Interplay of Chiral and Helical States in a Quantum Spin Hall Insulator Lateral Junction.

We study the electronic transport across an electrostatically gated lateral junction in a HgTe quantum well, a canonical 2D topological insulator, with and without an applied magnetic field. We control the carrier density inside and outside a junction region independently and hence tune the number and nature of 1D edge modes propagating in each of those regions. Outside the bulk gap, the magnetic field drives the system to the quantum Hall regime, and chiral states propagate at the edge. In this regime, we observe fractional plateaus that reflect the equilibration between 1D chiral modes across the junction. As the carrier density approaches zero in the central region and at moderate fields, we observe oscillations in the resistance that we attribute to Fabry-Perot interference in the helical states, enabled by the broken time reversal symmetry. At higher fields, those oscillations disappear, in agreement with the expected absence of helical states when band inversion is lifted.

One-dimensional weak antilocalization due to the berry phase in HgTe wires.

We study the weak antilocalization (WAL) effect in the magnetoresistance of narrow HgTe wires fabricated in quantum wells with normal and inverted band ordering. Measurements at different gate voltages indicate that the WAL is only weakly affected by Rashba spin-orbit splitting and persists when the Rashba splitting is about zero. The WAL amplitude in wires with normal band ordering is an order of magnitude smaller than for wires with an inverted band structure. These observations are attributed to the Dirac-like dispersion of the energy bands in HgTe quantum wells. From the magnetic-field and temperature dependencies we extract the dephasing lengths and band Berry phases. The weaker WAL for samples with a normal band structure can be explained by a nonuniversal Berry phase which always exceeds π, the characteristic value for gapless Dirac fermions.

Continuous intraventricular pressure monitoring for diagnosis of normal-pressure hydrocephalus.

OBJECTIVES: Normal-pressure hydrocephalus (NPH) syndrome is treatable by implantation of a cerebrospinal fluid (CSF) shunt. However, diagnosis of NPH by clinical and radiological findings alone is unreliable, and co-existing structural dementia can contribute to low success rates after shunt implantation. The aim of our study was to investigate whether long-term results after shunt implantation in NPH improve when surgical candidates are selected by continuous intraventricular pressure monitoring (CIPM). PATIENTS AND METHODS: Ninety-two consecutive patients who were admitted with suspected NPH received CIPM for 48 h including an intraventricular steady-state infusion test to determine the resistance outflow. With positive CIPM, shunt implantation was performed and the patients were prospectively followed up for 1 to 10 years (median 6.5 years). RESULTS: CIPM was negative in 37 patients. Fifty-five patients had a positive CIPM and received CSF shunt. 96.1% of them improved from gait disturbance, 77.1% from cognitive impairment and 75.7% from urinary dysfunction. Clinical improvement remained during long-term follow-up in all but 3 patients who showed a decline at 4, 5 and 7 years, respectively. CIPM-related complications (ventriculitis) occurred in only one patient. CONCLUSION: CIPM is a safe and valuable tool to establish a reliable diagnosis of NPH and to identify promising surgical candidates.

Fecal estradiol and progesterone metabolite levels in the three-toed sloth (Bradypus variegatus).

The present study was carried out to assess the possibility of measuring fecal steroid hormone metabolites as a noninvasive technique for monitoring reproductive function in the three-toed sloth, Bradypus variegatus. Levels of the estradiol (E2) and progesterone (P4) metabolites were measured by radioimmunoassay in fecal samples collected over 12 weeks from 4 captive female B. variegatus sloths. The validation of the radioimmunoassay for evaluation of fecal steroid metabolites was carried out by collecting 10 blood samples on the same day as defecation. There was a significant direct correlation between the plasma and fecal E2 and P4 levels (P < 0.05, Pearson's test), thereby validating this noninvasive technique for the study of the estrous cycle in these animals. Ovulation was detected in two sloths (SL03 and SL04) whose E2 levels reached 2237.43 and 6713.26 pg/g wet feces weight, respectively, for over four weeks, followed by an increase in P4 metabolites reaching 33.54 and 3242.68 ng/g wet feces weight, respectively. Interestingly, SL04, which presented higher levels of E2 and P4 metabolites, later gave birth to a healthy baby sloth. The results obtained indicate that this is a reliable technique for recording gonadal steroid secretion and thereby reproduction in sloths.

