Effect of calcium ion concentration on the ability of fibrinogen and von Willebrand factor to support the ADP-induced aggregation of human platelets

To investigate the suggestion that von Willebrand factor (vWf) can substitute for fibrinogen in supporting ADP-induced aggregation of human platelets, we studied platelet reactions in two media: (1) a high calcium medium, Tyrode-albumin solution containing calcium ions in the physiological range of 2 mmol/L, and (2) a low calcium medium, modified Tyrode-albumin solution from which calcium salt was omitted (calcium ion concentration approximately 20 mumol/L). In the high calcium medium vWf even at concentrations up to six times as high as physiological, showed little or no potentiation of ADP-induced platelet aggregation, whereas fibrinogen strongly potentiated reversible aggregation without thromboxane formation or release of granule contents. In the low calcium medium, either vWf or fibrinogen supported biphasic aggregation in response to ADP, with thromboxane formation and release of granule contents. Aspirin and the thromboxane receptor blocker BM 13.177 inhibited these secondary responses to von Willebrand factor, indicating that they require thromboxane A2 formation and feedback amplification by thromboxane A2. A monoclonal antibody, 10E5, to the platelet glycoprotein IIb/IIIa complex inhibited both primary and secondary aggregation. Although vWf supports ADP-induced aggregation when the concentration of ionized calcium is in the micromolar range, it does not support ADP-induced aggregation in the presence of a concentration of ionized calcium in the physiological range, indicating that vWf probably cannot substitute for fibrinogen in supporting ADP- induced aggregation in vivo.     

The effect of gastroenterology training on the efficiency and cost of care provided to patients with diverticulitis

BACKGROUND & AIMS: National trends emphasize the need for cost- efficient medical care with no diminution in quality. The most appropriate role for various physician groups has yet to be determined. The aim of this study was to investigate the efficiency of medical care provided by family practitioners (FPs), internists (IMs), and gastroenterologists (GIs) for acute diverticulitis. METHODS: All medicare hospitalizations from 1990 to 1993 in Illinois caused by acute diverticulitis, with FPs, IMs, or GIs as the primary attending physician, were included in the study. RESULTS: The primary attending physician was an FP in 1019 cases, an IM in 2535 cases, and a GI in 163 cases. The age and sex distributions were similar. The length of stay was significantly shorter (P < 0.0001) for GIs (7.4 +/- 6 days) than for FPs (7.9 +/- 14 days) or IMs (8.6 +/- 7 days). Readmission rate was significantly less (P < 0.03) for GIs (4.5%) than for FPs (7.7%) or IMs (10.0%). No significant differences were noted in complication rates or mortality. CONCLUSIONS: Patients with diverticulitis treated by GIs have a shorter hospital stay and a lower risk for readmission than patients treated by FPs or IMs. This improved quality of care should be considered by managed care organizations because they decide the role of various physician groups. (Gastroenterology 1997 Jun;112(6):1859-62)     

Haemoglobin disorders in Australia: where are we now and where will we be in the future?

Inherited disorders of haemoglobin (Hb), such as thalassaemia and sickle cell disease (SCD) are common and responsible for significant morbidity and mortality on a global scale. As Australia becomes increasingly ethnically diverse, their prevalence will increase. However, we lack important demographic and epidemiological data to manage these disorders and their consequences and to support affected individuals and communities. Thalassaemia and SCD are lifelong conditions. Affected individuals have reduced life expectancies, poorer quality of life and complex healthcare needs. Treatment strategies currently focus on prenatal diagnosis, red blood cell transfusion, iron chelation, management of iron‐related complications, haemopoietic stem cell transplantation (HSCT) and hydroxyurea. Currently, the only curative therapy is HSCT; however, gene therapy offers the possibility of cure and trials are currently underway. These therapies are associated with significant complications and substantial costs; there is also evidence of variation in approaches to diagnosis and care. Optimal strategies for many aspects of management are not yet defined and more research is necessary to inform clinical care and health service delivery.     

Serum amyloid A serum concentrations and genotype do not explain low incidence of amyloidosis in Hyper-IgD syndrome

Background.?Hyper-IgD and periodic fever syndrome (HIDS) is an autosomal recessively inherited disorder characterized by recurrent episodes of fever and inflammation. Unlike other chronic inflammatory conditions, amyloidosis is very rare in HIDS. For deposition of amyloid of the AA type, high concentrations of SAA are a prerequisite, together with certain SAA1 gene polymorphisms. The SAA1.1 genotype predisposes for amyloidosis, while SAA1.5 genotype exerts a protective effect.

Aim of the study.?To determine if SAA concentrations and SAA1 gene polymorphisms could explain the virtual absence of amyloidosis in HIDS patients.

Methods.?We measured SAA and CRP concentrations in serum of 20 HIDS patients during an attack and during the asymptomatic phase. Genotype of SAA1 gene was determined in 60 HIDS patients.

Results.?SAA serum concentrations during attacks were very high (median 205?mg/l; range 75–520?mg/l, normal?<?3.1?mg/l). During attack-free periods 45% of patients still had elevated SAA concentrations. The distribution of the genotype of SAA1 gene in HIDS was similar to healthy controls (SAA1.1 0.41 vs. 0.50 p?=?0.32).

Conclusion.?Patients with HIDS have high SAA during attacks and show sub-clinical inflammation when asymptomatic. The low incidence of amyloidosis cannot be explained by a predominance of non amyloidogenic SAA related genotypes.     

Visual identification of bacterially contaminated red cells

There have been increasing numbers of reports of transfusion-acquired Yersinia enterocolitica bacteremia (including several fatal cases). Fifteen units of whole blood were inoculated with various concentrations of Y. enterocolitica serotype 0:3 and processed into AS-3 preserved red cells (RBCs). Consistent growth of the organism was found at inoculum concentrations greater than or equal to 10 colony-forming units per mL. In all 13 units of RBCs that supported the growth of Y. enterocolitica, a darkening in color (due to hemolysis and a decrease in pO2) was observed in the bag. The attached sample segments, which were sealed from the main unit, remained sterile and did not darken. This color change was apparent in all the contaminated units by Day 35, which was 1.5 to 2 weeks after the bacteria were first detected in cultures of the blood. Hence, by comparison of the color of the segment tubing with that of the unit itself, units grossly contaminated with Y. enterocolitica can be identified prior to transfusion. Moreover, review of photographs on file at the Centers for Disease Control revealed this dramatic color change in 2 units of blood that caused transfusion-transmitted sepsis (Enterobacter agglomerans and an unidentified gram-negative bacillus, not Yersinia sp.), which demonstrated that the color change was not limited to Y. enterocolitica. This method of visual identification of contaminated units of blood could decrease the incidence of posttransfusion bacterial sepsis.     

A Toxicological Basis to Derive a Generic Interspecies Uncertainty Factor.

A new method is proposed to derive the size of the interspecies uncertainty factor (UF) that is toxicologically and statistically based. The method involves quantifying interspecies variation in susceptibility to numerous toxic substances via the use of binary interspecies comparisons that are converted to a 95% UF. This interspecies UF represents an estimate of the upper 95% of the population of 95% prediction intervals (PI) for binary interspecies comparisons within four categories of phylogenetic relatedness (species within genus, genera within family, families within order, orders within class). The 95% interspecies UFs range from a low of 10 for species within genus up to 65 for orders within class. Most mammalian toxicology studies involving mice, rats, cats, dogs, gerbils, and rabbits are orders-within- class categories for human risk assessment and would be provided a 65-fold UF. Larger or smaller interspecies UF values could be selected on the level of protection desired.