Prevalence of cerebral venous thrombosis with the use of oral contraceptive pills during the Holy month of Ramadan

Objectives:To identify the epidemiologic profile of cerebral vein thrombosis (CVT) among fasting women using oral contraceptive pills (OCPs) during the holy month of Ramadan.Methods:This retrospective study was conducted on all patients diagnosed with CVT and using OCPs from records at a tertiary care hospital in Riyadh, Saudi Arabia during 2016-2017. The study participants were categorized into 2 groups (an intermittently fasting group during the holy month of Ramadan and a non-fasting group).Results:Out of 108 female patients with CVT, 36.1% were secondary to OCP, of whom 41% participants were fasting. The most affected site was the transverse sinus. Holocephalic headache was more common amongst fasting group (68.8%) compared to non-fasting group (30.4%) (p=0.025). Dehydration (p=0.003) amongst the fasting group and protein S deficiency (p=0.027) in the non-fasting group were identified as the 2 prominent risk factors. Unfractionated heparin was the most common anticoagulant therapies used during the initiation phase for non-fasting (36.4%) and fasting groups (50%).Conclusion:All women who are using OCP should undergo formal written risk assessments for factors of CVT. Our study suggests that the negative effects of OCPs use might outweigh its benefits; thus, it should be prescribed with caution, more so in fasting patients.     

Exposure–effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis

Aims

The aim was to examine relationships between total and unbound mycophenolic acid (MPA) and prednisolone exposure and clinical outcomes in patients with lupus nephritis.

Methods

Six blood samples were drawn pre- and at 1, 2, 4, 6 and 8 h post-dose and total and unbound MPA and prednisolone pre-dose (C₀), maximum concentration (C_max) and area under the concentration–time curve (AUC) were determined using non-compartmental analysis in 25 patients. The analyses evaluated drug exposures in relation to treatment response since starting MPA and drug-related adverse events.

Results

Dose-normalized AUC varied 10-, 8-, 7- and 19-fold for total MPA, unbound MPA, total prednisolone and unbound prednisolone, respectively. Median values (95% CI) of total MPA AUC(0,8 h) (21.5 [15.0, 42.0] vs. 11.2 [4.8, 30.0] mg l^–1 h, P= 0.048) and C_max (11.9 [6.7, 26.3] vs. 6.1 [1.6, 9.2] mg l^–1, P = 0.016) were significantly higher in responders than non-responders. Anaemia was significantly associated with higher total (37.8 [14.1, 77.5] vs. 18.5 [11.7, 32.7] mg l^–1 h, P = 0.038) and unbound MPA AUC(0,12 h) (751 [214, 830] vs. 227 [151, 389] mg l^–1 h, P = 0.004). Unbound prednisolone AUC(0,24 h) was significantly higher in patients with Cushingoid appearance (unbound: 1372 [1242, 1774] vs. 846 [528, 1049] nmol l^–1 h, P = 0.019) than in those without. Poorer treatment response was observed in patients with lowest tertile exposure to both total MPA and prednisolone as compared with patients with middle and higher tertile exposure (17% vs. 74%, P = 0.023).

Conclusions

This study suggests a potential role for therapeutic drug monitoring in individualizing immunosuppressant therapy in patients with lupus nephritis.     

Spiraeamide, new sphingolipid from Spiraea brahuica

Spiraeamide, a new sphingolipid, has been isolated from the ethyl acetate-soluble fraction of the methanolic extract of the whole plant of Spiraea brahuica, along with marrubiin, 19-acetylmarrubenol, and 6-acetylmarruenol. Their structures were elucidated by 1H and 13C NMR spectra, and COSY, NOESY, HMQC, HMBC, EI-MS, and FAB-MS experiments.     