Low-grade astrocytoma: a decade of experience at St. Jude Children's Research Hospital.

PURPOSE: To evaluate the impact of primary tumor site, age at diagnosis, extent of resection, and histology on progression-free survival (PFS) in pediatric low-grade astrocytoma. PATIENTS AND METHODS: Medical, pathologic, and imaging information were reviewed for 142 children (ages 2 months to 19 years) with low-grade astrocytoma treated between January 1984 and July 1994. Gross total resection (GTR) was attempted for cerebellar and cerebral hemisphere tumors, with biopsy or less aggressive resection used predominantly for tumors in other sites. Surgery was followed by observation in 107 cases, radiation therapy in 31, and chemotherapy in four. RESULTS: The overall survival rate was 90% +/- 3% (SE) at 4 years. PFS was significantly better for patients with cerebellar and cerebral hemisphere tumors (n = 75) than those with tumors in all other sites (P = .0006). Within the former group, there was no significant difference in PFS for patients in whom GTR was achieved versus those with incomplete resections (4-year estimates, 89% and 77%, respectively). Histology (juvenile pilocytic v astrocytoma not otherwise specified [NOS]) was not related to PFS in an analysis that controlled for tumor site and patient age. Patients younger than 5 years at diagnosis had a significantly poorer PFS than older children, regardless of histology (P < .03) or tumor site (P < .002). Treatment for progressive/recurrent disease was effective in a majority of patients, but appeared more successful in patients with hemispheric than thalamic or hypothalamic tumors. CONCLUSION: The overall survival in this series of pediatric low-grade astrocytomas is excellent. Age at diagnosis and tumor location, but not histology, had a significant impact on PFS. Efforts to improve treatment outcome should focus on young patients (< 5 years) and on those with central midline tumors. The majority of patients with completely resected hemispheric tumors were monitored without further therapy, which supports attempted GTR of cerebral and cerebellar hemisphere low-grade astrocytoma.

Detection of melanoma cells in the blood of melanoma patients by melanoma-inhibitory activity (MIA) reverse transcription-PCR.

The detection of tumor-specific mRNA transcripts in the blood of patients by reverse transcription (RT)-PCR has been used as a very sensitive technique for determining systemically disseminated tumor cells. On the basis of previous expression studies, we aimed to trace melanoma cells in the blood of melanoma patients by RT-PCR of melanoma-inhibitory activity (MIA) mRNA. To detect sensitively MIA transcripts in total RNA isolated from peripheral blood mononuclear cells (PBMCs), we established a sensitive PCR-ELISA system. With this assay, we detected one melanoma cell in 2 ml of blood by a single round of 32 PCR cycles. A total of 295 PBMC samples isolated from 166 patients with melanocytic tumors were tested with the MIA RT-PCR-ELISA: (a) 58 patients (99 samples) with malignant melanomas in stage I; (b) 49 patients (65 samples) with malignant melanomas in stage II; and (c) 47 patients (116 samples) with metastasized melanomas (stages III and IV), with an additional 12 patients (15 samples) with benign melanocytic nevi. Forty-four (26.8%) of 164 samples isolated from patients with melanomas in stages I and II were positive for MIA mRNA; in stages III/IV, 33 (28.4%) of 116 samples of patients, irrespective of clinically evident disease, were positive. Eleven (84.6%) of 13 PBMC samples from patients with metastasized melanoma and clinically evident disease without treatment were MIA mRNA-positive in contrast to only 19 (25.7%) of 74 samples isolated from patients in stage IV with metastasis during chemotherapy. Furthermore, none of the 16 PBMC samples of patients in stage IV without clinically detectable metastases at that time point during chemotherapy was MIA mRNA-positive. Interestingly, of the 44 positive samples (26.8%) isolated from patients with melanomas in stages I and II, 20 were still positive when retested after complete excision of the tumor. Our results reveal that amplification of MIA mRNA from the PBMCs of patients with malignant melanomas by PCR-ELISA provides a useful means to detect tumor cells in the systemic blood circulation. A correlation between positive blood samples and tumor burden in stages III and IV was detected, and, in addition, a significant effect of chemotherapy with respect to the reduction of the number of systemically spread tumor cells was observed. However, MIA amplification seems to be of little value as a surrogate marker for clinical staging or the detection of metastatic disease.

