The relation of platelet density to platelet age: survival of low- and high-density 111indium-labeled platelets in baboons

The relationship between platelet density and platelet age has been studied using continuous linear Percoll density gradients and 111In- labeling of autologous platelets in baboons. To investigate changes in platelet density during senescence in the circulation, baboons were infused with 111In-labeled autologous platelets, and blood was collected at one hour postinfusion and twice daily thereafter for six days. Platelets were isolated from these samples in high yield (greater than 95%) and separated in continuous linear Percoll density gradients following density equilibrium centrifugation. Although at one hour postinfusion the density distribution of radiolabeled platelets coincided closely with the distribution of the total platelet population, a detectable symmetrical shift toward higher densities was observed after five days. The relative specific radioactivity (RSR) of high-density platelets (1.064 to 1.067 g/mL) decreased at a slower rate than that of the total platelet population (platelets of all densities), whereas the RSR of low-density platelets (1.053 to 1.056 g/mL) showed a more immediate and rapid decrease. These results give rise to one of two interpretations: (1) low-density platelets have a shorter survival time than more dense platelets and are therefore cleared from the circulation at a faster rate, or (2) platelets of all densities increase in density upon aging in the circulation. To determine the explanation for changing RSR of different density fractions we studied the in vivo disappearance characteristics of low- and high-density 111In-labeled platelets. There were no significant differences between the mean survival times of low-density platelets (5.0 +/- 0.49 days, +/- 1 SD, n = 6), high-density platelets (4.9 +/- 0.56 days, n = 6), or control platelets representing platelets of all densities (4.9 +/- 0.38 days, n = 6). Although a slight increase in the density of all platelets during platelet senescence is indicated by these studies, we conclude that platelet density heterogeneity is not primarily a consequence of age-related changes in platelet density.     

The effect of liposomal cefoperazone againstPseudomonas aeruginosa in a granulocytopenic mouse model of acute lung infection

Summary The therapeutic efficacy of liposomal cefoperazone againstPseudomonas aeruginosa was investigated in a granulocytopenic mouse model of acute lung infection. Granulocytopenia was induced in mice by intraperitoneal (i.p.) injection of 200 mg/kg cyclophosphamide. Mice were challenged by exposure to an aerosol containingP. aeruginosa and were treated i.p. with liposomal cefoperazone prepared by the dehydration-rehydration method. The half-life of free cefoperazone in the lungs following i.p. administration of the liposomal drug was significantly lengthened (13 min vs. 261 min), and the cefoperazone activity in the lungs remained above the MIC longer after administration of liposomal cefoperazone than after treatment with cefoperazone. Liposomal cefoperazone was more effective than cefoperazone alone in preventing death of granulocytopenic mice from lethal pulmonary challenge withP. aeruginosa (75% vs. 38% survival, p=0.031). Finally,P. aeruginosa was cleared faster from the lungs of mice treated with liposomal cefoperazone when compared with those treated with cefoperazone. This study shows that incorporation of cefoperazone into liposomes enhances the activity of the antibiotic againstP. aeruginosa in a granulocytopenic host.

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Wirksamkeit von liposomalem Cefoperazon gegen akute Lungeninfektionen durch Pseudomonas aeruginosa bei granulozytopenischen Mäusen

Zusammenfassung Die therapeutische Wirksamkeit von liposomalem Cefoperazon bei akuter Lungeninfektion durchPseudomonas aeruginosa wurde am Modell der granulozytopenischen Maus untersucht. Die Granulozytopenie wurde durch intraperitoneale (i.p.) Injektion von 200 mg/kg Cyclophosphamid hervorgerufen. Die Inokulation mitP. aeruginosa erfolgte durch Aerosol. Liposomales Cefoperazon, das mit der Dehydratations-Rehydratations-Methode hergestellt wurde, wurde intraperitoneal appliziert. Nach intraperitonealer Gabe von liposomalem Cefoperazon war die Halbwertszeit von freiem Cefoperazon in der Lunge signifikant länger als bei Applikation des Antibiotikums in freier Form (13 gegenüber 261 min.) und die Lungenkonzentration lag länger über den minimalen Hemmkonzentrationen. In der Prävention tödlicher Lungeninfektionen durchP. aeruginosa war die liposomale Präparation effektiver als freies Cefoperazon (Überlebensrate bei letaler Pseudomonas- Dosis 75% gegenüber 38%; p=0,031). Die Elimination vonP. aeruginosa aus der Lunge erfolgte bei Behandlung der Mäuse mit liposomalem Cefoperazon rascher als bei Gabe des freien Antibiotikums. Die Experimente zeigen, daß die Aktivität von Cefoperazon gegenP. aeruginosa-Infektionen bei Granulozytopenie durch Inkorporation in Liposomen gesteigert werden kann.

