Mathematical modeling of platelet survival with implications for optimal transfusion practice in the chronically platelet transfusion- dependent patient

BACKGROUND: It is known that in vivo platelet survival varies as the platelet count changes. Previous attempts at curve fitting fail to predict the decreased platelet survival in thrombocythemia. Therefore, mathematical relations that more closely approximate platelet survival were derived and used in models of platelet transfusion practice. STUDY DESIGN AND METHODS: A differential equation for platelet loss was derived that included a constant (constant homeostatic loss), a first- order term (senescent loss), and a second-order term (one proportional to the square of the platelet concentration and whose contribution is expected to be significant only at higher platelet concentrations). Data derived from this model was compared to platelet survival data in normal, thrombocytopenic, and thrombocythemic patients and to the platelet decay after high-dose chemotherapy. To provide further validation of this model, predicted and actual platelet requirements were calculated or obtained (chart review) in bone marrow patients with uncomplicated thrombocytopenia after ablation and at two platelet- transfusion thresholds (20 and 10 × 10(9)/L). RESULTS: The equations accurately modeled normal, thrombocytopenic, and thrombocythemic platelet survival. Chart review demonstrated a 12.5 percent reduction in platelet transfusion requirements when the transfusion threshold was reduced from 20 to 10 × 10(9) per L. The model predicted a reduction of 14.0 percent. For 100 days of uncomplicated thrombocytopenia and a transfusion threshold of 10 × 10(9) per L, transfusion of 3 units of platelet concentrates compared to a 6-unit pool of platelet concentrates, resulted in a 22-percent savings of platelet units. CONCLUSION: Platelet survival as a function of platelet concentration can be modeled by use of a differential equation. This model challenges current dogma regarding platelet destruction and predicts decreased platelet survival in thrombocythemic patients. The model illustrates that large doses of platelets would result in greater time between transfusions, however, more units of platelets are used. Consideration should be given to the more frequent use of smaller doses of platelets in patients who chronically require platelet transfusion support.     

Gene and other biological therapies for vascular diseases

Summary— Gene transfer and antisense therapy offer novel approaches to the study and treatment of vascular diseases. The localized nature of vascular diseases like restenosis has made the application of genetic material an attractive therapeutic option. Viral and nonviral vectors have been developed to facilitate the entry of foreign DNA or RNA into cells. Vector improvement and production, demonstration of vector safety and demonstration of therapeutic efficacy are among the main present challenges. Various strategies have already been shown to be successful in preventing restenosis in animal models and include: the transfer of the herpes simplex virus thymidine kinase associated with ganciclovir; transfection of the cell cycle regulatory genes encoding for the active form of retinoblastoma gene product (Rb) or the cyclin-dependant kinase inhibitor p21, and antisense therapy. Therapeutic angiogenesis using gene transfer is a new strategy for the treatment of severe limb ischemia. Transfection of DNA encoding for the vascular endothelial growth factor has resulted in increasing collateral flow in animal models of peripheral ischemia. This approach is currently being investigated in a clinical trial in patients with distal ischemia. Other potential targets for genetic treatment in cardiovascular diseases include thrombosis, extracellular matrix synthesis and lipid metabolism.     

Post-infection fatigue syndrome following Q fever

In 1989, 147 individuals in the West Midlands, UK, were infected with Q fever. Five years later, following anecdotal reports of fatigue, we used a questionnaire-based case-control study to determine the prevalence of chronic fatigue syndrome symptoms in this group. Replies from 71 patients were compared with those from 142 age- and sex-matched controls. Increased sweating (52.9% vs. 31.6%, p = 0.006), breathlessness (50.7% vs. 30.6%, p = 0.006), blurred vision (34.3% vs. 17.8%, p = 0.016) and undue tiredness (68.7% vs. 51.5%, p = 0.03) were found in controls compared to cases. These findings were similar to those in Australian abbatoir workers occupationally exposed to Q fever. CDC criteria for chronic fatigue syndrome were fulfilled by 42.3% of cases and 26% of controls. Using visual analogue scores, symptoms were more severe in cases than in controls. Our findings support the existence of a chronic fatigue state following acute Q fever, in a group of patients exposed just once to the organism, and in circumstances free of such confounding factors as lawsuits over compensation.      

A Chromatographic Study on the Glycosides of Aerva lanata L.

AIM:In order to identify the HPTLC profile(bio-marker),at species level,for the identification and confirmation of crude drugs,HPTLC separation was initiated on different parts of Aerva lanata L.from South India.METHODS:Preliminary phyto-chemical screening was done by the method of Harborne.HPTLC studies were carried out following Harborne and Wagner et al method.The Ethyl acetate-ethanol-water(8:2:1.2)was employed as mobile phase for glycosides.RESULTS:The methanolic extract of stem,leaves,root,flowers and...     

Recent advances of genetic ancestry testing in biomedical research and direct to consumer testing

In the post-Human Genome Project era, the debate on the concept of race/ethnicity and its implications for biomedical research are dependent on two critical issues: whether and how to classify individuals and whether biological factors play a role in health disparities. The advent of reliable estimates of genetic (or biogeographic) ancestry has provided this debate with a quantitative and more objective tool. The estimation of genetic ancestry allows investigators to control for population stratification in association studies and helps to detect biological causation behind population-specific differences in disease and drug response. New techniques such as admixture mapping can specifically detect population-specific risk alleles for a disease in admixed populations. However, researchers have to be mindful of the correlation between genetic ancestry and socioeconomic and environmental factors that could underlie these differences. More importantly, researchers must avoid the stigmatization of individuals based on perceived or real genetic risks. The latter point will become increasingly sensitive as several 'for profit companies' are offering ancestry and genetic testing directly to consumers and the consequences of the spread of the services of these companies are still unforeseeable.     

Knowledge,attitudes and practices about malaria among communities: Comparing epidemic and non-epidemic prone communities of Muleba district,North-western Tanzania

Background  

Muleba district in North-western Tanzania has experienced malaria epidemics in recent years. Community knowledge, attitudes and practices are important in enhancing disease control interventions. This study investigated determinants of malaria epidemics in the study area in relation to household knowledge, attitudes and practice on malaria.     

A 7-year old white-male boy with progressive neurological deterioration

A 9-month-old boy presented with rapid deterioration of psychomotor development. He developed seizures at 2 months, and shortly thereafter lost motor skills and developed feeding difficulties, increased startle response, red maculas, and decreased vision. His measurements, including head circumference, were greater than the 95th centile. No organomegaly was found. Serum determination of the hemoxsaminidases confirmed the diagnosis of Sandhoff disease.     

Esophageal motility: assessment with synchronous video tape fluoroscopy and manometry

Synchronous video tape fluoroscopy and manometry of the esophagus was performed in 11 subjects (seven men and four women; mean age, 49 years). Four had normal and seven had abnormal esophageal motility (diffuse esophageal spasm, n = 4; nonspecific esophageal motility disorder, n = 3) that was shown by previous manometry. A digital timer appeared on the video tape recording and marked the manometric tracing synchronously. Alternate 5-mL and 10-mL barium boluses were recorded for a total of 10 swallows per patient. Video tape examinations were reviewed prospectively, and the status of primary peristalsis and presence and severity of tertiary activity were noted. A total of 98 swallows (58 normal, 40 abnormal) were correlated, and a 96% agreement was found in assessing primary peristalsis. Overall results of fluoroscopic examinations of each subject during all swallows showed complete agreement with those of manometry; segregating the swallows into groups of five showed 92% concordance. Severe tertiary activity was invariably seen with abnormal primary peristalsis at fluoroscopy.