Proton spectroscopic imaging (Dixon method) of the liver: clinical utility

The contribution of proton spectroscopic (PS) imaging to magnetic resonance (MR) imaging of the liver was assessed at 0.5 T in 55 patients with known or suspected hepatic malignancy. PS images were compared subjectively with T1- and T2-weighted spin-echo (SE) images for hepatic lesion detection and conspicuity. For hepatic metastases (n = 27), PS images were equal to T1-weighted images in lesion detection in 17 patients but showed fewer lesions in five patients and false-negative results in two. When compared with T2-weighted images, PS images depicted more lesions in six patients, an equal number of lesions in 18, and fewer lesions in two. Hepatomas (n = 8) were detected with each sequence in all patients. Hepatomas were often more conspicuous on PS images than on T2-weighted images; they were of equal conspicuity on PS and T1-weighted images in most cases. Whereas fatty infiltration (n = 16) appeared on PS images as areas of low signal intensity similar to that of paraspinal muscle, it produced no detectable abnormality on either T1- or T2-weighted images. PS imaging is inferior to T1-weighted SE imaging in the detection of hepatic metastases. The major role of PS imaging at intermediate field strength is to differentiate focal fatty infiltration from hepatic metastases.     

Magnetic resonance imaging of the brainstem: normal structure and basic functional anatomy

Normal structure and basic functional anatomy of the brainstem were studied using anatomic sections obtained with a cryomicrotome whole-organ sectioning technique. Major tracts and nuclei were identified and their function summarized. Magnetic resonance imaging of the brainstem was performed on 10 normal volunteers. By comparing these images with the corresponding anatomic sections, normal structures, including major tracts and nuclei, were identified. Knowledge of location and function of clinically important brainstem nuclei and tracts is necessary for optimal magnetic resonance image interpretation.     

SNAP-25 deficit and hippocampal connectivity in schizophrenia

Regional abnormalities of brain connectivity may be an important substrate for the expression of schizophrenia, a severe form of mental illness. Brain imaging and postmortem morphometric studies indicate hippocampal structure is abnormal in schizophrenia. To study molecular components of hippocampal connectivity the presynaptic proteins SNAP-25 and synaptophysin were assayed in postmortem samples. Immunocytochemical studies indicated reduced SNAP-25 immunoreactivity in schizophrenia compared to controls, particularly in the terminal fields of entorhinal cortex projections. Although there were no overall changes in synaptophysin immunoreactivity, in the granule cell layer of the dentate gyrus synaptophysin immunoreactivity was increased in schizophrenia. These results indicate that disconnection of a subset of hippocampal circuitry from the entorhinal cortex, as well as intrinsic changes in hippocampal connectivity, may contribute to the mechanism of illness in schizophrenia.      

TREK-1 channels do not mediate nitrergic neurotransmission in circular smooth muscle from the lower oesophageal sphincter

Background and purpose:

The ionic mechanisms underlying nitrergic inhibitory junction potentials (IJPs) in gut smooth muscle remain a matter of debate. Recently, it has been reported that opening of TWIK-related K⁺ channel 1 (TREK-1) K⁺ channels contributes to the nitrergic IJP in colonic smooth muscle. We investigated the effects of TREK-1 channel blockers on nitrergic neurotransmission in mouse and opossum lower oesophageal sphincter (LOS) circular smooth muscle (CSM).

Experimental approach:

The effects of TREK-1 channel blockers were characterized pharmacologically in murine and opossum gut smooth muscle using conventional intracellular and tension recordings.

Key results:

In LOS, L-methionine depolarized the resting membrane potential (RMP) but did not inhibit the nitrergic IJP. Cumulative application of theophylline hyperpolarized the RMP and inhibited the nitrergic IJP concentration dependently. The induced membrane hyperpolarization was prevented by pre-application of caffeine, but not by 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one. 8-Br-cAMP significantly hyperpolarized membrane potential and increased the amplitude of the nitrergic IJP. In opossum LOS muscle strips, L-methionine increased resting tone but had no effect on nerve-mediated LOS relaxation. On the other hand, theophylline markedly inhibited tone. In CSM from mouse proximal colon, L-methionine caused modest inhibition of nitrergic IJPs.

Conclusions and implications:

TREK-1 channels were not involved in the nitrergic IJP in LOS CSM. Not only does L-methionine have no effect on the nitrergic IJP or LOS relaxation, but the effect of theophylline appears to be due to interruption of Ca²⁺-releasing pathways (i.e. caffeine-like effect) rather than via blockade of TREK-1 channels.     

