Normal, viii

Deficiency of the VIII C portion of the Factor VIII complex results in classic hemophilia or hemophilia A and is inherited as a sex-finked recessive disorder. Based on the degree of deficiency of the VIII C molecule three different forms of hemophilia A are recognized. Less than 1% VII I C activity equals severe hemophilia A. Two to 10% of normal VIII C activity equals moderately severe hemophilia A. Ten to 25% of normal VIII C activity equals minimal symptomatic disease. Deficiency of the VIIkvWFAg portion of the Factor VIII complex results in von Willebrand disease. There are at present five principal types of von Willebrand disease and numerous subtypes or variants. For the most part, von Willebrand disease is inherited as an autosomal dominant, and a few subtypes may be inherited as an autosomal recessive trait. 

The diffraction is essentially that of a grating. As illustrated in Fig. VIII-7, the Laue condition for incidence normal to the surface is... 

Determination of the potency of Factor VIII is also difficult. This is normally measured by the abiUty of the sample to correct the clotting time of plasma deficient in Factor VIII. A number of methods and practices have evolved for this purpose (231), but these give very different results, particularly when activation of products may also occur (232). International standards have been used, but further standardization of the analytical method and harmonization of working standards is underway (233,234) under the auspices of the ISTH and the EC. 

Factors I, II, III, V, VII, VIII, IX, X, XI, XII, and XIII, Protein C, and Protein S are synthesized in the Hver. Factor III is present in many different organs throughout the body. Factor IV is the divalent cation calcium. The concentration of calcium required for normal function of the blood coagulation system is much less than required for normal physiologic function of many organs in the body, eg, myocardium. 

Antihemophilic factor [9001-28-9] (AHF) is a protein found in normal plasma that is necessary for clot formation. It is needed for transformation of prothrombin to thrombin. Administration of AHF by injection or infusion can temporarily correct the coagulation defect present in patients with hemophilia. Antihemophilic factor VIII (Alpha Therapeutic) has been approved by the FDA as replacement therapy in patients with hemophilia B to prevent bleeding episodes, and also during surgery to correct defective hemostasis (178). 

Borohydrides reduce a-substituted ketones to the corresponding a-substituted alcohols, and such products can be further reduced to olefins (see section VIII). Other reagents serve, through participation of the carbonyl group, to remove the substituent while leaving the ketone intact. The zinc or chromous ion reduction of a-halo ketones is an example of this second type, which is not normally useful for double bond introduction. However, when the derivative being reduced is an a,jS-epoxy ketone, the primary product is a -hydroxy ketone which readily dehydrates to the a,jS-unsaturated ketone. Since... 

Glycogenosis type VIII (phosphorylase b kinase deficiency) gives rise to myopathy and liver disease, either singly or in combination. Phosphorylase b kinase (PBK) converts the inactive b form of both muscle and liver phosphorylases to the active a forms of the enzymes. The ischemic lactate test sometimes shows a flat result as in McArdle s disease, but is more likely to be normal. Histochemical demonstration of myophosphorylase activity in tissue sections shows a near-normal reaction due to the presence of phosphorylase a. Accumulation of glycogen is modest and found mainly in type 2 (fast-twitch glycolytic) muscle fibers. 

Factor VIII 2332 amino acids Mammalian cells Treatment of haemophilia Normally obtained from plasma but now concern over potential contamination with AIDS virus... 

To Illustrate the utility of the technique, we have addressed the question of the anomalous chemlsorptlve behavior of tltanla-supported group VIII metals reduced at high temperatures. The suppression of strong H2 chemisorption on these catalysts has been ascribed to a strong-metal-support Interaction (SMSI) ( ). It has also been found that the reaction activity and selectivity patterns of the catalysts are different In normal and SMSI states... 

Plagioclase has a single large cation site (M) into which all U-series elements partition. This site is normally occupied by Ca and Na, with coordination number increasing with increasing Na content. For simplicity we will assume VIII coordination... 

The severity of bleeding associated with hemophilia correlates with the degree of factor VIII or factor IX deficiency as measured against the normal plasma standard. Table 64-1 summarizes the age at onset and laboratory and clinical manifestations of hemophilia.3... 

Normal range of factor VIII/IX activity level is 0.5-1.5 units/mL (50%—1 50%). 1 unit/mL corresponds to 1 00% of the factor found in 1 mL of normal plasma. CNS, central nervous system ICH, intracranial hemorrhage PCB, postcircumceisional bleeding. 

