Urine Color Change Research Articles

Can Using a Detoxification Kit Result in Bizarre Behavior and Hallucinations?

To the Editor: I read with great interest the study by Mittal et al in which the authors present the case of a 19-year-old cannabis-addicted Asian man who experienced bizarre behavior and hallucinations after using a detoxification kit in a desperate effort to apply for a job. The authors noted the patient’s history of cannabis smoking 2 to 3 times per week for the last year. The patient was treated with lorazepam and haloperidol. They interestingly attributed the patient’s signs and symptoms to the contents of the detoxification kit. Ingredients of the kit used by the patient included riboflavin (vitamin B2), cyanocobalamin (vitamin B12), dandelion, cascara sagrada, turmeric, burdock, milk thistle, guarana extract, green tea, Echinacea purpurea, potassium, proprietary blend, creatine monohydrate, alfalfa leaf, slippery elm bark, reishi mushroom, uva ursi leaf, cayenne pepper, licorice, peppermint leaf, red root, schisandra, and sorbitol. Interestingly, none of the above-mentioned ingredients can result in such a presentation as that exhibited by the patient. Riboflavin and cyanocobalamin have been reported not to have any significant side effects except for an anaphylactoid reaction when given parenterally.2 Dandelion may cause ragweed allergy.3 Cascara sagrada has been reported to cause abdominal pain, allergic rhinitis, immunoglobulin E–mediated asthma, diarrhea, melanosis, steatorrhea, vomiting, change in urine color, fluid and electrolyte abnormalities, and osteomalacia.4 Turmeric has been shown to slow blood clotting.5 Burdock has resulted in diaphoresis and increased perspiration because of its oily ingredient.6 Milk thistle may cause diarrhea, nausea, bloating, and upset stomach.7 Guarana extract contains caffeine, theobromine, and theophylline in varying quantities. Guarana is currently thought to have no adverse effects other than potential caffeine toxicity.8 Echinacea purpurea has been accompanied by nausea, allergic reactions, asthma, skin rashes, trouble in breathing, and dizziness.9 No side effects have been reported for proprietary blend,10 while the reported side effects for creatine monohydrate include gastrointestinal distress; muscle strain, cramp, and tear; flatulence; and renal distress in those with previous history of renal disease.11 Only isolated reports of allergy with alfalfa leaf have been published.12 To date, there is no report of side effects of slippery elm bark.13 The reported side effects of reishi mushroom are dryness of the mouth, stomach upset, nose bleed, and allergy.14 Uva ursi leaf contains arbutin and hydroquinone as well as tannin and may cause nausea and vomiting, insomnia, and irritability.15 Cayenne pepper is prohibited in pregnancy and has resulted in allergy in those allergic to chestnut, banana, kiwi, and avocado.16 Side effects associated with licorice are increased blood pressure, water storage (hence, may worsen the condition of patients with congestive heart failure), hypokalemia, sexual problems in men, and worsening kidney diseases.17 Peppermint leaf is thought to be safe; however, its enteric-coated tablets may cause diarrhea and anal burning.18 Red root and schisandra are thought to be safe.19,20 Finally, sorbitol may induce allergy, blurred vision, chest pain, confusion, diarrhea, nausea, seizure, shortness of breath, thirst, tiredness, and vomiting.21 Although the manufacturers of such commercial compounds may exaggerate their safety, there is another point about this patient that may cause the reader to doubt that the detoxification kit caused his psychosis. As the authors mentioned, the patient’s urine drug screen showed a tetrahydrocannabinol level of 268 ng/mL when he was admitted to the psychiatric ward. How do the authors know that his symptoms were not due to acute cannabis intoxication? Thank you for this interesting study.