     

Frequency of ST-segment depression produced by mental stress in stable angina pectoris from coronary artery disease

Physical exertion is a well-documented trigger of transient myocardial ischemia in patients with coronary disease. More recently, studies have shown that mental stress may also be a cause of myocardial ischemia. The purpose of this study was to examine the relationship of physical activities and perceived mental states to myocardial ischemia while patients were going about their normal daily activities. Twenty-eight patients with documented coronary artery disease underwent ambulatory monitoring of the electrocardiogram. Physical activity and perceived mental status were recorded by patients in a diary which was then graded according to intensity of the activity. Analyses of the continuous electrocardiographic recordings were done separately from the analysis of the diaries. The time of each episode of ischemia, the duration of each episode in minutes and the number of episodes in each 24-hour period were calculated. A total of 372 episodes of ST-segment depression occurred in 912 hours of monitoring. Ischemic events occurring during usual physical and usual mental activities were most frequent (36%). Twenty-six percent of ischemic episodes occurred during increased physical activity, but usual mental activities. Interestingly, 22% of the ischemic events occurred at high levels of mental stress, but low physical activity. Ten percent of episodes occurred during sleep. Although the majority of events occurred during usual daily activities, when duration of ischemia was normalized for time spent in each category, increasing physical or mental activity was associated with an increasing duration of ischemia per unit (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Peripheral blood monoclonal plasma cells as a predictor of survival in patients with multiple myeloma [see comments]

The purpose of this study was to quantitate the number and labeling index of monoclonal plasma cells in the blood of patients with newly diagnosed multiple myeloma (MM) to learn if these values were independent prognostic factors for survival. Patients were candidates for this study if they had untreated myeloma requiring therapy, were evaluated at our institution between 1984 and 1993, and had a sample of blood analyzed with a sensitive immunofluorescence technique for monoclonal plasma cells and the blood B-cell labelling index (BLI). The % blood monoclonal plasma cells (%BPC) and the BLI were analyzed along with stage, marrow plasma cell LI, % marrow plasma cells, calcium, creatinine, albumin, beta-2-microglobulin, and C-reactive protein as univariate and multivariate factors for survival. Eighty percent of the 254 patients accrued to this study had monoclonal BPC detected. The median % BPC was 6% and 57% (144 of 254) of patients had a high number (> or = 4%). Patients with > or = 4% BPC had a median survival of 2.4 years vs 4.4 years for those with < 4% BPC (P < .001). The BLI was also prognostic (P = .008). In a multivariate analysis, the % BPC, age, albumin, stage, marrow plasma cell LI, and the BLI were independent factors for survival. The %BPC and the marrow plasma cell LI best separated the group into low, intermediate, and high risk myeloma with median survivals of 52, 35, and 26 months, respectively. Patients with high %BPC were less likely to have lytic bone disease from their MM (P = .002). The %BPC and the BLI are independent prognostic factors for survival and are useful in identifying patients as low, intermediate, and high risk. Clonal cells in the blood should be quantified in future clinical trials for myeloma.     

The excitability of the trigeminal motor system in sleep bruxism: a transcranial magnetic stimulation and brainstem reflex study