Primary therapy is based on disease severity and type of hemorrhage.7 Most patients with mild to moderate disease and a minor bleeding episode can be treated with l-desamino-8-D-arginine vasopressin [desmopressin acetate (DDAVP)], a synthetic analog of the antidiuretic hormone vasopressin. DDAVP causes release of von Willebrand factor (vWF) and factor VIII from endogenous storage sites. This formulation increases plasma factor VIII levels by three- to fivefold within 30 minutes. The recommended dose is 0.3 mcg/kg intravenously (in 50 mL normal saline infused over 15 to 30 minutes) or subcutaneously or 300 meg intranasally via concentrated nasal spray every 12 hours. Peak effect with intranasal administration occurs 60 to 90 minutes after administration, which is somewhat later than with intravenous administration. Desmopressin infusion may be administered daily for up to 2 to 3 days. Tachyphylaxis, an attenuated response with repeated administration, may occur after several doses.8... 

Type of Hemorrhage Desired Plasma Factor VIII Level (% of Normal) Desired Plasma Factor XI Level (% of Normal) Duration of Therapy (Days)... 

Because it is a small protein, the factor IX molecule passes into the intravascular and the extravascular spaces. Therefore, the volume of distribution of recombinant factor IX is twice that of factor VIII. Consequently, 1 unit of factor IX administered per kilogram of body weight yields a 1% rise in the plasma factor IX level (0.01 unit/mL, or 1 IU/dL). Thus 1750 units of factor IX provides an incremental increase of 50% of normal (0.5 unit/mL, or 50 IU/dL), that is, 1750 units/70 kg x 0.01 unit/mL (1 IU/dL).12 Additionally, the recovery rate with recombinant factor IX is 20% lower than that with the plasma-derived products. Therefore, initial and subsequent maintenance doses should be adjusted accordingly. 

Most patients with type 1 vWD (functionally normal vWF) and a minor bleeding episode can be treated successfully with desmopressin, which induces secretion of autologous factor VIII and vWF into plasma. The recommended dose is the same as that used to treat mild factor VIII deficiency (0.3 mcg/kg intravenously in 50 mL of normal saline infused over 15 to 30 minutes). This therapy generally is ineffective in type 2A patients who secrete qualitatively abnormal vWF and is controversial in type 2B patients because it may increase the risk of postinfusion thrombocytopenia. Type 3 vWD patients who lack releasable stores of vWF do not respond to DDAVP therapy.18... 

The limits described by these curves are based on experience with cast steel as well as annelaed and normalized steels at stress levels defined by Section VIII, Division I, of the ASME code. See 3.3 and 5.4 in text for additional information. 

Many users have reported satisfactory performance of annealed or normalized and tempered steels produced before 1969, as shown in Figure 1. These steels have been used for pressure-retaining equipment at design stress levels allowed by the 1969 or earlier editions of commonly-accepted codes (such codes include the ASME Code, Section VIII, Division 1 the standards of the American National Standards Institute and, for the lower-strength materials, those of Deutsche Industrie-Normen). However, pressure vessels in hydrogen service have also been constructed using the higher allowable stresses permitted in either Section VIII, Division 2, or modifications of Section III of the ASME Code. Quenched and tempered or normalized and tempered steels have normally... 

The difference in velocities between process (32) and process (34) probably derives from the difference in structure of (VIII) and (XXXI), in the former the Zr-C-C6H6 is distorted due to interaction of the phenyl group with metal from the normal tetrahedral angle of 109° to 90° (see Section II.B). Interaction between the adjacent phenyl group on the polymer chain and metal atom in (XXXI) is probably prevented because of the polymer chain attached to the a-carbon atom as shown below... 

Tables I, III, V, and VII give the kinetic mass loss rate constants. Tables II, IV, VI, and VIII present the activation parameters. In addition to the activation parameters, the rates were normalized to 300°C by the Arrhenius equation in order to eliminate any temperature effects. Table IX shows the char/residue (Mr), as measured at 550°C under N2.

Persons suffering from (the rarer) von Willebrand s disease lack both components of mature factor VIII complex (Figure 12.6). The severity of the resultant disease is somewhat dependent upon the level of intact factor VIII complex produced. Persons completely devoid of it (or expressing levels below 1 per cent of normal values) will experience frequent, severe and often spontaneous bouts of bleeding. 

Persons expressing 5 per cent or above of the normal complex levels experience less severe clinical symptoms. Treatment normally entails administration of factor VIII complex purified from donated blood. More recently, recombinant forms of the product have also become available. Therapeutic regimens can require product administration on a weekly basis, for life. About 1 in 10 000 males are born with a defect in the factor VIII complex and there are approximately 25 000 haemophiliacs currently resident in the USA. 

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