Hyperthyroidism associated with papilloedema and pyramidal tract involvement

Summary In a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes [MELAS] who had normal mitochondrial enzyme activity, high doses of coenzyme Q₁₀ (CoQ) were administered. Clinical improvement with decreased serum lactate and pyruvate levels was observed. Though the mechanism of action of CoQ is not known, a trial is worthwhile in patients with MELAS.     

Chronic encapsulated intracerebral hematoma associated with cavernous angioma: a case report

The case of a patient with a chronic encapsulated intracerebral hematoma associated with a cavernous angioma is reported. In spite of a huge space-occupying lesion in the frontal lobe, our patient showed no focal neurological deficit. The clinical picture suggested a slowly growing brain tumor. Intraoperative findings revealed a liquefied intracerebral hematoma with a thick capsule. Pathological investigations demonstrated a capsule rich in neovascularity with a cavernous angioma attached to it. It is presumed that initial bleeding from the cavernous angioma encouraged capsule formation similar to the membrane of chronic subdural hematomas and that repeated bleeding from the capillaries of the capsule allowed the expansion of the hematoma.     

The frontal cortex is activated during learning of endoscopic procedures

Background

To date, several training and evaluation systems for endoscopic surgery have been developed, such as virtual-reality simulators and box trainers. However, despite current advances in these objective assessments, no functional brain studies during learning of endoscopic surgical skills have been carried out. In the present study, we investigated cortical activation using near-infrared spectroscopy (NIRS) during endoscopic surgical tasks.

Study design

A total of 21 right-handed subjects, comprising 4 surgical experts, 4 trainees, and 13 novices, participated in the study. Suturing and knot-tying tasks were performed in a box trainer. Cortical activation was assessed in all subjects by task-related changes in hemoglobin (Hb) oxygenation using NIRS.

Results

In surgical experts and novices with no experience of endoscopic surgical training, we found no changes in oxy-Hb, deoxy-Hb or total-Hb levels in any of the frontal channels. In surgical trainees and one novice with experience of endoscopic surgical training, we found significant increases in oxy-Hb and total-Hb levels in most of the frontal channels. There were significant differences in oxy-Hb and total-Hb levels in CH-19 between surgical experts and trainees (p = 0.02 for both), and between surgical trainees and novices with no experience of endoscopic surgical training (p = 0.008 for both). Furthermore, additional training increased oxy-Hb levels in the frontal cortex of novices with no experience of endoscopic surgical training but had no such effect on surgical experts.

Conclusions

The present data suggest that NIRS is a feasible tool for assessing brain activation during endoscopic surgical tasks, and may have a large impact on the future development of teaching, training, and assessment methods for endoscopic surgical skills.     

Next-Generation Sequencing-Based Molecular Diagnosis of Choroideremia

We screened patients with choroideremia using next-generation sequencing (NGS) and identified a novel mutation and a known mutation in the CHM gene. One patient presented an atypical fundus appearance for choroideremia. Another patient presented macular hole retinal detachment in the left eye. The present case series shows the utility of NGS-based screening in patients with choroideremia. In addition, the presence of macular hole in 1 of the 2 patients, together with a previous report, indicated the susceptibility of patients with choroideremia to macular hole.Key Words: Choroideremia, Next-generation sequencing, Diagnosis, Utility     

Effectiveness of continuous arteriovenous hemofiltration for patients with refractory heart failure

Continuous arteriovenous hemofiltration (CAVH) was carried out in 8 patients with refractory congestive heart failure. All these patients had heart failure and oliguria for over 24 hours and intensive treatment with digitalis, diuretics, catecholamines and vasodilators was prescribed. Hemodynamics were followed closely during CAVH. During CAVH, pulmonary arterial pressure and pulmonary capillary wedge pressure were significantly reduced in all patients, the right atrial pressure decreased in 6 with right cardiac failure, the heart rate decreased in 3 with tachycardia and the blood pressure and cardiac index were elevated in 3 with hypotension. These observations show that CAVH can be performed safely and effectively in patients with congestive heart failure, oliguria and hypotension.     

