NONSTEROIDAL ANTI-INFLAMMATORY DRUG ASSOCIATE D LOWER GASTROINTESTINAL TOXICITY. J.T. Jacob 1 , A.K. Jaffer 1 ; 1 Cleveland Clinic Foundation, Cleveland, OH (Tracking ID #74333) LEARNING OBJECTIVES: 1) Recognize the lower gastrointestinal (GI) adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs). 2) Examine the differential diagnosis of multiple gastrointestinal ulcers. 3) Implement appropriate testing and treatment of NSAIDinduced lower GI pathology. CASE INFORMATION: An 80-year-old female with coronary artery disease, hypertension, dyslipidemia and osteoarthritis was admitted to the hospital with chest pain and two episodes of syncope. Each episode of syncope was preceded by use of sublingual nitroglycerin. Review of systems was positive for chronic fatigue, but negative for weight loss, nausea, vomiting, abdominal pain or GI blood loss. Medications were metoprolol, omeprazole, hydrochlorothiazide, indomethacin, and gemfibrozil. Exam revealed a BP = 113/60 without orthostasis, a Pulse = 95 and 97% O2 sat. The exam of the abdomen was normal except for guaiac positive stool on rectal exam. A CBC showed a hemoglobin of 8.9 g/dl with a normal MCV and RDW. An iron panel, B12, folate, LDH, bilirubin, and haptoglobin were also normal. A dipyridamole thallium stress test was negative. The syncope was felt to be related to transient hypotension from nitroglycerin in the setting of anemia. She was therefore transfused blood and underwent upper and lower endoscopies. Multiple ulcers were noted in the stomach, terminal ileum, ileocecal valve, transverse colon and descending colon. Biopsies demonstrated acute nonspecific inflammation. Gastrin levels were normal. Indomethacin was discontinued, acetaminophen was initiated and omeprazole continued. She was discharged home in stable condition with a two-month follow up endoscopy. IMPLICATIONS/DISCUSSION: Adverse gastrointestinal (GI) effects of NSAIDs are not limited to the stomach and duodenum. Although these sites are most commonly affected, adverse effects related to the large bowel and the distal small intestine are increasingly being recognized in practice. NSAIDs can cause a variety of pathology in the lower GI tract including erosions, ulcers, diaphragms, strictures, small bowel enteropathy, diverticular bleeding and colitis resembling or exacerbating inflammatory bowel disease (IBD). The pathophysiology of these changes has not been elucidated. Other etiologies of multiple GI ulcers include: viral and bacterial infections, vasculitides, IBD and Zollinger-Ellison syndrome. Treatment consists of discontinuation and avoidance of all NSAIDs. Gastrin levels should be checked to rule out a gastrinoma. A repeat endoscopy in 6±8 weeks is needed to confirm healing otherwise other etiologies need to be considered. An increase in reporting of these adverse effects will lead to a better understanding of NSAID induced lower gastrointestinal toxicity amongst physicians. -old male with a history of DM1, inflammatory bowel disease (IBD) and PG was admitted for ileostomy closure. The patient discontinued his insulin pump the night prior to surgery. The preoperative glucose was 500 and the surgery was canceled. He was well until three weeks prior when his shin lesions started to get worse after minor trauma. Review of systems was otherwise negative. On exam, he appeared lethargic, T = 38.3 8C, Pulse = 145, and BP = 110/50 mmHg. The patient had four necrotic shin and ankle ulcers with exposed bone and tendon. Labs revealed a serum bicarbonate of 9 mg/dl, potassium of 4.6 mg/dl, glucose of 527 mg/dl, anion gap of 26 and elevated serum ketones. A blood gas revealed a pH of 7.24, pCO2 of 17 mmHg, pO2 of 123 mm Hg and HCO3 of 7 mg/dl. Culture of the ulcers grew gram positive and negative bacteria. The patient was treated with intravenous (IV) Insulin, fluids and antibiotics. After the DKA resolved, therapy for PG was begun using infliximab, topical cromolyn, clobetasol and whirlpool therapy. During infliximab infusion the patient developed transient hypotensive and shortness of breath. He was treated with diphenhydamine and hydrocortisone with resolution of his symptoms. He was