dose distribution of the target can be expected, the actual absorbed dose distribution is not clearly determined. Therefore, it is important to clarify the absorbed dose at the tumor and at the evaluation points according to the patient's respiration. We have developed a phantom system that simulates patient respiration (TNK Co., Ltd.), to evaluate the absorbed dose and ensure precise RG radiotherapy. Actual patient respiratory signals were obtained using a respiratory synchronization and gating system (AZ-733V, Anzai Medical). The acquired data were then transferred to a phantom system driven by a ball screw to simulate the shifting of internal structures caused by respiratory movement. We measured the absorbed dose using a micro-ionization chamber dosimeter and the dose distribution using the film method for RG irradiation at expiratory phase by using Linac (PRIMUS, Toshiba Medical Systems Corp.) X-rays. When the distance of phantom movement was set to the average patient respiratory movement distance of 1.5 cm, we first compared absorbed dose with RG irradiation with a gating signal of 50% or less, and without RG irradiation. The absorbed dose at the iso-center was improved by 6.0% and 4.4% at a field size of 4x4 cm2, and by 1.3% and 0.7% at a field size of 5x5 cm2 with an X-ray energy of 6 MV and 10 MV, respectively. There was, however, no dose change at a field size of 10x10 cm2 and 15x15 cm2. When the gating signal was reduced to 25% and 10%, absorbed dose was also improved. With regard to the flatness of the dose profile, no changes in dose distribution were observed in the lateral direction, e.g., beam flatness was within 1.4% and 1.6% at field sizes of 5x5 cm2 and 10x10 cm2, respectively, with an X-ray energy of 6 MV. In the cranial-caudal direction, the dose profile was relatively large even if a gating signal of 50% was applied, i.e., 8.1% and 10.4% at field sizes of 5x5 cm2 and 10x10 cm2, respectively. Beam flatness without RG was much worse, i.e., 37.8% and 38.2%, at field sizes of 5x5 cm2 and 10x10 cm2, respectively. In both cases, the dose was insufficient in the expiratory direction. Although RG radiotherapy is quite useful, the margins in the inspiratory and expiratory phases should be considered based on the level of gating signal and field size in order to formulate appropriate radiotherapy planning in terms of the shifting of internal structures. To ensure accurate radiotherapy, the characteristics of the RG irradiation technique and the radiotherapy equipment must be clearly understood when this technique is to be employed in clinical practice.     

Effects of rugby sevens matches on human neutrophil-related non-specific immunity

Aims

To evaluate the influences of the accumulative effect of two consecutive rugby sevens matches (Sevens) on aspects of human neutrophil‐related non‐specific immunity.

Methods

In seven players participating in the Japan Sevens, neutrophil reactive oxygen species (ROS) production capability and phagocytic activity were measured using flow cytometry, and serum opsonic activity (SOA) was assessed by measuring neutrophil ROS using the peak height of lucigenin‐dependent chemiluminescence before and after two consecutive matches.

Results

ROS showed no change immediately after the first match, and had significantly (P<0.05) increased 4 h later, but showed a decrease after the second match. Phagocytic activity showed no change immediately after the first match, but had significantly (P<0.01) decreased 4 h later, and showed a further decrease after the second match, although it was not significant. SOA significantly (P<0.01) increased after the first match, and still maintained its high 4 h later, but decreased after the second match. ROS production capability, phagocytic activity and SOA significantly (P<0.01) decreased after the second match.

Conclusions

When rugby players play two consecutive Sevens matches, the exercise loading is thought to be hard, similar to that experienced during a marathon race and intensive or long training in a training camp, although the expected changes were not seen after the first match. Differences between after the first and the second matches may be due to the “cumulative effect”.Rugby is a competitive ball game with a long history, which usually has 15 players per team. The rugby sevens match (Sevens), played with seven players, was recently derived from the original game of rugby, with its own World Cup, and many competitions are held in and outside Japan.Rugby is one of the most intense contact sports among competitive sports, and requires a high degree of physical fitness. The incidence of injuries during rugby matches is higher compared with other sports.¹ The basic rules of Sevens, including the size of the pitch, are the same as for an ordinary rugby match, except for a shorter match duration. As Sevens players must play on a full‐sized pitch, it follows that they have a potentially higher exercise loading than under the conditions of a normal game. Usually, more than two games are held on the same day. It can thus be assumed that Sevens players experience high levels of physiological stress, and the incidence of injury will probably be higher than in the case of a 15‐a‐side game. However, to the best of our knowledge, no study on sports medicine concentrating on Sevens players has ever been carried out.Some reports have shown that intense exercise can adversely affect the immune system. The incidence of upper respiratory tract infection among endurance athletes is notably high, and may be due to decreased neutrophil function.^2,3 In addition, decreases in neutrophil functions have been reported after a rugby match.⁴Neutrophils are one of the cellular factors playing an important part in the first line of defence against foreign substances, including microorganisms. Neutrophils engulf microorganisms (phagocytic activity) and produce reactive oxygen species (ROS).^5,6 Serum opsonic activity (SOA) contributes to this microbicidal activity through opsonisation of microorganisms—that is, an acceleration of adhesion of neutrophils to opsonised substances via immunoglobulin (Ig) G, C3 and others. The expression of CD11b (complement receptor type 3; CR3) and CD16 (Fc γ receptor type 3; FcγR3) on the surface of neutrophils facilitates efficient phagocytosis of opsonised foreign bodies and consequent production of ROS.^7,8A single bout of exercise has been reported to change the neutrophil functions. Depending on the report one reads, ROS production increases^9,10 or decreases after acute exercise.^11,12,13 Phagocytic activity decreases after intense exercise^9,12,14 or increases or does not change after moderate exercise.^15,16,17 SOA does not change or increase after a long‐distance race.^18,19 As changes in these functions are linked to the intensity and duration of exercise, measurements of these functions become interesting when the immune response to repeated bouts of exercise is assessed. The influence of repeated bouts of intense exercise on the same day, such as Sevens matches, on immune function has not been investigated. In addition, as recovery of neutrophil function needs >2 days,⁴ repeated bouts of intense exercise with incomplete immunological recovery might increase the risk of infection.In this study, we examined the influence of two consecutive Sevens games on neutrophil function (ROS and phagocytic activity) and neutrophil‐related activity (SOA).     

