Needle tract implantation of hepatoblastoma after percutaneous needle biopsy: report of a case

A 13-year-old boy was referred to us for investigation of a giant liver mass, approximately 16 cm in diameter. Sonographically guided percutaneous needle biopsy was performed and histological examination revealed a fetal-type hepatoblastoma. After four courses of chemotherapy, we performed a left hepatic trisegmentectomy. Follow-up computed tomography, 55 months after the surgery, showed a 1-cm tumor on the route of the preoperative needle biopsy. A second laparotomy revealed a peritonealised tumor, which was excised. The histology of this tumor was identical to that of the primary hepatoblastoma. To our knowledge, this is only the second report of needle tract implantation of hepatoblastoma after percutaneous needle biopsy.     

Alterations in calcium-handling of erythrocytes in spontaneously hypertensive rats. Calcium-induced changes in the osmotic fragility of erythrocytes in hypertension

To investigate the sensitivity to calcium of erythrocytes in hypertension, changes in the osmotic fragility of erythrocytes following Ca-loading were observed. Washed erythrocytes were obtained from spontaneously hypertensive rats (SHR, Okamoto and Aoki) and age-matched normotensive Wistar Kyoto rats (WKY). Treatment of erythrocytes with Ca-ionophore A23187 and Ca in the medium caused a reduction in the osmotic fragility which correlated with the Ca-concentration. The degree of alteration in the osmotic fragility of erythrocytes was greater in SHR than in WKY. Oral administration of hydralazine to SHR significantly reduced the blood pressure. However, the alterations in the osmotic fragility of erythrocytes secondary to Ca-loading were not different between hydralazine-treated and untreated SHR. In the presence of a Ca-antagonist (verapamil or diltiazem) in the medium, the reduction of the osmotic fragility of erythrocytes caused by Ca-loading was inhibited, and the differences between SHR and WKY were abolished by Ca-antagonists. These results suggest that the greater changes in osmotic fragility of erythrocytes caused by Ca-loading in SHR could be due to a genetic abnormality of Ca-handling by the cell membranes, and that this abnormality might cause an increase in intracellular Ca, which contributes, in part, to the pathogenesis of hypertension.     

Usefulness of dobutamine stress echocardiography in a patient with aortic valve stenosis and left ventricular dysfunction: a case report

A 76-year-old man with previous antero-septal myocardial infarction and aorto-coronary bypass surgery developed exertional dyspnea. Echocardiography revealed diffuse left ventricular hypokinesis and aortic stenosis with a mean pressure gradient of 29 mmHg. Coronary angiography showed no significant lesions in the bypass grafts and total occlusions of the proximal left anterior descending artery and mid circumflex artery. Dobutamine stress echocardiography was performed to evaluate the severity of aortic stenosis and left ventricular functional reversibility. Administration of dobutamine increased the mean pressure gradients to 48 mmHg and increased the stroke volume by 28% without change in aortic valve area of about 0.5 cm2. We considered that our patient had severe aortic stenosis with contractile reserve. After aortic valve replacement, he improved with better left ventricular function.     

Improvement in Castleman's disease by humanized anti-interleukin-6 receptor antibody therapy

Castleman's disease, an atypical lymphoproliferative disorder, can be classified into 2 types: hyaline-vascular and plasma cell types according to the histologic features of the affected lymph nodes. The plasma cell type is frequently associated with systemic manifestations and is often refractory to systemic therapy including corticosteroids and chemotherapy, particularly in multicentric form. Dysregulated overproduction of interleukin-6 (IL-6) from affected lymph nodes is thought to be responsible for the systemic manifestations of this disease. Therefore, interference with IL-6 signal transduction may constitute a new therapeutic strategy for this disease. We used humanized anti-IL-6 receptor antibody (rhPM-1) to treat 7 patients with multicentric plasma cell or mixed type Castleman's disease. All patients had systemic manifestations including secondary amyloidosis in 3. With the approval of our institution's ethics committee and the consent of the patients, they were treated with 50 to 100 mg rhPM-1 either once or twice weekly. Immediately after administration of rhPM-1, fever and fatigue disappeared, and anemia as well as serum levels of C-reactive protein (CRP), fibrinogen, and albumin started to improve. After 3 months of treatment, hypergammaglobulinemia and lymphadenopathy were remarkably alleviated, as were renal function abnormalities in patients with amyloidosis. Treatment was well tolerated with only transient leukopenia. Histopathologic examination revealed reduced follicular hyperplasia and vascularity after rhPM-1 treatment. The pathophysiologic significance of IL-6 in Castleman's disease was thus confirmed, and blockade of the IL-6 signal by rhPM-1 is thought to have potential as a new therapy based on the pathophysiologic mechanism of multicentric Castleman's disease. (Blood. 2000;95:56-61)     

