Patient-related blood drives

Ten patient-related blood drives were evaluated and compared to five other blood drives. The patient-related blood drives were easier to organize, more fruitful, and more satisfying for the donors and workers. The authors suggest a role for patient-related blood drives in the present recruitment system and discuss how hospitals and blood centers can coordinate their efforts to have this type of blood drive. Finally, it is suggested that patient-related blood drives can increase recruitment, especially in large metropolitan areas that suffer from chronic blood shortages.     

Hepatitis A virus infections associated with clotting factor concentrate in the United States

BACKGROUND: Two cases of hepatitis A among persons exposed to the same lot of solvent/detergent-treated antihemophilic factor VIII concentrate were reported to a surveillance system. An investigation was conducted to find additional cases and determine the source of infection. STUDY DESIGN AND METHODS: A seroprevalence study was conducted among persons with exposure to the suspect lot for serologic evidence of recent infection with hepatitis A virus (HAV). RESULTS: Six cases of recent HAV infection were discovered: four of the patients had been infused with material from the suspect lot of factor VIII, and two had received infusions of factor IX concentrate made from plasma pools common to the suspect factor VIII lot. HAV was identified in one of the plasma pools, in the factor VIII product, and in serum or stool from two factor VIII recipients and one factor IX recipient. The genetics sequence of the virus in the plasma pool, the factor VIII lot, and the factor VIII recipients were identical, while that of the virus in the factor IX recipient differed by a single base. CONCLUSION: These data document the transmission of HAV by a factor VIII concentrate and implicate factor IX products manufactured from a common source-plasma pool.     

Prodromal Herpes Zoster Mimicking Odontalgia - A Diagnostic Challenge

Herpes zoster (shingles) is caused by reactivation of the latent varicella zoster virus which is present due to an earlier varicella infection (chicken-pox). Herpes Zoster is a less common and endemic disease than varicella, although factors causing reactivation are still not well known, but it occurs in older and/or immunocompromised individuals. Involvement of C3, T5, L1, L2 and first division of trigeminal nerve are the most frequently encountered whereas the involvement of second and third division of trigeminal nerve is rarely seen. During the prodromal stage, the only presenting symptom may be odontalgia, which may prove to be a diagnostic challenge for the dentist, since many diseases can cause orofacial pain, and the diagnosis must be properly established before final treatment. Here we present a case of herpes zoster involving the second division of trigeminal nerve masquerading as odontalgia. The difficulties in diagnosis and management are discussed.     

The emerging role of Rab GTPases in the pathogenesis of Parkinson's disease

The identification of pathogenic mutations in Ras analog in brain 39B (RAB39B) and Ras analog in brain 32 (RAB32) that cause Parkinson's disease (PD) has highlighted the emerging role of protein trafficking in disease pathogenesis. Ras analog in brain (Rab) Guanosine triphosphatase (GTPase) function as master regulators of membrane trafficking, including vesicle formation, movement along cytoskeletal networks, and membrane fusion. Recent studies have linked Rab GTPases with α‐synuclein, Leucine‐rich repeat kinase 2, and Vacuolar protein sorting 35, 3 key proteins in PD pathogenesis. In this review, we discuss the various RAB GTPases associated with PD, current progress in the research, and potential future directions. Investigations into the function of RAB GTPases will likely provide significant insight into the etiology of PD and identify novel therapeutic targets for a currently incurable disease. © 2018 International Parkinson and Movement Disorder Society     

Selection of highly responsive T cell receptors by an analysis combining the expression of multiple markers

The clinical success of T cell receptor (TCR) gene–transduced T (TCR-T) cell therapy is expected as one of the next-generation immunotherapies for cancer, in which the selection of TCRs with high functional avidity (high-functional TCRs) is important. One widely used approach to select high-functional TCRs is a comparison of the EC50 values of TCRs, which involves laborious experiments. Therefore, the establishment of a simpler method to select high-functional TCRs is desired. We herein attempted to establish a simple method to select high-functional TCRs based on the expression of T cell activation markers using the mouse T cell line BW5147.3 (BW). We examined relationships between the EC50 values of TCRs in interleukin-2 production and the expression levels of TCR activation markers on BW cells. In TCR-expressing BW cells stimulated with antigenic peptides, the CD69, CD137, and PD-1 expression was differentially induced by various doses of peptides. An analysis of TCRs derived from the tumor-infiltrating lymphocytes of murine melanoma and peripheral blood T cells of hepatocellular carcinoma patients treated with a peptide vaccination revealed that an analysis combining CD69, CD137, and PD-1 expression levels in BW cells stimulated with a single dose of an antigenic peptide selected high-functional TCRs with functional avidity assessed by EC50 values. Our method facilitates the section of high-functional TCRs among tumor-reacting TCRs, which will promote TCR-T cell therapy. The stimulation of BW cells expressing objective TCRs with a single dose of antigenic peptides and analysis combining the expression of CD69, CD137, and PD-1 allows us to select highly responsive TCRs.     

