A paradigm for awake intraoperative memory mapping during forniceal stimulation

We report the case of a chess player with superior premorbid cognitive function who presented to the Cognitive Disorders clinic at the National Hospital for Neurology and Neurosurgery with a 2-year history of symptoms of possible memory loss. Initially the MRI scan appearance was within normal limits and his cognitive scores inside the normal range; subsequently his cognitive function deteriorated and he fulfilled criteria for Mild Cognitive Impairment (MCI) two years later. Unexpectedly he died of an unrelated illness seven months later and post mortem examination of the brain was carried out, revealing advanced Alzheimer’s disease (CERAD definite and NIA-Regan Institute high likelihood).

This case highlights the difficulties encountered in assessing patients with superior premorbid function in the early stages of Alzheimer’s disease, and reveals the value of serial MRI and neuropsychological assessment in detecting and monitoring early neurodegenerative disease.     

Common bile duct calculi: updated experience with dissolution with methyl tertiary butyl ether

The authors describe their experience with methyl tertiary butyl ether (MTBE) in a larger series of patients than previously reported in order to acquaint physicians with both its effectiveness for dissolution of common bile duct calculi and the limitations of its use. Ten patients with 13 biliary calculi underwent percutaneous stone dissolution treatment with the experimental cholesterol solvent, MTBE. Three stones completely dissolved within 30 minutes, seven were reduced in size, and three were visibly unaffected. All stones not completely dissolved were easily extracted by means of a stone basket except for one in a patient taken to surgery. Although MTBE perfusion is an effective technique for management of biliary calculi, practitioners should be aware that its use is quite time consuming and its odor difficult to control.     

Monocyte-mediated antibody-dependent cell-mediated cytotoxicity: the role of the metabolic burst

Human monocytes respond to opsonized microorganisms with a "metabolic burst" composed of an increase in oxygen consumption, an increase in hexose monophosphate shunt (HMPS) activity, and the generation of reactive oxygen species (ROS). We investigated the role of the metabolic burst in antibody-dependent cell-mediated cytotoxicity (ADCC) by human monocytes toward anti-D coated erythrocyte target cells because recent studies suggested a role for oxygen-dependent bactericidal mechanisms in ADCC. In normal monocytes, we found that ADCC was nearly halved under hypoxic conditions. Several agents known to impair activation of the burst, such as vincristine, cation chelators, and a sulfhydryl reagent, all decreased cytotoxicity if added before initiation of contact between target and effector cells. Cytotoxicity was inhibited by 2-deoxyglucose but not fluoride, suggesting a nonglycolytic role for glucose in ADCC, perhaps in the HMPS pathway. Although these data suggested a role for the metabolic burst in ADCC, scavengers of ROS did not impair cytotoxicity, and monocytes from chronic granulomatous disease (CGD) patients who had a defective metabolic burst had normal levels of ADCC. We conclude that ADCC toward anti-D coated erythrocyte target cells was the result of at least two independent but closely related cytotoxic pathways. Although one of these pathways appeared to involve the metabolic burst, the potentially cytotoxic reactive oxygen species did not appear to play a role in this system.     

Ischemic preconditioning reduces infarct size in swine myocardium

We evaluated the hypothesis that stunning swine myocardium with brief ischemia reduces oxygen demand in the stunned region and increases tolerance of myocardium to longer periods of ischemia. Wall function was quantified with ultrasonic crystals aligned to measure wall thickening, and stunning was achieved with two cycles of left anterior descending coronary artery (LAD) occlusion (10 minutes) and reperfusion (30 minutes), after which the LAD was occluded for 60 minutes and reperfused for 90 minutes. Infarct size (as a percent of risk region) was then determined by incubating myocardium with para-nitro blue tetrazolium. Regional oxygen demand was measured as myocardial oxygen consumption before the 60-minute LAD occlusion in the stunned region; tracer microspheres were used to determine blood flow, and blood from the anterior interventricular vein and left atrium was used to calculate oxygen saturations. After the second reperfusion period, wall thickening in the stunned region was reduced to 1.4 +/- 2.4% compared with 36.7 +/- 2.5% (mean +/- SEM) before ischemia (p less than 0.001). Regional myocardial oxygen consumption after stunning (3.1 +/- 0.7 ml O2/min/100 g) was no different from regional myocardial oxygen consumption before stunning (3.7 +/- 0.6 ml O2/min/100 g). In the nine pigs "preconditioned" by stunning, infarct size was 10.4 +/- 6.3% of the risk region compared with 48.0 +/- 12.7% in the six control pigs subjected to 60 minutes of ischemia without prior stunning (p less than 0.005). The risk regions were similar (14.4 +/- 1.5% vs. 14.6 +/- 1.9% of the left ventricle, preconditioned vs. control pigs, respectively). We conclude that stunning swine myocardium with two cycles of a 10-minute LAD occlusion followed by reperfusion increases ischemic tolerance but that changes in regional demand in stunned myocardium do not predict the marked reduction in infarct size that follows a subsequent 60-minute period of ischemia.     

