Elizabeth V. Potter

Failure of AHF concentrate to control bleeding in von Willebrand's disease

Abstract A newly available dried concentrate of antihemophilic factor (Profilate ® , Abbott Laboratories) was compared with standard, blood-bank prepared cryoprecipitate In the control of bleeding in a patient with von Willebrands disease. Profilate effectively raised plasma levels of factor VIII but produced only half the expected increase in plasma ristocetin aggregation factor (RAF), and this RAF did not bind readily to the platelets in the presence of ristocetin. Furthermore, the Profilate had little effect upon the bleeding time or the clinical hemorrhage. In contrast, the cryoprecipitate did increase plasma RAF to the expected level, and this RAF bound readily to the patients platelets in the presence of ristocetin. Cryoprecipitate promptly controlled bleeding. We conclude that the RAF present in Profilate retains in vitro activity but is incapable of augmenting platelet function in vivo.

Tropical acute rheumatic fever and associatedstreptococcal infections compared with concurrent acute glomerulonephritis

Ninety-three patients with acute rheumatic fever and 195 patients with acute glomerulonephritis were observed in Trinidad during an outbreak of scabies with a high incidence of secondary streptococcal infections. Clinical and laboratory manifestations of ARF were the same as those seen in temperate zones, except that antistreptolysin O titers were less markedly increased. The patients with ARF were similar to those with AGN in respect to sex, race, location of residence, and living conditions, but were older and had markedly fewer skin infections. Currently prevalent nephritogenic streptococcal strains never were isolated from patients with ARF even when M55 streptococci appeared and led to an epidemic of AGN.

Continued absence of clinical renal disease seven to 12 years after poststreptococcal acute glomerulonephritis in Trinidad.

Abstract Continued improvement was noted among 722 patients in Trinidad seven to 12 years after the onset of poststreptococcal glomerulonephritis. In the five years since earlier follow-up, two of 709 patients with previous symptomatic disease apparently had died from renal failure, and 10 patients had died from unrelated causes. Nineteen patients presently had proteinuria, three had hematuria, and three had proteinuria plus hematuria. Of these abnormalities, proteinurias in only three patients and proteinuria plus hematurias in three more patients were persistent. Thus, 0.8 per cent of the study group had persistent abnormalities. When one adds those dead with renal disease, the percentage with renal damage becomes 1.1 per cent. In addition, six patients had protein in the two urine samples obtained after assuming the lordotic position for 10 minutes and in only one of the two urine samples obtained upon rising in the morning, making 1.4 per cent with probable evidence of chronic renal disease, including the dead patients. Hypertension was present in 16 (2.3 per cent) of the patients and was much more common in those more than 20 years old (18.4 per cent). However, this prevalence of hypertension did not exceed that found in normal Trinidadians. Only three patients had serum creatinine values greater than 1.2 mg/dl. None of 13 patients with previous asymptomatic glomerulonephritis presently showed any abnormality. Thus, very few cases of chronic poststreptococcal glomerulonephritis appear to have developed in the 722 patients studied.

Changing types of nephritogenic streptococci in Trinidad

The relation of seven different M types of streptococci to acute glomerulonephritis associated with skin lesions in South Trinidad has been studied by means of type-specific antibody assays as well as by isolation and identification of the strains. The data indicate that, one after another, five of these strains have prevailed among patients with acute glomerulonephritis during the past five years. At least three of the strains (M-types 55, 49, 57, and/or 60) were associated with epidemic increases in nephritis cases. The appearance of five consecutively predominant types of nephritogenic streptococci during a relatively short period of time is in contrast to the continuing prevalence of M-type 12 strains among nephritogenic streptococci primarily associated with respiratory infections in temperate zones. These observations suggest that the skin sores commonly found on children in tropical Trinidad, provide a particularly suitable environment for development of nephritogenic types. It remains to be seen whether these types will recur or whether new types will continue to emerge in Trinidad.

