Recurrent mutations of CD79B and MYD88 are the hallmark of primary central nervous system lymphomas.

AIMS: Primary central nervous system lymphoma (PCNSL) manifest aggressive clinical behaviour and have poor prognosis. Although constitutive activation of the nuclear factor-κB (NF-κB) pathway has been documented, knowledge about the genetic alterations leading to the impairment of the NF-κB pathway in PCNSLs is still limited. This study was aimed to unravel the underlying genetic profiles of PCNSL. METHODS: We conducted the systematic sequencing of 21 genes relevant to the NF-κB signalling network for 71 PCNSLs as well as the pyrosequencing of CD79B and MYD88 mutation hotspots in a further 35 PCNSLs and 46 glioblastomas (GBMs) for validation. RESULTS: The results showed that 68 out of 71 PCNSLs had mutations in the NF-κB gene network, most commonly affecting CD79B (83%), MYD88 (76%), TBL1XR1 (23%), PRDM1 (20%) and CREBBP1 (20%). These mutations, particularly CD79B and MYD88, frequently coincided within each tumour in various combinations, simultaneously affecting diverse pathways within the network. No GBMs had hotspot mutation of CD79B Y196 and MYD88 L265. CONCLUSIONS: The prevalence of CD79B and MYD88 mutations in PCNSLs was considerably higher than reported in systemic diffuse large B-cell lymphomas. This observation could reflect the paucity of antigen stimuli from the immune system in the central nervous system (CNS) and the necessity to substitute them by the constitutive activation of CD79B and MYD88 that would initiate the signalling cascades. These hotspot mutations may serve as a genetic hallmark for PCNSL serving as a genetic marker for diagnose and potential targets for molecular therapy.

Recurrent craniopharyngioma with nasopharyngeal extension.

We report the case of a 10-year-old boy having a recurrent craniopharyngioma with nasopharyngeal extension during a course of growth hormone therapy, in whom the nasopharyngeal craniopharyngioma was totally resected despite its extensive growth by using a transbasal approach. There has been no evidence of recurrence during 6 years of follow-up. A literature review was made with respect to nasopharyngeal extension of craniopharyngiomas, and the efficacy of the transbasal approach for those tumors is discussed.

Transient mutism resolving into cerebellar speech after brain stem infarction following a traumatic injury of the vertebral artery in a child.

A 3.7-year-old girl presented with an anterior neck injury followed by progressive subcutaneous emphysema and loss of consciousness. After resuscitation, a laceration on the first tracheal cartilage was closed surgically. As she was extubated one week later, she was found to have right hemiplegia and muteness. MRI showed a T2-bright lesion on the tegmentum of the left midbrain down to the upper pons. Right vertebral angiography disclosed an intimal flap with stenosis at the C3 vertebral level presumably caused by a fracture of the right C3 transverse process later confirmed in a cervical 3D-CT scan. Her muteness lasted for 10 days, after which she began to utter some comprehensible words in a dysarthric fashion. Her neurological deficits showed improvement within 3 months of her admission. Transient mutism after brain stem infarction has not been reported previously. We discuss the anatomical bases for this unusual reversible disorder in the light of previous observations and conclude that bilateral damage to the dentatothalamocortical fibers at the decussation of the superior cerebellar peduncle may have been responsible for her transient mutism.

Contralateral transcondylar approach for aneurysms of the posterior inferior cerebellar artery-vertebral artery complex.

We report a patient with an aneurysm of the left vertebral artery (VA)-posterior inferior cerebellar artery (PICA) complex that was treated successfully via a contralateral transcondylar approach. The aneurysm was small, pointed laterally to the right, and was located across the midline just above the level of the foramen magnum. This unusual location required special consideration during diagnostic evaluation and surgical planning. To simulate the operative view, the patient's head was turned 45 degrees. This extreme oblique view offered useful information with respect to the choice of side from which the surgical approach should be made. Removal of the posteromedial part of the occipital condyle allowed us to clip the aneurysmal neck without difficulty although the surgical approach was made on the side contralateral to the parent artery. We conclude that the contralateral approach for VA-PICA aneurysms should be considered when aneurysms cross the midline, and that extradural removal of the basal bony structures, including the occipital condyle, can provide a wide wirking space without excessive retraction on the brain stem.

Clinical evaluation of serum amlodipine level in patients with angina pectoris.

Serum amlodipine levels were determined in 18 patients with vasospastic angina. Patients were divided into two groups: Group A (n = 9) received amlodipine 5 mg by single daily administration, and Group B (n = 9) received 10 mg given by single daily administration for the first 3 days, then 5 mg from the 4th day on. The serum amlodipine concentration in Group A took 7 days to reach a steady state of around 8 ng/ml. The level in Group B was 8.9 ng/ml at 3 days. From these results, the optimal dosage of amlodipine in the treatment of angina pectoris is 10 mg for the initial 3 days followed by 5 mg thereafter.

Clustered lipid droplets in the endomyocardial biopsies from a patient with neuroleptic malignant syndrome.

