Branched oligomerization of cell-permeable peptides markedly enhances the transduction efficiency of adenovirus into mesenchymal stem cells.

Cell-permeable peptides (CPPs) promote the transduction of nonpermissive cells by recombinant adenovirus (rAd) to improve the therapeutic efficacy of rAd. In this study, branched oligomerization of CPPs significantly enhanced the transduction of human mesenchymal stem cells (MSCs) by rAd in a CPP type-independent manner. In particular, tetrameric CPPs increased transduction efficiency at 3000-5000-fold lower concentrations than did monomeric CPPs. Although branched oligomerization of CPPs also increases cytotoxicity, optimal concentrations of tetrameric CPPs required for maximum transduction are at least 300-1000-fold lower than those causing 50% cytotoxicity. Furthermore, although only approximately 60% of MSCs were maximally transduced at 500 muM of monomeric CPPs, >95% of MSCs were transduced with 0.1 muM of tetrameric CPPs. Tetrameric CPPs also significantly increased the formation and net surface charge of CPP/rAd complexes, as well as the binding of rAd to cell membranes at a greater degree than did monomeric CPPs, followed by rapid internalization into MSCs. In a critical-size calvarial defect model, the inclusion of tetrameric CPPs in ex vivo transduction of rAd expressing bone morphogenetic protein 2 into MSCs promoted highly mineralized bone formation. In addition, MSCs that were transduced with rAd expressing brain-derived neurotrophic factor in the presence of tetrameric CPPs improved functional recovery in a spinal cord injury model. These results demonstrated the potential for tetrameric CPPs to provide an innovative tool for MSC-based gene therapy and for in vitro gene delivery to MSCs.

Diagnostic criteria for the clinical syndrome of internal disc disruption: are they reliable?

A new disease, named internal disc disruption (IDD), has provoked debate. Some insist that discography is specific for the diagnosis, while others disagree. Without scientific verification, some doctors have performed invasive operations for this uncertain disease. It is necessary to explore the diagnostic criteria and characteristics of IDD. We investigated the background, history, diagnostic methods and criteria of IDD by a review of the literature. The criteria for diagnosis of IDD are diverse. The minimum requirements for the diagnosis were the pattern of pain and the shape on discography. Although the pain pattern is important for the correct diagnosis, it depends on the subjective report of the patient. The diagnosis is up to the patient, and the examiner alone cannot make it. We conclude that IDD is not a real, but a hypothetical disease. Until scientific verification is forthcoming any invasive procedures should be restricted.

Spinal stabilization by using crossed-screw anterior-posterior fixation after multisegmental total spondylectomy for thoracic chondrosarcoma. Case report.

The authors describe the case of a 41-year-old man with high-grade chondrosarcoma who presented with a paraspinous mass extending into three thoracic vertebrae (T10-12). Crossfixed long anterior and posterior instrumentation was placed after three complete spondylectomies (T10-12). This technique augments spinal stability with an outrigger effect by using crossfixators placed between paired dorsal rods, as well as between the anterior and posterior hardware components. This technique may be used as an alternative when multiple vertebrae or all three spinal columns are involved by radioresistant malignant tumors in patients in whom there is a relatively long life expectancy.

Location of the chronic subdural haematoma: role of the gravity and cranial morphology.

Chronic subdural haematoma (SDH) frequently originates from subdural hygroma (SDG). The cranial morphology can determine the location of SDG. Since SDG is the precursor of chronic SDH, the shapes of the cranium wall act an important role in location of chronic SDH. The authors tried to test this hypothesis. The computed tomographic scans or magnetic resonance images of 118 consecutive patients with chronic SDH were re-evaluated, and the symmetry of the cranium and location of the lesion were checked. The cranium was symmetrical in 55 patients (47%) and asymmetrical in 63 patients (53%). Chronic SDH was bilateral in 25 patients (21%) and unilateral in 93 patients (79%). It was more commonly bilateral in symmetrical craniums than in asymmetrical craniums (29.1% vs. 14.3%) (p = 0.0496). In 63 patients with asymmetric cranium, the chronic SDH was bilateral in nine patients, located on the opposite side of the flat side in 38 patients, and located on the same side of the flat side in 17 patients. This unequal distribution was statistically significant (p = 0.03). In four patients, the haematoma originated from the acute SDH located on the same side of the flat side. No reason could be found in the remaining 13 patients. Chronic SDH originating from SDG usually locates on the opposite to the flat side of the skull. The shape and posture of the cranium can predict the location of chronic SDH, as in the SDG.

