Redefining the Koizumi model of mouse cerebral ischemia: A comparative longitudinal study of cerebral and retinal ischemia in the Koizumi and Longa middle cerebral artery occlusion models

Cerebral and retinal ischemia share similar pathogenesis and epidemiology, each carrying both acute and prolonged risk of the other and often co-occurring. The most used preclinical stroke models, the Koizumi and Longa middle cerebral artery occlusion (MCAO) methods, have reported retinal damage with great variability, leaving the disruption of retinal blood supply via MCAO poorly investigated, even providing conflicting assumptions on the origin of the ophthalmic artery in rodents. The aim of our study was to use longitudinal in vivo magnetic resonance assessment of cerebral and retinal vascular perfusion after the ischemic injury to clarify whether and how the Koizumi and Longa methods induce retinal ischemia and how they differ in terms of cerebral and retinal lesion evolution. We provided anatomical evidence of the origin of the ophthalmic artery in mice from the pterygopalatine artery. Following the Koizumi surgery, retinal responses to ischemia overlapped with those in the brain, resulting in permanent damage. In contrast, the Longa method produced only extensive cerebral lesions, with greater tissue loss than in the Koizumi method. Additionally, our data suggests the Koizumi method should be redefined as a model of ischemia with chronic hypoperfusion rather than of ischemia and reperfusion.     

Pelvic Floor Muscle Problems Mediate Sexual Problems in Young Adult Rape Victims

IntroductionPrior studies have addressed sexual abuse and sexual function in adult women. No studies have focused on the effect of adolescence rape on sexual functioning.AimTo investigate the effect of rape on sexual problems and on pelvic floor problems, as well as the mediating role of pelvic floor problems on sexual problems, in a homogenous group of victims of adolescence rape without a history of childhood sexual, physical, and/or emotional abuse.Main Outcome MeasuresSexual functioning and pelvic floor functioning were assessed using self‐report questionnaires.MethodsIn this cross‐sectional study, a group of 89 young women aged 18–25 years who were victimized by rape in adolescence was compared with a group of 114 nonvictimized controls. The rape victims were treated for posttraumatic stress disorder (PTSD) 3 years prior to participation in the study.ResultsThree years posttreatment, rape victims were 2.4 times more likely to have a sexual dysfunction (lubrication problems and pain) and 2.7 times more likely to have pelvic floor dysfunction (symptoms of provoked vulvodynia, general stress, lower urinary tract, and irritable bowel syndrome) than nonvictimized controls. The relationship between rape and sexual problems was partially mediated by the presence of pelvic floor problems. Rape victims and controls did not differ with regard to sexual activities.ConclusionsRape victims suffer significantly more from sexual dysfunction and pelvic floor dysfunction when compared with nontraumatized controls, despite the provision of treatment for PTSD. Possibly, physical manifestations of PTSD have been left unaddressed in treatment. Future treatment protocols should consider incorporating (physical or psychological) treatment strategies for sexual dysfunction and/or pelvic floor dysfunction into trauma exposure treatments. Postma R, Bicanic I, van der Vaart H, and Laan E. Pelvic floor muscle problems mediate sexual problems in young adult rape victims. J Sex Med 2013;10:1978–1987.     

Cardiopulmonary exercise testing in the evaluation of functional capacity after treatment of lymphomas in adults

