Iron, ascorbate and copper status of Sowetan Blacks with calcific chronic pancreatitis

Vitamin C can be used to overcome oxidative stress and ease pain in chronic pancreatitis. But its use is deprecated in conditions of tissue iron overload, because its bioactive form, ascorbate, can accelerate free-radical reactions that are driven by transition metals. We measured iron, ascorbate and copper in Sowetan Blacks (RSA) with chronic pancreatitis, obtaining serum/plasma from 14 consecutive patients and 15 controls. Compared with data from corresponding groups in Manchester, African samples had less ascorbate (p < 0.0001), but more caeruloplasmin (p < 0.0001). African and British controls had comparable iron and iron-binding capacity. Plasma from African patients had less ascorbate than that from African controls (p < 0.005) and in six samples, ferritin exceeded 300 micrograms/l (677 pmol/l). Low- molecular-mass iron or copper, capable of participating in free radical reactions, was not detected. British patients, had similar caeruloplasmin levels to African patients but higher ascorbate levels. There is no evidence of iron overload in our African samples. Outwardly healthy controls from Soweto have elevated levels of caeruloplasmin, possibly to compensate for dietary deficiency of ascorbate. Persistent oxidative stress is a unifying feature of chronic pancreatitis, but its degree is higher in African than British patients. Supplements of vitamin C should be safe in Blacks of southern Africa.      

Winning the battle but losing the war: methicillin-resistant Staphylococcus aureus (MRSA) infection at a teaching hospital

A methicillin-resistant Staphylococcus aureus (MRSA) control policy, aimed at eradication, was established at a 1000-bed hospital in 1985, applied consistently for 10.5 years, and then relaxed. Its components included screening of high-risk patients, transfer of carriers to exhaust-ventilated isolation rooms, closure of wards to new admissions when local transmission was detected, MRSA screening during outbreaks, and prospective collection of clinical and epidemiological information. During the eradication policy period, every 6 months, a mean of 5.1 patients (range 1-12) already carrying MRSA were admitted, and a mean of 3.6 (range 0-16) acquired carriage in the hospital. The largest outbreak comprised 11 patients despite epidemic MRSA strain EMRSA-16 being introduced six times, and MRSA did not become endemic. MRSA- positive admissions increased progressively from 1993; nursing staff workload increased, areas available for alternative patient accommodation were reduced, the resulting ward closures interfered with clinical services, and hence the control policy was relaxed in mid- 1995. Isolation facilities were overwhelmed with 622 new patient- isolates in the next 18 months, and there were 67 clinical infections in 1996. The proportion of blood cultures positive for MRSA rose nearly sevenfold by 1996 and 27-fold by 1997. Thus, repeated eradication of MRSA, even epidemic strains, by use of a stringent policy, is possible given sufficient resources, whereas flexible national guidelines designed to control, but not eradicate, epidemic staphylococci, are currently unlikely to be successful. The costs of eradication policies need to be weighed against those of endemicity.      

Sentinel lymph node biopsy in melanoma: Which hot nodes should be harvested and is blue dye really necessary?

Objectives

The ‘10% rule’ has become widely accepted by surgeons performing sentinel lymph node biopsy (SLNB) for melanoma. The purpose of this study was to compare the ‘10% rule’ with alternative node harvesting criteria. In particular, we were interested to see whether the use of blue dye had any impact on the sensitivity of the test and whether it is necessary to remove all hot nodes.

Rapid determination of brain natriuretic peptide in patients with acute myocardial infarction.

We evaluated a rapid brain natriuretic peptide (BNP) assay (Triage BNP, Biosite Diagnostics) as indicator of infarct size, left ventricular (LV) dysfunction, and longterm survival in patients with acute myocardial infarction (AMI) during the coronary care unit stay. We studied 64 AMI patients in whom infarct size was estimated by creatine kinase isoenzyme MB (CK-MB) peak concentrations and single-photon emission computed tomography (SPECT) myocardial perfusion using technetium-99m sestamibi, and LV function by gated SPECT imaging. Measurements of BNP and SPECT were performed approximately 3 days after admission. SPECT was also repeated 3 months later. We found a significant correlation between BNP and both the peak CK-MB concentrations (r = 0.40, p = 0.001) and the perfusion defect size at SPECT (r = 0.38, p = 0.002). BNP was weakly related to LV ejection fraction (LVEF) assessed both early and 3 months after AMI (r = -0.29, p = 0.02; and r = -0.27, p = 0.04, respectively). The sensitivity and specificity of BNP for predicting survival of patients over 1 year of follow-up was 100% and 43%, respectively, with a negative predictive value of 100%. The positive predictive power of BNP was very modest (12%). Considering our results, the measurement of BNP did not look nearly as promising when tested in the setting of our cardiological intensive care.     

