Cerebral Palsy

Neurofibromatosis type 1 (NF1) is a genetic disorder characterized inter alia by cognitive and motor dysfunction and appearance of high-signal foci on T2-weighted images in the brain. Nf1(+/-) mice are useful models for studying aspects of NF1, including cognitive deficits. Here we assessed their motor performance and used quantitative transverse T2 relaxation MRI to identify structural abnormalities in their brains. Nf1(+/-) mice exhibited both enhanced and reduced T2 signals in distinct brain regions compared to wild-type mice, and their motor performance was impaired. As in NF1 patients, enhanced T2 signals in Nf1(+/-) mice were observed in the thalamus and basal ganglia. Reduced T2 signals were seen in motor-associated regions along the motor pathway, predominantly in the white matter of the cerebral peduncle and the optic tract. Correlation analysis between T2 signals and motor performance suggested that the motor deficits are associated with impairments in the cerebral peduncle and the amygdala. Copyright (c) 2010 John Wiley & Sons, Ltd.

Saccades and hand-tapping are both potential biomarkers in patients with Huntington’s disease (HD). While it is well known that patients with manifest Huntington’s disease display abnormalities in both of these tasks, less is known about how these abnormalities progress over time, or to what extent premanifest patients are affected. This study was designed to address these issues. We examined premanifest and manifest Huntington’s cohorts, together with a group of controls, over a 3-year period. Data were collected using a portable head-mounted saccadometer and a computerised hand-tapping device. Both premanifest and manifest Huntington’s disease patients display significant and systematic changes from year to year in the parameters describing saccadic latency, while controls remain unchanged. By contrast, although hand-tapping was abnormal in HD patients, annual changes were much smaller. Measuring the rate of progression of saccadic abnormalities in manifest HD patients may provide a way to track disease progression, and thus help to evaluate novel therapies to modify the disease. The clear-cut progression in saccadic abnormalities in the premanifest group may prove useful in the future as a predictor of time to disease onset.

Takotsubo cardiomyopathy is characterized by transient left ventricular dysfunction, electrocardiographic changes, and minimal release of myocardial enzymes that mimic acute myocardial infarction in patients without coronary artery disease. Takotsubo cardiomyopathy is frequently triggered by emotional or physical stress and occurs primarily in post-menopausal women. The pathomechanism of Takotsubo cardiomyopathy is, so far, unknown. Stress-induced amnesia is probably induced by perturbation of the hippocampal function. Assault-induced Takotsubo cardiomyopathy associated with amnesia has not been reported so far. In a 77-year-old Caucasian female, hospitalized because of confusion, anterograde amnesia, and hypertension after she had been assaulted by a female who sneaked up to her when she was unlocking the door of her apartment, Takotsubo cardiomyopathy was diagnosed based on clinical findings, electrocardiography, echocardiography, and coronary angiography. Follow-up after 8 weeks showed a regression of electrocardiographic and echocardiographic abnormalities; the amnesia for the assault, however, remained unchanged. This case shows that Takotsubo cardiomyopathy may be triggered by emotional stress induced during an assault. Assault-induced stress may not only induce Takotsubo cardiomyopathy but also amnesia for some of the events that occurred during the act.

Three related proteins of the plakophilin family (PKP1_3) have been identified as junctional proteins that are essential for the formation and stabilization of desmosomal cell contacts. Failure of PKP expression can have fatal effects on desmosomal adhesion, leading to abnormal tissue and organ development. Thus, loss of functional PKP 1 in humans leads to ectodermal dysplasia/skin fragility (EDSF) syndrome, a genodermatosis with severe blistering of the epidermis as well as abnormal keratinocytes differentiation. Mutations in the human PKP 2 gene have been linked to severe heart abnormalities that lead to arrhythmogenic right ventricular cardiomyopathy (ARVC). In the past few years it has been shown that junctional adhesion is not the only function of PKPs. These proteins have been implicated in cell signaling, organization of the cytoskeleton, and control of protein biosynthesis under specific cellular circumstances. Clearly, PKPs are more than just cell adhesion proteins. In this paper we will give an overview of our current knowledge on the very distinct roles of plakophilins in the cell.

We report here a human case probably mixed-infected with Clonorchis sinensis and Fasciola sp. who was diagnosed by computed tomography (CT) scan, serological findings, and/or fecal examination. The patient was a 43-year-old Korean female and was admitted to Kyung Hee University Hospital with the complaints of fever and abdominal pain. On admission, marked eosinophilia was noted in her peripheral blood. CT scan showed specific lesions for clonorchiasis and fascioliasis in the liver, along with lesions suggestive of amebic abscess. Micro-ELISA revealed positive results for the 2 helminthic infections. Eggs of C. sinensis and trophozoites of Entamoeba histolytica were observed in the stool. Treatment with praziquantel followed by metronidazole and tinidazole reduced abnormalities in the liver and eosinophilia. This is the first case report of a possible co-infection with 2 kinds of liver flukes in the Republic of Korea.