Rapid purification and characterization of human platelet glycoprotein V: the amino acid sequence contains leucine-rich repetitive modules as in glycoprotein Ib

Glycoprotein V (GPV) is a membrane-associated, 82 Kd platelet glycoprotein that is hydrolyzed during thrombin activation to yield 69 Kd fragment. We have developed a rapid and simple method for isolation of the protein from platelet extracts using a combination of gel permeation, anion-exchange, and lectin affinity chromatography. The partial amino acid sequence was determined by analysis of peptides generated by digestion of the S-carboxyamido-methylated protein with Achromobacter protease I or cyanogen bromide. The sequence shows a remarkable periodicity of leucine residues, which is homologous to the consensus sequence of a highly diversified protein super-family with a common repetitive module. Thrombin cleavage site was determined to be located at the C-terminal region of GPV by analysis of the products separated by sizing and reversed-phase high performance liquid chromatography. By lectin blot analysis, the existence of mucin-type carbohydrate chains was indicated, as well as the existence of asparagine-linked carbohydrate chains shown by the amino acid sequence analysis. From these data, we report a structural model of GPV that is analogous to glycoprotein Ib.     

Rho kinase inhibition protects kidneys from diabetic nephropathy without reducing blood pressure

Rho-associated kinases (ROCK) are activated in the kidney as well as in cultured cells of diabetic models and have been implicated in renal pathophysiology. To explore whether inhibition of ROCK is protective, we studied its role in a model of accelerated diabetic nephropathy where uninephrectomized rats were made diabetic by streptozotocin. After establishing diabetes, rats were treated with the ROCK inhibitor fasudil continuously or for the final 6 weeks of an 18-week experimental period. The results were compared to similar rats given losartan, an established treatment of clinical and experimental diabetic nephropathy, or a combination of both agents. Vehicle-treated diabetic and non-diabetic uninephrectomized rats served as controls. Diabetes resulted in a rapid development of albuminuria, higher glomerulosclerosis and interstitial fibrosis scores, lower glomerular filtration rates, and increased expression of several molecular markers of diabetic nephropathy. Eighteen weeks of fasudil treatment reduced renal ROCK activity, and ameliorated diabetes-induced structural changes in the kidney and expression of the molecular markers in association with a modest anti-proteinuric effect but no change in blood pressure. Late intervention with fasudil reduced glomerulosclerosis, but did not influence proteinuria. Most effects of fasudil were comparable to those of losartan, although losartan lowered blood pressure and further lowered proteinuria. The combination of both treatments was no different than losartan alone. Thus, ROCK inhibition protected the kidney from diabetic nephropathy even though it did not reduce the blood pressure.     

Acute subdural hematoma originating from the lacerated intracranial internal carotid arteries--case report

A 51-year-old male presented with laceration of the bilateral intracranial internal carotid arteries (ICAs) manifesting as acute subdural hematoma (SDH) after a fall of 3 m. Brain computed tomography showed acute SDH appearing as irregular mixed high and low density and causing midline shift. During the operation, massive liquiform hematoma flowed out from the deep portion around the cranial base and systemic blood pressure decreased abruptly. Hemostasis was impossible and he died soon after the operation. Autopsy revealed skull fractures in the bilateral sphenoidal, orbital, temporal, frontal, parietal, and occipital bones, and laceration of the bilateral ICAs in the cavernous sinuses at the fracture sites. Acute SDH can be caused by laceration of the ICA.     

The effects of exercise training associated with low-level laser therapy on biomarkers of adipose tissue transdifferentiation in obese women

Investigations suggest the benefits of low-level laser therapy (LLLT) to improve noninvasive body contouring treatments, inflammation, insulin resistance and to reduce body fat. However, the mechanism for such potential effects in association with exercise training (ET) and possible implications in browning adiposity processes remains unclear. Forty-nine obese women were involved, aged between 20 and 40 years with a body mass index (BMI) of 30–40 kg/m². The volunteers were divided into Phototherapy (808 nm) and SHAM groups. Interventions consisted of exercise training and phototherapy applications post exercise for 4 months, with three sessions/week. Body composition, lipid profile, insulin resistance, atrial natriuretic peptide (ANP), WNT5 signaling, interleukin-6 (IL-6), and fibroblast growth factor-21 (FGF-21) were measured. Improvements in body mass, BMI, body fat mass, lean mass, visceral fat, waist circumference, insulin, HOMA-IR, total cholesterol, LDL-cholesterol, triglycerides, and ANP in both groups were demonstrated. Only the Phototherapy group showed a reduction in interleukin-6 and an increase in WNT5 signaling. In addition, it was possible to observe a higher magnitude change for the fat mass, insulin, HOMA-IR, and FGF-21 variables in the Phototherapy group. In the present investigation, it was demonstrated that exercise training associated with LLLT promotes an improvement in body composition and inflammatory processes as previously demonstrated. The Phototherapy group especially presented positive modifications of WNT5 signaling, FGF-21, and ANP, possible biomarkers associated with browning adiposity processes. This suggests that this kind of intervention promotes results applicable in clinical practice to control obesity and related comorbidities.