Different effects of a CD14 gene polymorphism on disease outcome in patients with alcoholic liver disease and chronic hepatitis C infection.

AIM: Clinical and experimental data suggest that gut-derived endotoxins are an important pathogenic factors for progression of chronic liver disease. Recently, a C-T (-159) polymorphism in the promoter region of the CD14 gene was detected and found to confer increased CD14 expression and to be associated with advanced alcoholic liver damage. Here, we investigated this polymorphism in patients with less advanced alcoholic liver disease (ALD) and chronic hepatitis C virus (HCV) infection. METHODS: CD14 genotyping was performed by PCR-RFLP analysis in (a) 121 HCV patients, (b) 62 patients with alcohol-associated cirrhosis (Alc-Ci), (c) 118 individuals with heavy alcohol abuse without evidence of advanced liver damage (Alc-w/o Ci), and (d) 247 healthy controls. Furthermore, serum levels of soluble CD14 (sCD14) and transaminases were determined. RESULTS: The TT genotype was significantly more frequent in Alc-Ci compared to Alc-w/o Ci or controls (40.3% vs 23.7% or 24.0%, respectively). In Alc-w/o Ci, serum levels of transaminases did not differ significantly between patients with different CD14 genotypes. In HCV patients, TT-homozygotes had significantly higher sCD14 levels and sCD14 serum levels were significantly higher in patients with advanced fibrosis or cirrhosis. However, no association was found between CD14 genotypes and histological staging or grading. CONCLUSION: Considering serum transaminases as surrogate markers for alcoholic liver damage, the CD14 polymorphism seems to exhibit different effects during the course of ALD. Differences in genotype distribution between cirrhotic HCV patients and alcoholics and the known functional impact of this polymorphism on CD14 expression levels further indicate differences in the pathophysiological role of CD14 and CD14-mediated lipopolysaccharides signal transduction with regard to the stage as well as the type of the underlying liver disease.

Alpha-1-antitrypsin deficiency in children: liver disease is not reflected by low serum levels of alpha-1-antitrypsin - a study on 48 pediatric patients.

BACKGROUND: Alpha-1-antitrypsin (alpha1-AT) is an important protease inhibitor. The phenotypes are characterized by a low total serum alpha1-AT or by an abnormal protein accumulating in the hepatocytes. The aim of our study was to examine a correlation of total serum alpha1-AT, phenotype, and liver involvement in pediatric patients. METHODS: 48 patients, deficient for alpha1-AT were included. The phenotypes for alpha1-AT were determined by isoelectric focusing. Liver disease was defined either as elevated transaminases or/and as elevated conjugated bilirubin and gammaGT. Patients were reexamined after a mean interval of 2 years. RESULTS: Homozygous alpha1-AD was found in 12 patients, heterozygous in 24 patients. In 12 children rare variants of alpha1-AD were diagnosed. Serum alpha1-AT levels less than 60% of normal were found in all patients with homozygous, in 37% of patients with heterozygous alpha1-antitrypsin deficiency (alpha1-AD), and in patients with the homozygous variant PiM(palermo). Liver disease was found in 8/12 patients with the phenotype PiZZ and in 15/24 patients with heterozygous alpha1-AD. Three of 4 patients with the phenotype PiMQ0 had severe liver disease despite normal serum levels for alpha1-AT. In 11 patients with heterozygous alpha1-AD liver disease was apparent despite normal serum alpha1-AT levels. In two patients with the variant type Mpalermo serum levels were as low as 11% of normal without any signs of liver disease. CONCLUSIONS: Our data clearly show that in the diagnostic workup of neonatal cholestasis measurement of total serum alpha1-AT does not exclude liver disease due to abnormal alpha1-AT variants. We suggest analysis of alpha1-AT-phenotype by isoelectric focussing in patients with unknown liver disease. Heterozygous or rare variant types might remain undiagnosed by measuring total alpha1-AT only.