OBJECTIVES: To assess the added benefit of scanning lower limbs in addition to the usual whole-body positron emission tomography/computed tomography (PET/CT) scan in patients with no known or suspected primary or metastatic melanoma involving the lower limbs. MATERIALS AND METHODS: This is a retrospective study of 122 consecutive patients [174 2-[F]-fluoro-2-deoxy-D-glucose (FDG) PET/CT] who underwent FDG PET/CT for staging of melanoma at different time points in the course of the disease from October 2005 to February 2009 at the Brest University Hospital. Reports of whole-body PET/CT scans including lower limbs were reviewed. PET/CT abnormalities on the lower extremities were tabulated by location and correlated with pathology, other imaging studies and at least a 6-month clinical follow-up. The usefulness of lower limbs acquisition in clinical management was evaluated according to imagery findings. RESULTS: Among the 174 consecutive PET/CT scans performed in 122 patients, 33 scans in 28 patients highlighted abnormal FDG uptakes considered as equivocal or suggestive of malignancy in the lower limbs. In 28 cases, uptakes were located at once in the lower limbs and in the rest of the body (lung, liver, mediastinal and sub-diaphragmatic lymph nodes, adrenal glands, bone) corresponding to disseminated disease. In five cases, PET/CT uptakes were located only in lower limbs; each pathological uptake corresponded to benign lesions. Lower limbs findings never impacted clinical and therapeutic decision. CONCLUSION: Lower limbs additional PET/CT acquisition seems to offer poor additional benefit with none unexpected lesion detected and routine skull base to upper thigh images might be sufficient for this subset of patients.

BACKGROUND:: The potential for a drug interaction between S/GSK1349572 and tenofovir disoproxil fumarate (TDF) was evaluated in an open-label, repeat dose, 3-period, drug-drug interaction study in healthy subjects. METHODS:: S/GSK1349572 was administered at 50 mg once daily for 5 days (period 1) followed by a 6-day washout period. TDF 300 mg once daily was then administered for 7 days (period 2). The combination of S/GSK1349572 and TDF was then coadministered for 5 days (period 3). Pharmacokinetic parameters were determined and compared between periods. RESULTS:: Fifteen subjects completed all periods and follow-up. S/GSK1349572 and TDF were generally well tolerated with few adverse events reported. No clinically significant trends in post-dose laboratory abnormalities, vital signs, or electrocardiogram values were noted. Pharmacokinetic parameters of S/GSK1349572 and tenofovir during combination therapy were similar to those when given alone, demonstrating no significant drug interaction. S/GSK1349572 geometric least squares mean ratios (90% confidence interval) for AUC(0-tau), Cmax, and Ctau were 1.01 (0.908, 1.11), 0.969 (0.867, 1.08), and 0.920 (0.816, 1.04), respectively. Tenofovir geometric least squares mean ratios (90% confidence interval) for AUC(0-tau), Cmax, and Ctau were 1.12 (1.01, 1.24), 1.09 (0.974, 1.23), and 1.19 (1.04, 1.35), respectively. CONCLUSION:: S/GSK1349572 and TDF can be coadministered without dose adjustment.

During the process of auricular reconstruction in cases of microtia patients with external auditory canals (EAC), bacterial contamination stemming from the EAC can cause cartilage infection. In this article, we retrospectively analyzed the data on bacterial flora present in the EAC of these patients to decrease infection rates during ear reconstruction.Preoperatively, in 91 microtia patients, culture samples were obtained, and isolates were tested for in vitro susceptibility to antibiotics. One hundred volunteers with no ear abnormalities were also evaluated as part of the control group.Seventy-nine specimens in 91 microtia patients showed growth of bacteria (86.8%): a total of 97 organisms were isolated. Dominating bacteria were of the staphylococci species (85.6%). Fourteen Staphylococcus isolates were resistant to methicillin. The percentage of microtia patients showing a presence of methicillin-resistant staphylococci isolates (15%) was significantly higher than the percentage in the “normal” volunteer group showing a presence of methicillin-resistant staphylococci isolates (2%; P = 0.0009).To decrease the complications that occurred due to cartilage infection during auricular reconstruction in the cases of microtia with EAC, we suggest that bacterial floras of the EAC be routinely examined and the patients be treated with susceptible antibiotics preoperatively.

The term “renal osteodystrophy” has recently been replaced with “CKD-mineral and bone disorder (CKD-MBD) ” , which includes vascular calcification as well as bone abnormalities. Following this paradigm shift, the Japanese Society for Dialysis Therapy released guidelines for the management of secondary hyperparathyroidism in chronic dialysis patients, which prioritized improvement in survival, but not in bone abnormalities. According to these guidelines, parathyroid intervention, such as parathyroidectomy and percutaneous ethanol injection therapy, should be indicated if mineral disorders cannot be managed by pharmacological means. Recently, several novel therapeutic tools, including sevelamer hydrochloride, calcitriol analogs, and cinacalcet hydrochloride have been introduced in the clinical setting in Japan. The other side 2009 KDIGO guideline suggest that, if the intact PTH levels fall below two times the upper limit of normal for the assay, calcitriol, vitamin D analogs, and/or calcimimetics be reduced or stopped . And in patients with CKD stages 3-5D with severe hyperparathyroidism (HPT) who fail to respond to medical/pharmacological therapy, this guideline suggest parathyroidectomy. Harmonizing these therapeutic modalities and parathyroid interventions, we should expect more effective management of CKD-MBD, leading to the improvement of morbidity and mortality in this patient population. In this part, we consider indication of parathyroid interventions surround the present condition.

The final goal of CKD-MBD (chronic kidney disease, mineral and bone disorder) is to reduce the risk of death in uremic patients. To achieve this objective, it is of importance to manage laboratory abnormalities, bone abnormalities, and vascular calcification appropriately. Many observation studies suggested that the good control of serum phosphate, calcium, and PTH concentration would lead to the lower risk of death. Fracture and vascular calcification would increase the risk for mortality. In addition, some randomized clinical trials have shown that the use of CKD-MBD related drugs, e.g. vitamin D, phosphate binder, might lead to reductions in the risk of death.