Spatial gradients of cytosolic calcium concentration in neurones during paradoxical activation by calcium

PURPOSE: To assess long-term survival following cladribine salvage treatment for previously treated patients with chronic lymphocytic leukemia. PATIENTS AND METHODS: Fifty-two patients aged 39-84 years with previously treated CLL received cladribine 0.12 mg/kg/day in 2-hour infusions for 5 days in monthly courses. Two-thirds were refractory to previous therapy, and 8 had prior fludarabine. RESULTS: Sixteen (31%) patients achieved complete response (CR) and 14 (27%) partial remission (PR) according to consensus criteria. Response correlated with clinical stage, number of previous treatment regimes, blood lymphocyte count, and lymphocyte halflife following the first cladribine course. Toxicity included pneumonia (n = 9), herpes zoster (n = 7), and septicemia (n = 2). Four patients in CR underwent high-dose chemotherapy with autologous blood stem cell support, and 2 remain in CR 48 and 60 months from start of cladribine, and 2 had relapse at 42 and 48 months, respectively. Median progression-free survival (Kaplan-Meier analysis) for CR patients was 23 months from start of cladribine treatment, and for PR patients 16 months. The projected overall survival was 80% at 3 years for CR patients, and the median survival 28 months for PR patients and 4 months for non-responding patients. CONCLUSIONS: Our previous finding of durable CRs from cladribine in advanced CLL is thus confirmed in a larger patient material, and follow-up indicate that long-term survival may be achieved.     

Asbestos-related pericardial thickening detected by magnetic resonance imaging

Magnetic resonance imaging was performed in four male asbestos workers in whom the chest radiograph revealed pleural but not pulmonary or pericardial disease. Patients underwent thoracic multislice spin echo imaging, with measurement of left and right ventricular volumes at end-diastole and end-systole, and a study of the flow in the superior vena cava as an indirect measure to the filling of the right ventricle. Patients also underwent respiratory function tests and high-resolution computed tomography (HRCT). Magnetic resonance, but not HRCT, showed pericardial thickening in two patients. Magnetic resonance demonstrated reduced diastolic flow in the superior vena cava in one patient, reflecting impaired right ventricular filling. All other magnetic resonance measurements of cardiac function were normal. HRCT demonstrated mild asbestosis in three patients in which neither the chest radiograph nor magnetic resonance showed signs of parenchymal disease, and pericardiac calcification without thickening in one patient. It is concluded that magnetic resonance is superior to HRCT in identifying pericardial thickening, but that HRCT is superior to magnetic resonance in identifying asbestos-related pleural and pulmonary disease.     

COAEs and SSOAEs in adults with increased age

OBJECTIVE: The purpose of this study was to compare click-evoked otoacoustic emissions (COAEs) of subjects having similar auditory thresholds but different age ranges. It is well known that elevated hearing thresholds are common with increasing age and that deterioration of outer hair cells is often noted in cases of hearing loss due to increased age. It has also been reported that evoked otoacoustic emissions (EOAEs) decrease with increased age. However, there is still some question whether changes in EOAEs with aging are associated with the increased hearing threshold or whether there is some additional effect of aging that enfluences EOAEs. DESIGN: COAE input/output functions and synchronized spontaneous OAEs (SSOAEs) were measured in two groups of subjects having similar auditory thresholds, one ranging in age from 19 to 29 yr, the other ranging in age from 40 to 61 yr. Mixed-model ANOVAs were performed to determine whether there were any statistically significant differences in COAEs based on age group. RESULTS: There were no statistically significant differences in COAE level or COAE threshold between age groups. Significant differences in COAEs were found for subjects based on whether they had measurable SSOAEs, regardless of age. CONCLUSIONS: Age does not significantly reduce COAE level nor increase COAE threshold. Other factors, such as presence of SSOAEs and hearing loss, undoubtedly have more influence on COAEs than the factor of age.     

Selective interference with class I major histocompatibility complex presentation of the major immediate-early protein following infection with human cytomegalovirus

Responses of cytotoxic T-cells (Tc) to human cytomegalovirus (CMV) represent the predominant mechanism by which hosts resist CMV infection. The CMV major immediate-early protein (IE) is present throughout the virus replicative cycle. Studies were performed to determine whether Tc specific for IE effectively lyse CMV-infected targets and are thus capable of providing protective immunity against infection. After in vitro stimulation of peripheral blood mononuclear cells with CMV-infected autologous fibroblasts, Tc specific for IE were not readily detectable in CMV-reactive polyclonal Tc lines. However, after stimulation of peripheral blood mononuclear cells with cells selectively expressing IE, weak but detectable IE-specific Tc responses were observed. The frequency of IE-specific Tc clones derived from cultures stimulated with IE-expressing cells was 50 to 100 times lower than the frequency of Tc clones specific for other CMV proteins isolated from cultures stimulated with CMV-infected cells. All of the IE-specific Tc clones, which efficiently lysed targets selectively expressing IE, demonstrated minimal lysis of CMV-infected fibroblasts, despite abundant IE expression in these target cells. In contrast to these results with IE, other viral proteins were efficiently presented during all phases of CMV infection. These data suggest that CMV has evolved a unique mechanism for selectively limiting the presentation of the potentially immunogenic IE protein, which may preclude IE-specific Tc from providing protective immunity to CMV infection.     

Excessive scapular motion in individuals recovering from painful and stiff shoulders: causes and treatment strategies

BACKGROUND AND PURPOSE: Scapular excursion and the wrist speed were studied before and after instruction and practice designed to achieve symmetrical scapular movement. SUBJECTS: Subjects were 10 female and 6 male patients, aged 44 to 78 years (chi=60.3, SD=11.2), with diagnosed shoulder pathologies. METHODS: Subjects were videotaped performing a reaching task. Pain status was monitored. The subjects were instructed to make the scapular movement symmetrical. They then repeated the task, while being videotaped, to monitor the effect of instruction. RESULTS: Individuals with asymmetric upper-extremity starting positions had excessive vertical motion of the involved scapula, which they controlled after instruction. Peak wrist speed of the involved upper extremity was lower only after instruction. CONCLUSION AND DISCUSSION: Even in the absence of biomechanical factors or pain, excessive scapular vertical motion appears to occur in the involved upper extremities of individuals recovering from unilateral shoulder problems. Improved scapular control can follow simple verbal instruction and practice, with a slight decrement in wrist speed.     

Structural studies of the putative O-specific polysaccharide of Acinetobacter baumannii O2 containing 3,6-dideoxy-3-N-(D-3-hydroxybutyryl)amino-D-galactose

A polysaccharide containing D-galactose, 2-deoxy-2-N-acetylamino-D-galactose and 3,6-dideoxy-3-N-(D-3-hydroxybutyryl)amino-D-galactose, probably corresponding to the lipopolysaccharide side chain, was obtained from an aqueous phenol extract of isolated cell walls from Acinetobacter baumannii strain O2. By means of NMR studies and chemical degradations, the repeating unit of the polymer was identified as a branched hexasaccharide of the structure shown, where Fuc3N represents 3-amino-3,6-dideoxygalactose and R represents D-3-hydroxybutyryl. Serological tests indicated that the polymer corresponded to the O2 antigen.