Coccidioidal meningitis in non-AIDS patients. A case series at a Mexican neurological referral center.

BACKGROUND: Coccidioidal meningitis is a life-threatening condition and a diagnostic challenge in cases of chronic meningitis. It is associated to severe complications, like basal arachnoiditis, hydrocephalus, and secondary vasculitis. OBJECTIVE: To present a 20-year retrospective clinical series of coccidioidal meningitis cases at a Mexican neurological referral center. RESULTS: The clinical records of 11 patients, predominantly males, were retrieved. Weight loss and night sweats were observed in 64 % of cases. Neurological signs included intracranial hypertension in 91 % of cases, altered alertness and meningeal syndrome in 72 %, and neuropsychiatric symptoms in 64 %. Mean CSF glucose levels were 30 ± 25 mg/dL, and pleocytosis ranged from 0 to 2218 cells/mm3. The diagnosis was confirmed by coccidioidal antigen latex agglutination in 91 % of cases. Radiological findings were hepatomegaly in 55 % of cases and pneumonia in 45 %. Neuroimaging findings included leptomeningitis in 73 % of cases, pachymeningitis in 45 %, and vascular involvement in 91 %. Less common findings included spinal cord lesion and mycotic aneurism, found in 18 % of cases. A molecular coccidioidal DNA test confirmed the predominance of Coccidioides immitis, detected in 64 % of cases. With respect to the clinical outcome, 46 % of patients died. The survivors suffered from sequels like chronic headache, cognitive alterations, and depression. CONCLUSIONS: Coccidioidal meningitis is an entity with high mortality rates. More than one half of patients suffered disseminated disease. Although meningeal signs are not frequent in chronic meningitis, more than two-thirds of our patients showed mild nuchal rigidity. In addition, cerebral and cerebellar volume loss, associated with cognitive impairment and depression, was often observed in surviving patients during the clinical-radiological follow-up.

Deficiency in STAT1 Signaling Predisposes Gut Inflammation and Prompts Colorectal Cancer Development.

Signal transducer and activator of transcription 1 (STAT1) is part of the Janus kinase (JAK/STAT) signaling pathway that controls critical events in intestinal immune function related to innate and adaptive immunity. Recent studies have implicated STAT1 in tumor⁻stroma interactions, and its expression and activity are perturbed during colon cancer. However, the role of STAT1 during the initiation of inflammation-associated cancer is not clearly understood. To determine the role of STAT1 in colitis-associated colorectal cancer (CAC), we analyzed the tumor development and kinetics of cell recruitment in wild-type WT or STAT1-/- mice treated with azoxymethane (AOM) and dextran sodium sulfate (DSS). Following CAC induction, STAT1-/- mice displayed an accelerated appearance of inflammation and tumor formation, and increased damage and scores on the disease activity index (DAI) as early as 20 days after AOM-DSS exposure compared to their WT counterparts. STAT1-/- mice showed elevated colonic epithelial cell proliferation in early stages of injury-induced tumor formation and decreased apoptosis in advanced tumors with over-expression of the anti-apoptotic protein Bcl2 at the colon. STAT1-/- mice showed increased accumulation of Ly6G⁺Ly6C-CD11b⁺ cells in the spleen at 20 days of CAC development with concomitant increases in the production of IL-17A, IL-17F, and IL-22 cytokines compared to WT mice. Our findings suggest that STAT1 plays a role as a tumor suppressor molecule in inflammation-associated carcinogenesis, particularly during the very early stages of CAC initiation, modulating immune responses as well as controlling mechanisms such as apoptosis and cell proliferation.

A New Method to Quantify Ifosfamide Blood Levels Using Dried Blood Spots and UPLC-MS/MS in Paediatric Patients with Embryonic Solid Tumours.

Ifosfamide blood concentrations are necessary to monitor its therapeutic response, avoiding any adverse effect. We developed and validated an analytical method by UPLC-MS/MS to quantify ifosfamide in dried blood spots (DBS). Blood samples were collected on Whatman 903® filter paper cards. Five 3 mm disks were punched out from each dried blood spot. Acetonitrile and ethyl acetate were used for drug extraction. Chromatographic separation was carried out in an Acquity UPLC equipment with a BEH-C18 column, 2.1 x 100 mm, 1.7 µm (Waters®). The mobile phase consisted in 5 mM ammonium formate and methanol:acetonitrile (40:48:12 v/v/v) at 0.2 mL/min. LC-MS/MS detection was done by ESI+ and multiple reaction mode monitoring, ionic transitions were m/z1+ 260.99 > 91.63 for ifosfamide and 261.00 > 139.90 for cyclophosphamide (internal standard). This method was linear within a 100-10000 ng/mL range and it was accurate, precise and selective. Ifosfamide samples in DBS were stable for up to 52 days at -80°C. The procedure was tested in 14 patients, ages 1 month to 17 years (9 males and 5 females), with embryonic tumours treated with ifosfamide, alone or combined, at a public tertiary referral hospital. Ifosfamide blood levels ranged from 11.1 to 39.7 µmol/L at 12 hours after the last infusion, while 24-hour levels ranged from 0.7-19.7 µmol/L. The median at 12 hours was 19.5 µmol/L (Q25 14.4-Q75 29.0) and 3.8 µmol/L (Q25 1.5-Q75 9.9) at 24 hours, p<0.001. This method is feasible to determine ifosfamide plasma levels in paediatric patients.

Chronic stress induces structural alterations in splenic lymphoid tissue that are associated with changes in corticosterone levels in wistar-kyoto rats.

Major depressive disorder patients present chronic stress and decreased immunity. The Wistar-Kyoto rat (WKY) is a strain in which the hypothalamic-pituitary-adrenal axis is overactivated. To determine whether chronic stress induces changes in corticosterone levels and splenic lymphoid tissue, 9-week-old male rats were subject to restraint stress (3 h daily), chemical stress (hydrocortisone treatment, 50 mg/Kg weight), mixed stress (restraint plus hydrocortisone), or control treatment (without stress) for 1, 4, and 7 weeks. The serum corticosterone levels by RIA and spleens morphology were analyzed. Corticosterone levels as did the structure, size of the follicles and morphology of the parenchyma (increase in red pulp) in the spleen, varied depending on time and type of stressor. These changes indicate that chronic stress alters the immune response in the spleen in WKY rats by inducing morphological changes, explaining in part the impaired immunity that develops in organisms that are exposed to chronic stress.

Choroid plexus acinar adenoma: a case report.

Mucus-secreting adenomas or acinar adenoma of the choroid plexus are very rare. We report the case of a 79-year-old male with a 3-year history of occipital headaches with vomiting, ataxia and cerebellar signs. He was first seen due to difficulty while walking. He was admitted to the hospital with significant tumor expansion and clinical deterioration. CT and MRI revealed obstructive hydrocephalus secondary to a large fourth ventricular cyst mass, which enhanced markedly on contrast administration. Pathological findings were consistent with an acinar choroid plexus adenoma. The tumor was attached to the ependymal lining and was strongly adhered to the walls and floor of the IV ventricle. Post-operative bleeding complicated partial removal of this tumor. The patient died 6 h after surgery.