Achondrogenesis type II (Langer-Saldino achondrogenesis): a case report.

Achondrogenesis is a lethal form of congenital chondrodystrophy characterized by extreme micromelia. We describe a case of achondrogenesis type II (Langer-Saldino achondrogenesis) detected by prenatal ultrasonography at 20-week gestation. A dwarfed fetus with large head, short neck and chest, prominent abdomen and short limbs was terminated transvaginally. Radiologic and histopathologic examination revealed features of mild form of achondrogenesis type II. Although the case had no known risk factor and the phenotypic abnormality was mild, modern development in prenatal screening made the early detection possible.

Location of the traumatic subdural hygroma: role of gravity and cranial morphology.

Traumatic subdural hygroma (TSH) is frequently bilateral and locates on the top of the head in a supine position. It suggests that the gravity and cranial posture act a certain role. The authors tried to test this hypothesis. The computed tomographic (CT) scans or magnetic resonance (MR) images of 86 consecutive patients with TSH were re-evaluated. The symmetry of the cranium, the posture of the head during the radiological examinations, and the location of the lesion were all checked. The cranium was symmetrical in 47 patients and asymmetrical in 39 patients. TSH was more commonly bilateral in patients with symmetrical cranium than those with asymmetrical cranium (77% vs 62%). The asymmetrical cranium tended to turn to the flat side. It was more frequently oblique in MR images, which has a long scanning time, than in CT (29% vs 18%). In 39 asymmetric craniums, TSH was bilateral and it was symmetrical in 14 cases. In the remaining 25 cases, TSH located opposite to the flat side in 18 cases. In seven patients with the same side TSHs, four patients had it on the side of atrophy, two on the opposite side of a mass lesion. The gravity and cranial posture can predict the location of TSH. TSH usually occurs at the least pressure in the cranium as a lesion of ex vacuo.

A co-operative study: clinical characteristics of 334 Korean patients with moyamoya disease treated at neurosurgical institutes (1976-1994). The Korean Society for Cerebrovascular Disease.

A co-operative study was conducted to determine the clinical characteristics of patients with moyamoya disease who were diagnosed and treated at neurosurgical institutes in Korea before 1995. Twenty-six hospitals contributed 505 cases and among them, the clinical characteristics of 334 patients with definite moyamoya disease were evaluated. The number of patients began to increase from the late 1980s, and after that approximately 20 patients were treated each year. There were two age peaks: from six to 15 and from 31 to 40 years of age. Haemorrhagic manifestations occurred in approximately 43% of the patients. The major clinical manifestations were haemorrhage in adults (62.4%) and ischaemia in children (61.2%). Overall 54.5% of the patients experienced decreased consciousness levels, mainly due to intracranial haemorrhage or cerebral infarction. In the patients with ischemic manifestations, the adult patients were more likely to have cerebral infarction than the pediatric patients (80% vs. 39%) and the pediatric patients were more likely to have TIA (61% vs. 25%). Thirty eight percent of the patients underwent bypass surgery and 53% of these procedures were performed bilaterally. Treatment policies, including indications for bypass surgery and commonly used drugs, were somewhat different according to the institution. Overall favorable outcome was 73%, and the most significant factor affecting poor outcome was haemorrhagic manifestation. This article describes the characteristics of 334 patients with moyamoya disease, who were diagnosed and treated at neurosurgical institutes in Korea before 1995.

Morphometric aspects of extraforaminal lumbar nerve roots.

