Digital subtraction in gadolinium-enhanced MR imaging of the brain: a method to reduce contrast dosage

The aim of the study was to investigate the feasibility of using digital subtraction in contrast-enhanced MR imaging of the brain to reduce the MR contrast dosage without jeopardizing patient care. Fifty-two patients with intracranial lesions, either intra-axial or extra-axial, detected by computerized tomography were selected for contrast-enhanced MR imaging with half-dose and full-dose of gadopentetate dimeglumine. The half-dose unsubtracted, full-dose unsubtracted, and half-dose subtracted MR images were visually assessed by counting the number of enhancing brain lesions in the images and quantitatively analyzed by computing their lesion contrast-to-background ratios (CBR). The visual conspicuity of the half-dose subtracted MR images was comparable to that of the full-dose unsubtracted MR images ( p>0.05), whereas the CBR of the half-dose subtracted images was approximately two to three times higher than that of the full-dose unsubtracted images. The half-dose subtracted T1-weighted spin-echo images might be able to replace the conventional standard-dose T1-weighted spin-echo images in MR imaging of the brain.     

Should cervical ultrasonography be a routine staging investigation for lung cancer patients with impalpable cervical lymph nodes?

OBJECTIVES: Detection of cervical N3 lymph nodes is currently not a routine preoperative investigation for lung cancer patients. We designed a study to assess if the frequency and accuracy of detection of metastatic cervical lymph nodes using cervical ultrasonography (US) and fine needle aspiration (FNA) justify their routine use in all lung cancer patients with impalpable cervical lymph nodes. METHODS: Fifty patients with suspected and potentially operable non-small cell lung cancer were enrolled. Patients with palpable cervical lymph nodes were excluded. In addition to routine preoperative investigations, all patients received cervical US to determine the presence of cervical lymph nodes. Nodes suspicious of harboring malignancy according to a specific set of sonographic criteria (which include shape, echogenicity, nodal architecture, and vascular patterns) were subjected to biopsy by ultrasound-guided FNA. RESULTS: Normal cervical lymph nodes were detected by cervical US in 30 patients (60%). Cervical lymph nodes suspicious of harboring malignancy were detected in 10 patients (20%). FNA confirmed cervical nodal metastasis in four of these patients (8%). The TNM staging of two patients (4%) was revised up to stage IIIb as a result, excluding them from further surgery. Cost analysis suggests this technique to be cost-effective when used as a routine preoperative investigation to exclude patients from unnecessary surgical intervention. No mortality or complications were encountered in all patients. CONCLUSIONS: Cervical US and FNA is a safe and cost-effective method of evaluating the status of impalpable cervical lymph nodes in lung cancer patients. Further study is warranted to establish the role of cervical US and FNA in lung cancer staging algorithms.     

Diabetes and the outcome of infrainguinal bypass for critical limb ischaemia

Aim: To examine the influence of diabetes mellitus (DM) on the outcome of infrainguinal bypass operations performed for critical foot ischaemia in Chinese patients. Methods: A prospective audit of 265 consecutive infrainguinal bypass operations. Results: Diabetic patients suffered more frequently from ischaemic heart disease (48%vs 25%, P= 0.001) and tissue loss (90%vs 79%, P = 0.01) at presentation. Cigarette smoking was more prevalent in the non‐diabetic (NDM) group (72%vs 51%, P = 0.001). Arterial segments distal to the common femoral artery were more often used as inflow to bypass graft in DM patients (36%vs 22%, P = 0.02). Operative mortality (seven DM vs one NDM, P = 0.19). Early graft failure (7% in DM group vs 10% in NDM group, P = 0.24), wound infection rate (24% in DM group vs 17% in NDM group, P = 0.21), early limb loss (9% in DM group vs 6% in NDM group, P = 0.66) were comparable. However, hospital mortality was higher in DM patients (8%vs 1%, P = 0.04). DM patients more frequently required further surgical debridement postoperatively (20%vs 9%, P = 0.04). Long‐term, patient survival was inferior in the DM group (43% NDM vs 33% DM at 5 years, P = 0.03). Primary graft patency (46% DM vs 34% NDM at 4 years P = 0.19), secondary graft patency (57% DM vs 47% NDM at 4 years P = 0.14) and limb salvage rate (78%vs 81% at 5 years, P = 0.79) were comparable. Conclusion: Diabetes mellitus adversely affects hospital mortality and long‐term survival. Graft patency and limb salvage are not compromised by the presence of DM.     

