Adverse events in therapeutic apheresis: a single center survey of various therapies

The aim of the study was to review the adverse events associated with various treatment modalities performed in a single apheresis facility. A total of 854 sessions with 10 types of apheresis therapies were performed and 154 (18.0%) adverse events were observed over a four-year period. Of the adverse events, 77 were related to operational problems and another 77 were complications associated with treatment. A transmembranous pressure abnormality constituted more than 80% of the operational problems. Nausea was the most frequent complication, accounting for 19 of the 77 treatment-related events. A total of 26 (16.9%) adverse events occurred in the early stage of the sessions, 40 (26.0%) in the middle stage, and 88 (57.1%) in the late stage. The information in this study can be used to improve the safety and efficacy of apheresis therapy.     

Contribution of nitrergic nerve in canine gingival reactive hyperemia

Reactive hyperemia reflects a compensatory vasodilation response of the local vasculature in ischemic tissue. The purpose of this study is to clarify the mechanism of regulation of this response in gingival circulation by using pharmacological analysis of reactive hyperemia and histochemical analysis of gingival tissue. Application of pressure to the gingiva was used to create temporary ischemia, and gingival blood flow was measured after pressure release. Reactive hyperemia increased in proportion to the duration of pressure. Systemic hemodynamics remained unaffected by the stimulus; therefore, the gingival reactive hyperemia reflected a local adjustment in circulation. Gingival reactive hyperemia was significantly suppressed by nitric oxide (NO) synthase inhibitors, especially the neural NO synthase-selective antagonist 7-nitroindazole, but not by anticholinergic drugs, β-blockers, or antihistaminergic drugs. Moreover, immunohistochemical staining for neural NO synthase and histochemical staining for NADPH diaphorase activity were both positive in the gingival perivascular region. These histochemical and pharmacological analyses show that reactive hyperemia following pressure release is mediated by NO-induced vasodilation. Furthermore, histochemical analysis strongly suggests that NO originates from nitrergic nerves. Therefore, NO may play an important role in the neural regulation of local circulation in gingival tissue ischemia.     

Clinical analysis of HLA-DR-negative non-M3 AML

The type of leukemia was defined as HLA-DR(-) non-M3-AML, when HLA antigens were detected by flow cytometry at an incidence of < 20% of the blast population excluding M3-AML. Out of 109 patients with de novo acute myeloid leukemia, 8 patients had HLA-DR(-) non-AML-M3. According to the French-American-British criteria, 7 patients could be subdivided into 3 patients with M1, 4 patients with M2 and 1 patient with M4. The morphological features of bone marrow aspiration demonstrated no dysplasia and peroxidase stain positivity was noted in over 86% of the blast cells in all patients, the blast cells with fine granularity in 7 patients. The cytogenetic analysis revealed a normal karyotype. There was no expression marker of the blast antigens except CD13, CD14, CD33, CD34 and CD56. All of 7 patients who underwent induction therapy attained complete remission. Overall survival and disease-free survival showed no significant differences between the HLA-DR(-) non- M3-AML group and the HLA-DR(+) AML group.     

Long-term follow-up of transvenous defibrillation leads: high incidence of fracture in coaxial polyurethane lead.

BACKGROUND: As a result of longer follow-up after implantation of cardioverter defibrillators (ICD), fatigue of the leads has become a concern. The aim of this study was to determine the incidence and clinical presentation of ICD lead failures. METHODS AND RESULTS: The study population consisted of 241 patients with 249 ICD leads who underwent implantation of an ICD with a transvenous lead system. After device implantation, the patients were routinely followed up every 4 months. Five lead failures (2.0%) occurred as an oversensing of artifact during the follow-up period (2.6+/-2.1 years); 4 of those 5 patients received inappropriate shocks and 1 case of lead failure was identified in a patient with frequent episodes of non-sustained ventricular fibrillation. In particular, the right ventricular polyurethane transvenous lead in the Medtronic model 6936 failed in 4 (13%) of 31 cases. Percutaneous lead extraction was not available in all cases, so an additional ICD lead was inserted through the same site of the subclavian vein. CONCLUSIONS: Lead failures may occur 5 years after ICD implantation and polyurethane leads have an especially high incidence of failure. However, there were no follow-up parameters observed that predicted lead failures.     

Nutritional assessment of elderly Japanese nursing home residents of differing mobility using anthropometric measurements, biochemical indicators and food intake

