A search for unknown blood-borne oncogenic viruses

In previous decades, infants who received blood transfusions shortly after birth or in utero might have been infected at a particularly vulnerable age by some blood-borne oncogen it virus. A cohort of such infants has therefore been followed into adult life to see if they suffered any excess of neoplastic disease or of non-neoplastic mortality. A total of 12,690 infants were identified who were transfused between 1 January 1942 and 31 December 1970, in most cases for the prevention or treatment of haemolytic disease of the newborn. All but 361 (2.8%) were found to have been registered with a National Health Service (NHS) practitioner and were followed in the NHS central records until they died, emigrated, were removed from NHS lists or until 1 January 1992, whichever occurred first. Mortality and cancer incidence were compared with that expected from national rates. No marked disparity was observed and there was no excess of childhood leukaemia. The incidence of non-Hodgkin's lymphoma at 15 to 49 years of age was about twice that expected, but the excess was not statistically significant.     

Morbidity and Mortality Associated with Typhoid Fever Among Hospitalized Patients in Hyderabad District,Pakistan, 2017-2018: Retrospective Record Review

BackgroundHyderabad, Pakistan, was the first city to witness an outbreak of extensively drug resistant (XDR) typhoid fever. The outbreak strain is resistant to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, fluoroquinolones, and third-generation cephalosporin, thus greatly limiting treatment options. However, despite over 5000 documented cases, information on mortality and morbidity has been limited.ObjectiveTo address the existing knowledge gap, this study aimed to assess the morbidity and mortality associated with XDR and non-XDR Salmonella serovar Typhi infections in Pakistan.MethodsWe reviewed the medical records of culture-confirmed typhoid cases in 5 hospitals in Hyderabad from October 1, 2016, to September 30, 2018. We recorded data on age, gender, onset of fever, physical examination, serological and microbiological test results, treatment before and during hospitalization, duration of hospitalization, complications, and deaths.ResultsA total of 1452 culture-confirmed typhoid cases, including 947 (66%) XDR typhoid cases and 505 (34%) non-XDR typhoid cases, were identified. Overall, ≥1 complications were reported in 360 (38%) patients with XDR typhoid and 89 (18%) patients with non-XDR typhoid (P<.001). Ileal perforation was the most commonly reported complication in both patients with XDR typhoid (n=210, 23%) and patients with non-XDR typhoid (n=71, 14%) (P<.001). Overall, mortality was documented among 17 (1.8%) patients with XDR S Typhi infections and 3 (0.6%) patients with non-XDR S Typhi infections (P=.06).ConclusionsAs this first XDR typhoid outbreak continues to spread, the increased duration of illness before hospitalization and increased rate of complications have important implications for clinical care and medical costs and heighten the importance of prevention and control measures.     

Treatment of Aggressive Fibromatosis: the Experience of a Single Institution

AimsAggressive fibromatosis is a locally aggressive infiltrative low-grade tumour, although pathologically benign, and it does not metastasise, yet it can cause serious local distressing symptoms by virtue of local destruction and impairment of local function. The aim of this study was to emphasise the role of radiotherapy and adequate surgery in the treatment of fibromatosis in patients presenting with newly diagnosed or recurrent disease and to analyse our treatment results over 15 years for this rare tumour type.Materials and methodsFifty-four patients with confirmed diagnosis of aggressive fibromatosis treated at King Faisal Specialist Hospital between 1990 and 2006 were identified from our local cancer registry. Forty-seven patients had surgery: complete resection (R0) in 20 patients, incomplete surgery (R1/2) in 27 patients, and seven patients had biopsy only. Forty-five patients were treated with radiotherapy: 38 patients were treated with postoperative radiotherapy, three patients were treated with preoperative radiotherapy and four patients had radiotherapy as the only treatment. The radiotherapy dose ranged between 45 and 60 Gy (median 50.4 Gy). Three patients did not receive any form of treatment apart from biopsy, but were still included in the final analysis.ResultsFifty-two per cent (28/54 patients) of our patient population had tumour recurrence when first presented to King Faisal Specialist Hospital. The median age was 29.5 years (range 2–63 years). The most common site of involvement was the extremities (28 patients). Among the 54 patients (with primary and recurrent presentation) there were 10 local recurrences, all of which were within the original primary site. The 5-year progression-free survival and overall survival rates for the whole group were 75 and 95%, respectively. Univariate and multivariate Cox regression analysis showed that the depth of invasion significantly affected progression-free survival.ConclusionAggressive fibromatosis is effectively treated with surgery and postoperative radiotherapy. Patients first presenting with tumour recurrence may still have local tumour control comparable with newly diagnosed patients.     