VEGF-B selectively regenerates injured peripheral neurons and restores sensory and trophic functions

VEGF-B primarily provides neuroprotection and improves survival in CNS-derived neurons. However, its actions on the peripheral nervous system have been less characterized. We examined whether VEGF-B mediates peripheral nerve repair. We found that VEGF-B induced extensive neurite growth and branching in trigeminal ganglia neurons in a manner that required selective activation of transmembrane receptors and was distinct from VEGF-A–induced neuronal growth. VEGF-B–induced neurite elongation required PI3K and Notch signaling. In vivo, VEGF-B is required for normal nerve regeneration: mice lacking VEGF-B showed impaired nerve repair with concomitant impaired trophic function. VEGF-B treatment increased nerve regeneration, sensation recovery, and trophic functions of injured corneal peripheral nerves in VEGF-B–deficient and wild-type animals, without affecting uninjured nerves. These selective effects of VEGF-B on injured nerves and its lack of angiogenic activity makes VEGF-B a suitable therapeutic target to treat nerve injury.Nerves can be damaged either through trauma or disease. Nerves from the peripheral nervous system (PNS) have significantly greater capacity to regenerate and reinnervate their original targets after injury, compared with nerves from the CNS. The successful regeneration of PNS neurons requires a number of intrinsic and extrinsic factors, as well as a permissive microenvironment for axonal regrowth (1). Among the numerous growth factors able to induce nerve regeneration, the family of VEGFs has been implicated as a potent mediator of developmental neurogenesis and adult nerve regeneration (2–4). VEGF-A is a well-characterized and potent angiogenic factor but is also a strong inducer of nerve growth. Several studies have demonstrated that both VEGF-A and -B are expressed during peripheral nerve injury (2, 5). In the setting of injury, VEGF-B plays a role in cell survival, nerve protection, and growth (5, 6). The survival effect of VEGF-B on brain cortical neurons, retinal neurons, and motor neurons in the spinal cord is indicative of its pleiotropic role (5). VEGF-B treatment reduced stroke volume in a middle cerebral artery ligation model and increased survival of retinal ganglion cells in an optic nerve crush injury model (7), and VEGF-B knockout mice suffered severe strokes and exacerbated retinal ganglion cell death in both injury models (7–9). VEGF-B has also been used with promising results in Parkinson’s disease (10) and amyotrophic lateral sclerosis models (11).Given the ability of VEGF-B to regulate both vascular endothelial cells (angiogenesis) as well as axonal growth and survival after injury, it is unclear whether VEGF-B exerts its effects on nerve regeneration through the increase in blood supply or through direct effects on nerve tissue. Indeed, specific studies on its role on peripheral neurons independent of its vascular role are lacking. We have previously reported that VEGF-A can stimulate trigeminal neuronal cell growth and enhance cornea nerve regeneration, resulting in anatomical and functional recovery of peripheral injured nerves independently of its angiogenic effects (12). Here we studied the neuro-regenerative potential of VEGF-B in an avascular model of peripheral nerve injury in mice and the signaling elements involved in the induction of nerve growth. Our results demonstrated tha (i) peripheral nerve regeneration is impaired in mice lacking VEGF-B, (ii) VEGF-B can restore the anatomic and function innervation of target tissues by induction of nerve growth and nerve regeneration, (iii) the effects of VEGF-B are specific for injured nerves and are independent of any vascular effect, and (iv) the effects of VEGF-B on nerve regeneration are distinct from those observed for VEGF-A.