Selenium levels in dilated cardiomyopathy

Thirty-seven dilated cardiomyopathy cases have been studied and compared with 20 normal controls. Serum selenium levels in relation to coronary risk factors were studied. Serum samples were analysed for selenium, total cholesterol, high density lipoprotein(HDL) cholesterol, triglycerides and glucose levels. Smoking, alcohol intake, positive family history, psychosocial tension, obesity, hypercholesterolaemia, hypertriglyceridaemia and hyperglycaemia were found in the following percentages 27%, 8%, 5%, 73%, 41%, 38%, 81%, 46% respectively in dilated cardiomyopathy patients. Low selenium (< 4.5 micrograms/dl) and HDL cholesterol levels and high total cholesterol, triglycerides, low density lipoprotein cholesterol, very low density lipoprotein cholesterol and glucose levels were observed in dilated cardiomyopathy cases compared to controls. The present results support the concept that low selenium levels along with other risk factors play an important role in developing dilated cardiomyopathy.     

Mutagenicity of the bile of dogs with an experimental model of an anomalous arrangement of the pancreaticobiliary duct

To learn the reasons for the high incidence of biliary carcinomain patients with anomalous arrangement of the pancreaticobiliaryduct (APBD) mutagenicity of the bile of APBD-modeled dogs thathad received a dorsal pancreatico-cholecystostomy was assayedby the Ames Salmonella mutation test. The bile from two outof 18 APBD dogs was mutagenic for Salmonella typhimurium strainTA98 under the condition of metabolic activation by rat liverS9 fraction, while the bile from 17 normal dogs was not mutagenic.Furthermore, the bile from five APBD dogs i.p. administered1-nitropyrene (1-NP), which is a typical environmental mutagen,was more mutagenic for strain TA98 than that from 1-NP-treatednormal dogs. The bile from the APBD dogs had very high amylaseactivity, indicating that the bile contained pancreatic juiceas a result of the pancreatico-cholecystostomy. When pancreaticjuice from a normal dog was added to the bile from 1-NP-treatednormal dogs, mutagenicity of the bile increased 1.6- to 2.0-fold.Furthermore, sulfatase increased the mutagenic activity of thebile in the presence of the pancreatic juice. HPLC revealedthat the bile from a 1-NP-treated APBD dog contained mutagenic1-nitro-6/8-hydroxypyrene and 1-nitro-3-hydroxypyrene, whilebile from a 1-NP-treated normal dog did not contain these deconjugatedproducts. The pancreatic juice from a normal dog had very high-glutamyltransferase (GGT) and aminopeptidase activities andlow sulfatase activity, but it had no ß-glucuronidaseactivity. In addition, the bacteria that easily infect the biliaryduct of APBD dogs, Escherichia coli, Klebsiella, Enterobacterand Proteus, had high ß-glucuronidase activity. Inparticular, Klebsiella showed a very high sulfatase activity.These results suggest that pancreatic juice enzymes and bacteriainfecting the biliary duct deconjugate the detoxified mutagensin the bile and induce mutagenicity of the bile from APBD dogsor APBD patients.     

Whole-Exome Sequencing of ETV6/RUNX1 in Four Childhood Acute Lymphoblastic Leukaemia Cases

Background: ETV6/RUNX1 gene fusion is the most frequently seen chromosomal abnormality in childhood acute lymphobastic leukamia (ALL). However, additional genetic changes are known to be required for the development of this type of leukaemia. Therefore, we here aimed to assess the somatic mutational profile of four ALL cases carrying the ETV6/RUNX1 fusion gene using whole-exome sequencing. Methods: DNA was isolated from bone marrow samples using a QIAmp DNA Blood Mini kit and subsequently sequenced using the Illumina MiSeq system. Results: We identified 12,960 to17,601 mutations in each sample, with a total of 16,466 somatic mutations in total. Some 15,533 variants were single nucleotide polymorphisms (SNPs), 129 were substitutions, 415 were insertions and 389 were deletions. When taking into account the coding region and protein impact, 1,875 variants were synonymous and 1,956 were non-synonymous SNPs. Among non-synonymous SNPs, 1,862 were missense, 13 nonsense, 35 frameshifts, 11 nonstop, 3 misstart, 15 splices disrupt and 17 in-frame indels. A total of 86 variants were located in leukaemia-related genes of which 32 variants were located in the coding regions of GLI2, SP140, GATA2, SMAD5, KMT2C, CDH17, CDX2, FLT3, PML and MOV10L1. Conclusions: Detection and identification of secondary genetic alterations are important in identifying new therapeutic targets and developing rationally designed treatment regimens with less toxicity in ALL patients.     