Sedation for Endoscopy

Abstract  In order to examine the investigators' clinical suspicion that Vietnamese patients were more sensitive to the sedative effects of midazolam than were Caucasians, the pharmacokinetics of a single, weight-adjusted intravenous dose of midazolam (0.05 mg/kg) were compared in a group of healthy Caucasian and Vietnamese male volunteers. The Vietnamese group ( n =8) had a significantly lower height, lean body mass and mean weight (59.8±5.5 vs 72.1±8.1 kg, respectively) compared with the Caucasian group ( n =8). No significant differences were found between the Vietnamese and Caucasian groups with regard to distribution half-life of midazolam (8.38±13.1 vs 1.49±0.63 min, respectively), elimination half-life (2.49±1.80 vs 1.48±0.66 h, respectively), clearance (4.93±1.31 vs 5.90±2.12 mL/min per kg, respectively), steady state volume of distribution (0.863±0.497 vs 0.530±0.132 L/kg, respectively) or percentage of unbound drug in plasma (4.89±0.74 vs 4.11±1.08, respectively). This suggests that dosage of midazolam in Vietnamese should be based on total body-weight. Two Vietnamese subjects who were brothers had marked elevation of distribution half-life and initial volume of distribution and lesser elevations in elimination half-life and volume of distribution at steady state. This suggests that the known subgroup of subjects who demonstrate dyshomogeneity in midazolam volume of distribution may be genetically determined.     

Vesiculation of sickle erythrocytes during thermal stress

Since it is not known why sickle RBCs tend to undergo microvesiculation, we have investigated their susceptibility to thermal stress. While normal RBCs start to vesiculate at 49.0 +/- 0 degrees C (n = 14), sickle RBCs begin to vesiculate at 47.9 +/- 0.5 degrees C, with a range of 46.5 to 48.5 degrees C (n = 14). This abnormality is reproduced by treating normal RBCs with phenazine methosulfate (PMS), which stimulates the excess intracellular generation of superoxide characteristic of sickle RBCs. For PMS-treated RBCs, there is a strong correlation between membrane protein thiol oxidation and vesiculation temperature (r = .977, P less than .001). The abnormal vesiculation temperature of both unmanipulated sickle RBCs and PMS-treated RBCs is significantly improved by treatment of the RBCs with dithiothreitol. The most dense sickle RBCs are most prone to vesiculation during thermal stress, and they are the subpopulation having the greatest amount of thiol oxidation. We conclude that the tendency of sickle RBCs to vesiculate during thermal stress is further evidence for functional abnormality of the RBC cytoskeleton due to thiol oxidation.     

Cutaneous T-cell lymphoma

Cutaneous T-cell lymphoma (CTCL) is a neoplasm of helper T cells whose first manifestations usually appear in the skin. The various forms of CTCL are distinguished by both clinical features and histopathology. Early on, the diagnosis may be difficult to establish because of its numerous, and often non-specific, clinical presentations. Further, the pathological findings of early lesions may lack the diagnostic features observed in well-developed or advanced disease. The diagnosis of CTCL must be considered in any patient with a chronic, therapy-resistant condition of the skin. In patients with non-specific histological findings, a high index of suspicion and multiple biopsies may eventually lead to a diagnosis of CTCL. Once the diagnosis of CTCL is established, accurate staging is essential both for its effect on treatment decisions and for its prognostic value. In general, CTCL is a chronic, slowly progressive disease with a long evolution. The development of tumours is a poor prognostic sign, as is erythroderma. The Sezary syndrome is a distinct form of erythrodermic CTCL that is characterized by exfoliative erythroderma, lymphadenopathy, lymphocytosis, intense pruritus, and circulating large, abnormal lymphocytes (Sezary cells). When death does occur, it is most often due to septicemia. Treatment of CTCL must be tailored to the individual patient. The most commonly employed treatment options are photochemotherapy and topical chemotherapy.