Effects of Apnea,Obesity, and Statin Therapy on Proprotein Convertase Subtilisin/Kexin 9 Levels in Patients with Obstructive Sleep Apnea

ObjectivesObstructive sleep apnea (OSA) is a common condition closely related to obesity, insulin resistance, dyslipidemia, and cardiovascular disease. The aim of this study was to explore the possible relationship between OSA and proprotein convertase subtilisin/kexin type 9 (PCSK9).MethodsFull-night polysomnography was performed on 150 participants who were divided into three groups: controls, OSA patients on statin therapy, and OSA patients not on statin therapy. Biochemical markers, plasma low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses, and PCSK9 were determined.ResultsPCSK9 was highest in OSA patients on statins compared to the control group and to OSA patients not on statins (p = 0.036 and p = 0.039, respectively), after adjustment for body mass index (BMI). LDL diameter was greater in OSA patients not on statins compared to OSA patients on statins (p = 0.032). PCSK9 was highest in the group of patients with all three risk factors (diagnosed OSA, statins, BMI ≥25 kg/m²) compared to groups with no, one, and two risk factors (p = 0.031, p = 0.001, and p = 0.029, respectively). Presence of OSA, statin therapy, and BMI ≥25 kg/m² when combined were independently associated with higher levels of PCSK9 when adjusted for antihypertensive therapy, small dense LDL, and HDL 3c subclass (odds ratio = 2.849; interquartile range [1.026–7.912], p = 0.044).ConclusionStatin therapy was closely related to PCSK9. OSA along with obesity and statin use induces elevation of PCSK9.     

Expression of Blood Group Antigens and Lectin Binding in Adenocarcinomas of the Endometrium

To investigate cytoplasmic alterations in cancers of the endometrium, monoclonal antibodies against H, A and B blood group substances and related lectins such as Ulex europaeus agglutinin 1 (UEA-l), Lotus fefragonolobus agglutinin (LTA), and Griffonia simplicifolia 1 (GS1-A4, -B4) were applied to 42 cases of endometrial adenocarcinoma (EAC) and 11 adenomyoses. The control specimens consisted of normal endometria with leiomyoma or adenomyosis from patients of known blood group type. The brightest and most consistent staining was obtained with GS1- A4, showing 98% positivity in EAC in contrast to 18% in normal endometria. In contrast, expression of A antigen was seen in only 24% of EAC and in 13% of normal endometria, UEA-1 binding was seen in 81% of EAC and in 10% of normal endometria, whereas H antigen was seen in 60% of EAC and 0% of normal endometria. In adenocar. cinomas, staining was seen not only along the luminal border of glands but also in the cytoplasm and the lateral or basal cell membranes, whereas in the normal endometrium staining was mostly along the luminal border. Thus, a difference in the positivity and localization of glycoconjugates was observed in neoplastic and non neoplastic endometrium.     