Effects of Odanacatib on Bone Structure and Quality in Postmenopausal Women With Osteoporosis: 5-Year Data From the Phase 3 Long-Term Odanacatib Fracture Trial (LOFT) and its Extension

Odanacatib (ODN), a selective oral inhibitor of cathepsin K, was an investigational agent previously in development for the treatment of osteoporosis. In this analysis, the effects of ODN on bone remodeling/modeling and structure were examined in the randomized, double-blind, placebo-controlled, event-driven, Phase 3, Long-term Odanacatib Fracture Trial (LOFT; NCT00529373) and planned double-blind extension in postmenopausal women with osteoporosis. A total of 386 transilial bone biopsies, obtained from consenting patients at baseline (ODN n = 17, placebo n = 23), month 24 (ODN n = 112, placebo n = 104), month 36 (ODN n = 42, placebo n = 41), and month 60 (ODN n = 27, placebo n = 20) were assessed by dynamic and static bone histomorphometry. Patient characteristics at baseline and BMD changes over 5 years for this subset were comparable to the overall LOFT population. Qualitative assessment of biopsies revealed no abnormalities. Consistent with the mechanism of ODN, osteoclast number was higher with ODN versus placebo over time. Regarding bone remodeling, dynamic bone formation indices in trabecular, intracortical, and endocortical surfaces were generally similar in ODN-treated versus placebo-treated patients after 2 years of treatment. Regarding periosteal modeling, the proportion of patients with periosteal double labels and the bone formation indices increased over time in the ODN-treated patients compared with placebo. This finding supported the observed numerical increase in cortical thickness at month 60 versus placebo. In conclusion, ODN treatment for 5 years did not reduce bone remodeling and increased the proportion of patients with periosteal bone formation. These results are consistent with the mechanism of action of ODN, and are associated with continued BMD increases and reduced risk of fractures compared with placebo in the LOFT Phase 3 fracture trial. © 2020 American Society for Bone and Mineral Research.     

Gadoxetic acid enhanced MRI for differentiation of FNH and HCA: a single centre experience

Objectives

Evaluation of enhancement characteristics of histopathologically confirmed focal nodular hyperplasias (FNHs) and hepatocellular adenomas (HCAs) with gadoxetic acid-enhanced MRI.

Methods

Sixty-eight patients with 115 histopathologically proven lesions (FNHs, n?=?44; HCAs, n?=?71) examined with gadoxetic acid-enhanced MRI were retrospectively enrolled (standard of reference: surgical resection, n?=?53 patients (lesions: FNHs, n?=?37; HCAs, n?=?53); biopsy, n?=?15 (lesions: FNHs, n?=?7; HCAs, n?=?18)). Two radiologists evaluated all MR images regarding morphological features as well as the vascular and hepatocyte-specific enhancement in consensus.

Results

For the hepatobiliary phase, relative enhancement of the lesions and lesion to liver enhancement were significantly lower for HCAs (mean, 48.7 (±48.4) % and 49.4 (±33.9) %) compared to FNHs (159.3 (±92.5) %; and 151.7 (±79) %; accuracy of 89 % and 90 %, respectively; P?<?0.001). Visual strong uptake of FNHs vs. hypointensity of HCAs in the hepatobiliary phase resulted in an accuracy of 92 %. This parameter was superior to all other morphological and dynamic vascular criteria alone and in combination (accuracy, 54–85 %).

Conclusions

For differentiation of FNHs and HCAs by means of MRI, gadoxetic acid uptake in the hepatobiliary phase was found to be superior to all other criteria alone and in combination.

Key Points

? EOB-MRI is well suited to differentiate FNHs and hepatocellular adenomas. ? For this purpose hepatobiliary phase is superior to unenhanced and dynamic imaging. ? Hepatobiliary phase (peripheral) hyper- or isointensity is typical for FNH. ? Hepatobiliary phase hypointensity is typical for hepatocellular adenomas. ? EOB-MRI helps to avoid misinterpretations of benign hepatocellular lesions.     