Phase I study of enzastaurin and bevacizumab in patients with advanced cancer: safety, efficacy and pharmacokinetics

Summary Purpose Given distinct mechanism of actions of enzastaurin and bevacizumab, preclinical studies suggest enhanced antitumor activity in combination. This phase I study assessed the combination’s safety and efficacy. Patients and methods Six advanced cancer patients could be enrolled in each of 11 cohorts. Patients received an enzastaurin loading dose. Oral enzastaurin (500 mg once daily [QD], 250 mg twice daily [BID], 375 mg BID, 500 mg BID, and 750 mg BID) was escalated in each cohort in combination with bevacizumab dosed at 5 mg/kg every 2 weeks, 10 mg/kg every 2 weeks, or 15 mg/kg every 3 weeks until a dose-limiting toxicity (DLT) occurred in 2 of 6 patients in any cohort. Results Sixty-seven patients (31, ovarian cancer [ovcar]) were evaluable for safety and efficacy. Six treatment-related DLTs occurred: grade 3 fatigue (n = 4), grade 4 cerebral hemorrhage, and grade 3 elevated aspartate transaminase. Common drug-related toxicities included change in color of urine and stool, fatigue, pain, diarrhea, and nausea. The maximum tolerated dose of enzastaurin was 750 mg BID in combination with any tested bevacizumab dose/schedule. Overall response rate was 19.4 % (32.3 % ovcar). Median time to progression was 3.7 months (95 % confidence interval [CI], 2.7–5.5), with 8.3 months (95 % CI, 3.7–11.1) in ovcar. Overall, 35.9 % (50.4 % ovcar) of patients remained without disease progression after 6 months. Conclusion The recommended phase II doses of enzastaurin were 500 mg QD up to 500 mg BID with any tested dose/schedule of bevacizumab. This combination demonstrated encouraging clinical activity, particularly in ovcar.Electronic supplementary materialThe online version of this article (doi:10.1007/s10637-012-9850-6) contains supplementary material, which is available to authorized users.

Abnormal Urine Color

A change in urine color can be distressing for patients and physicians alike. Many of the causes of abnormal urine color are benign effects of medications and foods; however, a change in urine color may be a sign of an underlying pathological condition. The good news is that in many cases the diagnosis can be determined from a thorough history and urinalysis. This article presents many of the conditions physicians may encounter and will help them form a narrow differential diagnosis and treatment plan.

A Phase 1B Dose-Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of FBS0701, a Novel Oral Iron Chelator for the Treatment of Chronic Iron Overload

