- Severe Plasmodium falciparum Malaria Treated With Investigational Artesunate in the United States. [Journal Article]
- JPJ Pharm Pract 2018 Jan 01; :897190018782367
- CONCLUSIONS: A 40-year-old Nigerian male was admitted to the medical intensive care unit for the treatment of severe malaria. The patient presented with the classic malaria paroxysm and altered mental status and was in acute renal failure. A blood parasite, thick and thin smear was performed revealing positive ring forms on smear which are characteristic of Plasmodium falciparum, with an estimated parasitemia of 2%. Per the Centers for Disease Control and Prevention (CDC) guidelines, the recommended treatment for severe malaria is with IV quinidine, the only Food and Drug Administration (FDA)-approved medication available for the treatment of severe malaria in the United States. However, quinidine was not immediately available, including from surrounding hospitals. As a result, the infectious diseases physician and pharmacist decided to contact the CDC to initiate the process for obtaining IV artesunate, an investigational drug only available via a FDA-approved Investigational New Drug (IND) protocol. Artesunate was flown into Houston later that night, and this drug was administered successfully to the patient. Patient responded to treatment and was discharged from the hospital on day 4.A patient with severe falciparum malaria was successfully treated with investigational artesunate procured from the CDC.
- Rapid and effective response of the R222Q SCN5A to quinidine treatment in a patient with Purkinje-related ventricular arrhythmia and familial dilated cardiomyopathy: a case report. [Journal Article]
- BMBMC Med Genet 2018 Jun 05; 19(1):94
- CONCLUSIONS: Patients with familial DCM and Purkinje-related ventricular arrhythmias should be offered genetic screening. The quinidine treatment for the SCN5A R222Q mutation can be life saving for patients.
- Imaging Peptide and Protein Chirality via Amino Acid Analysis by Chiral × Chiral Two-Dimensional Correlation Liquid Chromatography. [Journal Article]
- ACAnal Chem 2018 Jun 15
- The present contribution illustrates the utilization of a chiral × chiral two-dimensional liquid chromatography (2DLC) setup with tert-butylcarbamoyl quinine chiral stationary phase (CSP) in the firs...
The present contribution illustrates the utilization of a chiral × chiral two-dimensional liquid chromatography (2DLC) setup with tert-butylcarbamoyl quinine chiral stationary phase (CSP) in the first dimension (1D) and tert-butylcarbamoyl quinidine CSP in the second dimension (2D) to analyze FMOC-derivatized d and l amino acids from peptide hydrolysates. Hereby, in the 1D and 2D chiral separation dimensions factors such as selector and immobilization chemistry of the CSPs, mobile phase, temperature, column hardware dimensions, stationary phase supports, particle type and packing were identical. Orthogonality between 1D and 2D CSPs was solely based on their stereochemistry, i.e. their opposite configurations in two chiral centers of the selector molecules, which results in inversion of enantiomer elution orders in the two dimensions. Using Coreshell CSPs for fast chromatography allowed 2D-flow rates which were 60 times faster than the 1D-flow rates to enable online comprehensive two-dimensional chromatography (LC × LC). Due to very similar chemoselectivity, yet opposite elution orders of corresponding enantiomers in 1D and 2D, characteristic 2D-elution patterns for achiral and chiral components can be generated. Peaks of achiral components and impurities are lined up on the diagonal line in the 2D separation space (contour plot) and thereby removed from the chromatographic space of the target enantiomers avoiding overlaps with potential interferences. Corresponding enantiomers provide cross peaks on the 2D chromatogram. Moreover, enantioselectivity of both single CSPs is combined to result in an enhanced overall 2D enantioselectivity. The concept is illustrated for the therapeutic peptides gramicidin and bacitracin. Since all amino acids give a consistent elution order as FMOC-derivatives, all enantiomers of the same configuration are either above or below the diagonal line allowing straightforward imaging of the configuration of the amino acids in peptides by the 2D chromatogram.
- DKA-induced Brugada phenocopy mimicking STEMI. [Journal Article]
- HAHeart Asia 2018; 10(2):e011027
- A 47-year-old Caucasian woman with type 1 diabetes presented with epigastric pain and vomiting. She had not been adherent with her diet and insulin therapy for the past 3 weeks. She never had a perso...