Atypical nuclear apoptosis downstream to caspase-3 activation in ara-C treated CCRF-CEM cells

The necessity of internucleosomal DNA fragmentation for the complete execution of apoptosis is still controversial. While investigating the apoptotic pathway induced by 1-beta-D-arabinofuranosylcytosine (ara-C) in the human T-lymphoblastic leukemia CCRF-CEM (CEM) cells, we could easily retrieve high molecular weight (HMW) DNA fragments with a predominant size of 50 kb. However, under the same circumstances, internucleosomal DNA fragmentation characteristic of apoptosis was undetectable despite estimated heightened caspase-3 activity. Paradoxically, generation of low molecular weight DNA fragments was readily demonstrable by flow cytometric and immunohistochemical evidence in the absence of any detectable DNA ladder formation. These findings present a proof that, within certain contexts, small-sized DNA fragmentation occurring in apoptosis may not necessarily be of the ladder yielding internucleosomal integer multiples' pattern. Our data also add to the evidence that the machinery underlying HMW DNA fragmentation is distinct from that responsible for the internucleosomal one.     

Process, rationale, and interventions of Pakistan's National Action Plan on Chronic Diseases

Most developing countries do not comprehensively address chronic diseases as part of their health agendas because of lack of resources, limited capacity within the health system, and the threat that the institution of national-level programs will weaken local health systems and compete with other health issues. An integrated partnership-based approach, however, could obviate some of these obstacles. In Pakistan, a tripartite public-private partnership was developed among the Ministry of Health, the nongovernmental organization (NGO) Heartfile, and World Health Organization. This was the first time an NGO participated in a national health program; NGOs typically assume a contractual role. The partnership developed a national integrated plan for health promotion and the prevention and control of noncommunicable diseases (NCDs), which as of January 2006 is in the first stage of implementation. This plan, called the National Action Plan on NCD Prevention, Control, and Health Promotion (NAP-NCD), was released on May 12, 2004, and attempts to obviate the challenges associated with addressing chronic diseases in countries with limited resources. By developing an integrated approach to chronic diseases at several levels, capitalizing on the strengths of partnerships, building on existing efforts, and focusing primary health care on chronic disease prevention, the NAP-NCD aims to mitigate the effects of national-level programs on local resources. The impact of the NAP-NCD on population outcomes can only be assessed over time. However, this article details the plan's process, its perceived merits, and its limitations in addition to discussing challenges with its implementation, highlighting the value of such partnerships in facilitating the missions and mandates of participating agencies, and suggesting options for generalizability.     

Safety of pregabalin among hemodialysis patients suffering from uremic pruritus

Objectives: The aim of this study was to assess the safety and probability of adverse events associated with the use of 75 mg pregabalin post hemodialysis (pHD) among patients with UP. Methods: A cross-sectional study done among the hemodialysis patients suffering from uremic pruritus (UP) Aljaber Kidney Center (AJKC), Al-Ahsa, Eastern Province, Saudi Arabia. Assessment for the safety profile of pregabalin was done using Naranjo’s algorithm. A predictive model was developed using binary multiple logistic regression to explore association of patients’ demographics and risk factors with the occurrence of AEs. Throughout statistical significance level was considered significant at 0.05. Key findings: Assessment of safety of pregabalin revealed that somnolence and dizziness were the two frequent adverse events followed by constipation, weight gain and edema. However, it was noticed that female patients aged less than 50 years were found to be at a higher risk in comparison with men. Moreover, those patients having one comorbid complication (i.e. hypertension or diabetes mellitus alone) were at a higher risk of somnolence, weight gain and dry mouth. Conclusion: Naranjo’s quantification for the possibility and probability of adverse events reflect that all the events were probable. Age, gender and comorbid medical conditions are some of the factors that might have clinical association with the occurrence of the AEs.