Neuroleptic malignant syndrome is caused by serious adverse effects of antipsychotic agents and occurs only rarely. Endomyocardial biopsies documented unique clustered lipid droplets in a Japanese man with this disease. After administration of haloperidol, he had symptoms of high fever, respiratory dysfunction, and cardiogenic shock, and subsequently suffered from multiple organ failure. Fortunately, he was completely cured with intensive therapy. In the convulsant stage, left ventricular endomyocardial biopsies were performed that yielded the interesting discovery of unique clustered lipid droplets among the myofibrils. It was suggested that although the pathomechanism of neuroleptic malignant syndrome is unknown, this disease may be characterized by a lipid metabolic disorder of the cardiac muscle cell.

Efficacy of amlodipine besilate therapy for variant angina: evaluation by 24-hour Holter monitoring.

The efficacy of amlodipine, a calcium antagonist, was investigated in 12 patients with variant angina. Amlodipine was administered at a dose of 5 mg once daily, and efficacy was assessed from the frequency of anginal attacks, the frequency of ST elevation or depression, and the extent of ST segment changes [ST segment elevation or depression (mm) x duration (seconds)] on the Holter ECG before and after treatment. The frequency of ST elevation during the observation period was 1.67 +/- 0.33 times/day (symptomatic attacks: 1.17 +/- 0.21/day; asymptomatic attacks: 0.50 +/- 0.19/day), and this significantly decreased to zero per day (both symptomatic and asymptomatic attacks) after treatment (p < 0.05). The extent of ST segment elevation during the observation period was 507.5 +/- 156.6 mm.sec/day (symptomatic: 382.5 +/- 102.9 mm.sec/day; asymptomatic: 125.0 +/- 62.0 mm.sec/day), and such changes were completely suppressed (both symptomatic and asymptomatic) by treatment (p < 0.05). The frequency of ST depression was 2.08 +/- 0.42 times/day (symptomatic: 0.25 +/- 0.13/day; asymptomatic: 1.83 +/- 0.37/day) during the observation period, while it was 1.50 +/- 0.36 times/day (symptomatic: 0.25 +/- 0.13/day; asymptomatic: 1.25 +/- 0.30/day) after treatment. Although anginal attacks remained unchanged, asymptomatic attacks tended to decrease (p = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

FK506 therapy of experimental autoimmune myocarditis after onset of the disease.

Preventive effects of FK506 on autoimmune myocarditis have been demonstrated, but the therapeutic efficacy of the agent in established myocarditis yet remains to be assessed. In this study, effects of FK506 on experimental autoimmune myocarditis were investigated by the use of the agent after the onset of the disease. Lewis rats were immunized with either cardiac myosin or bovine serum albumin (BSA) in complete Freund's adjuvant. The onset of the disease was ascertained by examining randomly chosen cardiac myosin-immunized rats. Animals were divided into four groups: the BSA-immunized saline-treated group (group A, n = 6); the BSA-immunized FK506-treated group (group B, n = 6); the myosin-immunized saline-treated group (group C, n = 6); and the myosin-immunized FK506-treated group (group D, n = 11). Saline or 1.0 mg/kg/day of FK506 were intramuscularly injected from day 16 to day 27. All the rats were put to death on day 28. Rats of group C became severely ill by the third week, while in contrast, rats of group D remained active, as did rats of groups A and B. The heart weight/body weight ratio was significantly lower in group D than in group C rats. Group mean values were 3.48 +/- 0.10 gm/kg for group A, 3.48 +/- 0.16 gm/kg for group B, 4.94 +/- 0.66 gm/kg for group C, and 3.88 +/- 0.43 gm/kg for group D. Rats of group C showed severe myocarditis with mononuclear cell infiltration, myocardial necrosis, and interstitial edema.(ABSTRACT TRUNCATED AT 250 WORDS)

Dystrophin negative skeletal and myocardial muscle cells in a carrier of Duchenne's muscular dystrophy.

A 47-year-old woman whose elder son had typical Duchenne's muscular dystrophy (DMD) was diagnosed as the manifesting carrier of the disease. She had developed congestive heart failure but had no evidence of skeletal muscular atrophy. Histological observation of the cardiac muscle revealed a mosaic pattern of dystrophin negative fibres detected by immunofluorescence analysis.

Electrophysiologic study and ergonovine provocation of coronary spasm in unexplained syncope.

A total of 38 patients with syncope in whom a cause was not assigned or suggested by the initial history, physical examination and electrocardiography (ECG) were studied. Twenty-four patients underwent cardiac examination with Holter ECG, electrophysiologic testing with programmed ventricular stimulation (EPS) and/or coronary arteriography including ergonovine provocation (ergonovine CAG). The study with Holter ECG, EPS and ergonovine CAG yielded a presumptive diagnosis in 36 patients (36/38 = 95%), 11 with vasopastic angina, 7 with ventricular tachycardia, 4 with ischemic heart disease, 9 with sick sinus syndrome (SSS), 1 with drug induced SSS, 3 with A-V block, 1 with supraventricular tachycardia, 1 with hypertrophic cardiomyopathy, 1 with aortic valve stenosis and 1 with carotid sinus syndrome (included are 1 patient with ventricular tachycardia+ischemic heart disease, 1 with SSS+vasopastic angina and 1 with ventricular tachycardia+vasospastic angina). Therapy based on these findings provided complete symptomatic relief in all patients during a mean follow up of 25 +/- 10 months (range 5-45 months). In conclusion, EPS and ergonovine CAG are useful in the diagnosis and therapy of unexplained syncope.