A 47-year-old Caucasian woman with type 1 diabetes presented with epigastric pain and vomiting. She had not been adherent with her diet and insulin therapy for the past 3 weeks. She never had a personal or family history of arrhythmia-related symptoms, ventricular tachycardia or fibrillation (VT/VF) or premature sudden cardiac death (SCD). Examination revealed dry mucosa, tachycardia and epigastric tenderness to palpation. Her ECG showed ST elevations (V1-V3) with associated T wave inversions (figure 1A). A baseline ECG 1 year ago had no abnormalities. Serial troponin I and T were negative, but Creatinine Kinase MB (CKMB) was elevated. Her biochemistry test showed sodium of 118 mM, potassium of 6.7 mM, bicarbonate of 4 mM, anion gap of 40, glucose of 985 mM and beta hydroxyl-butyrate of >45.0 mg/dL. Cardiac catheterisation revealed normal anatomy with all vessels widely patent; left ventricular end diastolic pressure (LVEDP) was 1 mm Hg. With treatment, diabetic ketoacidosis (DKA) resolved after 8 hours and repeat ECG showed all changes had resolved (figure 1B). She was monitored on telemetry without any VT/VF episodes. Serial ECGs were done with resolution of changes. She had no positive studies for inducible VT. The rest of her admission was uneventful.Figure 1(A) ECG on presentation. (B) ECG 8 hours after admission.
- Quinidine-associated skin discoloration in KCNT1-associated pediatric epilepsy. [Journal Article]
- NeurNeurology 2018 Jun 05; 90(23):1084
- Author response: Quinidine-associated skin discoloration in KCNT1-associated pediatric epilepsy. [Journal Article]
- NeurNeurology 2018 Jun 05; 90(23):1083
- Reader response: Quinidine-associated skin discoloration in KCNT1-associated pediatric epilepsy. [Journal Article]
- NeurNeurology 2018 Jun 05; 90(23):1083
- Editors' note: Quinidine-associated skin discoloration in KCNT1-associated pediatric epilepsy. [Journal Article]
- NeurNeurology 2018 Jun 05; 90(23):1083
- Intestinal permeability determinants of norfloxacin in Ussing chamber model. [Journal Article]
- EJEur J Pharm Sci 2018 May 31; 121:236-242
- Recently, many efforts are taken to identify the intestinal uptake and efflux transporters since they are responsible for the absorption of many drugs as their interactions. Norfloxacin (NFX) is a fl...
Recently, many efforts are taken to identify the intestinal uptake and efflux transporters since they are responsible for the absorption of many drugs as their interactions. Norfloxacin (NFX) is a fluoroquinolone that presents low solubility and low permeability, and as a consequence, low bioavailability. In this context, the aim of this study is evaluate for the first time the intestinal permeability mechanisms of NFX by Ussing chamber model. The low permeation of NFX at low temperature, where the efflux pumps are not active, reveals that NFX permeation is transporter-dependent. The permeation study at different level of intestine demonstrated that NFX passage is in the decrescent order: ileum > jejunum > duodenum > colon, probably attributed to transporters that are expressed differently along the intestinal tract. NFX intestinal flow was evaluated in the presence of many inhibitors and substrates to identify the uptake and efflux transporters implicate in NFX permeability mechanism. It could be observed that BCRP and MRPs are involved in the NFX efflux and PEPT1, PMAT and OCT in the NFX uptake transport. Furthermore, this work revealed that NFX has itself an affinity for OCTN and OATP, demonstrating that NFX could inhibit these transporters and influence the absorption of other drugs. The updated description of NFX intestinal permeability factors could contribute to the development of rational pharmaceutical formulations that could circumvent the efflux problems and consequently improve NFX biopharmaceutical properties and avoid drug-drug interactions.
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- Severe Babesia microti infection presenting as multiorgan failure in an immunocompetent host. [Journal Article]
- BCBMJ Case Rep 2018 May 30; 2018
- A previously healthy 67-year-old farmer presented to an outside hospital after a 2-week history of non-specific respiratory symptoms. A certain diagnosis was not initially apparent, and the patient w...
A previously healthy 67-year-old farmer presented to an outside hospital after a 2-week history of non-specific respiratory symptoms. A certain diagnosis was not initially apparent, and the patient was discharged home on a regimen for presumed chronic obstructive pulmonary disease exacerbation. He re-presented to the emergency department with shock and hypoxaemic respiratory failure requiring prompt intubation and fluid resuscitation. He was then transferred to our institution due to multiorgan failure. On arrival, the patient demonstrated refractory shock and worsening acute kidney injury, severe anaemia and thrombocytopaenia. The peripheral smear revealed absence of microangiopathic haemolytic anaemia. A closer review of the smear displayed red blood cell inclusion bodies consistent with babesiosis. The patient was started on clindamycin and loaded with intravenous quinidine, and subsequently transitioned to oral quinine. A red cell exchange transfusion was pursued with improvement of the parasite load. The patient was discharged home on clindamycin/quinine and scheduled for outpatient intermittent haemodialysis.