Kratom-induced acute liver injury: A case study and the importance of herbal supplement regulation.

Alternative medicine supplements have become the second most common cause of drug-induced liver injury (DILI) in the US. Kratom is a herbal supplement that is popular for its psychotropic and opioid-like activity. It has become increasingly available in western countries, which often have no specific regulations on its use. However, reports of adverse events linked to kratom use have been increasing; it has been implicated in acute liver injury (mostly cholestatic), acute liver failure, organ dysfunction, toxicity, coma, seizures, and death. Herein, we aim to increase healthcare provider and public awareness of the risks posed by kratom and ultimately support increased regulation of its use.

Analysis of dose and duration dependent effects of Allium sativum Linn and other hypocholesterolemic agents exhibited on dyslipidemia in patients with essential hypertension.

Globally, cardiovascular diseases (CVD) are one of the most significant cause of organ failure, mortality and substantial escalation of health care cost. Dyslipidemia and hypertension poses significant risks in cardiovascular diseases and morbidity and mortality can be minimized by altering risks factors. Dyslipidemia is one of the major leading cause of rise of global incidences and socioeconomic burden which necessitates to explore the pharmacological options of significant antilipemic activity with minimal untoward effects at affordable price. Allium Sativum (Garlic) proved medicinally effective in different clinical trials, but further investigations are required to investigate its effects on diabetes, hypertension and dyslipidemia based on variable doses and duration. In this study dose and duration dependent effects of Garlic were evaluated on hypertensive patients with dyslipidemia. Study was randomized, single blind and placebo controlled. Effects of tablets of garlic (KWAI) 300 mg in doses of daily 0.3g, 0.6g, 0.9g, 1.2g and 1.5g for 24 weeks were compared in humans. Each tablet contains 1.3 percent of alliin and 0.6 % of allicin. Results showed remarkable improvements in different serum lipid levels (Cholesterol, Triglycerides, Low density lipoproteins and High density lipoproteins) based on different doses and duration as compared to placebo and standard Lipid-lowering agent simvastatin.

A Rare Case of a Gastric Ulcer Causing Left Gastric Artery Pseudoaneurysm.

Upper gastrointestinal hemorrhage is an uncommon but can be a lethal presentation of a pseudoaneurysm because a rupture is associated with a 40%-80% mortality rate. We report a rare case of left gastric artery pseudoaneurysm secondary to peptic ulcer disease presenting as an upper gastrointestinal hemorrhage.

Unusual Case of Mirizzi Syndrome Presenting as Painless Jaundice.

BACKGROUND Isolated painless jaundice is an uncommon presenting sign for Mirizzi syndrome, which is typically characterized by symptoms of acute or chronic cholecystitis. We report a rare case of Mirizzi syndrome with an acute onset of painless obstructive jaundice. CASE REPORT A 60-year-old man with an unremarkable prior medical history presented with 1 week of jaundice, dark urine, and acholic stools. His laboratory studies revealed a pattern of cholestasis with marked direct hyperbilirubinemia. Ultrasound and magnetic resonance imaging studies demonstrated intrahepatic ductal dilation and cholelithiasis, including a stone within the cystic duct. Endoscopic retrograde cholangiopancreatography with SpyGlass cholangioscopy confirmed the diagnosis of Mirizzi syndrome. CONCLUSIONS An atypical presentation of Mirizzi syndrome should be suspected in the setting of biliary obstruction without pain. The differential diagnosis is broad and includes choledocholithiasis, ascending cholangitis, and hepatobiliary malignancy. Evaluation should include laboratory studies and biliary tract imaging. Noninvasive biliary tract imaging can help exclude malignancy and confirm ductal dilation but is not sensitive for Mirizzi syndrome. Endoscopic retrograde cholangiopancreatography can serve both diagnostic as well as therapeutic purposes via stone extraction and stent placement. SpyGlass cholangioscopy can also augment management in the form of Electrohydraulic lithotripsy. Although therapeutic biliary endoscopy can be very effective, cholecystectomy remains the definitive treatment for Mirizzi syndrome.

Significance of silent ischemia and microalbuminuria in predicting coronary events in asymptomatic patients with type 2 diabetes.

OBJECTIVES: The aim of this study was to investigate the relationships between future coronary heart disease (CHD) events and baseline silent myocardial ischemia (SMI) and microalbuminuria (MA) in subjects with type 2 diabetes (T2D) free from known CHD. BACKGROUND: Coronary heart disease is often asymptomatic in subjects with diabetes. There is limited information on the prognostic value of SMI and MA in this group. METHODS: Eighty-six patients with T2D and no history of CHD were studied (43 with MA individually matched with 43 normoalbuminuric patients; mean [SD] age 62 [+/-7] years, 62 men). Metabolic assessment, three timed overnight urine collections for albumin excretion rate, a treadmill exercise test and ankle brachial index (ABI) were performed at baseline. Patients were followed for 2.8 years. RESULTS: Forty-five (52%) patients had SMI during treadmill testing. At review, there had been 23 coronary (CHD) events in 15 patients. Univariate Cox regression analysis showed that CHD events were significantly related to baseline ABI (p = 0.014), SMI (p = 0.020), MA (p = 0.046), 10-year Framingham CHD risk >30% (p = 0.035) and fibrinogen (p = 0.026). In multivariate analysis, SMI was the strongest independent predictor of CHD events (p = 0.008); risk ratio (95% confidence interval) for SMI: 21 (2 to 204). In the prediction of CHD events, SMI showed higher sensitivity and positive predictive value than MA or Framingham calculated CHD risk. CONCLUSIONS: The presence of baseline SMI and MA are associated with future CHD events in asymptomatic patients with T2D and may be of practical use in risk stratification.