GA2LEN skin test study I: GA²LEN harmonization of skin prick testing: novel sensitization patterns for inhalant allergens in Europe

Background:  Skin prick testing is the standard for diagnosing IgE-mediated allergies. However, different allergen extracts and different testing procedures have been applied by European allergy centres. Thus, it has been difficult to compare results from different centres or studies across Europe. It was, therefore, crucial to standardize and harmonize procedures in allergy diagnosis and treatment within Europe.
Aims:  The Global Asthma and Allergy European Network (GA²LEN), with partners and collaborating centres across Europe, was in a unique position to take on this task. The current study is the first approach to implement a standardized procedure for skin prick testing in allergies against inhalant allergens with a standardized pan-European allergen panel.
Methods:  The study population consisted of patients who were referred to one of the 17 participating centres in 14 European countries ( n  = 3034, median age = 33 years). Skin prick testing and evaluation was performed with the same 18 allergens in a standardized procedure across all centres.
Results:  The study clearly shows that many allergens previously regarded as untypical for some regions in Europe have been underestimated. This could partly be related to changes in mobility of patients, vegetation or climate in Europe.
Conclusion:  The results of this large pan-European study demonstrate for the first time sensitization patterns for different inhalant allergens in patients across Europe. The standardized skin prick test with the standardized allergen battery should be recommended for clinical use and research. Further EU-wide monitoring of sensitization patterns is urgently needed.     

The evidence for hippocampal long-term potentiation as a basis of memory for simple tasks

Long-term potentiation (LTP) is the enhancement of postsynaptic responses for hours, days or weeks following the brief repetitive afferent stimulation of presynaptic afferents. It has been proposed many times over the last 30 years to be the basis of long-term memory. Several recent findings finally supported this hypothesis: a) memory formation of one-trial avoidance learning depends on a series of molecular steps in the CA1 region of the hippocampus almost identical to those of LTP in the same region; b)hippocampal LTP in this region accompanies memory formation of that task and of another similar task. However, CA1 LTP and the accompanying memory processes can be dissociated, and in addition plastic events in several other brain regions(amygdala, entorhinal cortex, parietal cortex) are also necessary for memory formation of the one-trial task, and perhaps of many others.     

Detection of circulating tumour DNA after neoadjuvant chemoradiotherapy in patients with locally advanced oesophageal cancer

Active surveillance instead of standard surgery after neoadjuvant chemoradiotherapy (nCRT) has been proposed for patients with oesophageal cancer. Circulating tumour DNA (ctDNA) may be used to facilitate selection of patients for surgery. We show that detection of ctDNA after nCRT seems highly suggestive of major residual disease. Tumour biopsies and blood samples were taken before, and 6 and 12 weeks after, nCRT. Biopsies were analysed with regular targeted next-generation sequencing (NGS). Circulating cell-free DNA (cfDNA) was analysed using targeted NGS with unique molecular identifiers and digital polymerase chain reaction. cfDNA mutations matching pre-treatment biopsy mutations confirmed the presence of ctDNA. In total, 31 patients were included, of whom 24 had a biopsy mutation that was potentially detectable in cfDNA (77%). Pre-treatment ctDNA was detected in nine of 24 patients (38%), four of whom had incurable disease progression before surgery. Pre-treatment ctDNA detection had a sensitivity of 47% (95% CI 24–71) (8/17), specificity of 85% (95% CI 42–99) (6/7), positive predictive value (PPV) of 89% (95% CI 51–99) (8/9), and negative predictive value (NPV) of 40% (95% CI 17–67) (6/15) for detecting major residual disease (>10% residue in the resection specimen or progression before surgery). After nCRT, ctDNA was detected in three patients, two of whom had disease progression. Post-nCRT ctDNA detection had a sensitivity of 21% (95% CI 6–51) (3/14), specificity of 100% (95% CI 56–100) (7/7), PPV of 100% (95% CI 31–100) (3/3), and NPV of 39% (95% CI 18–64) (7/18) for detecting major residual disease. The addition of ctDNA to the current set of diagnostics did not lead to more patients being clinically identified with residual disease. These results indicate that pre-treatment and post-nCRT ctDNA detection may be useful in identifying patients at high risk of disease progression. The addition of ctDNA analysis to the current set of diagnostic modalities may not improve detection of residual disease after nCRT. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.