Streptococcal infections and epidemic acute glomerulonephritis in South Trinidad

Streptococcal cultures and antibody studies of patients during an epidemic of nephritis in Trinidad, W. I., provided evidence of a streptococcal etiology associated with impetiginous sores. Similar studies of “well” schoolchildren throughout the year revealed high incidences of sores and of streptococci in areas both with and without nephritis. The relation of these infections to antibody responses and to renal disease is considered but not completely defined.

Immunoglobulins and complement components in synovial fluid of patients with acute rheumatic fever.

Three components of complement and six other serum proteins were assayed in synovial fluid and serum samples from 25 patients with acute rheumatic fever in Trinidad. The resulting data indicate a relative decrease in both early and late components of complement within the synovial fluids which suggests local activation by immune complexes. Such activation of complement within the joint spaces may play a primary role in development of the inflammatory arthritis of acute rheumatic fever.

Clinical Healing Two to Six Years after Poststreptococcal Glomerulonephritis in Trinidad

To determine the incidence of chronic nephritis after poststreptococcal acute glomerulonephritis in Trinidad, 760 patients (41 adult) were examined two to six years after recovery from the illness, 344 being studied twice (four and six years). Only 1.8 per cent had persistent urine abnormalities on their last follow-up examination, and another 8.0 per cent had abnormalities that were transient or occurred only after the patient had assumed the lordotic position. In 1.4 per cent hypertension was present, whereas only one had azotemia. Both persistent urine abnormalities and hypertension increased in prevalence with age at onset of prior poststreptococcal glomerulonephritis but did not vary between sexes, races or epidemic versus endemic forms. Half the urine abnormalities present four years after recovery were absent two years later. Thus, poststreptococcal acute glomerulonephritis appears to have a low incidence of chronicity in Trinidad, with continuing resolution for more than four years.

Recall of type specific antibodies in man by injections of streptococcal cell walls.

In the early part of this century several attempts were made to immunize human beings against beta hemolytic streptococci (1-4). These attempts generally were considered to be unsuccessful. The results were difficult to evaluate, however, because of the multiplicity and toxicity of streptococcal antigens and the limited understanding of their relationship to virulence. Subsequently, immunity was correlated with antibody against type specific Mprotein contained in streptococcal cell walls (5-9), and sensitive methods were developed for the assay of these type specific antibodies (6, 7). Partially purified preparations of M protein were employed thereafter as vaccines (10-15). Large doses proved antigenic in rabbits (10-11). Toxic reactions, however, limited vaccination in human beings to the administration of very small amounts of M protein. These quantities rarely provoked an immune response (12-15). Investigators, therefore, have been discouraged by the possibility that the amount of Mprotein which can be tolerated in single doses may be below the threshold of antigenicity. In the course of a controlled study of the immune response to streptococcal pharyngitis (16, 17), patients with infections of known serologic type have been observed for the development of type specific antibody. During the 4 years that this study has been in progress, type specific antibody has disappeared from the blood of approxi-

The Nature of the Vascular Lesion in Thrombotic Thrombocytopenic Purpura.

Excerpt Despite evidence of extensive intravascular microthrombi formation in thrombotic thrombocytopenic purpura (TTP), there is absence of defibrination suggesting an unusual type of vascular les...

Effects of Ancrod (Arvin) in Mice: Studies of Plasma Fibrinogen and Fibrinolytic Activity

Plasma fibrinogen and its degradation products (FDP) were examined in mice given single injections of Ancrod, the purified coagulative fraction of Malayan pit viper venom previously called Arvin. Clottable fibrinogen had disappeared completely 5 min after the injection and slowly reappeared 12 hr later. At least 2 FDP appeared in the plasma 30 min after the injections while 5 hr later only one FDP was present which corresponded to human fragment E. This was in contrast to in vitro lysis of mouse fibrinogen which yielded two late FDP corresponding to human fragments D and E.