Ultra-fast and accurate assessment of cardiac function in rats using accelerated MRI at 9.4 Tesla.

MRI can accurately and reproducibly assess cardiac function in rodents but requires relatively long imaging times. Therefore, parallel imaging techniques using a 4-element RF-coil array and MR sequences for cardiac MRI in rats were implemented at ultra-high magnetic fields (9.4 Tesla [T]). The hypothesis that these developments would result in a major reduction in imaging time without loss of accuracy was tested on female Wistar rats under isoflurane anesthesia. High-resolution, contiguous short-axis slices (thickness 1.5 mm) were acquired covering the entire heart. Two interleaved data sets (i) with the volume coil (eight averages) and (ii) with the four-element coil array (one average) were obtained. In addition, two-, three-, and fourfold accelerated data sets were generated through postprocessing of the coil array data, followed by a TGRAPPA reconstruction, resulting in five data sets per rat (in-plane voxel size 100 x 100 microm). Using a single blinded operator, excellent agreement was obtained between volume coil (acquisition time: 88 min) and the fourfold accelerated (<3 min) data sets (e.g., LV mass 436 +/- 21 mg vs 433 +/- 19 mg; ejection fraction 74 +/- 5% vs 75 +/- 4%). This finding demonstrates that it is possible to complete a rat cine-MRI study under 3 min with low variability and without losing temporal or spatial resolution, making high throughput screening programs feasible.     

Human ALKBH7 is required for alkylation and oxidation-induced programmed necrosis

Programmed necrosis has emerged as a crucial modulator of cell death in response to several forms of cellular stress. In one form of programmed necrotic cell death, induced by cytotoxic alkylating agents, hyperactivation of poly-ADP-ribose polymerase (PARP) leads to cellular NAD and ATP depletion, mitochondrial dysfunction, reactive oxygen species formation, and ensuing cell death. Here, we show that the protein encoded by the human AlkB homolog 7 (ALKBH7) gene plays a pivotal role in DNA-damaging agent-induced programmed necrosis by triggering the collapse of mitochondrial membrane potential and large-scale loss of mitochondrial function that lead to energy depletion and cellular demise. Depletion of ALKBH7 suppresses necrotic cell death induced by numerous alkylating and oxidizing agents while having no effect on apoptotic cell death. Like wild-type cells, ALKBH7-depleted cells undergo PARP hyperactivation and NAD depletion after severe DNA damage but, unlike wild-type cells, exhibit rapid recovery of intracellular NAD and ATP levels. Consistent with the recovery of cellular bioenergetics, ALKBH7-depleted cells maintain their mitochondrial membrane potential, plasma membrane integrity, and viability. Our results uncover a novel role for a mammalian AlkB homolog in programmed necrosis, presenting a new target for therapeutic intervention in cancer cells that are resistant to apoptotic cell death.     

Diagnostic value of plasma levels of tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) in newborns with sepsis

The aim of this study was to examine if TNFα and IL-6 plasma levels could be of value in diagnosing neonatal sepsis. Tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) plasma levels were determined in 15 newborn infants with confirmed sepsis (group I), 18 with suspected sepsis (group II) and 22 control infants (group III). In 33 newborns, initially suspected of having sepsis (groups I and 11), a positive test result for plasma concentration of TNFα (> 70 pg/ml) had a sensitivity of 73 % and a specificity of 94%. A positive test result for IL-6 (>500 pg/ml) had a sensitivity of 80% and a specificity of 78%. When plasma levels of TNFα and IL-6 were combined for the diagnosis of neonatal sepsis, a positive test result for both tests had a sensitivity of 60% and a specificity of 100%. When both tests are positive the diagnosis of neonatal sepsis is almost certain (likelihood ratio =α. The combination of TNFα and IL-6 determinations appears to be a good predictor of neonatal sepsis.     

New formulations of demineralized bone matrix as a more effective graft alternative in experimental posterolateral lumbar spine arthrodesis