OBJECTIVE: In the posterolateral extraforaminal and anterolateral retroperitoneal approaches to lumbar spinal lesions, the neural structures in the lumbar extraforaminal region are unfamiliar to many spinal surgeons. The purpose of this study was to determine the normal anatomic morphometric parameters for all lumbar nerve roots around their exits, from the intervertebral foramen to the surrounding bony structure. METHODS: A total of 15 adult fixed cadavers were studied. The extraforaminal course of the lumbar nerve roots and the forming plexus were measured segmentally, using standard calipers, and we selected the shortest distance from the bony landmarks to the nerve roots in the horizontal plane. The bony landmarks were the most medial superior border of the transverse process (TP), the most medial inferior border of the TP, the tip of the superior articular process, and the most dorsolateral margin of the intervertebral disc space. In addition, the angle of each root exiting from the intervertebral foramen was measured using a goniometer. RESULTS: The mean distance from the medial superior border of the TP to the upper segment of the nerve root was 5.1 to 6.4 mm at L2-L5. The mean distance from the medial inferior border of the TP to the corresponding nerve root was 8.5 mm at L2 and L3 and 6 mm at L4 and L5. The mean distance from the tip of the superior articular process to the most dorsal border of the descending nerve trunk was 19 mm at L2 and L3 and 22 mm at L4 and L5. The main lumbar nerve trunk was located close to the most dorsolateral surface of the vertebral body and the intervertebral disc space, and it was topographically arranged dorsoventrally from the L5 to L2 nerve components. The average widths of the nerve trunk were 10, 14, and 25 mm at L3-L4, L4-L5, and L5-S1, respectively. The mean angles of the exiting roots in the extraforaminal region were 16 degrees at L2 and L3 and 25 degrees at L4 and L5. CONCLUSION: The lumbar nerve component, including both the lumbar trunk and each exiting nerve root in the extraforaminal region (the so-called "danger zone"), was located anteriorly at a distance more than 5 mm from the TP, more than 19 mm from the superior articular process, and up to 25 mm from the intervertebral disc space. Based on our results, the danger zone occupied up to 25 mm forward from the intervertebral foramen at the lower lumbar segments. Therefore, during operations such as percutaneous posterolateral procedures and open posterolateral or anterolateral approaches, great care should be taken within 25 mm of the extraforaminal region, especially for the lower lumbar spine.

Recurrence of bleeding in patients with hypertensive intracerebral hemorrhage.

To characterize the recurrence of bleeding in patients who had hypertensive intracerebral hemorrhage (HICH), the authors reviewed 989 patients who underwent treatment for HICH between 1989 and 1995. Fifty-three patients (5.4%) had two episodes of HICH within a median interval of 22.9 +/- 16.3 months (range 1.5-72 months), and of these 3 (5.7%) had three episodes of HICH. The recurrence of bleeding most commonly occurred within 2 years of the first hemorrhage: in 66% of the 53 patients the second hemorrhage occurred soon after the first (within 1 year in 34%, within 1-2 years in 32.1%). The site of the second hemorrhage was different from the initial site in all patients. Only 1 patient had a third hemorrhage in the same site as the second hemorrhage. The common patterns of recurrence were 'ganglionic (putamen/caudate nucleus)-thalamic' in 26.8% and 'ganglionic-ganglionic' in 21.4%. The 'lobar-lobar' pattern was noted in only 2 patients. The volume of the hematoma was increased at the second hemorrhage. The overall mortality was 28.3%. The risk of recurrent hemorrhage significantly increased in the patients who had antihypertensive therapy of less than 3 months after the initial attack compared to those with further long-term therapy (p < 0.005). Long-term regular control for hypertension is needed to prevent recurrent hemorrhage.

Origin of chronic subdural haematoma and relation to traumatic subdural lesions.

The origin of chronic subdural haematoma (CSDH) and the pathogenesis of subdural hygroma (SDG) are still controversial issues. These issues and relationships between these traumatic subdural lesions are discussed. The origin of CSDH is usually a SDG, although a few cases are caused by acute subdural haematomas (ASDH). Subdural hygroma is produced by separation of the dura-arachnoid interface, when there is sufficient subdural space. When the brain remains shrunken, the SDG remains unresolved. Any pathologic condition inducing cleavage of tissue within the dural border layer at the dura-arachnoid interface can induce proliferation of dural border cells with production of neomembrane. In-growth of new vessels will follow, especially along the outer membrane, then bleeding from these vessels occurs. These unresolved SDGs become CSDHs by repeated microhaemorrhage from the neomembrane. Although most victims with ASDH underwent surgery or died, some patients could be managed conservatively. Since the ASDH is usually absorbed within a few weeks, only a very few ASDHs become CSDHs, when there is a sufficient potential subdural space. Chronic subdural haematoma can arise from ASDH, but more commonly from SDG. Such transformation, or development of a new subdural lesion, is a function of the premorbid status and the dynamics of absorption and expansion.

The computed tomographic attenuation and the age of subdural hematomas.