Homogeneity of lithium distribution in cylinder-type Li-ion batteries.

Spatially-resolved neutron powder diffraction with a gauge volume of 2 × 2 × 20 mm(3) has been applied as an in situ method to probe the lithium concentration in the graphite anode of different Li-ion cells of 18650-type in charged state. Structural studies performed in combination with electrochemical measurements and X-ray computed tomography under real cell operating conditions unambiguously revealed non-homogeneity of the lithium distribution in the graphite anode. Deviations from a homogeneous behaviour have been found in both radial and axial directions of 18650-type cells and were discussed in the frame of cell geometry and electrical connection of electrodes, which might play a crucial role in the homogeneity of the lithium distribution in the active materials within each electrode.

Stereotactic injection of herpes simplex thymidine kinase vector producer cells (PA317-G1Tk1SvNa.7) and intravenous ganciclovir for the treatment of progressive or recurrent primary supratentorial pediatric malignant brain tumors.

This study will evaluate the safety and efficacy of in vivo gene transfer of the herpes simplex thymidine kinase (HSV-Tk1) gene using PA317/G1Tk1SvNa.7 vector producer cells (VPC) in pediatric patients with progressive or recurrent primary supratentorial malignant brain tumors. Insertion of the HSV-Tk1 gene confers a sensitivity to the anti-herpes drug ganciclovir. It has been demonstrated that the direct injection of HSV-Tk vector producer cells into growing tumors in animals can result in their complete destruction with ganciclovir therapy. This selective destruction of growing tumors in situ is thought to result from the transfer of the HSV-Tk gene into the tumor cells and the production of toxic ganciclovir metabolites which result from the interaction of HSV-Tk and ganciclovir. This procedure can result in the cure of some experimental animals with limited systemic toxicity due to selective gene transfer into tumors. This clinical trial will focus on maximizing the relative number of vector producer cells to the tumor mass by stereotactically injecting VPCs into the tumor mass. Children with progressive or recurrent primary supratentorial malignant brain tumor which is accessible to stereotactic injection will be evaluated for the extent and location(s) of their disease before being entered into the study. Fifteen days after stereotactic injection of the tumor mass, ganciclovir will be administered at 5 mg/kg IV b.i.d. for 14 days. Upon completion of the treatment with HSV-Tk1 vector producer cells and ganciclovir, the patient will be followed monthly for the first three months, then every two months for the next twenty-one months, and annually for life thereafter.

Platelet-derived growth factor-alpha receptor expression supports the growth of conventional chondrosarcoma and is associated with adverse outcome.

Bone cells are important targets of platelet-derived growth factors (PDGFs) because they stimulate proliferation of osteoblasts and chondrocytes. In this study we wanted to determine the expression of PDGF-AA and PDGF-alpha receptor in conventional chondrosarcomas and to compare the results with those obtained from benign enchondromas and non-neoplastic cartilage tissue. Sixty-seven chondrosarcomas, 20 enchondromas, and 5 specimens of healthy cartilage as well as 7 specimens of hypertrophic callus cartilage were immunohistochemically analyzed for the expression of PDGF-AA and PDGF-alpha receptor, respectively. Additionally, the proliferation activity was examined with the MIB-1 antibody. Clinical follow-up data were available from 53 patients. A significant overexpression of receptor and factor was found in chondrosarcomas as compared with enchondromas (PDGF-AA p = 0.013, PDGF-alpha receptor p <0.001). MIB-1 values were significantly higher in chondrosarcomas (p <0.001). In healthy joint cartilage no staining was detectable, whereas reactive cartilage of callus formation showed high expression levels. PDGF-alpha receptor expression was significantly higher in grade 3 chondrosarcomas compared with grade 2 (p = 0.022) and grade 1 tumors (p = 0.002). Survival analysis documented a significantly shorter overall survival for patients with high PDGF-alpha receptor expression (p = 0.0172, log-rank test). Because PDGF-alpha receptor expression positively correlates with the aggressiveness of chondrosarcoma, it may be considered as a possible target for novel therapeutic strategies.