Background: Awareness and evaluation of individual nutritional status are required for optimal support of the elderly population. A Japanese Anthropometric Reference Data ( JARD 2001) was established as a new gold standard, however, its utility for very frail elderly with differing mobility and the relationship with biochemical parameters and food intake remains unclear. The purpose of this study was to investigate the possible relationship between nutritional status and mobility deficits in Japanese nursing home residents, and to compare the ability of JARD 2001 to detect malnutrition with other indicators. Methods: In 130 Japanese nursing home residents (26 men, 104 women; mean age 82.2 ± 9.0 years), anthropometric measurements (body mass index, mid‐arm circumference, triceps skinfold thickness and calf circumference), serum markers (albumin, total protein, prealbumin, retinol binding protein, total cholesterol, HDL‐cholesterol, triglyceride, white blood cells, erythrocyte, hemoglobin and lymphocytes) and food intake were assessed. The nutritional indicators were compared among categories according to severity of mobility deficits, and the ability to detect malnutrition was examined in each parameter. Results: The bedridden elderly had significantly lower nutritional indicators, including anthropometric indexes, albumin, HDL‐cholesterol and food intake, compared with other elderly who can move with or without a wheelchair. When protein‐energy malnutrition was defined as below 1.2 g/kg/day protein intake, 36.7% of the residents were considered to have an intake deficiency. The JARD 2001 was better able to identify the deficiency than albumin level in the independent and the chair‐bound, while albumin could detect the malnourished subjects more sensitively than anthropometric measurements in the bedridden. Conclusion: Poor nutritional indicators could relate with mobility deficits among institutionalized Japanese frail elderly. The ability of indicators to detect malnutrition diverged with the severity of mobility deficits. The JARD 2001 criteria should be adopted for the elderly with at least an ability to move about by wheelchair, and appropriate anthropometric reference standards for very frail people must be reconsidered.     

The structure of the avian fast skeletal muscle troponin T gene: seven novel tandem-arranged exons in the exon x region

To elucidate the mechanism that produces enormous molecular diversity in troponin T (TnT) of fast skeletal muscle, we determined the 5-half genomic sequence of the chicken fast muscle TnT gene. The sequence of ca. 16 kb included seven exons (exons 1, 2, 3, 4, w, 5, and 6), which have been reported previously and presumed by sequencing TnT cDNAs. Additionally we found six 15 nt and one 18 nt sequences in the region between exons 5 and 6 (i.e. the exon x region). They were encompassed by consensus splice donor and acceptor sites and preceded by putative branch sites, and designated herein as exons xa to xg. Our result shows that the sequence derived from exons x1, x2, and x3, the exons presumed previously by cDNA sequencing, is actually encoded by the seven exons xa to xg, establishing the precise gene structure in the exon x region. Based on our data, together with that on the 3-half genomic sequence of the quail fast muscle TnT gene, we conclude that the avian fast skeletal muscle TnT gene includes 27 exons, 16 of which are alternatively spliced.     

Pioglitazone,a peroxisome proliferator–activated receptor γ agonist,reduces the progression of experimental osteoarthritis in guinea pigs

Objective

To evaluate the in vivo therapeutic effect of pioglitazone, a peroxisome proliferator–activated receptor γ (PPARγ) agonist, on the development of lesions in a guinea pig model of osteoarthritis (OA), and to determine the influence of pioglitazone on the synthesis of matrix metalloproteinase 13 (MMP‐13) and interleukin‐1β (IL‐1β) in articular cartilage.

Methods

The OA model was created by partial medial meniscectomy of the right knee joint. The guinea pigs were divided into 4 treatment groups: unoperated animals that received no treatment (normal), operated animals (OA guinea pigs) that received placebo, OA guinea pigs that received oral pioglitazone at 2 mg/kg/day, and OA guinea pigs that received oral pioglitazone at 20 mg/kg/day. The animals began receiving medication 1 day after surgery and were killed 4 weeks later. Macroscopic and histologic analyses were performed on the cartilage. The levels of MMP‐13 and IL‐1β in OA cartilage chondrocytes were evaluated by immunohistochemistry.

Results

OA guinea pigs treated with the highest dosages of pioglitazone showed a significant decrease, compared with the OA placebo group, in the surface area (size) and grade (depth) of cartilage macroscopic lesions on the tibial plateaus. The histologic severity of cartilage lesions was also reduced. A significantly higher percentage of chondrocytes in the middle and deep layers stained positive for MMP‐13 and IL‐1β in cartilage from placebo‐treated OA guinea pigs compared with normal controls. Guinea pigs treated with the highest dosage of pioglitazone demonstrated a significant reduction in the levels of both MMP‐13 and IL‐1β in OA cartilage.

Conclusion

This is the first in vivo study demonstrating that a PPARγ agonist, pioglitazone, could reduce the severity of experimental OA. This effect was associated with a reduction in the levels of MMP‐13 and IL‐1β, which are known to play an important role in the pathophysiology of OA lesions.

     

Normal motor learning during pharmacological prevention of Purkinje cell long-term depression

Systemic delivery of (1R-1-benzo thiophen-5-yl-2[2-diethylamino)-ethoxy] ethanol hydrochloride (T-588) prevented long-term depression (LTD) of the parallel fiber (PF)-Purkinje cell (PC) synapse induced by conjunctive climbing fiber and PF stimulation in vivo. However, similar concentrations of T-588 in the brains of behaving mice and rats affected neither motor learning in the rotorod test nor the learning of motor timing during classical conditioning of the eyeblink reflex. Rats given doses of T-588 that prevented PF-PC LTD were as proficient as controls in learning to adapt the timing of their conditioned eyeblink response to a 150- or 350-ms change in the timing of the paradigm. The experiment indicates that PF-PC LTD under control of the climbing fibers is not required for general motor adaptation or the learning of response timing in two common models of motor learning for which the cerebellum has been implicated. Alternative mechanisms for motor timing and possible functions for LTD in protection from excitotoxicity are discussed.