switched to oral cyclosporine and discharged home. IMPLICATIONS/DISCUSSION: There are two accepted alternatives in the preoperative management of DM1. Patients can hold short-acting insulin on the morning of surgery and take one-half to two-thirds of their normal long-acting insulin dose or omit their morning insulin regimen entirely and be administered regular insulin on arrival to the hospital based on their glucose level. Patients with insulin pumps should continue their pumps at a basal rate until the morning of surgery. PG is an idiopathic dermatosis associated with epidermal and/or dermal inflammation. It is most commonly associated with systemic diseases such as IBD, rheumatoid arthritis and lymphoproliferative disorders. These lesions typically involve the lower extremities and are painful. Treatment is directed at the underlying systemic disease. Systemic steroids were avoided in this patient's case due to concerns for recurrent hyperglycemia. Alternatives include infliximab, dapsone, thalidomide, azathioprine, cyclophosphamide, 6-mercatopurine, tacrolimus and cyclosporine. Adjunctive therapies include antimicrobials, topical cromolyn, clobetasol and whirlpool therapy. female with Crohn's disease on long term TPN presented with shallow breathing, paresthesias involving the extremities and progressive motor weakness over a period of 2 days. Two weeks prior to presentation she was diagnosed with linerelated candidemia; the port was removed and she was treated with intravenous fluconazole. Exam revealed a cachectic female who was afebrile, BP = 110/80, HR = 90, RR=22, O2 sat = 97%. Neurological exam revealed a right facial droop, dysarthria, motor strength was 2/5 in the upper extremities (UE) and 0/5 in the lower extremities (LE) bilaterally. All reflexes were absent. Brain and spine MRI were unremarkable. The CSF cell count and glucose were normal while the protein was elevated. Blood, urine and CSF cultures were negative. The initial vital capacity (VC) was decreased to 0.89 L and the negative inspiratory force (NIF) was unobtainable. EMG revealed features of generalized sensorimotor polyneuropathy with demyelination and axonal loss. Recurrent asymptomatic episodes of non-sustained ventricular tachyarrhythmia were observed on telemetry but cardiac evaluation revealed no structural heart disease. The patient was diagnosed with GBS with cranial nerve involvement, a GBS variant called Miller-Fisher syndrome. Plasmapheresis was instituted and after a couple exchanges improvement was noted in her motor strength, VC and NIF. She was discharged after completing five session of plasmapheresis. 6-weeks post-discharge, her neurological examination was remarkable only for mild residual diplegia. IMPLICATIONS/DISCUSSION: GBS is an acute ascending inflammatory demyelinating polyradiculoneuropathy. The management of GBS requires early recognition because the respiratory muscles can be involved. Elective intubation should be considered when the forced VC falls below 15 mL/kg or when the patient is unable to generate more than 20 cm H2O of maximal NIF. Initial symptoms include parasthesias with rapid progressive muscle weakness and areflexia. The Miller-Fisher syndrome is a variant of GBS in which the cranial nerves are affected. Autonomic dysfunction with cardiac dysrythmias occurs in one half to two thirds of patients. The disease generally has a good prognosis with close cardiopulmonary monitoring. Plasmapheresis and IVIG have been shown to alter the natural history of GBS if treatment is instituted quickly. year old male presented for further workup after suffering a seizure episode on two separate occasions. 