Contrast enhancement of the cerebrospinal fluid on MRI in two cases of spirochaetal meningitis

We report two patients with meningitis due to spirochaetal infection, both of whom showed diffusely enhancing meninges around the brain and spinal cord. In addition, there was enhancement of the cerebrospinal fluid after intravenous administration of Gd-DTPA. Received: 1 March 1998/Accepted: 21 August 1999     

Low-dose outpatient chemobiotherapy with temozolomide, granulocyte-macrophage colony stimulating factor, interferon-alpha2b, and recombinant interleukin-2 for the treatment of metastatic melanoma.

PURPOSE: The objective of this study was to further investigate the efficacy and safety of low-dose outpatient chemobiotherapy in patients with unresectable metastatic melanoma. PATIENTS AND METHODS: Thirty-one patients with histologically confirmed unresectable measurable metastatic melanoma were enrolled onto an open-label, multicenter phase II study. The treatment regimen consisted of oral temozolomide followed by subcutaneous biotherapy with granulocyte macrophage colony-stimulating factor, interferon-alfa, and recombinant interleukin-2 (rIL-2). RESULTS: Twenty-eight patients (90%) had M1c disease, and 58% had three or more sites of metastasis. Four patients (13%), all with M1c disease, had a complete response, and four patients had a partial response. The median progression-free survival was 4.9 months and the median overall survival was 13.1 months. Two patients (6%) developed CNS metastasis as the first site of disease progression, and 7 (23%) of 30 experienced CNS progression after receiving chemobiotherapy. A total of 112 cycles of therapy were administered. Toxicity occurred in 78% of the cycles and was grade 1 or 2 in the majority of cases and easily managed. Grade 4 toxicity occurred in 3% of the cycles. CONCLUSION: This low-dose chemobiotherapy combination produces clinical responses in patients with metastatic melanoma, even in those with M1c disease, is well tolerated, and allows home dosing. It offers a reasonable alternative to high-dose regimens, such as high-dose biochemotherapy or rIL-2 requiring prolonged periods of hospitalization, or single agent outpatient regimens, such as dacarbazine, which is usually not effective in patients with M1c disease. Furthermore, it may protect against the development of brain metastases.     

Effect of intravenous immune globulin on natural killer cell activity: possible association with autoimmune neutropenia and idiopathic thrombocytopenia

Natural killer cell (NK) activity was assessed in patients before and after treatment with intravenously administered immune globulin (IVIG). In eight patients with hypogammaglobulinemia or agammaglobulinemia receiving 300 mg/kg/dose IVIG every 4 weeks, NK activity was significantly lower after therapy than before. In two patients, one with idiopathic thrombocytopenic purpura and one with autoimmune neutropenia, receiving high doses (2 gm/kg) of IVIG, NK activity was unusually high before therapy. After treatment, NK activity decreased in correlation with the clinical response and elevation of peripheral cell counts. These data show that IVIG diminishes NK activity in vivo and that reduction of NK activity may be associated with clinical improvement in idiopathic thrombocytopenic purpura and autoimmune neutropenia. NK activity of lymphocytes obtained from healthy volunteers was reduced by the same concentrations of maltose or sucrose present in Gamimune or Sandoglobulin, respectively; IVIG preparations, however, were more inhibitory. The diminution of NK activity therefore may be related to two components of IVIG preparations, monomeric IgG and maltose or sucrose.     

Investigation of COVID-19 Outbreak among Wildland Firefighters during Wildfire Response,Colorado, USA, 2020

A COVID-19 outbreak occurred among Cameron Peak Fire responders in Colorado, USA, during August 2020–January 2021. The Cameron Peak Fire was the largest recorded wildfire in Colorado history, lasting August–December 2020. At least 6,123 responders were involved, including 1,260 firefighters in 63 crews who mobilized to the fire camps. A total of 79 COVID-19 cases were identified among responders, and 273 close contacts were quarantined. State and local public health investigated the outbreak and coordinated with wildfire management teams to prevent disease spread. We performed whole-genome sequencing and applied social network analysis to visualize clusters and transmission dynamics. Phylogenetic analysis identified 8 lineages among sequenced specimens, implying multiple introductions. Social network analysis identified spread between and within crews. Strategies such as implementing symptom screening and testing of arriving responders, educating responders about overlapping symptoms of smoke inhalation and COVID-19, improving physical distancing of crews, and encouraging vaccinations are recommended.     

