A Fatal Case of Primary Amoebic Meningoencephalitis from Recreational Waters.

BACKGROUND: Naegleria Fowleri is a single-cell, thermophilic amphizoid amoeba, and a rare known causative agent for primary amoebic meningoencephalitis with >97% mortality rate. The amoeba resides in freshwater lakes and ponds but can also survive in inadequately chlorinated pools and recreational waters. The mode of infection includes activities such as diving or jumping into freshwater or submerging the head under the water. Although most commonly seen in the southern United States, it is essential to keep this clinical suspicion in mind regardless of geography, as presenting symptoms can be very similar to classic bacterial meningitis. Case Summary. We report the first-ever case in the state of New Jersey of a 29-year-old male presented after a visit to a recreational water park in Texas five days before his presentation with altered mental status. In ICU, his ICP remained refractory to multiple therapies, including antibiotics and antivirals, external ventriculostomy drain, hypertonic saline, pentobarbital-induced coma, and bilateral hemicraniectomies. The CSF analysis revealed trophozoites indicating a protozoan infection, which we diagnosed in the neurocritical unit, and the patient was then immediately started with treatment that included amphotericin B, rifampin, azithromycin, and fluconazole. This suspicion was promptly confirmed by the Center for Disease Control (CDC). Unfortunately, despite all the aggressive intervention by the multidisciplinary team, the patient did not survive. CONCLUSION: As per the CDC, only four people out of 143 known infected individuals in the United States from 1962 to 2017 have survived. Symptoms start with a median of 5 days after exposure to contaminated water. Given the rarity of this case and its very high mortality rate, it is crucial to diagnose primary amoebic meningoencephalitis accurately as its presentation can mimic bacterial meningitis. It is vital to obtain a careful and thorough history, as it can aid in prompt diagnosis and treatment.

A Rare Case of Intracranial Nongerminomatous Germ Cell Tumor in a 21-Year-Old Romanian Male.

Extragonadal germ cell tumors are a rare entity that is more prevalent in infants and young children, with preference to midline structures. The category of intracranial germ cell tumors is divided into pure germ cell tumors (GCTs) versus nongerminomatous germ cell tumors (NGGCTs). They are usually present in the second decade of life with a male preponderance. We present here a rare case of intracranial NGGCT in a 21-year-old Romanian male, who presented with complaints of emesis, ataxic gait, and diplopia. A computed tomography scan of the head in the emergency department revealed a pineal/suprapineal mass along with obstructive hydrocephalus and dilated lateral and third ventricles without any bleeding. MRI of the cervical, thoracic, and lumbar spine showed no evidence of leptomeningeal metastasis. The patient had elevated serum markers of beta-hCG and AFP, which pointed towards a diagnosis of nongerm cell tumor, as in pure GCTs, these markers are normal. To relieve the obstruction from the mass effect, the patient had an endoscopic third ventriculostomy (EVT). However, after the procedure, he developed central diabetes insipidus as a complication with a triphasic response. Biopsy of the mass revealed atypical cells with granular architecture and atypical glands with positive immune histological markers for NGGCT. These findings supported the diagnosis of mixed germ cell tumor with yolk sac carcinoma and seminoma components. Patient's transient central diabetes resolved with normalization in his urine output. He was eventually stabilized and returned to Romania for further management. In summary, intracranial germ cell tumors are rare brain tumors that should be distinguished based on histology and tumor markers as they will help in the guidance of therapy. An initial evaluation with neuroimaging, tumor markers, cytology from CSF, and biopsy is a must to distinguish further treatment and prognosis.

Behcet's disease in acquired immune deficiency syndrome.

HIV/AIDS patients often present with orogenital ulcers. In the immunocompromised patient diagnosis of these ulcers pose a challenge, as there is a myriad of etiologies. We present a case of an HIV/AIDS patient with recurrent orogenital aphthosis that was confirmed to have concomitant diagnosis of Behcet's disease. Proper awareness of the causes of these ulcers is essential for prompt and effective treatment. While rare causes may be at the bottom of a differential list in an immunocompetent host, when HIV/AIDS is involved these rare causes often percolate to the top.

The first documented case of hemorrhagic stroke caused by Group B streptococcal meningitis.