Efficacy and feasibility of stereotactic radiosurgery in the primary management of unfavorable pediatric ependymoma.

Stereotactic radiosurgery was given as a boost in the initial radiation management of five children with localized intracranial ependymoma. Preliminary results in young children with high-risk tumors indicate good local control without excessive neurotoxicity.

Reformatted sagittal images in the differential diagnosis of meningiomas and pituitary adenomas with suprasellar extension.

Approximately 3 to 4 times a year, a tumor with suprasellar extension escapes classification on high resolution coronal and transaxial computed tomography. When arteriography failed to determine the diagnosis, the differential choices were usually meningioma or pituitary adenoma. The authors report the use of sagittal reformatted images in this differential diagnosis and conclude that these images may aid in the distinction between pituitary tumors with suprasellar extension and meningiomas located in this area.

Malignant nerve sheath tumor of the facial nerve: case report and discussion.

The third reported case of a malignant nerve sheath tumor of the facial nerve is presented. The clinical course and pathological findings are described and serve as the basis for a discussion concerning malignant nerve sheath tumors arising in the cranial nerves.

Complications of intracranial pressure monitoring in trauma patients.

A retrospective review of 175 intracranial pressure (ICP) monitors placed in 140 trauma patients over a recent 3-year period showed a 10.3% infection rate. Factors that were related to the development of an ICP monitor-related infection included: 1) duration of monitoring; 2) requirement for serial monitors; and 3) concurrent infection at other sites. These findings are discussed in light of the related literature concerning ICP monitoring and recommendations made to decrease the incidence of infection-related complications.

Mycobacterium tuberculosis meningitis: a report of twelve cases and a literature review.

Twelve recent cases of Mycobacterium tuberculosis meningitis were presented, and the literature was reviewed. There are no particularly new or unique therapies or approaches to the management of this most serious disease. The major obstacle to successful diagnosis and treatment of tuberculous meningitis continues to be a lack of clinical suspicion of its presence. As illustrated in the cases presented, it has been our experience that patients already moribund or nonresponsive do not respond, regardless of the intervention undertaken. The most sensitive and economical method of detecting M. tuberculosis in the CSF may be LPA. However, this has not yet been widely validated or accepted. Larger volumes of CSF should be sent to the laboratory for testing and centifuged to about 5x concentrations before both acid-fast bacilli staining and culture are attempted. If tuberculous meningitis is suspected, three-drug therapy can be started immediately without jeopardizing subsequent culture confirmation of the presence of the TB bacillus. In addition, these patients must be followed closely to detect hydrocephalus at the earliest possible moment. When patients fail to respond to appropriate antituberculosis and pressure-reducing therapy, hydrocephalus should be actively sought by either CT or radioisotope cisternography. Although the decision to proceed to ventricular drainage or shunting must be individually made in adult patients with infection-related hydrocephalus, we agree with others that surgical intervention should be considered early and should be performed if the level of consciousness deteriorates, intracranial pressure increases, or ventricular enlargement or enhancing basal exudates are identified on CT.

Minimally invasive retroperitoneal approach for lumbar corpectomy and anterior reconstruction. Technical note.