AbstractAbstract 2057 Background:Iron chelators in current use (parenteral deferoxamine, oral deferasirox and deferiprone) are individually efficacious in many patients with transfusion dependent anemias, but each has liabilities relating to safety, ease of administration, patient acceptance, or narrow therapeutic index. The oral chelator FBS0701 is a polyether derivative of the siderophore-related compound, desazadesferrithiocin, a tri-dentate chelator with high affinity binding and selectivity for Fe(III). Animal studies of FBS0701 demonstrated a 4-fold higher no-observable-adverse-effect level in pre-clinical studies compared to deferasirox suggesting a favorable clinical safety profile with respect to nephrotoxicity. Single dose safety and pharmacokinetic studies in both healthy volunteers and iron overloaded patients have established preliminary data to guide further clinical trials. Objectives:To assess multiple-dose pharmacokinetics, safety, and tolerability of FBS0701 in patients with congenital transfusion-dependent anemias. Methods:This was a multicenter, open-label, dose-escalating, multiple dose study of four dose levels (3, 8, 16 and 32 mg/kg/d) of FBS0701. Sixteen patients with documented transfusional iron overload over the age of seventeen were studied. Each dose cohort consisted of 4 patients. After a washout period, patients were dosed daily for seven days. Patients were clinically evaluated on Days 3, 6, 7, 8, 9, 10 and 15 and then weekly thereafter for three weeks. Assessments included physical exam, clinical pathology and ECG. A standard pharmacokinetic protocol of plasma sampling was performed throughout Day 7 and continuing to Day 10. Urine was collected in three intervals over the 24 hour period following the last dose. Each dose level was separated by a minimum of three weeks to assess safety before escalating to the next dose level. Results:FBS0701 was well tolerated in all dose cohorts. There were no serious adverse events related to the drug. With the exception of a change in urine color that was regarded as without clinical significance, adverse events did not show dose-dependency in frequency or severity. Pharmacokinetic parameters derived from plasma and urine drug levels are shown in the table below. There was no evidence of accumulation after 7 days of dosing. Dose- dependent pharmacokinetics were observed as predicted.Parameter*Dose3 mg/kg/day8mg/kg/day16 mg/kg/day32 mg/kg/dayCmax (ng/mL)5,910 ± 2,298 (4)15,000 ± 4,439 (4)38,225 ± 3,947 (4)68, 250 ± 27,519 (4)Tmax (h)1.31 (4)1.18 (4)1.00 (4)1.49 (4)AUC(0-24) (h×ng/mL)19,476 ± 11,327 (4)44,916 ± 30,751 (4)92,261 ± 36,560 (4)157,577 ± 43,484 (4)ëz(h-1)0.0655 ± 0.0606 (4)0.0424 ± 0.0249 (4)0.0421 ± 0.0246 (4)0.0381 ± 0.0091 (2)t ½ (h)16.2 ± 8.32 (4)20.9 ± 11.3 (4)21.3 ± 11.8 (4)18.7 ± 4.48 (2)CL/F (mL/min)162 ± 85.0 (4)225 ± 142 (4)206 ± 78.4 (4)172 ± 60.1 (4)Vz/F (L)185 ± 84.1 (4)311 ± 137 (4)339 ± 166 (4)214 ± 2.94 (2)Ue(0-24)(mg)66.1 ± 24.0 (4)201 ± 68.1 (4)402 ± 203 (4)641 ± 208 (4)Fe(0-24) (%Dose)44.0 ± 16.0 (4)47.4 ± 13.8 (4)39.2 ± 5.86 (4)43.1 ± 15.8 (4)CLr (mL/min)75.2 ± 46.8 (4)105 ± 62.9 (4)83.2 ± 36.5 (4)73.6 ± 37.8 (4)AUC0–24: area under the plasma concentration versus time, zero time point to 24 hours; Cmax: time to maximum observed plasma concentration; tmax: time to maximum plasma concentration; kel: terminal elimination rate constant; t½: half-life calculated by the equation t½ = 0.693/kel; CL/F: the apparent total plasma clearance of drug after oral administration; Vz/F: the apparent volume of distribution during terminal phase after oral administration; Ue: amount of drug excreted into urine; Fe: the fraction of orally administered drug excreted unchanged in urine; CLr: renal clearance Conclusions:FBS0701, a novel tridentate iron chelator, was well tolerated for 7 days at doses up to 32 mg/kg, the high end of the predicted therapeutic dose range. The compound is of interest because in preclinical animal studies there was no evidence of gastrointestinal toxicity and FBS0701 was less able to cause renal toxicity than deferasirox. The pharmacokinetic parameters suggest good dose proportionality and support once-daily dosing that might provide 24 hour protection from non-transferrin bound iron based on the gradual terminal-phase elimination. FBS0701 warrants Phase 2 safety and efficacy studies in transfusional iron overloaded patients. Disclosures:Rienhoff:Ferrokin, Inc.: Employment, Equity Ownership. Viprakasit:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Ferrokin, Inc.: Research Funding. Tay:Ferrokin, Inc.: Research Funding. Harmatz:Ferrokin, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding. Vichinsky:Novartis: Research Funding. Chirnomas:Novartis: Research Funding. Kwiatkowski:Ferrokin, Inc.: Research Funding. Tapper:Ferrokin, Inc.: Employment. Porter:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Neufeld:Novartis, Inc: Research Funding; Ferrokin, Inc: Research Funding.

A Case of Green Urine after Ingestion of Herbicides

The development of discolored urine may have many possible causes. Here we present the case of a 76-year-old woman who was admitted after ingesting the inorganic herbicides, mefenacet and imazosulfuron. Her urine color changed to green almost immediately. Since the patient had no specific medication or medical history we considered that the most likely cause of the change in urine color was the ingestion of the herbicides. Spectrophotometric analysis of the urine was conducted and a peak was observed in the green area of the wavelength spectrum. These findings show that mefenacet and imazosulfuron should be considered in the differential diagnosis of green discolored urine.