Partial tachyphylaxis to somatostatin (SST) analogues in a patient with acromegaly: the role of SST receptor desensitisation and circulating antibodies to SST analogues.

OBJECTIVE: Somatostatin (SST) analogues are a key option in the management of a variety of conditions, including acromegaly. Tachyphylaxis to SST analogues is not documented in acromegaly. We describe such a phenomenon. DESIGN AND METHODS: A 74-year-old female with acromegaly previously treated with (90)Y implant, external radiotherapy and thrice daily s.c. octreotide had stable GH levels of 19 mU/l. GH progressively rose following switches to lanreotide and depot octreotide as Sandostatin LAR: from 29 to 126 mU/l. Magnetic resonance imaging and (111)In-pentetreotide scanning revealed no tumour growth or alteration in SST receptor (SSTR) status. Tachyphylaxis to SST analogues was considered. Therapy was discontinued and re-introduced in daily 200 microg/24 h increments by continuous s.c. infusion, to a maximum of 1000 microg/24 h, and maintained over 3 weeks with daily, followed by weekly, GH profiles. Competitive (125)I-octreotide radioligand binding assays measured in vitro bio-activity of anti-SST analogue antibodies. In vitro SSTR binding studies utilised SSTR-expressing rat cortex membrane. RESULTS: Median GH fell by 93% from 504 to 39.5 mU/l and rose reproducibly on continued infusion to 120 mU/l. Octreotide withdrawal for 16 h produced a 64% increase in sensitivity. High-affinity IgG anti-lanreotide (IC(50)=187 pmol/l) and anti-octreotide (IC(50)=82 nmol/l) antibody, with no crossreactivity with natural SST, was demonstrated. In vitro inhibition of (125)I-octreotide SSTR binding by anti-SST analogue crossreacting antibody was observed at 1:1 serum dilution. CONCLUSIONS: This is the first report of tachyphylaxis to SST analogues in acromegaly. We believe that the short time course of resensitisation following acute octreotide withdrawal is suggestive of an effect(s) on receptor function or on the receptor signal transduction cascade at sites further downstream, rather than an immune-mediated phenomenon.

Low failure rate of fixed administered activity of 400 MBq 131I with pre-treatment with carbimazole for thyrotoxicosis: the Gateshead Protocol.

BACKGROUND: Thyrotoxicosis is associated with significant morbidity, therefore adequate control of the disease is paramount. The outcome of treatment of thyrotoxicosis using radioiodine shows variable failure rates depending, amongst other things, on the administered activity of radioiodine and the use of anti-thyroid drugs. Thus, management should follow an evidence based protocol, which has a low failure rate. METHOD: We prospectively analysed the outcome of treatment using our Gateshead protocol of a fixed administered activity of radioiodine therapy (400 MBq) given to 201 patients (including 140 with Graves' disease, 48 with toxic multinodular goitre (TMNG) and 13 with toxic nodule) followed up for a median period of 12 months (range, 6-77 months). Carbimazole was discontinued in patients rendered euthyroid 16 days prior to radioiodine. No routine anti-thyroid drugs or thyroxine were given following radioiodine unless hypothyroidism or thyrotoxicosis occurred. RESULTS: Following the Gateshead protocol led to a failure rate of 6.5% (eight females with Graves' disease, four females with TMNG and one female with toxic nodule), 29% euthyroidism and 64% hypothyroidism. The rates of hypothyroidism for women and for men were: in Graves' disease 77% and 79%, in TMNG 29% and 75%, in toxic nodule 42% and 0%, respectively. CONCLUSIONS: Our observations show that withholding an antithyroid drug in excess of just over 2 weeks prior to administering a fixed administered activity of radioiodine in patients with thyrotoxicosis leads to the lowest reported failure rate, irrespective of the underlying cause. One possible mechanism for this could be the avoidance of drug induced radio-resistance.

Inhibition of gastric cancer cell proliferation by resveratrol: role of nitric oxide.

Resveratrol is a dietary phytochemical that has been shown to inhibit proliferation of a number of cell lines, and it behaves as a chemopreventive agent in assays that measure the three stages of carcinogenesis. We tested for its chemopreventive potential against gastric cancer by determining its interaction with signaling mechanisms that contribute to the proliferation of transformed cells. Low levels of exogenous reactive oxygen (H(2)O(2)) stimulated [(3)H]thymidine uptake in human gastric adenocarcinoma SNU-1 cells, whereas resveratrol suppressed both synthesis of DNA and generation of endogenous O(2)(-) but stimulated nitric oxide (NO) synthase (NOS) activity. To address the role of NO in the antioxidant action of resveratrol, we measured the effect of sodium nitroprusside (SNP), an NO donor, on O(2)(-) generation and on [(3)H]thymidine incorporation. SNP inhibited DNA synthesis and suppressed ionomycin-stimulated O(2)(-) generation in a concentration-dependent manner. Our results revealed that the antioxidant action of resveratrol toward gastric adenocarcinoma SNU-1 cells may reside in its ability to stimulate NOS to produce low levels of NO, which, in turn, exert antioxidant action. Resveratrol-induced inhibition of SNU-1 proliferation may be partly dependent on NO formation, and we hypothesize that resveratrol exerts its antiproliferative action by interfering with the action of endogenously produced reactive oxygen. These data are supportive of the action of NO against reactive oxygen and suggest that a resveratrol-rich diet may be chemopreventive against gastric cancer.