AIMS: Since sleep bruxism (SB) is characterized by grinding and clenching of the teeth during sleep and could be an exaggerated manifestation of normal spontaneous rhythmic masticatory muscle activity, the aim of this study was to obtain a neurophysiological assessment of the excitability of the central jaw motor pathways in patients with signs and symptoms suggestive of SB. METHODS: A total of 30 subjects diagnosed with SB on the basis of self-report of tooth grinding were studied using the "recovery cycle" of the masseter inhibitory reflex (MIR) elicited by electric and magnetic stimulation of the mental nerves and by recording the motor potentials evoked in masseter muscles by transcranial magnetic stimulation. Tests were done during daytime, when the subjects were awake. The data obtained were compared with data from a population of normal subjects. RESULTS: In the putative SB patients and in normal subjects, the MIRs evoked by single electric and magnetic stimuli were similar. With paired stimuli, the degree of suppression of the late silent period was significantly lower (P < .01) in the patients compared to normal subjects, particularly for magnetic stimuli, at various interstimulus intervals. No significant differences were found between the 2 groups of subjects in the masseter motor potentials evoked by transcranial magnetic stimulation. CONCLUSION: Although the data were only obtained during wakefulness in patients self-reporting signs and symptoms suggestive of SB, the findings suggest that an abnormal excitability of the central jaw motor pathways may be present in SB subjects. This increased excitability could derive from an impaired modulation of brainstem inhibitory circuits and not from altered cortical mechanisms. These results support the view that bruxism is mainly centrally mediated and that it involves subcortical structures. The study also indicates that use of the MIR elicited by the double-shock technique could be valuable in the evaluation of bruxism.     

Primary systemic amyloidosis: multivariate analysis for prognostic factors in 168 cases

One hundred sixty-eight patients with primary systemic amyloidosis (AL) were identified. Median survival after diagnosis was 12 months and ranged from 4 months for patients presenting with congestive heart failure to 50 months for those presenting with peripheral neuropathy only. Utilizing the proportional-hazards model in a stepwise multivariate fashion to evaluate the simultaneous influence of putative risk factors as of diagnosis revealed that congestive heart failure, urine light chain, hepatomegaly, and multiple myeloma were the major factors adversely affecting survival during the first year after diagnosis. Serum creatinine, multiple myeloma, orthostatic hypotension, and monoclonal serum protein were the most important variables adversely affecting survival for patients surviving 1 year. These models were used to categorize patients according to the variables in the models into low-, moderate-, and high-risk groups for the first year after diagnosis and separately for subsequent years. The influence of these variables on survival is important in stratification of patients randomized to prospective clinical trials.     

PML risk is the main factor driving the choice of discontinuing natalizumab in a large multiple sclerosis population: results from an Italian multicenter retrospective study

Journal of Neurology - Natalizumab (NTZ) is an effective treatment for relapsing–remitting multiple sclerosis (RRMS). However, patients and physicians may consider discontinuing NTZ therapy...     

Exploring Patient Perceptions of Noninvasive Brain Stimulation: A Systematic Review

ObjectiveTo synthesize and critically appraise literature exploring patient perceptions regarding the therapeutic use of noninvasive brain stimulation.Material and MethodsA systematic search of CINHAL, PUBMED, Web of Science, and Medline was performed. Reference lists of relevant articles were also screened. Studies exploring participant perceptions regarding the therapeutic use of noninvasive brain stimulation were eligible for inclusion. Perceptions were divided into three domains: knowledge, experience, and attitudes. Noninvasive brain stimulation was defined as any neuromodulation technique that alters brain activity but does not require invasive methods such as surgery. No restrictions were placed upon study design or participant population. Two reviewers performed data extraction and risk of bias assessment. Data relating to methodological characteristics, participant demographics, type of noninvasive brain stimulation, and nature of perceptions (knowledge, experience, or attitudes) were extracted.ResultsFour studies comprising data from 163 participants met the inclusion criteria. All studies investigated perceptions of repetitive transcranial magnetic stimulation (rTMS) in psychiatric populations. Most participants perceived rTMS to be safe and beneficial, demonstrated low levels of fear, and were willing to recommend the intervention to others. No studies were found investigating patient perception of transcranial direct current stimulation (tDCS).ConclusionThe findings from this review suggest that rTMS is well accepted as a therapeutic treatment among psychiatric populations, providing support for its clinical utility. Future work is needed to determine if similar findings exist for other conditions (eg, chronic pain) and for other therapeutic forms of brain stimulation (eg, tDCS).     

Adult-onset sporadic chorea: real-world data from a single-centre retrospective study

Neurological Sciences - Adult-onset sporadic chorea includes a wide and heterogeneous group of conditions whose differential diagnosis and treatments are often challenging and extensive. To analyse...