The present study assessed several parameters of cardiopulmonary function in patients, after treatment for aggressive non-Hodgkin's lymphoma and Hodgkin's disease, to determine the influence of these parameters on patient's performance status. One hundred and six patients (66 male and 40 female) aged 40 +/- 15 years were examined 1-2 years (median 14 months) after anticancer treatment. The patients were examined by means of rest and dynamic stress echocardiography and cardiopulmonary exercise. The rest and post-exercise ejection fraction (EF), Doppler parameters of left ventricular diastolic function and peak oxygen consumption (pVO2) were used as parameters of cardiopulmonary performance. The cumulative dose (CD) of doxorubicin (DOX) given was 240 +/- 70 (240 mg/m2). Thirty-seven percent of patients received mediastinal irradiation in accordance with the used treatment protocol. Sixty-four patients (60%) experienced fatigue after the treatment. Three patients (3%) demonstrated an decreased EF <50%, 34 (32%) demonstrated impaired diastolic function, 14 (13%) demonstrated decreased pVO2<20 ml/kg/min and 15 (14%) demonstrated a value of pVO2 below the reference value, respectively. None of the patients exhibited clinical signs of heart failure. Apart from three patients with a rest EF<50%, all the other patients responded to stress echocardiography with an increment of EF > 5%. The parameter pVO2 significantly correlated with stress EF (0.58, P < 0.0002). A significant relationship was found with all parameters of diastolic function: to index E/A of diastolic filling (r = 0.67, P < 0.0001), isovolumic relaxation time (r = -0.56, P < 0.0009) and to deceleration time (r = -0.54, P < 0.009), respectively. A negative relationship was found with age (r = -0.74, P < 0.0001), CD of DOX (r = -0.53, P < 0.003) and radiotherapy-involving mediastinum (r = - 0.44, P < 0.04), respectively. Using multivariate analysis, a significant relationship was found between pVO2 and parameters of diastolic filling, age, female sex and CD of DOX, respectively (r = 0.58, P < 0.0001). Diastolic dysfunction was correlated with age, CD of DOX and radiotherapy-involving mediastinum, respectively (r = 0.51, P < 0.01). The results show that diastolic dysfunction was the most affected parameter of cardiopulmonary function in cancer survivors. This parameter negatively influenced cardiopulmonary performance and was significantly correlated with the cumulative dose of doxorubicin given and radiotherapy on mediastinum. Despite a high number of patients experiencing fatigue, the study demonstrates that only a relatively small number of patients show a depressed pVO2 on a cardiopulmonary stress test and other cardiac abnormalities. The results of the tests support the introduction of regular aerobic exercise for cancer survivors to increase their cardiopulmonary performance and well-being. Hypothetically, aerobic training may also positively influence diastolic function. However, this assumption warrants a prospective follow-up.     

Treatment of Squamous Cell Carcinoma with Interferon

Human natural leukocytic interferon and recombinant HulFN alpha 2c can be used in the therapy of squamous cell carcinoma. The duration of treatment was 3-6 weeks. A single dose was 400,000-5,000,000 units given weekly for 3-6 weeks. Clinically and histologically 19 of 32 patients were cured and tumor cells were not found in the material taken after interferon treatment for the second biopsy. In ten patients tumor size was reduced 25-90%, and in three patients tumor size was not reduced according to clinical findings. With recombinant HulFN alpha 2c therapy given 5 times per week for 4 weeks. Four of ten patients with similar tumors were cured clinically and histologically clinical findings. In five patients tumor size was reduced 25-90%, while in one patient there was no reduction in tumor size. Both types of interferons are effective in the treatment of squamous cell carcinoma. Side reactions were mild.     

Surgical treatment of Wolff-Parkinson-White syndrome

The results of surgical treatment of 365 patients with the WPW syndrome are analysed. They underwent operation at the surgical department of the Kanazawa University Medical School in the period between 1973 and 1989. In 1969 T. Iva suggested an endocardial approach from the direction of the atrium for removal of the additional pathways, which the authors use at present also. The anomalies were congenital in 47 and acquired in 12 patients and were corrected in one stage during removal of the additional pathways. Multiple additional pathways were found in 33 patients. The additional pathways were completely removed in 33 patients. Paroxysms of tachycardia do not occur after the operation in 364 patients among the 365 who were operated on.     

Naloxone interferes with granulocytopoiesis in long-term cultures of mouse bone marrow; buffering by the stromal layer

Long-term cultures of mouse bone marrow cells were treated with naloxone, starting at the time of culture initiation or in the 2nd or 4th week of culture. Cell proliferation was suppressed and the ratio of immature and mature granulocytes to macrophages diminished by naloxone treatment. The effect depended on the timing of naloxone addition to the cultures and on its concentration, with a bell-shaped dose-response curve. High and low concentrations of naloxone (10⁻⁴, 10⁻⁶, 10⁻¹⁴ M) interfered with hematopoiesis more strongly than the intermediate concentrations (10⁻⁸ to 10⁻¹² M). Early cultures lacking the stromal layer were more sensitive to naloxone than the cultures with established stroma. The bell-shaped dose-response curve has been attributed to an interplay of specific (opioid-receptor-mediated) and nonspecific mechanisms. Opioidergic mechanisms apparently participate in the regulation of hematopoiesis.