Exertional Rhabdomyolysis

Exertional Rhabdomyolysis

Clinical Features of Cholestatic Hepatitis

Background: Cholestatic hepatitis is failure of bile to reach the duodenum with hepatocellular damage and no demonstable obstruction of the major bile ducts. The prognosis is usually good with recovery in less than 4 weeks after withdrawal of the offending drug. However, a prolonged course lasting over 3 months is possible and, in rare cases, progression to ductopenia with development of a vanishing bile duct syndrome occurs. A differential diagnosis with other causes of Chronic liver disease is needed. Materials and Methods: From January 1991 through January 2000, 14 patients diagnosed as cholestatic hepatitis by liver biopsy were included. The possible causative drug, clinical features, laboratory findings, and progression of cholestatic hepatitis were evaluated. The semiquantitative study of liver lesions was performed by two independent observers. Results: Causes of cholestatic hepatitis are 5 cases of oriental medicine, 3 cases of anti-tuberculosis medication, 1 case of ticlopidine and antibiotics and 4 cases of unknown causes. The clinical features of cholestatic hepatitis were jaundice, itching, urine color change, and general weakness. During 6 to 30 months, LFT of 5 patients showed prolonged elevation. Elevated total cholesterol 250 mg/dL in 6 patients, pheripheral blood eosinophilia in 5 patients, auto-antibody positive in 6 patients were observed respectively. The biopsies showed intralobular bilirubinostasis with a mixed portal inflammatory infiltration. Conclusion: In cholestatic hepatitis, durations of abnormal LFT are variable regardless of causative drugs. If cholestatic hepatitis progresses toward chronic course, viral hepatitis, primary biliary cirrhosis, and autoimmune hepatitis should be differentially diagnosed and sequential liver biopsies are needed.

Assessment of Management Guidelines

A review of 339 treated acute iron ingestions was conducted to define treatment guidelines better. According to the poison center protocol, ingestions of 20-40 mg/kg of elemental iron required only home treatment, and ingestions of greater than or equal to 40 mg/kg required hospital referral. Gastrointestinal symptoms developed in 23% of patients. There were no seriously ill patients. No serious toxicity developed in patients ingesting 40-60 mg/kg. In 199 cases in which the dose ingested was known, the mean dose was 39.5 mg/kg. The peak measured serum iron levels ranged from 12 to 539 micrograms/dl. In 129 cases with serum iron levels reported, increasing serum iron levels were associated with vomiting (p = 0.006). Of 88 patients who received deferoxamine, 14 had urine color change. Urine color change was associated with symptoms (p = 0.005) but not with iron dose or peak serum iron level. The poison center protocol was changed to home management for ingestions of 20-60 mg/kg unless significant symptoms developed and hospital referral for ingestions greater than or equal to 60 mg/kg.

Ultrasound as an Aid in the Diagnosis of Hydrops of the Gallbladder

ACUTE cholecystitis and acute hydrops of the gallbladder present as a surgical emergency. Ultrasonography provides a simple, rapid, and noninvasive procedure, which is helpful in the evaluation and diagnosis of gallbladder disease. A case of acute hydrops of the gallbladder in which cholecystosonography was helpful in its management is presented. Report of a Case A 96-year-old woman was admitted for abdominal pain of one day's duration. The patient experienced crampy abdominal pain in the right upper quadrant but denied nausea or vomiting, alteration in bowel habits, or change in color of stool or urine. The patient had no jaundice, abdominal distention, or fever. She gave a history suggesting mild cholecystitis for 55 years. Tenderness was present in the right upper quadrant and the right costovertebral angle. A complete blood count showed leukocytosis with shift to the left. Hematocrit reading was 40%, and hemoglobin level was 10 gm/100 ml. The patient