An epitope on class II antigens that is maintained across species barriers and important in immunologic functions

Serological, functional, and chemical analyses of murine class II antigens were performed using a unique monoclonal antibody, 1E4, which was obtained from a rat-mouse hybridoma. 1E4, which is specific for a monomorphic determinant on HLA-DR antigens in humans and a polymorphic determinant on RT1-Da antigens in rats, detected class II antigens on the cells from mice carrying H-2 haplotypes of b, d, p, q, u, v, k, j, r, but not those with f or s haplotypes. Analysis of two-dimensional gel electrophoresis revealed that 1E4 monoclonal antibody recognized at least Ek/b, d, k and Ab, d molecules. 1E4 blocked the T cell proliferative responses to beef insulin and TGAL in B10 and BALB/c mice, as well as proliferative responses to GLT in BALB/c mice and to PPD in C3H/He mice, as had been demonstrated in other species. Furthermore 1E4 inhibited MLR to stimulator cells that expressed Ab, d or Ek/b, k, d molecules. Taken together, these findings indicate that an epitope detected by 1E4 on class II antigens has been well preserved across species barriers. This epitope may play a major role or be closely related to the functional site that is involved in recognition of nominal antigens by T cells.     

Early psychosis in Indonesia: reflections on illness and treatment

Abstract

This paper provides an overview of more than 22?years of research conducted in the central Javanese province of Yogyakarta, Indonesia, by teams of researchers associated with Gadjah Mada University and Harvard University, led by the authors of this essay. This work is placed in the context of the very limited literature on early psychosis and mental health services in Indonesia. It provides an overview of mental health services in Indonesia and of this team’s research trajectory, then addresses four key domains: the cultural phenomenology of early experiences of psychotic illness; patterns of onset, with a particular focus on extremely rapid onset psychoses; patterns of care-seeking for first episode illness; and mental health services and patterns of utilization. It then discusses the importance of rapid onset psychosis for research on early psychosis, and the question of whether collinearity of rapidity of onset and rapidity of care-seeking raises questions about the long-standing finding that a short duration of untreated psychosis leads to better outcomes. It concludes by discussing difficulties of prioritizing early intervention models in settings with very low mental health resources.     

Detection of inadvertent catheter movement into a pulmonary vein during radiofrequency catheter ablation by real-time impedance monitoring

Introduction: During radiofrequency ablation to encircle or isolate the pulmonary veins (PVs), applications of radiofrequency energy within a PV may result in stenosis. The aim of this study was to determine whether monitoring of real-time impedance facilitates detection of inadvertent catheter movement into a PV.
Methods and Results: In 30 consecutive patients (mean age 53 ± 11 years) who underwent a left atrial ablation procedure, the three-dimensional geometry of the left atrium, the PVs, and their ostia were reconstructed using an electroanatomic mapping system. The PV ostia were identified based on venography, changes in electrogram morphology, and manual and fluoroscopic feedback as the catheter was withdrawn from the PV into the left atrium. Real-time impedance was measured at the ostium, inside the PV at approximately 1 and 3 cm from the ostium, in the left atrial appendage, and at the posterior left atrial wall. There was an impedance gradient from the distal PV (127 ± 30 Ω) to the proximal PV (108 ± 15 Ω) to the ostium (98 ± 11 Ω) in each PV (P < 0.01). There was no significant impedance difference between the ostial and left atrial sites. During applications of radiofrequency energy, movement of the ablation catheter into a PV was accurately detected in 80% of the cases (20) when there was an abrupt increase of ≥4 Ω in real-time impedance.
Conclusion: There is a significant impedance gradient from the distal PV to the left atrium. Continuous monitoring of the real-time impedance facilitates detection of inadvertent catheter movement into a PV during applications of radiofrequency energy. (J Cardiovasc Electrophysiol, Vol. 15, pp. 1-5, June 2004)     

Effect of β-amyloid block of the fast-inactivating K+ channel on intracellular Ca2+ and excitability in a modeled neuron

β-Amyloid peptide (Aβ), one of the primary protein components of senile plaques found in Alzheimer disease, is believed to be toxic to neurons by a mechanism that may involve loss of intracellular calcium regulation. We have previously shown that Aβ blocks the fast-inactivating potassium (A) current. In this work, we show, through the use of a mathematical model, that the Aβ-mediated block of the A current could result in increased intracellular calcium levels and increased membrane excitability, both of which have been observed in vitro upon acute exposure to Aβ. Simulation results are compared with experimental data from the literature; the simulations quantitatively capture the observed concentration dependence of the neuronal response and the level of increase in intracellular calcium.