The sequential change in density (attenuation coefficient) of subdural hematomas (SDHs) in computed tomography (CT) is important in understanding the pathogenesis and evolution of SDHs. We retrospectively investigated the age of SDHs by CT in 446 cases. We included 30 cases of chronic SDHs, in whom the density was directly measured in the CT. The density of acute (within 7 days) SDH was hyperdense in 98.6%, isodense in 1.1%, and hypodense in 0.3% of the cases. In subacute (8-22 days) SDHs, it was hypodense in 45.7%, isodense in 42.9%, and hyperdense in 11.4%. In chronic (over 22 days) SDHs, 86.7% was isodense and only 13.3% was hypodense. In hypodense SDHs, 64.0% was the subacute, and 73.2% of the isodense SDHs was the chronic one. The mean interval from injury to CT was 0.5 +/- 1.6 days in hyperdense SDHs, 20.9 +/- 20.7 days in hypodense SDHs, and 54.9 +/- 44.0 days in isodense SDHs. In 30 cases of chronic SDH, the average density was 38.0 +/- 6.9 Hounsfield number(H) in 20 approximately 30 days, 43.8 +/- 12.8 H in 31 approximately 60 days, 51.8 +/- 5.1 H in 61 approximately 90 days, and 44.2 +/- 8.3 H in over 90 days. The density of acute SDH is usually hyperdense. It becomes hypodense within 3 weeks. Then the density progressively increases by the repeated microhemorrhage, which is the mechanism of enlargement of chronic SDH. The density of chronic SDH increases with time up to 90 days, then decreases again after maturation of the neomembrane, which is the mechanism of spontaneous resolution.

Delayed central cord syndrome after a handstand in a child: case report.

We report a case of a central cord syndrome in a 7 year-old girl. After several handstands, with sudden upper thoracic back pain and weakness of the legs 2 to 3 h later, then rapidly progressive tetraplegia with apnea. Plain X-rays and CT myelography of the cervical spine revealed no abnormalities. Although the initial neurological deficit was severe enough to require the child to be placed on a mechanical ventilator, she recovered to be able to walk on the 24th hospital day. Since the development of a central cord syndrome after handstands is exceptional in a child with a normal cervical spine, we report here briefly.

Relations among traumatic subdural lesions.

Acute subdural hematoma (ASDH), chronic subdural hematoma (CSDH) and subdural hygroma (SDG) occur in the subdural space, usually after trauma. We tried to find a certain relationship among these three traumatic subdural lesions in 436 consecutive patients. We included all subdural lesions regardless of whether they were main or not. We evaluated the distribution, age incidence and interval from injury to diagnosis of these lesions, and the frequency of new subdural lesions in each lesion. ASDH constituted 68.6%, SDG 15.8%, and CSDH 15.6%, Age incidence of CSDH was similar to that of SDG, but differed from that of ASDH. Mean interval from injury to diagnosis was 0.4 days in ASDH, 13.4 days in SDG, and 51.6 days in CSDH. Focal brain injuries accompanied in 37.5% of ASDH, 5.8% of SDG, and no CSDH. In ASDH, 2 recurrent ASDHs, 17 SDGs and 9 CSDHs occurred. In SDG, 3 postoperative ASDHs and 8 CSDHs occurred. In CSDH, 2 postoperative ASDHs, 2 SDGs and 1 CSDH occurred. These results suggest that the origin of CSDH is not only ASDH, but also SDG in upto a half of cases. SDG is produced as an epiphenomenon by separation of the dural border cell layer when the potential subdural space is sufficient. A half of CSDHs may originate from ASDHs. ASDH may occur in CSDH by either a repeated trauma or surgery. Such transformation or development of new lesions is a function of a premorbid condition and the dynamics between the absorption capacity and expansile force of the lesion.

Hydrothorax from intrathoracic migration of a ventriculoperitoneal shunt catheter.

BACKGROUND: The intrathoracic complications of the ventriculoperitoneal (VP) shunt are very rare. We report an unusual case of VP shunt complication with intrathoracic migration, associated with pleural effusion in a 55-year-old man. METHODS: We reviewed the seven cases reported in the literature and the mechanism of shunt-tip migration and preventive measures are presented. RESULTS: The patient was successfully managed with revision. The catheter was retrieved and replaced in the peritoneal cavity. CONCLUSIONS: With VP shunting, it is important to keep in mind the possibility of peritoneal shunt-tip migration into the chest. To prevent this kind of complication, we stressed precise location of a subcutaneous tunneling device above the ribs during subcutaneous passage.

Brain abscess from a ganglionic hemorrhage--a case report.

We present a unique case of a brain abscess that occurred secondary to a ganglionic hemorrhage in a 64-year-old man. This abscess appeared to be metastatic after septicemia. Aspiration with antibiotics eliminated this infection.