How Hip and Whole-Body Bone Mineral Density Predict Hip Fracture in Elderly Women: The EPIDOS Prospective Study

We conducted a population-based cohort study in 7598 white healthy women, aged 75 years and over, recruited from the voting lists. We measured at baseline bone mineral density (BMD g/cm²) of the proximal femur (neck, trochanter and Ward's triangle) and the whole body, as well as fat and lean body mass, by dual-energy X-ray absorptiometry (DXA). One hundred and fifty-four women underwent a hip fracture during an average 2 years follow-up. Each standard deviation decrease in BMD increased the risk of hip fracture adjusted for age, weight and centre by 1.9 (95% CL 1.5, 2.3) for the femoral neck, 2.6 times (2.0, 3.3) for the trochanter, 1.8 times (1.4, 2.2) for Ward's triangle, 1.6 times (1.2, 2.0) for the whole body, and 1.3 times (1.0, 1.5) for the fat mass. The areas under the receiver operating characteristic (ROC) curves were not significantly different between trochanter and femoral neck BMD, whereas ROC curves of femoral neck and trochanter BMD were significantly better than those for Ward's triangle and whole-body BMD. emsp;Women who sustained an intertrochanteric fracture were older (84 ± 4.5 years) than women who had a cervical fracture (81 ± 4.5 years) and trochanter BMD seemed to be a stronger predictor of intertrochanteric ([RR = 4.5 (3.1, 6.5)] than cervical fractures ([RR = 1.8 (1.5, 2.3]). emsp;In very elderly women aged 80 years and more, hip BMD was still a significant predictor of hip fracture but the relative risk was significantly lower than in women younger than 80 years. emsp;In the 48% of women who had a femoral neck BMD T-score less than –2.5, the relative risk of hip fracture was increased by 3, and the unadjusted incidence of hip fracture was 16.4 per 1000 woman-years compared with 1.1 in the population with a femoral neck BMD T-score 5–1. Received: 19 May 1997 / Accepted: 16 October 1997     

Do Markers of Bone Resorption Add to Bone Mineral Density and Ultrasonographic Heel Measurement for the Prediction of Hip Fracture in Elderly Women? The EPIDOS Prospective Study

We have previously shown that hip bone mineral density (BMD), heel broadband ultrasound attenuation (BUA) and bone resorption markers are independent predictors of hip fracture in elderly women. We investigated whether a combination of these three parameters could improve the predictive value of a single test in a nested case–control analysis (75 hip fractures and 228 age-matched controls) of the EPIDOS prospective study comprising 7598 healthy women 75 years of age and older followed prospectively for a mean 22 months. At baseline, prior fracture, femoral neck BMD by dual-energy X-ray absorptiometry (DXA), heel BUA and urinary type I collagen C-telopeptide breakdown products (CTX) were assessed. The area under the receiver operating characteristic curve was significant for the three diagnostic tests, heel BUA being the best single predictor. The added value of urinary CTX to either BMD or BUA depends on the cutoff point chosen to define patients at risk and on the therapeutic strategy that is considered. Defining patients at risk as those with low BMD (or low BUA) or high CTX resulted in a significant increase in the sensitivity compared with BMD or BUA alone – a strategy that could be applied when a broad treatment is considered. However, this increased sensitivity was also obtained simply by increasing the BMD and BUA cutoffs, suggesting that a combination of CTX with BMD/BUA is not useful for that type of treatment strategy. Conversely, defining patients at risk as those with both low BMD and high CTX increases the specificity (88% vs 78%) with a similar number of hip fracture patients being identified (30% vs 32%) – a combination that could be useful when the strategy is to target treatment to a subset of high-risk patients. This strategy appears to be more cost-effective than bone mass measurement alone as indicated by the 37% fewer patients who need to be treated to avoid one fracture per year. If DXA or ultrasound is not available, the combination of a bone resorption marker with a history of any type of fracture after the age of 50 years gave a predictive value similar to that obtained with femoral neck BMD or heel BUA alone, for both types of treatment strategy. We conclude that the combination of urinary CTX with hip BMD could be useful for the identification of elderly women at high risk for hip fracture, resulting in higher specificity for a given sensitivity threshold than BMD measurement alone. If DXA is not available, the combination of history of fracture and urinary CTX performs as well as hip BMD to assess hip fracture risk in elderly women. Received: 24 November 1997 / Revised: 3 March 1998