Gene expression changes in aging retinal microglia: relationship to microglial support functions and regulation of activation

Microglia, the resident immune cells of the central nervous system (CNS), are thought to contribute to the pathogenesis of age-related neurodegenerative disorders. It has been hypothesized that microglia undergo age-related changes in gene expression patterns that give rise to pathogenic phenotypes. We compared the gene expression profiles in microglia isolated ex vivo from the retinas of mice ranging from early adulthood to late senescence. We discovered that microglial gene expression demonstrated progressive change with increasing age, and involved genes that regulate microglial supportive functions and immune activation. Molecular pathways involving immune function and regulation, angiogenesis, and neurotrophin signaling demonstrated age-related change. In particular, expression levels of complement genes, C3 and CFB, previously associated with age-related macular degeneration (AMD), increased with aging, suggesting that senescent microglia may contribute to complement dysregulation during disease pathogenesis. Taken together, senescent microglia demonstrate age-related gene expression changes capable of altering their constitutive support functions and regulation of their activation status in ways relating to neuroinflammation and neurodegeneration in the CNS.     

Population pharmacokinetics of mizoribine in pediatric patients with kidney disease

Background

The present study aimed to obtain information enabling optimisation of the clinical effect of mizoribine (MZR) in pediatric patients with kidney disease.

Methods

A total of 105 pediatric patients with kidney disease treated at our institutions were enrolled. Kidney transplant patients were excluded. Population pharmacokinetic analysis of MZR was performed based on serum concentration data. Area under the curve from time zero to infinity (AUC_∞) and maximal concentration (C _max) were calculated by Bayesian analysis.

Results

In children, the appearance of MZR in the blood tended to be slower and the subsequent rise in blood concentration tended to be more sluggish, compared to healthy adults. Apparent volume of distribution and oral clearance were also higher in children compared to adults. A significant positive correlation was observed between patient age and AUC_∞. There were significant differences of AUC_∞ and C _max by age group. No relationship was observed between the administration method of MZR and serum concentration.

Conclusion

The pharmacokinetics of MZR was different in children compared to adults. To obtain the expected clinical efficacy, the regular MZR dosage schedule (2–3 mg/kg/day) might be insufficient for pediatric patients. In particular, younger patients might require a higher dosage of MZR per unit body weight.

     

Effects of chlorogenic acid on carbachol-induced contraction of mouse urinary bladder

Chlorogenic acid (CGA) is a polyphenol found in coffee and medicinal herbs such as Lonicera japonica. In this study, the effect of CGA-induced relaxation on carbachol (CCh)-induced contraction of mouse urinary bladder was investigated. CGA (30–300 μg/ml) inhibited CCh- or U46619-induced contraction in a concentration-dependent manner. SQ22536 (adenylyl cyclase inhibitor) recovered CGA-induced relaxation of CCh-induced contraction; however, ODQ (guanylyl cyclase inhibitor) did not have the same effect. In addition, 3-isobutyl-1-methylxanthine (IBMX) enhanced CGA-induced relaxation; however, forskolin or sodium nitroprusside did not have the same effect. Moreover, Ro 20–1724, a selective phosphodiesterase (PDE) 4 inhibitor, enhanced CGA-induced relaxation, but vardenafil, a selective PDE5 inhibitor, did not have the same effect. In the presence of CCh, CGA increased cyclic adenosine monophosphate (cAMP) level, whereas SQ22536 inhibited the increase of cAMP levels. Moreover, higher cAMP levels were obtained with CGA plus IBMX treatment than the total cAMP levels obtained with separate CGA and IBMX treatments. In conclusion, these results suggest that CGA inhibited CCh-induced contraction of mouse urinary bladder by partly increasing cAMP levels via adenylyl cyclase activation.