STUDY DESIGN: A rabbit model of posterolateral intertransverse process spine arthrodesis was used. OBJECTIVE: To determine the efficacy of two new formulations of demineralized bone matrix. SUMMARY OF BACKGROUND DATA: The flowable gel form of Grafton (Osteotech, Eatontown, NJ) demineralized bone matrix has been shown to have osteoinductive properties in various models and currently is used clinically as bone graft material in posterolateral lumbar spine arthrodesis. Two new formulations of Grafton, one made of flexible sheets (Flex) and the other made in a malleable consistency (Putty), have improved handling characteristics compared with the gel form. METHODS: In this study, 108 New Zealand white rabbits underwent bilateral posterolateral intertransverse spine arthrodesis at L5-L6 using autogenous iliac crest bone graft alone (control), one of the new forms of demineralized bone matrix (DBM; made from rabbit bone) alone or in combination with autogenous iliac crest bone. Rabbits were killed 6 weeks after surgery. The lumbar spines were excised, and fusion success or failure was determined by manual palpation and radiography. Specimens also were processed for undecalcified histologic analysis. RESULTS: Manual palpation of the harvested lumbar spines revealed that the fusion rates of the Flex-DBM/Auto group (9/9, 100%) and Putty-DBM/Auto group (10/10, 100%) were superior (P < 0.01) to those of the Auto/control group (3/9, 33%). As a stand-alone graft substitute, Flex-DBM performed superiorly with a fusion rate of 11/11 (100%) compared with that of Putty-DBM (10/12, 83%) and Gel-DBM (7/12, 58%). The devitalized version of Flex-DBM had a fusion rate of 4/11 (36%), which was comparable with the devitalized Putty-DBM rate of 4/12 (33%). Both were superior (P < 0.05) to the devitalized Gel-DBM rate of 0/12 (0%). More mature fusions with greater amounts of trabecular bone were present radiographically and histologically in rabbits that received all forms of demineralized bone matrix than in those in which autograft was used. CONCLUSIONS: The new flexible sheet and malleable putty forms of demineralized bone matrix were effective as graft extender and graft enhancer in a model of posterolateral lumbar spine fusion. These newer formulations of Grafton appear to have a greater capacity to form bone than the gel form or autogenous bone graft alone in this model.     

Primary somatosensory cortex activation is not altered in patients with ventroposterior thalamic lesions: a PET study

BACKGROUND AND PURPOSE: We know remarkably little about the mechanisms underlying cortical activation. Such mechanisms might be better understood by studying the effect of well-localized lesions on the cortical activations in simple paradigms. METHODS: We used H(2)(15)O and positron emission tomography to measure regional cerebral blood flow (rCBF) at rest and during hand vibration in 7 patients with unilateral thalamic lesion involving the ventroposterior (VP) somatosensory thalamic relay nuclei. We compared the results with those obtained in 6 patients with thalamic lesions sparing the VP nuclei and 6 healthy controls. RESULTS: The patients with VP lesions had a selective hypoperfusion at rest in the ipsilesional primary sensorimotor cortex (SM1). This hypoperfusion was significantly correlated with the degree of contralateral somatosensory deficit. This abnormality may reflect the deafferentation of SM1 from its somatosensory thalamic input. Despite this deafferentation, the ipsilesional SM1 was normally activated by the vibration of the hypoesthetic hand. CONCLUSIONS: The fact that a lesion of the somatosensory thalamic relay nuclei alters the rCBF at rest in SM1 but not its activation by hand vibration indicates that the mechanism of cortical activation is complex, even in the case of simple sensory stimulation. In addition, a dissociation may occur between obvious neurological deficits and apparently normal activation patterns, which suggests that activation studies should be interpreted cautiously in patients with focal brain lesions.     

A multi-centre rapid assessment of injecting drug use in India

In 1998, a series of five rapid situation assessments (RSA) of injecting drug use were undertaken by The Society for Service to Urban Poverty (SHARAN) covering the major Metropolitan cities of Mumbai, Chennai, Calcutta, Delhi and Imphal. The RSA determined the extent and patterns of injecting drug use (IDU), the available responses, current and planned interventions, and drug users' perceptions of injecting and sexual-related risk behaviour. The RSA was necessary as there are a lack of data on IDU in India. This has resulted in the denial of injecting drug use except for the north-eastern states by official sources, thereby affecting the inputs for IDU-related interventions. The draft assessment reports were disseminated though city workshops, held between April 1998 and January 1999. Local NGOs involved in drug treatment and HIV related interventions, government officials, and the relevant State AIDS Cells were invited to the workshops in order to contribute to final city assessment reports, so as to promote ownership and to enhance coverage. While the data obtained from the RSA were largely as anticipated, the outcome of the dissemination workshops was phenomenal.     

Solitary malignant peripheral nerve sheath tumor of the pancreas

Primary malignant peripheral nerve sheath tumors of the pancreas are rare. This is a report of a 72 year-old African male who presented with an 8 lb. weight loss and anorexia. A computed tomography (CT) scan revealed a 12 cm mid pancreatic mass. An 85% pancreatectomy (with splenectomy) was performed. Immunohistopathologic and ultrastructural (electron microscopy) evaluation established the schwann cell origin of this neoplasm. The clinical management and pathologic findings are discussed in this report as well as a review of the literature.