ABSTRACT
INTRODUCTION: This case is a presentation of isolated central nervous system (CNS) Mucormycosis in an immunocompetent patient. This case is unique in its demonstration of isolated CNS involvement while lacking clear evidence elucidating an entry point. CASE PRESENTATION: The patient is a 36-year-old man without a pertinent past medical history, who initially presented with altered mental status and a 5-day history of progressively slurred speech. His social history is significant for intravenous drug use and outdoor pest control work. The patient's head computed tomography (CT) scan without contrast demonstrated the presence of possible bilateral infarcts or masses involving the basal ganglia and periventricular white matter. The patient then progressed to facial diplegia with new onset hemiplegia. High-dose steroids were initiated due to concern for neurosarcoidosis. A lumbar puncture was ordered due to minimal improvement and suggested an inflammatory process. A stereotactic brain biopsy was then performed, demonstrating non-caseating granulomatous inflammation with giant cells. Liposomal amphotericin B was added to cover possible fungal etiology. The pathology report was consistent with an isolated cerebral mucormycosis infection. The etiology remained elusive with clear paranasal sinuses and no cutaneous manifestations. Due to extensive gray matter involvement, the patient was not a candidate for surgery. CONCLUSION: This is a report of mucormycosis in a seemingly immunocompetent patient with either isolated CNS involvement or disseminated mucormycosis without an identifiable source. Although this patient did have two risk factors including intravenous drug use and outdoor working history, his lack of peripheral involvement demonstrates an uncommon presentation.
ABSTRACT
INTRODUCTION: Visceral leishmaniasis, caused by the Leishmania donovani complex, is responsible for over 20 000 deaths per year. This disease often affects the immunocompromised with an increased prevalence in those with human immunodeficiency virus (HIV). The immunocompromised are not only more susceptible to infection, but disseminated disease including gastric leishmaniasis. This is a case of gastric leishmaniasis occurring in a non-endemic region in a patient with comorbid HIV. CASE PRESENTATION: The patient is a 39 year old originally from Central America currently living in Southeast Georgia. His history is significant for HIV, alcohol abuse, tobacco dependency and bone marrow biopsy-proven leishmaniasis. He denied any recent travel. At initial presentation, he had abdominal pain, nausea/vomiting, chills and dysphagia along with leukopenia and thrombocytopenia. Treatment with amphotericin B was initiated for his leishmaniasis as well as highly active antiretroviral therapy (HAART). The patient was discharged home on a 3 month course of amphotericin B with continued HAART therapy. Following resolution of his acute symptoms, six months later, the patient developed acute abdominal pain with nausea prompting presentation to the emergency department. Leishmaniasis was found again following bone marrow biopsy and the patient restarted amphotericin B and HAART. Several years later the patient presented again with similar symptoms, this time with accompanying rectal bleeding. The patient received an esophagogastroduodenoscopy and on gastric mucosal biopsy was found to have gastric leishmaniasis. CONCLUSION: This manuscript highlights the key features of this case, including recognizing leishmaniasis clinically, proving diagnosis through definitive testing and understanding the connection between leishmaniasis and HIV.
ABSTRACT
Intracranial neoplasia is a significant cause of morbidity and mortality in both human and veterinary patients, and is difficult to treat with traditional therapeutic methods. Cisplatin is a platinum (Pt)-containing chemotherapeutic agent approved by the Food and Drug Administration; however, substantial limitations exist for its application in canine brain tumor treatment due to the difficulty in crossing the blood-brain barrier (BBB), development of resistance, and toxicity. A modified Pt(iv)-prodrug of cisplatin, Platin-M, was recently shown to be deliverable to the brain via a biocompatible mitochondria-targeted lipophilic polymeric nanoparticle (NP) that carries the drug across the BBB and to the mitochondria. NP mediated controlled release of Platin-M and subsequent reduction of this prodrug to cisplatin allowed cross-links to be formed with the mitochondrial DNA, which have no nucleotide excision repair system, forcing the overactive cancer cells to undergo apoptosis. Here, we report in vitro effects of targeted Platin-M NPs (T-Platin-M-NPs) in canine glioma and glioblastoma cell lines with results indicating that this targeted NP formulation is more effective than cisplatin. In both the cell lines, T-Platin-M-NP was significantly more efficacious compared to carboplatin, another Pt-based chemotherapy, which is used in the settings of recurrent high-grade glioblastoma. Mitochondrial stress analysis indicated that T-Platin-M-NP is more effective in disrupting the mitochondrial bioenergetics in both the cell types. A 14-day distribution study in healthy adult beagles using a single intravenous injection at 0.5 mg kg(-1) (with respect to Platin-M) of T-Platin-M-NPs showed high levels of Pt accumulation in the brain, with negligible amounts in the other analyzed organs. Safety studies in the beagles monitoring physical, hematological, and serum chemistry evaluations were within the normal limits on days 1, 7, and 14 after injection of either 0.5 mg kg(-1) or 2 mg kg(-1) or 2.2 mg kg(-1) (with respect to Platin-M) of T-Platin-M-NPs. At all doses over the 14-day period, no neurotoxicity was observed based upon periodic neurological examinations and cerebrospinal fluid analysis. These studies demonstrated the translational nature of T-Platin-M-NPs for applications in the treatment of brain tumors.