Lack of association between low HDL-cholesterol and elevated circulating cellular adhesion molecules in normolipidemic CAD patients and healthy subjects

High plasma HDL-cholesterol (HDL-c) is a well-established protective factor in coronary artery disease (CAD). One of its potential protective mechanisms is the inhibition of the cytokine-induced upregulation of expression of cellular adhesion molecules (CAMs). High sCAM levels were found to be associated with low HDL-c in some studies performed mostly in hyperlipidemic subjects, but this association has not yet been investigated in CAD patients. In addition, conflicting results were obtained from in vitro studies that explored the proposed HDL effect on cytokine-induced CAM expression. The aim of the present case-control study was to investigate whether low HDL-c values are associated with CAM overexpression in normolipidemic CAD patients and healthy individuals, matched according to age and gender. Plasma HDL-c, sICAM-1, sVCAM-1, and sE-selectin were measured in 37 normolipidemic patients with angiographically verified coronary artery disease and in 52 healthy normolipidemic subjects. The sCAM values obtained in the subjects (patients or controls) with low HDL-c levels (< 1.03 mmol/L) were compared with the values in the subjects with high HDL-c (>or= 1.03 mmol/L). No significant difference was found between sICAM-1, sVCAM-1, and E-selectin values obtained in subjects with low and high HDL-c, either among the patients or the healthy controls. In conclusion, low HDL-c levels are not associated with CAM overexpression in normolipidemic CAD patients and healthy subjects.     

Lipid peroxidation as risk factor for endothelial dysfunction in antiphospholipid syndrome patients

The aim of this study was to evaluate oxidative stress markers and it relations to endothelial damage as risk factor for thrombosis in patients with primary (PAPS) and secondary (SAPS) antiphospholipid syndrome (APS) in correlation to traditional risk factors. Flow-mediated (FMD) and nitroglycerine (NMD)-induced dilation of the brachial artery were studied in 140 APS patients (90 PAPS, 50 SAPS) and 40 controls matched by age, sex, and conventional risk factors for atherosclerosis. Markers of oxidative stress, lipid hydroperoxydes (LOOH), advanced oxidation protein products (AOPP), total sulfhydryl groups (tSHG), and paraoxonase 1 activity (PON1) were determined by spectrophotometric method. Oxidative stress dominates in APS patients. LOOH and AOPP correlate to lipid fractions (p < 0.05), unlike PON1, tSHG that correlated to antiphospholipid antibody positivity (p < 0.05). FMD was lower in APS patients comparing to controls (p < 0.001). Cholesterol is independent variable for FMD impairment in control group (p = 0.011); LOOH in PAPS (p = 0.004); LOOH, aCL, and triglycerides in SAPS patients (p = 0.009, p = 0.049, and p = 0.012, respectively). Combined predictive of aCL and LOOH is better for FMD impairment than LOOH alone in both PAPS and SAPS patients (AUC 0.727, p = 0.001, 95 % CI 0.616–0.837 and AUC 0.824, p?0.001, 95 % CI 0.690–0.957, respectively). Lipid peroxidation is independent predictor for endothelial dysfunction in APS patients. We demonstrated synergistic effect of aCL and LOOH as risk for endothelial impairment in both PAPS and SAPS patients.     

The aging eyewitness: effects of age on face, delay, and source-memory ability

As a way to examine the nature of age-related differences in lineup identification accuracy, young (16-33 years) and older (60-82 years) witnesses viewed two similar videotaped incidents, one involving a young perpetrator and the other involving an older perpetrator. The incidents were followed by two separate lineups, one for the younger perpetrator and one for the older perpetrator. When the test delay was short (35 min), the young and older witnesses performed similarly on the lineups, but when the tests were delayed by 1 week, the older witnesses were substantially less accurate. When the target was absent from the lineups, the older witnesses made more false alarm errors, particularly when the faces were young. When the target was present in the lineups, correct identifications by both young and older witnesses were positively correlated with a measure of source recollection derived from a separate face-recognition task. Older witnesses scored poorly on this measure, suggesting that source-recollection deficits are partially responsible for age-related differences in performance on the lineup task.