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Background The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions.Methods This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting.Findings Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey.Conclusions The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown.Subject terms: Breast cancer, Surgical oncology, Health care economics, Quality of life, Health policy     

The Transition from Medicaid Fee-for-Service to Managed Care Among Private Practitioners in New York City: Effect on Immunization and Screening Rates

Objectives: This study examined the association between participation in Medicaid managed care and up-to-date coverage for childhood immunizations and screenings among private practice physicians serving New York City's poorest neighborhoods. Method: A random sample of 2174 children 3–35 months of age was drawn from 60 physician practices in 1995, and a cross-sectional analysis was used to compare up-to-date status for immunizations, and lead and anemia screening tests, for children cared for by managed care and nonmanaged care physicians. In 1996, an independent sample of 2380 children from the same practices was used to compare up-to-date status for individual children enrolled in Medicaid managed care and children predominantly enrolled in traditional fee-for-service Medicaid. Information from physician interviews augmented chart review data. Chi-square analysis and logistic regression were used. Results: Physicians who participate in Medicaid managed care and those who do not had equal up-to-date coverage for immunizations (41.0 vs. 36.9%, p = .527), and lead (46.8 vs. 38.7%, p = .199) and anemia screening (63.2 vs. 56.5%, p = .272). Measures of the process of care were also similar for the two groups of physicians. Children themselves enrolled in Medicaid managed care appeared significantly more likely to be up-to-date than their nonmanaged care counterparts for immunizations (OR = 1.53, p = .027) and anemia screening (OR = 2.95, p = .000). Conclusions: Participation in managed care does not seem to change physicians' overall preventive care practice behavior. Available data did not reveal major differences in demographics or health status between individual children enrolled in managed care and those not enrolled. That children enrolled in managed care were better immunized and screened than those in fee-for-service Medicaid suggests that physicians receiving compensation under two payment systems may treat children differently depending on each child's mode of reimbursement.     

Quinazoline sulfonamides as dual binders of the proteins B-cell lymphoma 2 and B-cell lymphoma extra long with potent proapoptotic cell-based activity

ABT-737 and ABT-263 are potent inhibitors of the BH3 antiapoptotic proteins, Bcl-x(L) and Bcl-2. This class of putative anticancer agents invariantly contains an acylsulfonamide core. We have designed and synthesized a series of novel quinazoline-based inhibitors of Bcl-2 and Bcl-x(L) that contain a heterocyclic alternative to the acylsulfonamide. These compounds exhibit submicromolar, mechanism-based activity in human small-cell lung carcinoma cell lines in the presence of 10% human serum. This comprises the first successful demonstration of a quinazoline sulfonamide core serving as an effective benzoylsulfonamide bioisostere. Additionally, these novel quinazolines comprise only the second known class of Bcl-2 family protein inhibitors to induce mechanism-based cell death.     

Ultrasound Guided Foam Sclerotherapy: Factors Associated with Outcomes and Complications

ObjectivesIn recent years ultrasound guided foam sclerotherapy (UGFS) has become an increasingly popular treatment for varicose veins. Although many published series detail the results of UGFS, little is known about the factors which are associated with outcomes and complications. The aim of this study was to identify these factors.DesignA review of a prospectively collected database of UGFS which commenced in July 2007.MethodsA successful outcome was defined as complete occlusion of the target vein on duplex scanning at follow-up. Eight factors were assessed to determine whether they were associated with outcomes and complications. These factors were age, gender, compliance with post-procedure compression hosiery, previous varicose vein surgery, single or multiple sites of injection, concentration of sclerosant, volume of sclerosant and pre-procedure severity score.ResultsBetween July 2007 and July 2009, a total of 126 patients (60 men, 66 women) attended follow-up visits and had a post-procedure duplex scan. Targets for UGFS included the great saphenous vein (n = 75), small saphenous vein (n = 13) and anterior accessory great saphenous vein (n = 8). The remainder of procedures involved other veins or more than a single target vein. The median timing of follow-up was 3 months (range 1.5–14 months) with duplex scans revealing complete occlusion of the target vein in 79% of patients. The only factor associated with a successful outcome was compliance with post-procedure compression hosiery (p < 0.05). The most frequently encountered complications following UGFS were skin staining (28%), superficial thrombophlebitis (18%) and pain (14%). The only factor associated with post-UGFS complications was female gender (p < 0.05). When complications were analysed in isolation female gender was also significantly associated with skin staining (p < 0.05), but no other complication.ConclusionsThese data suggest that compliance with post-procedure compression hosiery and gender are important factors associated with a successful outcome and reported complications following UGFS, respectively.