The anterior decompressive procedure in which spinal fusion is performed is considered an effective treatment for thoracolumbar fractures and tumors. However, it is also known to be associated with considerable surgery-related trauma. The purpose of this study was to show that lumbar corpectomy and anterior reconstruction can be performed via a minimally invasive retroperitoneal approach (MIRA) and therefore the surgical approach-related trauma can be reduced. The authors studied retrospectively the hospital records and radiological studies obtained in five patients (mean age 67.4 years, range 59-76 years) who underwent lumbar corpectomy and spinal fusion via an MIRA followed by posterior fixation. Four patients presented with osteoporotic compression fractures at L-2 and L-3, and one patient presented with metastatic disease in L-4 from prostate cancer. Neurological deficits due to cauda equina compression were demonstrated in all patients. The MIRA provided excellent exposure to facilitate complete decompression and anterior reconstruction in all patients, as verified on follow-up radiographic studies. All patients improved clinically. A 1-year follow-up record is available for four patients and a 6-month follow-up record for the fifth patient; continuing clinical improvement has been observed in all. Radiography demonstrated anatomically correct reconstruction in all patients, as well as a solid fusion or a stable compound union in the four patients for whom 1-year follow-up records were available. The MIRA allows the surgeon to perform anterior lumbar spine surgery via a less invasive approach. The efficacy and safety of this technique and its potential to reduce perioperative morbidity compared with conventional retroperitoneal lumbar spine surgery should be further investigated in a larger series.

Traumatic carotid artery dissection: diagnosis and treatment.

Early diagnosis and successful management of traumatic carotid artery dissections require a high index of clinical suspicion. The diagnostic study of choice is cerebral arteriography. In this paper, 24 cases of traumatic carotid artery dissection are described. Presenting signs and symptoms include Horner's syndrome, dysphasia, hemiparesis, obtundation, and monoparesis. Patients detected early with mild neurological deficits fared well with treatment, while those with profound neurological deficits and delayed diagnoses had poor outcomes. Aggressive nonsurgical treatment is advocated including anticoagulation therapy for prevention of progressive thrombosis and arterial occlusion and/or distal arterial embolization with resultant cerebral ischemia. Direct surgical thromboendarterectomy is considered to carry high morbidity and mortality rates.

Pediatric spinal epidural metastases.

A total of 2259 children with solid malignant tumors were treated at St. Jude Children's Research Hospital between the years 1962 and 1987. Of these, 112 (5%) developed spinal epidural metastasis with spinal cord compression during the course of their disease process. Metastatic epidural spinal cord compression was caused most commonly by Ewing's sarcoma and neuroblastoma, followed by osteogenic sarcoma, rhabdomyosarcoma, Hodgkin's disease, soft-tissue sarcoma, germ-cell tumor, Wilm's tumor, and (rarely) hepatoma. There was no significant difference in outcome between patients with small-cell tumors (neuroblastoma, Hodgkin's disease, and germ-cell tumors) who received only chemotherapy and/or radiation therapy and the patients with similar lesions who received a decompressive laminectomy alone or prior to chemotherapy and/or radiation therapy. Patients with spinal cord compression from metastatic sarcoma (Ewing's sarcoma, soft-tissue sarcoma, osteogenic sarcoma, and rhabdomyosarcoma) showed a significant improvement with decompressive laminectomy alone or before medical therapy, compared to those who received radiation therapy and/or chemotherapy without posterior decompression. Pediatric tumors invade the spinal canal via the neural foramen, compressing the spinal cord in a circumferential manner, allowing decompressive laminectomy (posterior approach) to be an effective surgical approach. Sixty-six percent of children who had no evidence of motor or sensory function below the level of the compression became ambulatory after surgical decompression and medical treatment, regardless of tumor type.

Analysis of 76 civilian craniocerebral gunshot wounds.

A retrospective analysis of 76 civilian craniocerebral gunshot wounds treated over a 20-month period is presented. The authors report a 62% mortality rate and conclude that the admission Glasgow Coma Scale (GCS) score is a valuable prognosticator of outcome. Other important findings were: patients with a GCS score of 3 invariably died, with or without surgical intervention; and the presence of intracranial hematomas, ventricular injury, or bihemispheric wounding was associated with a poor outcome. Standardized methods of data reporting should be adopted in order to allow multicenter trials or comparisons that might lead to management practices that could improve results.