10 days prior to his presentation at the university hospital, the patient experienced a witnessed tonic-clonic event and was taken to a local hospital. The patient was admitted to that hospital and found to have a normal CT, MRI, and EEG. While preparing for discharge home, he had another tonic-clonic event which was witnessed by hospital personnel, and he was transferred to the university hospital for further evaluation. He complained of feelings of mild generalized weakness over the past few months as well as some tingling and numbness in his hands and feet. He denied any recent trauma or seizure history. He also denied any chills, fevers, nausea, vomiting, or weight loss. Past medical history was noncontributory. He denied the use of illicit or prescription drugs, tobacco, ethanol, or herbals. On examination, his vital signs were pulse 101, blood pressure 146/90, and temp 35.4C. Physical exam was unremarkable including normal neurological exam. Labs on admission were significant for K of 3.1 meq/L (nl 3.5±5.0), Cl of 96 meq/L (nl 100±110), CO2 33 meq/l (nl 20±32), Ca 9.0 mg/dl (nl 8.5±10.5), and Mg 1.0 meq/l (nl 1.5± 2.4). Records received from the outside hospital showed low Mg and K levels during the time of both wintessed seizures. Patient was repleted with IV Mg and K and placed on phenytoin. Repeat MRI and EEG were negative. The patient continued to have low serum magnesium levels in spite of aggressive IV and PO repletion. 24 hour urine studies revealed a significantly elevated urine magnesium excretion of 25 MEq/24hr (nl 6±10 MEq/24hr), as well as a decreased urine calcium excretion of 94 mg/24hr (nl100±300 mg/24hr). Urine diuretic screen was negative. Renin and aldosterone were both elevated at 15.8 ng/ml/hr (nl 0.2±1.6 ng/ml/hr) and 38.4 ng/dl (nl 1.6±16) respectively. The patient was diagnosed with Gitelman's Syndrome and discharged home on magnesium oxide, amiloride, aldactone and potassium supplements. He suffered no further episodes of seizure activity and his weakness improved. IMPLICATIONS/DISCUSSION: Seizures presenting with normal MRIs and EEGs can present a diagnostic dilemma for internists. This case emphasizes the importance of considering metabolic disorders as a cause of seizures especially in the setting of normal MRIs and EEGs. Gitelman's Syndrome, an autosomal recessive disorder which usually presents in early adulthood, is a rare variant of Bartter's syndrome resulting from defects in renal tubular function. Unlike Bartter's, Gitelman's patients present with hypomagnesemia and hypocalciuria, along with complaints of severe fatigue, cramps, muscle spasms, and polyuria. with progressive failure to thrive. Three exploratory laparotomies over that time for acute abdomen revealed no pathologic diagnosis. PMH includes asthma, G1P1. P.E. reveals a cachectic, female, 4ft. 11in., 36.1 kg. Evidence of hypotelorism, bilateral ptosis, decreased lateral gaze with nystagmus at end gaze. Abdominal exam reveals distended and tympanic epigastrum. Neurological exam reveals normal visual acuity, decreased C.N. 8 bilaterally, strength of proximal muscle groups 4/5 with atrophy, while distal muscle groups 5/5 bilaterally. DTR's brisk through out. Laboratory studies included CBC, basic metabolic panel, thyroid function tests, Vitamin B12, folate, and lactic acid which were normal except hemoglobin 9.9g/dl, low iron saturation 11%, ferritin 51. She underwent EGD which was normal including duodenal biopsies, aspirates and electronmicroscopy of duodenal biopsies. Her esophageal manometry revealed hypotensive LES, gastric emptying scan showed prolonged liquid gastric emptying with T 1/2 = 136 minutes (mean is 90 minutes). SBFT showed slow emptying of barium. In consultation with neurology, work up included urine porphyrin studies that were negative, while MRI of brain showed diffuse leukoencephalopathy. LP was recommended but nondiagnostic. Fatty acid levels were normal. Ophthalmology evaluation revealed retinal pigmented degeneration while audiometry revealed bilateral moderate sensorineural hearing loss. Muscle biopsy would be indicated if genetic testing were not available. Pt. had chromosomal karyotyping, as well as mitochondrial DNA and thymidine phosphorylase levels, which are absent in specific mitochondrial disorders. These confirmed the diagnosis of a mitochondrial disorder, subtype called mitochondrial neurogastrointestinal leukoencephalopathy(MNGIE). IMPLICATIONS/DISCUSSION: Mitochondrial disorders certainly accounts for <0.1% of causes of nausea and vomiting. On review of the patient's history and physical exam she also had salient findings of proximal muscle weakness, hearing and eye abnormalities.