The threshold current in the intrathecal space to elicit motor response is lower and does not overlap that in the epidural space: a porcine model

Purpose

Using electrical epidural stimulation, a current of 1 to 10 mA is required to confirm the presence of the tip of an epidural catheter in the epidural space. The purpose of this study was to examine the hypothesis that the threshold current required to elicit a motor response in the intrathecal space is significantly lower than that in the epidural space in a porcine model.

Methods

Four 20-kg pigs were used in this experiment. Eighteen gauge, insulated, Tuohy needles were advanced into the epidural space using the loss of resistance technique at five different spinal levels in each pig. When the epidural space was entered, an electrical current was applied to the needle and increased progressively until a motor response was elicited. The needle was then further advanced until cerebrospinal fluid (CSF) was observed or until the needle had been advanced a maximum of 1 cm. At this point, the current was reapplied and increased until motor activity was evident.

Results

A total of 20 needles were inserted in four pigs. The current required to produce a motor response in the epidural space was 3.45 ± 0.73 mA (mean ± SD). The current required to produce a motor response in the intrathecal space (entry confirmed by the presence of CSF) was 0.38 ± 0.19 mA (mean ± SD). Two needles were advanced 1 cm without obtaining CSF but the current thresholds were similar to those obtained when CSF was evident (0.4 mA and 0.3 mA, respectively).

Conclusion

The threshold current of an insulated needle required to elicit a motor response in the intrathecal space, was significantly (P < 0.01) lower than that in the epidural space in a porcine model.     

Brain‐derived neurotrophic factor prevents dendritic retraction of adult mouse retinal ganglion cells

We used cultured adult mouse retinae as a model system to follow and quantify the retraction of dendrites using diolistic labelling of retinal ganglion cells (RGCs) following explantation. Cell death was monitored in parallel by nuclear staining as ‘labelling’ with RGC and apoptotic markers was inconsistent and exceedingly difficult to quantify reliably. Nuclear staining allowed us to delineate a lengthy time window during which dendrite retraction can be monitored in the absence of RGC death. The addition of brain‐derived neurotrophic factor (BDNF) produced a marked reduction in dendritic degeneration, even when application was delayed for 3 days after retinal explantation. These results suggest that the delayed addition of trophic factors may be functionally beneficial before the loss of cell bodies in the course of conditions such as glaucoma.     

Toll-like receptor 4 promotes tubular inflammation in diabetic nephropathy

Inflammation contributes to the tubulointerstitial lesions of diabetic nephropathy. Toll-like receptors (TLRs) modulate immune responses and inflammatory diseases, but their role in diabetic nephropathy is not well understood. In this study, we found increased expression of TLR4 but not of TLR2 in the renal tubules of human kidneys with diabetic nephropathy compared with expression of TLR4 and TLR2 in normal kidney and in kidney disease from other causes. The intensity of tubular TLR4 expression correlated directly with interstitial macrophage infiltration and hemoglobin A1c level and inversely with estimated glomerular filtration rate. The tubules also upregulated the endogenous TLR4 ligand high-mobility group box 1 in diabetic nephropathy. In vitro, high glucose induced TLR4 expression via protein kinase C activation in a time- and dose-dependent manner, resulting in upregulation of IL-6 and chemokine (C-C motif) ligand 2 (CCL-2) expression via IκB/NF-κB activation in human proximal tubular epithelial cells. Silencing of TLR4 with small interfering RNA attenuated high glucose-induced IκB/NF-κB activation, inhibited the downstream synthesis of IL-6 and CCL-2, and impaired the ability of conditioned media from high glucose-treated proximal tubule cells to induce transmigration of mononuclear cells. We observed similar effects using a TLR4-neutralizing antibody. Finally, streptozotocin-induced diabetic and uninephrectomized TLR4-deficient mice had significantly less albuminuria, renal dysfunction, renal cortical NF-κB activation, tubular CCL-2 expression, and interstitial macrophage infiltration than wild-type animals. Taken together, these data suggest that a TLR4-mediated pathway may promote tubulointerstitial inflammation in diabetic nephropathy.