We report the case of a 47 year-old female with Streptococcus agalactiae (Group B beta-hemolytic streptococcus) meningitis complicated by hemorrhagic stroke. The patient presented to the emergency department with altered mental status, agitation, confusion, respiratory distress and fever of one-day duration. Labs showed left shift leukocytosis. CSF exhibited a high white blood cell count with a predominant population of polymononuclear cells, high glucose and protein concentration. CSF cultures grew S. agalactiae. Despite appropriate antimicrobial treatment, her mental status did not improve and head CT showed two hemorrhages, diffuse cerebral edema and a right to left midline shift. After completing the course of her therapy, her mental status improved and the patient was discharged.

GPCR somatostatin receptor extracellular loop 2 is a key ectodomain for making subtype-selective antibodies with agonist-like activities in the pancreatic neuroendocrine tumor BON cell line.

OBJECTIVES: The extracellular loop 2 (ECL2) ectodomain of the G protein-coupled receptor class A is thought to function like an inactivation "lid." We created polyclonal somatostatin receptor ECL2 (anti-SSTR ECL2) antibodies to target this lid and to examine if these antibodies can selectively activate the SSTR. METHODS: Western blots and live-cell immunofluorescence microscopy determined anti-SSTR ECL2 antibody receptor binding selectivity. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay (MTS assay) and cell cycle assay (fluorescence-activated cell sorting) checked for antibody effect on antiproliferation. Nexin assay examined the antibody's ability to induce apoptosis. LANCE cAMP kit (Perkin Elmer) detected antibody-dependent cAMP decrease. Enzyme-linked immunosorbent assay measured antibody effect on suppressing serotonin secretion. Ligand-receptor binding interference assay with the fluorescent somatostatin (FAM-SST) was used to examine antibody interference to SST-SSTR binding. RESULTS: Anti-SSTR ECL2 antibodies are SSTR subtype selective and agonist-like, and they suppress cell proliferation via cell cycle arrest and apoptosis. In addition, these antibodies decrease cAMP production and inhibit serotonin secretion. Interestingly, these antibodies do not interfere with SST-SSTR binding. CONCLUSIONS: The ECL2 is an important ectodomain for G protein-coupled receptor activation and required for ligand binding selectivity. The anti-SSTR2, anti-SSTR3, and anti-SSTR5 ECL2 antibodies independently inhibited BON proliferation and decreased hormone secretion. Unlike octreotide, our antibodies do not interfere with SST-SSTR binding.

The effect of transforming growth factor beta on human neuroendocrine tumor BON cell proliferation and differentiation is mediated through somatostatin signaling.

The dual effect of the ubiquitous inflammatory cytokine transforming growth factor beta1 (TGF beta) on cellular proliferation and tumor metastasis is intriguing but complex. In epithelial cell- and neural cell-derived tumors, TGF beta serves as a growth inhibitor at the beginning of tumor development but later becomes a growth accelerator for transformed tumors. The somatostatin (SST) signaling pathway is a well-established antiproliferation signal, and in this report, we explore the interplay between the SST and TGF beta signaling pathways in the human neuroendocrine tumor cell line BON. We defined the SST signaling pathway as a determinant for neuroendocrine tumor BON cells in responding to TGF beta as a growth inhibitor. We also determined that TGF beta induces the production of SST and potentially activates the negative growth autocrine loop of SST, which leads to the downstream induction of multiple growth inhibitory effectors: protein tyrosine phosphatases (i.e., SHPTP1 and SHPTP2), p21(Waf1/Cip1), and p27(Kip1). Concurrently, TGF beta down-regulates the growth accelerator c-Myc protein and, collectively, they establish a firm antiproliferation effect on BON cells. Additionally, any disruption in the activation of either the TGF beta or SST signaling pathway in BON leads to "reversible" neuroendocrine-mesenchymal transition, which is characterized by the loss of neuroendocrine markers (i.e., chromogranin A and PGP 9.5), as well as the altered expression of mesenchymal proteins (i.e., elevated vimentin and Twist and decreased E-cadherin), which has previously been associated with elevated metastatic potential. In summary, TGF beta-dependent growth inhibition and differentiation is mediated by the SST signaling pathway. Therefore, any disruption of this TGF beta-SST connection allows BON cells to respond to TGF beta as a growth accelerator instead of a growth suppressor. This model can potentially apply to other cell types that exhibit a similar interaction of these pathways.