The worldwide use of opiates is increasing yet there is little evidence that in long-term, non-cancer patients, they have an efficacious effect on functional outcomes and quality of life measures. Although it seems paradoxical, chronic opiate use may lead to a pro-nociceptive state. Mechanisms for the development of the hyperalgesic state include activation of the opiate bimodal regulatory systems, dynorphin and spinal cord glia. A potential consequence of chronic opiate usage is the development of narcotic bowel syndrome, which is characterized by chronic or intermittent colicky abdominal pain or discomfort that worsens after the narcotic effects of opiates wear off. It is likely that this is an under-recognized diagnosis. We describe here a case of 26-year old female who had visited our institution multiple times with intractable chronic abdominal pain in the context of normal findings on haematological, biochemical, metabolic, endoscopic and radiological investigations. She had been treated with a multitude of opioid agonists with escalating doses. A diagnosis of narcotic bowel syndrome was made. On elective admission her daily analgesic requirements were 150 microg/hr fentanyl, 100 mg oramorph and 400 mg tramadol (equating to 740 mg oral morphine/24 hr). A detoxification regimen was prescribed which included rapid opiate withdrawal couple with the commencement of methadone, lorazepam, clonidine and duloxetine. She was discharged opiate free, with no abdominal pain, 14 days after admission. Clinicians must be aware of narcotic bowel syndrome, which is often erroneously labelled as a functional gastrointestinal disorder, in patients who have been on long-term opiates.
Abdominal Pain ; Analgesics ; Analgesics, Opioid ; Clonidine ; Dynorphins ; Female ; Fentanyl ; Gastrointestinal Diseases ; Gastrointestinal Tract ; Humans ; Lorazepam ; Methadone ; Narcotics ; Neuroglia ; Quality of Life ; Spinal Cord ; Thiophenes ; Tramadol ; Duloxetine Hydrochloride

Introduction: Lowering levels of low-density lipoprotein cholesterol (LDL-C) are proven to reduce cardiovascular risk. However, some individuals experience acute coronary events despite normal LDL-C levels. Recent studies have focused on modifiable lipoprotein targets, such as apolipoprotein B (apo-B) and apolipoprotein A-1 (apo A-1) and lipoprotein (a), as targets for therapy. Apo-B is the primary apolipoprotein of LDL-C representing total number of atherogenic particles. Apolipoprotein A-1 is the major component of HDL complex. This study will determine the prevalence of elevated apo-B and low apo A-1 among adult Filipinos with acute coronary syndrome (ACS). Methods: This is a cross-sectional study involving 95 patients with ACS admitted in a tertiary hospital from November 2015 to May 2016. Levels of apo-B, apoA-1, lipoprotein (a), total cholesterol, triglyceride, LDL-C, and high-density lipoprotein cholesterol (HDL-C) were measured within 24 hours upon admission. Results: Forty-eight (48%) percent of patients was diagnosed with Non ST-Elevation-ACS, 39% with ST-Elevation myocardial infarction (STEMI) and 13% with unstable angina.Thirtytwo (32%) percent were on low- to high-intensity statin treatment. The mean LDL-C, non-HDL-C, and HDL-C levels were 109 mg/dL, 135 mg/dL, and 36.89 mg/dL, respectively. The prevalence of elevated apo-B (mean=103.79 mg/ dL; target:<80 mg/dL) was 82%, while that of low apo A-1 (mean=119 mg/dL; target: >120 mg/dL for males, >140 mg/dL for females) was 63%. Lipoprotein (a) levels are high (mean = 48.51 nmol/L; normal:<35 nmol/L) in 42% of patients. Among those on statin therapy, the mean LDL-C was 85 mg/dl, but the mean apo B and lipoprotein (a) levels were elevated at 87.57 mg/dL and 41 nmol/L, respectively. Conclusion Elevated levels of apo B and lipoprotein (a) and low level of apo A-1 are highly prevalent in patients with ACS. Apo-B and lipoprotein (a) levels are likewise elevated among patients with normal LDL levels.
Acute Coronary Syndrome ; Apolipoproteins

Objective. Several studies showed that genetic factors affect responsiveness to statins among different populations. This study investigated the associations of candidate genetic variants with poor response to statins among Filipinos.

Methods. In this unmatched case-control study, dyslipidemic participants were grouped into statin responders and poor responders based on the degree of reduction in LDL-c from baseline. DNA from blood samples were genotyped and analyzed. The association of candidate variants with statin response was determined using chi-square and logistic regression analysis.

Results. We included 162 adults on statins (30 poor responders as cases, 132 good responders as controls). The following variants are nominally associated with poor response to statin among Filipinos at a per-comparison error rate of 0.05: rs173539 near CETP (OR=3.05, p=0.015), rs1800591 in MTTP (OR=3.07, p=0.021), and rs1558861 near the BUD13-ZPR1-APOA5 region (OR=5.08, p=0.004).

Conclusion. Genetic variants near CETP, MTTP and the BUD13-ZPR1-APOA5 region are associated with poor response to statins among Filipinos. Further study is recommended to test the external validity of the study in the general Filipino population.

Lipids ; Hydroxymethylglutaryl-CoA Reductase Inhibitors

Background. Low levels of high-density lipoprotein cholesterol (HDL-c) is a well-recognized risk factor in the development of cardiovascular diseases. Associated gene variants for low HDL-c have already been demonstrated in various populations. Such associations have yet to be established among Filipinos who reportedly have a much higher prevalence of low HDL-c levels compared to other races.

Objective. To determine the association of selected genetic variants and clinical factors with low HDL-c phenotype in Filipinos.

Methods. An age- and sex-matched case-control study was conducted among adult Filipino participants with serum HDL-c concentration less than 35 mg/dL (n=61) and those with HDL-c levels of more than 40 mg/dL (n=116). Genotyping was done using DNA obtained from blood samples. Candidate variants were correlated with the low HDL-c phenotype using chi-squared test and conditional logistic regression analysis.

Results. Twelve single nucleotide polymorphisms (SNPs) were associated with low HDL-c phenotype among Filipinos with univariate regression analysis. The variant rs1260326 of glucokinase regulator (GCKR) (CT genotype: adjusted OR=5.17; p-value=0.007; TT genotype: adjusted OR=6.28; p-value=0.027) remained associated with low HDL-c phenotype, together with hypertension and elevated body mass index, after multiple regression analysis.

Conclusion. The variant rs1260326 near GCKR is associated with low HDL-c phenotype among Filipinos. Its role in the expression of low HDL-c phenotype should be further investigated prior to the development of possible clinical applications.

Cardiovascular Diseases ; Dyslipidemias ; Genetics ; Polymorphism, Single Nucleotide